Insights into Chromatin Structure and Dynamics in Plants

Directory of Open Access Journals (Sweden)

Stefanie Rosa

2013-11-01

Full Text Available The packaging of chromatin into the nucleus of a eukaryotic cell requires an extraordinary degree of compaction and physical organization. In recent years, it has been shown that this organization is dynamically orchestrated to regulate responses to exogenous stimuli as well as to guide complex cell-type-specific developmental programs. Gene expression is regulated by the compartmentalization of functional domains within the nucleus, by distinct nucleosome compositions accomplished via differential modifications on the histone tails and through the replacement of core histones by histone variants. In this review, we focus on these aspects of chromatin organization and discuss novel approaches such as live cell imaging and photobleaching as important tools likely to give significant insights into our understanding of the very dynamic nature of chromatin and chromatin regulatory processes. We highlight the contribution plant studies have made in this area showing the potential advantages of plants as models in understanding this fundamental aspect of biology.

Highlighting micrographic structures of uranium-zirconium alloys with 6 per cent of weight of Zr

International Nuclear Information System (INIS)

Bouleau, Maurice

1961-01-01

In order to study the transformation kinetics of U-Zr alloys with a Zr content of 6 per cent in weight, the authors searched for a slow enough electrolytic polishing bath, and for an attack and examination method to highlight martensite structures produced by austempering and water tempering, and ultra-fine decomposition structures obtained by austempering. The authors explain the choice of a perchloric-butyl glycol polishing bath, of an examination under polarized light or normal light after appropriate attacks. These studies are reported for annealed alloys, and for processed alloys with martensite or ultra-fine decomposition structures [fr

Crystal structures from the Plasmodium peroxiredoxins: new insights into oligomerization and product binding.

Science.gov (United States)

Qiu, Wei; Dong, Aiping; Pizarro, Juan C; Botchkarsev, Alexei; Min, Jinrong; Wernimont, Amy K; Hills, Tanya; Hui, Raymond; Artz, Jennifer D

2012-03-19

Plasmodium falciparum is the protozoan parasite primarily responsible for more than one million malarial deaths, annually, and is developing resistance to current therapies. Throughout its lifespan, the parasite is subjected to oxidative attack, so Plasmodium antioxidant defences are essential for its survival and are targets for disease control. To further understand the molecular aspects of the Plasmodium redox system, we solved 4 structures of Plasmodium peroxiredoxins (Prx). Our study has confirmed PvTrx-Px1 to be a hydrogen peroxide (H2O2)-sensitive peroxiredoxin. We have identified and characterized the novel toroid octameric oligomer of PyTrx-Px1, which may be attributed to the interplay of several factors including: (1) the orientation of the conserved surface/buried arginine of the NNLA(I/L)GRS-loop; and (2) the C-terminal tail positioning (also associated with the aforementioned conserved loop) which facilitates the intermolecular hydrogen bond between dimers (in an A-C fashion). In addition, a notable feature of the disulfide bonds in some of the Prx crystal structures is discussed. Finally, insight into the latter stages of the peroxiredoxin reaction coordinate is gained. Our structure of PyPrx6 is not only in the sulfinic acid (RSO2H) form, but it is also with glycerol bound in a way (not previously observed) indicative of product binding. The structural characterization of Plasmodium peroxiredoxins provided herein provides insight into their oligomerization and product binding which may facilitate the targeting of these antioxidant defences. Although the structural basis for the octameric oligomerization is further understood, the results yield more questions about the biological implications of the peroxiredoxin oligomerization, as multiple toroid configurations are now known. The crystal structure depicting the product bound active site gives insight into the overoxidation of the active site and allows further characterization of the leaving group

Insights into bacterioplankton community structure from Sundarbans mangrove ecoregion using Sanger and Illumina MiSeq sequencing approaches: A comparative analysis

Directory of Open Access Journals (Sweden)

Anwesha Ghosh

2017-03-01

Full Text Available Next generation sequencing using platforms such as Illumina MiSeq provides a deeper insight into the structure and function of bacterioplankton communities in coastal ecosystems compared to traditional molecular techniques such as clone library approach which incorporates Sanger sequencing. In this study, structure of bacterioplankton communities was investigated from two stations of Sundarbans mangrove ecoregion using both Sanger and Illumina MiSeq sequencing approaches. The Illumina MiSeq data is available under the BioProject ID PRJNA35180 and Sanger sequencing data under accession numbers KX014101-KX014140 (Stn1 and KX014372-KX014410 (Stn3. Proteobacteria-, Firmicutes- and Bacteroidetes-like sequences retrieved from both approaches appeared to be abundant in the studied ecosystem. The Illumina MiSeq data (2.1 GB provided a deeper insight into the structure of bacterioplankton communities and revealed the presence of bacterial phyla such as Actinobacteria, Cyanobacteria, Tenericutes, Verrucomicrobia which were not recovered based on Sanger sequencing. A comparative analysis of bacterioplankton communities from both stations highlighted the presence of genera that appear in both stations and genera that occur exclusively in either station. However, both the Sanger sequencing and Illumina MiSeq data were coherent at broader taxonomic levels. Pseudomonas, Devosia, Hyphomonas and Erythrobacter-like sequences were the abundant bacterial genera found in the studied ecosystem. Both the sequencing methods showed broad coherence although as expected the Illumina MiSeq data helped identify rarer bacterioplankton groups and also showed the presence of unassigned OTUs indicating possible presence of novel bacterioplankton from the studied mangrove ecosystem.

Fabricating graphene supercapacitors: highlighting the impact of surfactants and moieties.

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Brownson, Dale A C; Banks, Craig E

2012-02-01

We highlight the impact of surfactants, routinely used in the fabrication of graphene, which can significantly influence the performance of supercapacitors. Through the utilisation of various graphitic forms we offer insight into the design and fabrication of graphene based supercapacitors. This journal is © The Royal Society of Chemistry 2012

New insight in magnetic saturation behavior of nickel hierarchical structures

Science.gov (United States)

Ma, Ji; Zhang, Jianxing; Liu, Chunting; Chen, Kezheng

2017-09-01

It is unanimously accepted that non-ferromagnetic inclusions in a ferromagnetic system will lower down total saturation magnetization in unit of emu/g. In this study, ;lattice strain; was found to be another key factor to have critical impact on magnetic saturation behavior of the system. The lattice strain determined assembling patterns of primary nanoparticles in hierarchical structures and was intimately related with the formation process of these architectures. Therefore, flower-necklace-like and cauliflower-like nickel hierarchical structures were used as prototype systems to evidence the relationship between assembling patterns of primary nanoparticles and magnetic saturation behaviors of these architectures. It was found that the influence of lattice strain on saturation magnetization outperformed that of non-ferromagnetic inclusions in these hierarchical structures. This will enable new insights into fundamental understanding of related magnetic effects.

Highlighting micrographic structures of uranium alloys containing 0.5 to 10 per cent wt molybdenum

International Nuclear Information System (INIS)

Laniesse, J.; Bouleau, M.

1959-02-01

The authors report a study which aimed at determining for different uranium molybdenum alloys and with respect to their molybdenum content a polishing method which allows a relatively simple grain examination in the as-cast condition, an as perfect as possible resolution of eutectic decompositions, and the appropriate conditions to highlight structures (beta-alpha and gamma-alpha martensite transformations, beta phase retention and decomposition, transient structures, eutectoid decomposition, and so on). Alloys differ by their molybdenum content: from 0.5 to 1 per cent wt, 1.5 to 3 per cent wt, 5 to 10 per cent wt

Structural insights into the intertwined dimer of fyn SH2.

Science.gov (United States)

Huculeci, Radu; Garcia-Pino, Abel; Buts, Lieven; Lenaerts, Tom; van Nuland, Nico

2015-12-01

Src homology 2 domains are interaction modules dedicated to the recognition of phosphotyrosine sites incorporated in numerous proteins found in intracellular signaling pathways. Here we provide for the first time structural insight into the dimerization of Fyn SH2 both in solution and in crystalline conditions, providing novel crystal structures of both the dimer and peptide-bound structures of Fyn SH2. Using nuclear magnetic resonance chemical shift analysis, we show how the peptide is able to eradicate the dimerization, leading to monomeric SH2 in its bound state. Furthermore, we show that Fyn SH2's dimer form differs from other SH2 dimers reported earlier. Interestingly, the Fyn dimer can be used to construct a completed dimer model of Fyn without any steric clashes. Together these results extend our understanding of SH2 dimerization, giving structural details, on one hand, and suggesting a possible physiological relevance of such behavior, on the other hand. © 2015 The Protein Society.

Insight, self-stigma and psychosocial outcomes in Schizophrenia: a structural equation modelling approach.

Science.gov (United States)

Lien, Y-J; Chang, H-A; Kao, Y-C; Tzeng, N-S; Lu, C-W; Loh, C-H

2018-04-01

Poor insight is prevalent in patients with schizophrenia and has been associated with acute illness severity, medication non-adherence and poor treatment outcomes. Paradoxically, high insight has been associated with various undesirable outcomes, including low self-esteem, depression and low subjective quality of life (QoL) in patients with schizophrenia. Despite the growing body of studies conducted in Western countries supporting the pernicious effects of improved insight in psychosis, which bases on the level of self-stigma, the effects are unclear in non-Western societies. The current study examined the role of self-stigma in the relationship between insight and psychosocial outcomes in a Chinese population. A total of 170 outpatients with schizophrenia spectrum disorders were recruited from two general university hospitals. Sociodemographic data and clinical variables were recorded and self-report scales were employed to measure self-stigma, depression, insight, self-esteem and subjective QoL. Structural equation modelling (SEM) was used to analyse the cross-sectional data. High levels of self-stigma were reported by 39% of the participants (n = 67). The influences of insight, self-stigma, self-esteem and depression on subjective QoL were confirmed by the SEM results. Our model with the closest fit to the data (χ 2 = 33.28; df = 20; p = 0.03; χ 2/df = 1.66; CFI = 0.98; TLI = 0.97; RMSEA = 0.06) demonstrated that self-stigma might fully mediate the association of insight with low self-esteem, depression and poor subjective QoL. High insight into illness contributed to self-stigma, which caused low self-esteem and depression and, consequently, low QoL. Notably, insight did not directly affect self-esteem, depression or QoL. Furthermore, the association of insight with poor psychosocial outcomes was not moderated by self-stigma. Our findings support the mediating model of insight relevant to the poor psychosocial outcomes of individuals diagnosed with

Structure of Human GIVD Cytosolic Phospholipase A2 Reveals Insights into Substrate Recognition

Energy Technology Data Exchange (ETDEWEB)

Wang, Hui; Klein, Michael G.; Snell, Gyorgy; Lane, Weston; Zou, Hua; Levin, Irena; Li, Ke; Sang, Bi-Ching (Takeda Cali)

2016-07-01

Cytosolic phospholipases A2 (cPLA2s) consist of a family of calcium-sensitive enzymes that function to generate lipid second messengers through hydrolysis of membrane-associated glycerophospholipids. The GIVD cPLA2 (cPLA2δ) is a potential drug target for developing a selective therapeutic agent for the treatment of psoriasis. Here, we present two X-ray structures of human cPLA2δ, capturing an apo state, and in complex with a substrate-like inhibitor. Comparison of the apo and inhibitor-bound structures reveals conformational changes in a flexible cap that allows the substrate to access the relatively buried active site, providing new insight into the mechanism for substrate recognition. The cPLA2δ structure reveals an unexpected second C2 domain that was previously unrecognized from sequence alignments, placing cPLA2δ into the class of membrane-associated proteins that contain a tandem pair of C2 domains. Furthermore, our structures elucidate novel inter-domain interactions and define three potential calcium-binding sites that are likely important for regulation and activation of enzymatic activity. These findings provide novel insights into the molecular mechanisms governing cPLA2's function in signal transduction.

Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA

International Nuclear Information System (INIS)

Sidhu, Navdeep S.; Schreiber, Kathrin; Pröpper, Kevin; Becker, Stefan; Usón, Isabel; Sheldrick, George M.; Gärtner, Jutta; Krätzner, Ralph; Steinfeld, Robert

2014-01-01

Mucopolysaccharidosis IIIA is a fatal neurodegenerative disease that typically manifests itself in childhood and is caused by mutations in the gene for the lysosomal enzyme sulfamidase. The first structure of this enzyme is presented, which provides insight into the molecular basis of disease-causing mutations, and the enzymatic mechanism is proposed. Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. Here, the crystal structure of glycosylated SGSH is presented at 2 Å resolution. Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder

Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA

Energy Technology Data Exchange (ETDEWEB)

Sidhu, Navdeep S. [University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen (Germany); University of Göttingen, Tammannstrasse 4, 37077 Göttingen (Germany); Schreiber, Kathrin [University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen (Germany); Pröpper, Kevin [University of Göttingen, Tammannstrasse 4, 37077 Göttingen (Germany); Becker, Stefan [Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany); Usón, Isabel [Instituto de Biologia Molecular de Barcelona (IBMB–CSIC), Barcelona Science Park, Baldiri Reixach 15, 08028 Barcelona (Spain); Institucio Catalana de Recerca i Estudis Avancats (ICREA), (Spain); Sheldrick, George M. [University of Göttingen, Tammannstrasse 4, 37077 Göttingen (Germany); Gärtner, Jutta; Krätzner, Ralph, E-mail: rkraetz@gwdg.de; Steinfeld, Robert, E-mail: rkraetz@gwdg.de [University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen (Germany)

2014-05-01

Mucopolysaccharidosis IIIA is a fatal neurodegenerative disease that typically manifests itself in childhood and is caused by mutations in the gene for the lysosomal enzyme sulfamidase. The first structure of this enzyme is presented, which provides insight into the molecular basis of disease-causing mutations, and the enzymatic mechanism is proposed. Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. Here, the crystal structure of glycosylated SGSH is presented at 2 Å resolution. Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder.

Planned Products of the Mars Structure Service for the InSight Mission to Mars

Science.gov (United States)

Panning, Mark P.; Lognonné, Philippe; Bruce Banerdt, W.; Garcia, Raphaël; Golombek, Matthew; Kedar, Sharon; Knapmeyer-Endrun, Brigitte; Mocquet, Antoine; Teanby, Nick A.; Tromp, Jeroen; Weber, Renee; Beucler, Eric; Blanchette-Guertin, Jean-Francois; Bozdağ, Ebru; Drilleau, Mélanie; Gudkova, Tamara; Hempel, Stefanie; Khan, Amir; Lekić, Vedran; Murdoch, Naomi; Plesa, Ana-Catalina; Rivoldini, Atillio; Schmerr, Nicholas; Ruan, Youyi; Verhoeven, Olivier; Gao, Chao; Christensen, Ulrich; Clinton, John; Dehant, Veronique; Giardini, Domenico; Mimoun, David; Thomas Pike, W.; Smrekar, Sue; Wieczorek, Mark; Knapmeyer, Martin; Wookey, James

2017-10-01

The InSight lander will deliver geophysical instruments to Mars in 2018, including seismometers installed directly on the surface (Seismic Experiment for Interior Structure, SEIS). Routine operations will be split into two services, the Mars Structure Service (MSS) and Marsquake Service (MQS), which will be responsible, respectively, for defining the structure models and seismicity catalogs from the mission. The MSS will deliver a series of products before the landing, during the operations, and finally to the Planetary Data System (PDS) archive. Prior to the mission, we assembled a suite of a priori models of Mars, based on estimates of bulk composition and thermal profiles. Initial models during the mission will rely on modeling surface waves and impact-generated body waves independent of prior knowledge of structure. Later modeling will include simultaneous inversion of seismic observations for source and structural parameters. We use Bayesian inversion techniques to obtain robust probability distribution functions of interior structure parameters. Shallow structure will be characterized using the hammering of the heatflow probe mole, as well as measurements of surface wave ellipticity. Crustal scale structure will be constrained by measurements of receiver function and broadband Rayleigh wave ellipticity measurements. Core interacting body wave phases should be observable above modeled martian noise levels, allowing us to constrain deep structure. Normal modes of Mars should also be observable and can be used to estimate the globally averaged 1D structure, while combination with results from the InSight radio science mission and orbital observations will allow for constraint of deeper structure.

Insight into DEG/ENaC channel gating from genetics and structure.

Science.gov (United States)

Eastwood, Amy L; Goodman, Miriam B

2012-10-01

The founding members of the superfamily of DEG/ENaC ion channel proteins are C. elegans proteins that form mechanosensitive channels in touch and pain receptors. For more than a decade, the research community has used mutagenesis to identify motifs that regulate gating. This review integrates insight derived from unbiased in vivo mutagenesis screens with recent crystal structures to develop new models for activation of mechanically gated DEGs.

Oligomeric protein structure networks: insights into protein-protein interactions

Directory of Open Access Journals (Sweden)

Brinda KV

2005-12-01

Full Text Available Abstract Background Protein-protein association is essential for a variety of cellular processes and hence a large number of investigations are being carried out to understand the principles of protein-protein interactions. In this study, oligomeric protein structures are viewed from a network perspective to obtain new insights into protein association. Structure graphs of proteins have been constructed from a non-redundant set of protein oligomer crystal structures by considering amino acid residues as nodes and the edges are based on the strength of the non-covalent interactions between the residues. The analysis of such networks has been carried out in terms of amino acid clusters and hubs (highly connected residues with special emphasis to protein interfaces. Results A variety of interactions such as hydrogen bond, salt bridges, aromatic and hydrophobic interactions, which occur at the interfaces are identified in a consolidated manner as amino acid clusters at the interface, from this study. Moreover, the characterization of the highly connected hub-forming residues at the interfaces and their comparison with the hubs from the non-interface regions and the non-hubs in the interface regions show that there is a predominance of charged interactions at the interfaces. Further, strong and weak interfaces are identified on the basis of the interaction strength between amino acid residues and the sizes of the interface clusters, which also show that many protein interfaces are stronger than their monomeric protein cores. The interface strengths evaluated based on the interface clusters and hubs also correlate well with experimentally determined dissociation constants for known complexes. Finally, the interface hubs identified using the present method correlate very well with experimentally determined hotspots in the interfaces of protein complexes obtained from the Alanine Scanning Energetics database (ASEdb. A few predictions of interface hot

Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight.

Science.gov (United States)

Regad, Leslie; Chéron, Jean-Baptiste; Triki, Dhoha; Senac, Caroline; Flatters, Delphine; Camproux, Anne-Claude

2017-01-01

Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC), obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at http://www.mti.univ-paris-diderot.fr/recherche/plateformes/logiciels.

Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight.

Directory of Open Access Journals (Sweden)

Leslie Regad

Full Text Available Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC, obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at

New Insights into the Microbiota of Moth Pests.

Science.gov (United States)

Mereghetti, Valeria; Chouaia, Bessem; Montagna, Matteo

2017-11-18

In recent years, next generation sequencing (NGS) technologies have helped to improve our understanding of the bacterial communities associated with insects, shedding light on their wide taxonomic and functional diversity. To date, little is known about the microbiota of lepidopterans, which includes some of the most damaging agricultural and forest pests worldwide. Studying their microbiota could help us better understand their ecology and offer insights into developing new pest control strategies. In this paper, we review the literature pertaining to the microbiota of lepidopterans with a focus on pests, and highlight potential recurrent patterns regarding microbiota structure and composition.

New insights into the structure and composition of technical lignins : A comparative characterisation study

NARCIS (Netherlands)

Constant, Sandra|info:eu-repo/dai/nl/374650519; Wienk, Hans L J|info:eu-repo/dai/nl/203884884; Frissen, Augustinus E.; Peinder, Peter De|info:eu-repo/dai/nl/325810818; Boelens, Rolf|info:eu-repo/dai/nl/070151407; Van Es, Daan S.; Grisel, Ruud J H; Weckhuysen, Bert M.|info:eu-repo/dai/nl/285484397; Huijgen, Wouter J J; Gosselink, Richard J A; Bruijnincx, Pieter C A|info:eu-repo/dai/nl/33799529X

2016-01-01

Detailed insight into the structure and composition of industrial (technical) lignins is needed to devise efficient thermal, bio- or chemocatalytic valorisation strategies. Six such technical lignins covering three main industrial pulping methods (Indulin AT Kraft, Protobind 1000 soda lignin and

New insights into the structure and composition of technical lignins: a comparative characterisation study

NARCIS (Netherlands)

Constant, Sandra; Wienk, Hans L.J.; Frissen, A.E.; Peinder, de Peter; Boelens, Rolf; Es, van D.S.; Grisel, Ruud J.H.; Weckhuysen, Bert M.; Huijgen, W.J.J.; Gosselink, R.J.A.; Bruijnincx, Pieter C.A.

2016-01-01

Detailed insight into the structure and composition of industrial (technical) lignins is needed to devise efficient thermal, bio- or chemocatalytic valorisation strategies. Six such technical lignins covering three main industrial pulping methods (Indulin AT Kraft, Protobind 1000 soda lignin and

Cassini's Grand Finale Science Highlights

Science.gov (United States)

Spilker, Linda

2017-10-01

After 13 years in orbit, the Cassini-Huygens Mission to Saturn ended in a science-rich blaze of glory. Cassini returned its final bits of unique science data on September 15, 2017, as it plunged into Saturn's atmosphere satisfying planetary protection requirements. Cassini's Grand Finale covered a period of roughly five months and ended with the first time exploration of the region between the rings and planet.The final close flyby of Titan in late April 2017 propelled Cassini across Saturn’s main rings and into its Grand Finale orbits; 22 orbits that repeatedly dove between Saturn’s innermost rings and upper atmosphere making Cassini the first spacecraft to explore this region. The last orbit turned the spacecraft into the first Saturn upper atmospheric probe.The Grand Finale orbits provided highest resolution observations of both the rings and Saturn, and in-situ sampling of the ring particle composition, Saturn's atmosphere, plasma, and innermost radiation belts. The gravitational field was measured to unprecedented accuracy, providing information on the interior structure of the planet, winds in the deeper atmosphere, and mass of the rings. The magnetic field provided insight into the physical nature of the magnetic dynamo and structure of the internal magnetic field. The ion and neutral mass spectrometer sampled the upper atmosphere for molecules that escape the atmosphere in addition to molecules originating from the rings. The cosmic dust analyzer directly sampled the composition from different parts of the main rings for the first time. Fields and particles instruments directly measured the plasma environment between the rings and planet.Science highlights and new mysteries gleaned to date from the Grand Finale orbits will be discussed.The research described in this paper was carried out in part at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration. Copyright 2017

New insights into apoptosome structure and function.

Science.gov (United States)

Dorstyn, Loretta; Akey, Christopher W; Kumar, Sharad

2018-05-15

The apoptosome is a platform that activates apical procaspases in response to intrinsic cell death signals. Biochemical and structural studies in the past two decades have extended our understanding of apoptosome composition and structure, while illuminating the requirements for initiator procaspase activation. A number of studies have now provided high-resolution structures for apoptosomes from C. elegans (CED-4), D. melanogaster (Dark), and H. sapiens (Apaf-1), which define critical protein interfaces, including intra and interdomain interactions. This work also reveals interactions of apoptosomes with their respective initiator caspases, CED-3, Dronc and procaspase-9. Structures of the human apoptosome have defined the requirements for cytochrome c binding, which triggers the conversion of inactive Apaf-1 molecules to an extended, assembly competent state. While recent data have provided a detailed understanding of apoptosome formation and procaspase activation, they also highlight important evolutionary differences with functional implications for caspase activation. CARD/CARD interactions in the CED-4, Dark and Apaf-1 apoptosomes. Type I, II and III interfaces that stabilize CARD-CARD interactions are indicated (left column). Note that the Type I interface appears to be unique to Apaf-1/pc-9 CARD interactions. Middle column shows cartoons of the active states of the CARD-CARD disks, illustrating the two CED-4 tetrameric ring layers (top) and the recruitment of 8 Dronc CARDs and between 3-4 pc-9 CARDs, to the Dark and Apaf-1 apoptosomes respectively (middle and lower panels). Ribbon diagrams of the CED-4, Dark and Apaf-1 apoptosomes are shown (right column).

New Insights about Enzyme Evolution from Large Scale Studies of Sequence and Structure Relationships*

Science.gov (United States)

Brown, Shoshana D.; Babbitt, Patricia C.

2014-01-01

Understanding how enzymes have evolved offers clues about their structure-function relationships and mechanisms. Here, we describe evolution of functionally diverse enzyme superfamilies, each representing a large set of sequences that evolved from a common ancestor and that retain conserved features of their structures and active sites. Using several examples, we describe the different structural strategies nature has used to evolve new reaction and substrate specificities in each unique superfamily. The results provide insight about enzyme evolution that is not easily obtained from studies of one or only a few enzymes. PMID:25210038

Magnetic apatite for structural insights on the plasma membrane

International Nuclear Information System (INIS)

Stanca, Sarmiza E; Müller, Robert; Dellith, Jan; Deckert, Volker; Krafft, Christoph; Popp, Jürgen; Fritzsche, Wolfgang; Nietzsche, Sandor; Stöckel, Stephan; Biskup, Christoph

2015-01-01

The iron oxide-hydroxyapatite (FeOxHA) nanoparticles reported here differ from those reported before by their advantage of homogeneity and simple preparation; moreover, the presence of carboxymethyldextran (CMD), together with hydroxyapatite (HA), allows access to the cellular membrane, which makes our magnetic apatite unique. These nanoparticles combine magnetic behavior, Raman label ability and the property of interaction with the cellular membrane; they therefore represent an interesting material for structural differentiation of the cell membrane. It was observed by Raman spectroscopy, scanning electron microscopy (SEM) and fluorescence microscopy that FeOxHA adheres to the plasma membrane and does not penetrate the membrane. These insights make the nanoparticles a promising material for magnetic cell sorting, e.g. in microfluidic device applications. (paper)

Magnetic apatite for structural insights on the plasma membrane

Science.gov (United States)

Stanca, Sarmiza E.; Müller, Robert; Dellith, Jan; Nietzsche, Sandor; Stöckel, Stephan; Biskup, Christoph; Deckert, Volker; Krafft, Christoph; Popp, Jürgen; Fritzsche, Wolfgang

2015-01-01

The iron oxide-hydroxyapatite (FeOxHA) nanoparticles reported here differ from those reported before by their advantage of homogeneity and simple preparation; moreover, the presence of carboxymethyldextran (CMD), together with hydroxyapatite (HA), allows access to the cellular membrane, which makes our magnetic apatite unique. These nanoparticles combine magnetic behavior, Raman label ability and the property of interaction with the cellular membrane; they therefore represent an interesting material for structural differentiation of the cell membrane. It was observed by Raman spectroscopy, scanning electron microscopy (SEM) and fluorescence microscopy that FeOxHA adheres to the plasma membrane and does not penetrate the membrane. These insights make the nanoparticles a promising material for magnetic cell sorting, e.g. in microfluidic device applications.

New insights about enzyme evolution from large scale studies of sequence and structure relationships.

Science.gov (United States)

Brown, Shoshana D; Babbitt, Patricia C

2014-10-31

Understanding how enzymes have evolved offers clues about their structure-function relationships and mechanisms. Here, we describe evolution of functionally diverse enzyme superfamilies, each representing a large set of sequences that evolved from a common ancestor and that retain conserved features of their structures and active sites. Using several examples, we describe the different structural strategies nature has used to evolve new reaction and substrate specificities in each unique superfamily. The results provide insight about enzyme evolution that is not easily obtained from studies of one or only a few enzymes. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Structural insights into viral determinants of nematode mediated Grapevine fanleaf virus transmission.

Directory of Open Access Journals (Sweden)

Pascale Schellenberger

2011-05-01

Full Text Available Many animal and plant viruses rely on vectors for their transmission from host to host. Grapevine fanleaf virus (GFLV, a picorna-like virus from plants, is transmitted specifically by the ectoparasitic nematode Xiphinema index. The icosahedral capsid of GFLV, which consists of 60 identical coat protein subunits (CP, carries the determinants of this specificity. Here, we provide novel insight into GFLV transmission by nematodes through a comparative structural and functional analysis of two GFLV variants. We isolated a mutant GFLV strain (GFLV-TD poorly transmissible by nematodes, and showed that the transmission defect is due to a glycine to aspartate mutation at position 297 (Gly297Asp in the CP. We next determined the crystal structures of the wild-type GFLV strain F13 at 3.0 Å and of GFLV-TD at 2.7 Å resolution. The Gly297Asp mutation mapped to an exposed loop at the outer surface of the capsid and did not affect the conformation of the assembled capsid, nor of individual CP molecules. The loop is part of a positively charged pocket that includes a previously identified determinant of transmission. We propose that this pocket is a ligand-binding site with essential function in GFLV transmission by X. index. Our data suggest that perturbation of the electrostatic landscape of this pocket affects the interaction of the virion with specific receptors of the nematode's feeding apparatus, and thereby severely diminishes its transmission efficiency. These data provide a first structural insight into the interactions between a plant virus and a nematode vector.

Structural insight to mutation effects uncover a common allosteric site in class C GPCRs

DEFF Research Database (Denmark)

Harpsøe, Kasper; Boesgaard, Michael W; Munk, Christian

2017-01-01

MOTIVATION: Class C G protein-coupled receptors (GPCRs) regulate important physiological functions and allosteric modulators binding to the transmembrane domain constitute an attractive and, due to a lack of structural insight, a virtually unexplored potential for therapeutics and the food industry....... Combining pharmacological site-directed mutagenesis data with the recent class C GPCR experimental structures will provide a foundation for rational design of new therapeutics. RESULTS: We uncover one common site for both positive and negative modulators with different amino acid layouts that can...

Highlighting the Structure-Function Relationship of the Brain with the Ising Model and Graph Theory

Directory of Open Access Journals (Sweden)

T. K. Das

2014-01-01

Full Text Available With the advent of neuroimaging techniques, it becomes feasible to explore the structure-function relationships in the brain. When the brain is not involved in any cognitive task or stimulated by any external output, it preserves important activities which follow well-defined spatial distribution patterns. Understanding the self-organization of the brain from its anatomical structure, it has been recently suggested to model the observed functional pattern from the structure of white matter fiber bundles. Different models which study synchronization (e.g., the Kuramoto model or global dynamics (e.g., the Ising model have shown success in capturing fundamental properties of the brain. In particular, these models can explain the competition between modularity and specialization and the need for integration in the brain. Graphing the functional and structural brain organization supports the model and can also highlight the strategy used to process and organize large amount of information traveling between the different modules. How the flow of information can be prevented or partially destroyed in pathological states, like in severe brain injured patients with disorders of consciousness or by pharmacological induction like in anaesthesia, will also help us to better understand how global or integrated behavior can emerge from local and modular interactions.

Sub-Tg enthalpy relaxation in an unstable oxide glass former: insights into the structural heterogeneity

DEFF Research Database (Denmark)

Yue, Yuanzheng; Zhang, Yanfei

Structural heterogeneity plays a crucial role in determining functionality of glasses. In this work we have found that the sub-Tg enthalpy relaxation pattern in a hyperquenched glass is highly sensitive to structural heterogeneity. As a consequence, the former can be used as an effective approach...... to detect and quantify the structural heterogeneity in glass-forming liquids. However, the chemical nature of structural heterogeneity should be revealed by other means such as high resolution microscopic and spectroscopic methods. To study the impact of the structural heterogeneity on the sub-Tg relaxation...... chemical features and degrees of structural heterogeneity in glass-forming liquids. This finding contributes to the microscopic origin of both the primary and secondary relaxation in terms of structural heterogeneity. Finally the results provide insights into the relation between structural heterogeneity...

Insight into the Disciplinary Structure of Nanoscience & Nanotechnology

Directory of Open Access Journals (Sweden)

Chunjuan Luan

2017-01-01

Full Text Available Purpose: This paper aims to gain an insight into the disciplinary structure of nanoscience & nanotechnology (N&N: What is the disciplinary network of N&N like? Which disciplines are being integrated into N&N over time? For a specific discipline, how many other disciplines have direct or indirect connections with it? What are the distinct subgroups of N&N at different evolutionary stages? Such critical issues are to be addressed in this paper. Design/methodology/approach: We map the disciplinary network structure of N&N by employing the social network analysis tool, Netdraw, identifying which Web of Science Categories (WCs mediate nbetweenness centrality in different stages of nano development. Cliques analysis embedded in the Ucinet program is applied to do the disciplinary cluster analysis in the study according to the path of “Network-Subgroup-Cliques,” and a tree diagram is selected as the visualizing type. Findings: The disciplinary network structure reveals the relationships among different disciplines in the N&N developing process clearly, and it is easy for us to identify which disciplines are connected with the core “N&N” directly or indirectly. The tree diagram showing N&N related disciplines provides an interesting perspective on nano research and development (R&D structure. Research limitations: The matrices used to draw the N&N disciplinary network are the original ones, and normalized matrix could be tried in future similar studies. Practical implications: Results in this paper can help us better understand the disciplinary structure of N&N, and the dynamic evolution of N&N related disciplines over time. The findings could benefit R&D decision making. It can support policy makers from government agencies engaging in science and technology (S&T management or S&T strategy planners to formulate efficient decisions according to a perspective of converging sciences and technologies. Originality/value: The novelty of this study

Effect of preparation processes and structural insight into the supermolecular system: Bisacodyl and β-cyclodextrin inclusion complex

International Nuclear Information System (INIS)

Li, Shanshan; Zhai, Yuanming; Yan, Jin; Wang, Lili; Xu, Kailin; Li, Hui

2016-01-01

In this study, β-cyclodextrin (β-CD) and bisacodyl were chosen as model host and guest molecule to explore the effect of preparation processes on the physicochemical properties of inclusion complexes (ICs) and to gain an insight into the structure of ICs. The influence of temperature and pH on complexation was studied by multiple temperature–pH phase solubility analysis. The most favorable conformation was predicted by molecular modeling using AutoDock. "1H nuclear magnetic resonance and rotating frame nuclear Overhauser effect spectroscopy further confirmed the structure. Moreover, bisacodyl·β-CD ICs in solid state were successfully prepared via three different procedures (co-crystallization, co-evaporation, and co-grinding) and fully characterized by several solid-state techniques, namely, Fourier transform infrared spectroscopy, X-ray powder diffraction, thermogravimetric analysis, differential scanning calorimetry, solid-state NMR spectroscopy, and scanning electron microscopy. It was found that acid solution and low temperature were unfavorable for formation of bisacodyl·β-CD. The pyridine moiety was suggested to be enclosed in the hydrophobic cavity of β-CD. The complexes prepared using co-crystallization showed properties similar to those prepared using co-evaporation. Moreover, ICs obtained by co-evaporation and co-grinding had higher loading efficiency, water solubility, and dissolution rate than ICs obtained by co-crystallization. - Highlights: • The structure of inclusion complex-bisacodyl·β-CD was determined. • Thermodynamic behaviors of complexation under different conditions were discussed. • Products from three different preparation methods were systemically compared. • Co-crystallization and co-evaporation produced similar complexes. • Co-evaporation and co-grinding had better effects than co-crystallization.

Effect of preparation processes and structural insight into the supermolecular system: Bisacodyl and β-cyclodextrin inclusion complex

Energy Technology Data Exchange (ETDEWEB)

Li, Shanshan [College of Chemical Engineering, Sichuan University, Chengdu 610065 (China); Zhai, Yuanming [Analytical and Testing Center, Sichuan University, Chengdu 610064 (China); Yan, Jin; Wang, Lili; Xu, Kailin [College of Chemical Engineering, Sichuan University, Chengdu 610065 (China); Li, Hui, E-mail: lihuilab@sina.com [College of Chemical Engineering, Sichuan University, Chengdu 610065 (China)

2016-01-01

In this study, β-cyclodextrin (β-CD) and bisacodyl were chosen as model host and guest molecule to explore the effect of preparation processes on the physicochemical properties of inclusion complexes (ICs) and to gain an insight into the structure of ICs. The influence of temperature and pH on complexation was studied by multiple temperature–pH phase solubility analysis. The most favorable conformation was predicted by molecular modeling using AutoDock. {sup 1}H nuclear magnetic resonance and rotating frame nuclear Overhauser effect spectroscopy further confirmed the structure. Moreover, bisacodyl·β-CD ICs in solid state were successfully prepared via three different procedures (co-crystallization, co-evaporation, and co-grinding) and fully characterized by several solid-state techniques, namely, Fourier transform infrared spectroscopy, X-ray powder diffraction, thermogravimetric analysis, differential scanning calorimetry, solid-state NMR spectroscopy, and scanning electron microscopy. It was found that acid solution and low temperature were unfavorable for formation of bisacodyl·β-CD. The pyridine moiety was suggested to be enclosed in the hydrophobic cavity of β-CD. The complexes prepared using co-crystallization showed properties similar to those prepared using co-evaporation. Moreover, ICs obtained by co-evaporation and co-grinding had higher loading efficiency, water solubility, and dissolution rate than ICs obtained by co-crystallization. - Highlights: • The structure of inclusion complex-bisacodyl·β-CD was determined. • Thermodynamic behaviors of complexation under different conditions were discussed. • Products from three different preparation methods were systemically compared. • Co-crystallization and co-evaporation produced similar complexes. • Co-evaporation and co-grinding had better effects than co-crystallization.

Structural Insights into the Coupling of Virion Assembly and Rotavirus Replication

Science.gov (United States)

Trask, Shane D.; McDonald, Sarah M.; Patton, John T.

2013-01-01

Preface Viral replication is rapid and robust, but it is far from a chaotic process. Instead, successful production of infectious progeny requires that events occur in the correct place and at the correct time. Rotavirus, a segmented double-stranded RNA virus of the Reoviridae family, seems to govern its replication through ordered disassembly and assembly of a triple-layered icosahedral capsid. In recent years, high-resolution structural data have provided unprecedented insight into these events. In this Review, we explore the current understanding of rotavirus replication and how it compares to other Reoviridae family members. PMID:22266782

Structure of the Hantavirus Nucleoprotein Provides Insights into the Mechanism of RNA Encapsidation

Directory of Open Access Journals (Sweden)

Daniel Olal

2016-03-01

Full Text Available Hantaviruses are etiological agents of life-threatening hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome. The nucleoprotein (N of hantavirus is essential for viral transcription and replication, thus representing an attractive target for therapeutic intervention. We have determined the crystal structure of hantavirus N to 3.2 Å resolution. The structure reveals a two-lobed, mostly α-helical structure that is distantly related to that of orthobunyavirus Ns. A basic RNA binding pocket is located at the intersection between the two lobes. We provide evidence that oligomerization is mediated by amino- and C-terminal arms that bind to the adjacent monomers. Based on these findings, we suggest a model for the oligomeric ribonucleoprotein (RNP complex. Our structure provides mechanistic insights into RNA encapsidation in the genus Hantavirus and constitutes a template for drug discovery efforts aimed at combating hantavirus infections.

What are System Dynamics Insights?

OpenAIRE

Stave, K.; Zimmermann, N. S.; Kim, H.

2016-01-01

This paper explores the concept of system dynamics insights. In our field, the term “insight” is generally understood to mean dynamic insight, that is, a deep understanding about the relationship between structure and behavior. We argue this is only one aspect of the range of insights possible from system dynamics activities, and describe a broader range of potential system dynamics insights. We also propose an initial framework for discussion that relates different types of system dynamics a...

Structural insights into human Kif7, a kinesin involved in Hedgehog signalling

Energy Technology Data Exchange (ETDEWEB)

Klejnot, Marta, E-mail: m.klejnot@beatson.gla.ac.uk; Kozielski, Frank, E-mail: m.klejnot@beatson.gla.ac.uk [The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, Scotland (United Kingdom)

2012-02-01

The human Kif7 motor domain structure provides insights into a kinesin of medical significance. Kif7, a member of the kinesin 4 superfamily, is implicated in a variety of diseases including Joubert, hydrolethalus and acrocallosal syndromes. It is also involved in primary cilium formation and the Hedgehog signalling pathway and may play a role in cancer. Its activity is crucial for embryonic development. Kif7 and Kif27, a closely related kinesin in the same subfamily, are orthologues of the Drosophila melano@@gaster kinesin-like protein Costal-2 (Cos2). In vertebrates, they work together to fulfil the role of the single Cos2 gene in Drosophila. Here, the high-resolution structure of the human Kif7 motor domain is reported and is compared with that of conventional kinesin, the founding member of the kinesin superfamily. These data are a first step towards structural characterization of a kinesin-4 family member and of this interesting molecular motor of medical significance.

Mechanism-based Inhibitors of the Human Sirtuin 5 Deacylase: Structure-Activity Relationship, Biostructural, and Kinetic Insight

DEFF Research Database (Denmark)

Rajabi, Nima; Auth, Marina; Troelsen, Kathrin Rentzius

2017-01-01

to date. We provide rationalization of the mode of binding by solving co-crystal structures of selected inhibitors in complex with both human and zebrafish SIRT5, which provide insight for future optimization of inhibitors with more "drug-like" properties. Importantly, enzyme kinetic evaluation revealed...

New Insights on Neurobiological Mechanisms underlying Alcohol Addiction

Science.gov (United States)

Cui, Changhai; Noronha, Antonio; Morikawa, Hitoshi; Alvarez, Veronica A.; Stuber, Garret D.; Szumlinski, Karen K.; Kash, Thomas L.; Roberto, Marisa; Wilcox, Mark V.

2012-01-01

Alcohol dependence/addiction is mediated by complex neural mechanisms that involve multiple brain circuits and neuroadaptive changes in a variety of neurotransmitter and neuropeptide systems. Although recent studies have provided substantial information on the neurobiological mechanisms that drive alcohol drinking behavior, significant challenges remain in understanding how alcohol-induced neuroadaptations occur and how different neurocircuits and pathways cross-talk. This review article highlights recent progress in understanding neural mechanisms of alcohol addiction from the perspectives of the development and maintenance of alcohol dependence. It provides insights on cross talks of different mechanisms and reviews the latest studies on metaplasticity, structural plasticity, interface of reward and stress pathways, and cross-talk of different neural signaling systems involved in binge-like drinking and alcohol dependence. PMID:23159531

Structural insights into the molecular mechanisms of myasthenia gravis and their therapeutic implications

Energy Technology Data Exchange (ETDEWEB)

Noridomi, Kaori; Watanabe, Go; Hansen, Melissa N.; Han, Gye Won; Chen, Lin (USC)

2017-04-25

The nicotinic acetylcholine receptor (nAChR) is a major target of autoantibodies in myasthenia gravis (MG), an autoimmune disease that causes neuromuscular transmission dysfunction. Despite decades of research, the molecular mechanisms underlying MG have not been fully elucidated. Here, we present the crystal structure of the nAChR α1 subunit bound by the Fab fragment of mAb35, a reference monoclonal antibody that causes experimental MG and competes with ~65% of antibodies from MG patients. Our structures reveal for the first time the detailed molecular interactions between MG antibodies and a core region on nAChR α1. These structures suggest a major nAChR-binding mechanism shared by a large number of MG antibodies and the possibility to treat MG by blocking this binding mechanism. Structure-based modeling also provides insights into antibody-mediated nAChR cross-linking known to cause receptor degradation. Our studies establish a structural basis for further mechanistic studies and therapeutic development of MG.

New Insights Toward Quantitative Relationships between Lignin Reactivity to Monomers and Their Structural Characteristics.

Science.gov (United States)

Ma, Ruoshui; Zhang, Xiumei; Wang, Yi; Zhang, Xiao

2018-04-27

The heterogeneous and complex structural characteristics of lignin present a significant challenge to predict its processability (e.g. depolymerization, modifications etc) to valuable products. This study provides a detailed characterization and comparison of structural properties of seven representative biorefinery lignin samples derived from forest and agricultural residues, which were subjected to representative pretreatment methods. A range of wet chemistry and spectroscopy methods were applied to determine specific lignin structural characteristics such as functional groups, inter-unit linkages and peak molecular weight. In parallel, oxidative depolymerization of these lignin samples to either monomeric phenolic compounds or dicarboxylic acids were conducted, and the product yields were quantified. Based on these results (lignin structural characteristics and monomer yields), we demonstrated for the first time to apply multiple-variable linear estimations (MVLE) approach using R statistics to gain insight toward a quantitative correlation between lignin structural properties and their conversion reactivity toward oxidative depolymerization to monomers. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Neurocognition, insight and medication nonadherence in schizophrenia: a structural equation modeling approach.

Directory of Open Access Journals (Sweden)

Laurent Boyer

Full Text Available OBJECTIVE: The aim of this study was to examine the complex relationships among neurocognition, insight and nonadherence in patients with schizophrenia. METHODS: DESIGN: Cross-sectional study. INCLUSION CRITERIA: Diagnosis of schizophrenia according to the DSM-IV-TR criteria. DATA COLLECTION: Neurocognition was assessed using a global approach that addressed memory, attention, and executive functions; insight was analyzed using the multidimensional 'Scale to assess Unawareness of Mental Disorder;' and nonadherence was measured using the multidimensional 'Medication Adherence Rating Scale.' ANALYSIS: Structural equation modeling (SEM was applied to examine the non-straightforward relationships among the following latent variables: neurocognition, 'awareness of positive symptoms' and 'negative symptoms', 'awareness of mental disorder' and nonadherence. RESULTS: One hundred and sixty-nine patients were enrolled. The final testing model showed good fit, with normed χ(2 = 1.67, RMSEA = 0.063, CFI = 0.94, and SRMR = 0.092. The SEM revealed significant associations between (1 neurocognition and 'awareness of symptoms,' (2 'awareness of symptoms' and 'awareness of mental disorder' and (3 'awareness of mental disorder' and nonadherence, mainly in the 'attitude toward taking medication' dimension. In contrast, there were no significant links between neurocognition and nonadherence, neurocognition and 'awareness of mental disorder,' and 'awareness of symptoms' and nonadherence. CONCLUSIONS: Our findings support the hypothesis that neurocognition influences 'awareness of symptoms,' which must be integrated into a higher level of insight (i.e., the 'awareness of mental disorder' to have an impact on nonadherence. These findings have important implications for the development of effective strategies to enhance medication adherence.

3.3 Å structure of Niemann–Pick C1 protein reveals insights into the function of the C-terminal luminal domain in cholesterol transport

Energy Technology Data Exchange (ETDEWEB)

Li, Xiaochun; Lu, Feiran; Trinh, Michael N.; Schmiege, Philip; Seemann, Joachim; Wang, Jiawei; Blobel, Günter

2017-08-07

Niemann–Pick C1 (NPC1) and NPC2 proteins are indispensable for the export of LDL-derived cholesterol from late endosomes. Mutations in these proteins result in Niemann–Pick type C disease, a lysosomal storage disease. Despite recent reports of the NPC1 structure depicting its overall architecture, the function of its C-terminal luminal domain (CTD) remains poorly understood even though 45% of NPC disease-causing mutations are in this domain. Here, we report a crystal structure at 3.3 Å resolution of NPC1* (residues 314–1,278), which—in contrast to previous lower resolution structures—features the entire CTD well resolved. Notably, all eight cysteines of the CTD form four disulfide bonds, one of which (C909–C914) enforces a specific loop that in turn mediates an interaction with a loop of the N-terminal domain (NTD). Importantly, this loop and its interaction with the NTD were not observed in any previous structures due to the lower resolution. Our mutagenesis experiments highlight the physiological relevance of the CTD–NTD interaction, which might function to keep the NTD in the proper orientation for receiving cholesterol from NPC2. Additionally, this structure allows us to more precisely map all of the disease-causing mutations, allowing future molecular insights into the pathogenesis of NPC disease.

What Do Structures Tell Us About Chemokine Receptor Function and Antagonism?

Energy Technology Data Exchange (ETDEWEB)

Kufareva, Irina; Gustavsson, Martin; Zheng, Yi; Stephens, Bryan S.; Handel, Tracy M. (UCSD)

2017-05-22

Chemokines and their cell surface G protein–coupled receptors are critical for cell migration, not only in many fundamental biological processes but also in inflammatory diseases and cancer. Recent X-ray structures of two chemokines complexed with full-length receptors provided unprecedented insight into the atomic details of chemokine recognition and receptor activation, and computational modeling informed by new experiments leverages these insights to gain understanding of many more receptor:chemokine pairs. In parallel, chemokine receptor structures with small molecules reveal the complicated and diverse structural foundations of small molecule antagonism and allostery, highlight the inherent physicochemical challenges of receptor:chemokine interfaces, and suggest novel epitopes that can be exploited to overcome these challenges. The structures and models promote unique understanding of chemokine receptor biology, including the interpretation of two decades of experimental studies, and will undoubtedly assist future drug discovery endeavors.

Linker histones: novel insights into structure-specific recognition of the nucleosome.

Science.gov (United States)

Cutter, Amber R; Hayes, Jeffrey J

2017-04-01

Linker histones (H1s) are a primary component of metazoan chromatin, fulfilling numerous functions, both in vitro and in vivo, including stabilizing the wrapping of DNA around the nucleosome, promoting folding and assembly of higher order chromatin structures, influencing nucleosome spacing on DNA, and regulating specific gene expression. However, many molecular details of how H1 binds to nucleosomes and recognizes unique structural features on the nucleosome surface remain undefined. Numerous, confounding studies are complicated not only by experimental limitations, but the use of different linker histone isoforms and nucleosome constructions. This review summarizes the decades of research that has resulted in several models of H1 association with nucleosomes, with a focus on recent advances that suggest multiple modes of H1 interaction in chromatin, while highlighting the remaining questions.

Some highlights of the Daresbury nuclear structure programme

International Nuclear Information System (INIS)

Gelletly, W.

1984-01-01

The paper concerns the nuclear structure programme at the Daresbury laboratory, United Kingdom. A description is given of the Nuclear Structure Facility (NSF), along with its principal properties and design features. Some of the latest equipment used at the NSF is discussed, including the isotope separator, recoil separator, magnetic spectrometer and gamma-ray detectors. Uses of this equipment at the NSF to study the nuclear properties at high angular momentum and nuclei far from stability, are also described. (U.K.)

Structure of uracil-DNA glycosylase from Mycobacterium tuberculosis: insights into interactions with ligands

International Nuclear Information System (INIS)

Kaushal, Prem Singh; Talawar, Ramappa K.; Varshney, Umesh; Vijayan, M.

2010-01-01

The molecule of uracil-DNA glycosylase from M. tuberculosis exhibits domain motion on binding to DNA or a proteinaceous inhibitor. The highly conserved DNA-binding region interacts with a citrate ion in the structure. Uracil N-glycosylase (Ung) is the most thoroughly studied of the group of uracil DNA-glycosylase (UDG) enzymes that catalyse the first step in the uracil excision-repair pathway. The overall structure of the enzyme from Mycobacterium tuberculosis is essentially the same as that of the enzyme from other sources. However, differences exist in the N- and C-terminal stretches and some catalytic loops. Comparison with appropriate structures indicate that the two-domain enzyme closes slightly when binding to DNA, while it opens slightly when binding to the proteinaceous inhibitor Ugi. The structural changes in the catalytic loops on complexation reflect the special features of their structure in the mycobacterial protein. A comparative analysis of available sequences of the enzyme from different sources indicates high conservation of amino-acid residues in the catalytic loops. The uracil-binding pocket in the structure is occupied by a citrate ion. The interactions of the citrate ion with the protein mimic those of uracil, in addition to providing insights into other possible interactions that inhibitors could be involved in

Structural insights into FRS2α PTB domain recognition by neurotrophin receptor TrkB.

Science.gov (United States)

Zeng, Lei; Kuti, Miklos; Mujtaba, Shiraz; Zhou, Ming-Ming

2014-07-01

The fibroblast growth factor receptor (FGFR) substrate 2 (FRS2) family proteins function as scaffolding adapters for receptor tyrosine kinases (RTKs). The FRS2α proteins interact with RTKs through the phosphotyrosine-binding (PTB) domain and transfer signals from the activated receptors to downstream effector proteins. Here, we report the nuclear magnetic resonance structure of the FRS2α PTB domain bound to phosphorylated TrkB. The structure reveals that the FRS2α-PTB domain is comprised of two distinct but adjacent pockets for its mutually exclusive interaction with either nonphosphorylated juxtamembrane region of the FGFR, or tyrosine phosphorylated peptides TrkA and TrkB. The new structural insights suggest rational design of selective small molecules through targeting of the two conjunct pockets in the FRS2α PTB domain. © 2014 Wiley Periodicals, Inc.

Insight in seasonal affective disorder.

Science.gov (United States)

Ghaemi, S N; Sachs, G S; Baldassano, C F; Truman, C J

1997-01-01

Lack of insight complicates the evaluation and treatment of patients with psychotic and affective disorders. No studies of insight in seasonal affective disorder (SAD) have been reported. Thirty patients with SAD diagnosed by the Structured Clinical Interview for DSM-III-R but no other axis I conditions were treated short-term with light-therapy. Insight was measured with the Scale to Assess Unawareness of Mental Disorder (SUMD) as modified by the authors to assess the self-report of insight into depressive symptoms. Increasing scores (1 to 5) indicated increasing unawareness of illness (i.e., less insight). SAD patients displayed a moderate amount of insight when depressed (mean SUMD score, 2.5). When recovered, they showed no significant change in insight into past depressive symptoms (mean SUMD score, 2.8). Greater insight into current depressive symptoms correlated with more depressive symptoms on the Hamilton Rating Scale for Depression score ([HRSD] r = .35, P depressive symptoms that does not change after recovery, a result in agreement with studies of insight in psychosis and mania. Further, in SAD, increased severity of illness may be associated with increased insight into depressive symptoms, consistent with the hypothesis of depressive realism.

Insight, grey matter and cognitive function in first-onset psychosis.

LENUS (Irish Health Repository)

Morgan, Kevin D

2010-08-01

Several studies have suggested that neuropsychological and structural brain deficits are implicated in poor insight. Few insight studies however have combined neurocognitive and structural neuroanatomical measures.

Modeling Insight into Battery Electrolyte Electrochemical Stability and Interfacial Structure.

Science.gov (United States)

Borodin, Oleg; Ren, Xiaoming; Vatamanu, Jenel; von Wald Cresce, Arthur; Knap, Jaroslaw; Xu, Kang

2017-12-19

Electroactive interfaces distinguish electrochemistry from chemistry and enable electrochemical energy devices like batteries, fuel cells, and electric double layer capacitors. In batteries, electrolytes should be either thermodynamically stable at the electrode interfaces or kinetically stable by forming an electronically insulating but ionically conducting interphase. In addition to a traditional optimization of electrolytes by adding cosolvents and sacrificial additives to preferentially reduce or oxidize at the electrode surfaces, knowledge of the local electrolyte composition and structure within the double layer as a function of voltage constitutes the basis of manipulating an interphase and expanding the operating windows of electrochemical devices. In this work, we focus on how the molecular-scale insight into the solvent and ion partitioning in the electrolyte double layer as a function of applied potential could predict changes in electrolyte stability and its initial oxidation and reduction reactions. In molecular dynamics (MD) simulations, highly concentrated lithium aqueous and nonaqueous electrolytes were found to exclude the solvent molecules from directly interacting with the positive electrode surface, which provides an additional mechanism for extending the electrolyte oxidation stability in addition to the well-established simple elimination of "free" solvent at high salt concentrations. We demonstrate that depending on their chemical structures, the anions could be designed to preferentially adsorb or desorb from the positive electrode with increasing electrode potential. This provides additional leverage to dictate the order of anion oxidation and to effectively select a sacrificial anion for decomposition. The opposite electrosorption behaviors of bis(trifluoromethane)sulfonimide (TFSI) and trifluoromethanesulfonate (OTF) as predicted by MD simulation in highly concentrated aqueous electrolytes were confirmed by surface enhanced infrared

Some physics highlights from the EUROBALL spectrometer

International Nuclear Information System (INIS)

Korten, W.

2004-01-01

The latest generation of large γ-ray spectrometers, such as EUROBALL, has boosted the explorations of nuclei under extreme conditions especially at the limits of angular momentum and at finite temperatures. But the coupling of this instrument to very selective ''ancillary'' devices allows for more and more refined investigations of the third important degree of freedom in contemporary nuclear-structure studies, the isospin. This contribution summarises some of the recent highlights from the physics at EUROBALL obtained in some of the different areas of nuclear-structure research

The Type IX Secretion System (T9SS: Highlights and Recent Insights into Its Structure and Function

Directory of Open Access Journals (Sweden)

Anna M. Lasica

2017-05-01

proteins is constantly growing. The actual structure of the translocon, situated in the OM of bacteria, remains the least explored area; however, new technical approaches and increasing scientific attention have resulted in a growing body of data. Therefore, we present a compact up-to-date review of this topic.

The Type IX Secretion System (T9SS): Highlights and Recent Insights into Its Structure and Function

Science.gov (United States)

Lasica, Anna M.; Ksiazek, Miroslaw; Madej, Mariusz; Potempa, Jan

2017-01-01

constantly growing. The actual structure of the translocon, situated in the OM of bacteria, remains the least explored area; however, new technical approaches and increasing scientific attention have resulted in a growing body of data. Therefore, we present a compact up-to-date review of this topic. PMID:28603700

Synthesis and evaluation of 8,4'-dideshydroxy-leinamycin revealing new insights into the structure-activity relationship of the anticancer natural product leinamycin.

Science.gov (United States)

Liu, Tao; Ma, Ming; Ge, Hui-Ming; Yang, Chunying; Cleveland, John; Shen, Ben

2015-11-01

Leinamycin (LNM, 1) is a novel antitumor antibiotic produced by Streptomyces atroolivaceus S-140 and features an unusual 1,3-dioxo-1,2-dithiolane moiety that is spiro-fused to a thiazole-containing 18-membered lactam ring. The 1,3-dioxo-1,2-dithiolane moiety of LNM is essential for its antitumor activity via an episulfonium ion-mediated DNA alkylation upon reductive activation in the presence of cellular thiols. We recently isolated leinamycin E1 (LNM E1, 2) from an engineered strain S. atroolivaceus SB3033, which lacks the 1,3-dioxo-1,2-dithiolane moiety. Here we report the chemical synthesis of 8,4'-dideshydroxy-LNM (5) from 2 and determination of the cytotoxicity of 5 against selected cancer cell lines in comparison with 1; 5 exhibits comparable activity as 1 with the EC50 values between 8.21 and 275 nM. This work reveals new insight into the structure-activity relationship of LNM and highlights the synergy between metabolic pathway engineering and medicinal chemistry for natural product drug discovery. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structural insights into lipid-dependent reversible dimerization of human GLTP

International Nuclear Information System (INIS)

Samygina, Valeria R.; Ochoa-Lizarralde, Borja; Popov, Alexander N.; Cabo-Bilbao, Aintzane; Goni-de-Cerio, Felipe; Molotkovsky, Julian G.; Patel, Dinshaw J.; Brown, Rhoderick E.; Malinina, Lucy

2013-01-01

It is shown that dimerization is promoted by glycolipid binding to human GLTP. The importance of dimer flexibility in wild-type protein is manifested by point mutation that ‘locks’ the dimer while diversifying ligand/protein adaptations. Human glycolipid transfer protein (hsGLTP) forms the prototypical GLTP fold and is characterized by a broad transfer selectivity for glycosphingolipids (GSLs). The GLTP mutation D48V near the ‘portal entrance’ of the glycolipid binding site has recently been shown to enhance selectivity for sulfatides (SFs) containing a long acyl chain. Here, nine novel crystal structures of hsGLTP and the SF-selective mutant complexed with short-acyl-chain monoSF and diSF in different crystal forms are reported in order to elucidate the potential functional roles of lipid-mediated homodimerization. In all crystal forms, the hsGLTP–SF complexes displayed homodimeric structures supported by similarly organized intermolecular interactions. The dimerization interface always involved the lipid sphingosine chain, the protein C-terminus (C-end) and α-helices 6 and 2, but the D48V mutant displayed a ‘locked’ dimer conformation compared with the hinge-like flexibility of wild-type dimers. Differences in contact angles, areas and residues at the dimer interfaces in the ‘flexible’ and ‘locked’ dimers revealed a potentially important role of the dimeric structure in the C-end conformation of hsGLTP and in the precise positioning of the key residue of the glycolipid recognition centre, His140. ΔY207 and ΔC-end deletion mutants, in which the C-end is shifted or truncated, showed an almost complete loss of transfer activity. The new structural insights suggest that ligand-dependent reversible dimerization plays a role in the function of human GLTP

Biotransformation and bioactivation reactions - 2015 literature highlights.

Science.gov (United States)

Baillie, Thomas A; Dalvie, Deepak; Rietjens, Ivonne M C M; Cyrus Khojasteh, S

2016-05-01

Since 1972, Drug Metabolism Reviews has been recognized as one of the principal resources for researchers in pharmacological, pharmaceutical and toxicological fields to keep abreast of advances in drug metabolism science in academia and the pharmaceutical industry. With a distinguished list of authors and editors, the journal covers topics ranging from relatively mature fields, such as cytochrome P450 enzymes, to a variety of emerging fields. We hope to continue this tradition with the current compendium of mini-reviews that highlight novel biotransformation processes that were published during the past year. Each review begins with a summary of the article followed by our comments on novel aspects of the research and their biological implications. This collection of highlights is not intended to be exhaustive, but rather to be illustrative of recent research that provides new insights or approaches that advance the field of drug metabolism. Abbreviations NAPQI N-acetyl-p-benzoquinoneimine ALDH aldehyde dehydrogenase AO aldehyde oxidase AKR aldo-keto reductase CES carboxylesterase CSB cystathionine β-synthase CSE cystathionine γ-lyase P450 cytochrome P450 DHPO 2,3-dihydropyridin-4-one ESI electrospray FMO flavin monooxygenase GSH glutathione GSSG glutathione disulfide ICPMS inductively coupled plasma mass spectrometry i.p. intraperitoneal MDR multidrug-resistant NNAL 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol NNK 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone oaTOF orthogonal acceleration time-of-flight PBK physiologically based kinetic PCP pentachlorophenol SDR short-chain dehydrogenase/reductase SULT sulfotransferase TB tuberculosis.

Absolute Molecular Orientation of Isopropanol at Ceria (100) Surfaces: Insight into Catalytic Selectivity from the Interfacial Structure

Energy Technology Data Exchange (ETDEWEB)

Doughty, Benjamin [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Goverapet Srinivasan, Sriram [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Indian Inst. of Technology (IIT), Rajasthan (India); Bryantsev, Vyacheslav S. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lee, Dongkyu [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lee, Ho Nyung [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ma, Ying-Zhong [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lutterman, Daniel A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2017-06-12

The initial mechanistic steps underlying heterogeneous chemical catalysis can be described in a framework where the composition, structure, and orientation of molecules adsorbed to reactive interfaces are known. However, extracting this vital information is the limiting step in most cases due in part to challenges in probing the interfacial monolayer with enough chemical specificity to characterize the surface molecular constituents. These challenges are exacerbated at complex or spatially heterogeneous interfaces where competing processes and a distribution of local environments can uniquely drive chemistry. To address these limitations, this work presents a distinctive combination of materials synthesis, surface specific optical experiments, and theory to probe and understand molecular structure at catalytic interfaces. Specifically, isopropanol was adsorbed to surfaces of the model CeO₂ catalyst that were synthesized with only the (100) facet exposed. Vibrational sum-frequency generation was used to probe the molecular monolayer, and with the guidance of density functional theory calculations, was used to extract the structure and absolute molecular orientation of isopropanol at the CeO₂ (100) surface. Our results show that isopropanol is readily deprotonated at the surface, and through the measured absolute molecular orientation of isopropanol, we obtain new insight into the selectivity of the (100) surface to form propylene. Our findings reveal key insight into the chemical and physical phenomena taking place at pristine interfaces thereby pointing to intuitive structural arguments to describe catalytic selectivity in more complex systems.

The importance of asking "how and why?" in natural product structure elucidation.

Science.gov (United States)

Brown, Patrick D; Lawrence, Andrew L

2017-10-18

Covering: up to 2017This review highlights why careful consideration of the biosynthetic origin (the how) and the biological function (the why) of a natural product can be so useful during the determination of its structure. Recent examples of structural reassignments inspired by biosynthetic and functional insights will be presented. This review will demonstrate the importance of viewing the origin, structure and function of a natural product as intertwined threads of a single story, best viewed as a whole rather than as discrete topics.

New insights into the structural organization of eukaryotic and prokaryotic cytoskeletons using cryo-electron tomography

International Nuclear Information System (INIS)

Kuerner, Julia; Medalia, Ohad; Linaroudis, Alexandros A.; Baumeister, Wolfgang

2004-01-01

Cryo-electron tomography (cryo-ET) is an emerging imaging technology that combines the potential of three-dimensional (3-D) imaging at molecular resolution (<5 nm) with a close-to-life preservation of the specimen. In conjunction with pattern recognition techniques, it enables us to map the molecular landscape inside cells. The application of cryo-ET to intact cells provides novel insights into the structure and the spatial organization of the cytoskeleton in prokaryotic and eukaryotic cells

STABILITY AND DYNAMICS OF SPATIO-TEMPORAL STRUCTURES

Energy Technology Data Exchange (ETDEWEB)

Hermann Riecke

2005-10-21

This document constitutes the final report for the grant. It provides a complete list of publications and presentations that arose from the project as well as a brief description of the highlights of the research results. The research funded by this grant has provided insights into the spontaneous formation of structures of increasing complexity in systems driven far from thermodynamic equilibrium. A classic example of such a system is thermally driven convection in a horizontal fluid layer. Highlights of the research are: (1) explanation of the localized traveling wave pulses observed in binary-mixture convection, (2) explanation of the localized waves in electroconvection, (3) introduction of a new diagnostics for spatially and temporally chaotic states, which is based on the statistics of defect trajectories, (4) prediction of complex states in thermally driven convection in rotating systems. Additional contributions provided insight into the localization mechanism for oscillons, the prediction of a new localization mechanism for traveling waves based on a resonant periodic forcing, and an analysis of the stability of quasi-periodic patterns.

Using an Electronic Highlighter to Eliminate the Negative Effects of Pre-Existing, Inappropriate Highlighting

Science.gov (United States)

Gier, Vicki; Kreiner, David; Hudnell, Jason; Montoya, Jodi; Herring, Daniel

2011-01-01

The purpose of the present experiment was to determine whether using an active learning technique, electronic highlighting, can eliminate the negative effects of pre-existing, poor highlighting on reading comprehension. Participants read passages containing no highlighting, appropriate highlighting, or inappropriate highlighting. We hypothesized…

B-physics and quarkonium highlights and recent results from ATLAS

CERN Multimedia

CERN. Geneva

2015-01-01

Studies of heavy flavour quark-antiquark bound states provide unique insights into the picture of strong interactions near the boundary between the perturbative and non-perturbative regimes. Despite the 40-year history since the discovery of the J/psi, quarkonia still challenge both theory and experiment. Data collected in Run 1 has now produced a comprehensive suite of measurements for a range of energies, states and decay modes. The open beauty sector tests a variety of theoretical models and provides sensitivity to beyond-standard-model processes through precision measurements, such as studies of CP violation. Highlights and most recent measurements from the B-physics and quarkonium programmes of the ATLAS experiment will be presented.

Structure of the Aeropyrum pernix L7Ae multifunctional protein and insight into its extreme thermostability

International Nuclear Information System (INIS)

Bhuiya, Mohammad Wadud; Suryadi, Jimmy; Zhou, Zholi; Brown, Bernard Andrew II

2013-01-01

The crystal structure of A. pernix L7Ae is reported, providing insight into the extreme thermostability of this protein. Archaeal ribosomal protein L7Ae is a multifunctional RNA-binding protein that directs post-transcriptional modification of archaeal RNAs. The L7Ae protein from Aeropyrum pernix (Ap L7Ae), a member of the Crenarchaea, was found to have an extremely high melting temperature (>383 K). The crystal structure of Ap L7Ae has been determined to a resolution of 1.56 Å. The structure of Ap L7Ae was compared with the structures of two homologs: hyperthermophilic Methanocaldococcus jannaschii L7Ae and the mesophilic counterpart mammalian 15.5 kD protein. The primary stabilizing feature in the Ap L7Ae protein appears to be the large number of ion pairs and extensive ion-pair network that connects secondary-structural elements. To our knowledge, Ap L7Ae is among the most thermostable single-domain monomeric proteins presently observed

Human acid sphingomyelinase structures provide insight to molecular basis of Niemann–Pick disease

Energy Technology Data Exchange (ETDEWEB)

Zhou, Yan-Feng; Metcalf, Matthew C.; Garman, Scott C.; Edmunds, Tim; Qiu, Huawei; Wei, Ronnie R. (Sanofi Aventis); (UMASS, Amherst)

2016-10-26

Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and phosphocholine, essential components of myelin in neurons. Genetic alterations in ASM lead to ASM deficiency (ASMD) and have been linked to Niemann–Pick disease types A and B. Olipudase alfa, a recombinant form of human ASM, is being developed as enzyme replacement therapy to treat the non-neurological manifestations of ASMD. Here we present the human ASM holoenzyme and product bound structures encompassing all of the functional domains. The catalytic domain has a metallophosphatase fold, and two zinc ions and one reaction product phosphocholine are identified in a histidine-rich active site. The structures reveal the underlying catalytic mechanism, in which two zinc ions activate a water molecule for nucleophilic attack of the phosphodiester bond. Docking of sphingomyelin provides a model that allows insight into the selectivity of the enzyme and how the ASM domains collaborate to complete hydrolysis. Mapping of known mutations provides a basic understanding on correlations between enzyme dysfunction and phenotypes observed in ASMD patients.

Rayleigh Wave Ellipticity Modeling and Inversion for Shallow Structure at the Proposed InSight Landing Site in Elysium Planitia, Mars

Science.gov (United States)

Knapmeyer-Endrun, Brigitte; Golombek, Matthew P.; Ohrnberger, Matthias

2017-10-01

The SEIS (Seismic Experiment for Interior Structure) instrument onboard the InSight mission will be the first seismometer directly deployed on the surface of Mars. From studies on the Earth and the Moon, it is well known that site amplification in low-velocity sediments on top of more competent rocks has a strong influence on seismic signals, but can also be used to constrain the subsurface structure. Here we simulate ambient vibration wavefields in a model of the shallow sub-surface at the InSight landing site in Elysium Planitia and demonstrate how the high-frequency Rayleigh wave ellipticity can be extracted from these data and inverted for shallow structure. We find that, depending on model parameters, higher mode ellipticity information can be extracted from single-station data, which significantly reduces uncertainties in inversion. Though the data are most sensitive to properties of the upper-most layer and show a strong trade-off between layer depth and velocity, it is possible to estimate the velocity and thickness of the sub-regolith layer by using reasonable constraints on regolith properties. Model parameters are best constrained if either higher mode data can be used or additional constraints on regolith properties from seismic analysis of the hammer strokes of InSight's heat flow probe HP3 are available. In addition, the Rayleigh wave ellipticity can distinguish between models with a constant regolith velocity and models with a velocity increase in the regolith, information which is difficult to obtain otherwise.

Structural insights into the elevator-like mechanism of the sodium/citrate symporter CitS.

Science.gov (United States)

Kim, Ji Won; Kim, Subin; Kim, Songwon; Lee, Haerim; Lee, Jie-Oh; Jin, Mi Sun

2017-05-31

The sodium-dependent citrate transporter of Klebsiella pneumoniae (KpCitS) belongs to the 2-hydroxycarboxylate transporter (2-HCT) family and allows the cell to use citrate as sole carbon and energy source in anaerobic conditions. Here we present crystal structures of KpCitS in citrate-bound outward-facing, citrate-bound asymmetric, and citrate-free inward-facing state. The structures reveal that the KpCitS dimerization domain remains stationary throughout the transport cycle due to a hydrogen bond network as well as extensive hydrophobic interactions. In contrast, its transport domain undergoes a ~35° rigid-body rotation and a ~17 Å translocation perpendicular to the membrane to expose the substrate-binding site alternately to either side of the membrane. Furthermore, homology models of two other 2-HCT proteins based on the KpCitS structure offer structural insights into their differences in substrate specificity at a molecular level. On the basis of our results and previous biochemical data, we propose that the activity of the 2-HCT CitS involves an elevator-like movement in which the transport domain itself traverses the lipid bilayer, carrying the substrate into the cell in a sodium-dependent manner.

Highlight shapes and perception of gloss for real and photographed objects.

Science.gov (United States)

van Assen, Jan Jaap R; Wijntjes, Maarten W A; Pont, Sylvia C

2016-01-01

Gloss perception strongly depends on the three-dimensional shape and the illumination of the object under consideration. In this study we investigated the influence of the spatial structure of the illumination on gloss perception. A diffuse light box in combination with differently shaped masks was used to produce a set of six simple and complex highlight shapes. The geometry of the simple highlight shapes was inspired by conventional artistic practice (e.g., ring flash for photography, window shape for painting and disk or square for cartoons). In the box we placed spherical stimuli that were painted in six degrees of glossiness. This resulted in a stimulus set of six highlight shapes and six gloss levels, a total of 36 stimuli. We performed three experiments of which two took place using digital photographs on a computer monitor and one with the real spheres in the light box. The observers had to perform a comparison task in which they chose which of two stimuli was glossiest and a rating task in which they rated the glossiness. The results show that, perhaps surprisingly, more complex highlight shapes were perceived to produce a less glossy appearance than simple highlight shapes such as a disk or square. These findings were confirmed for both viewing conditions, on a computer display and in a real setting. The results show that variations in the spatial structure of "rather simple" illumination of the "extended source" type highlight influences perceived glossiness.

Structural insights and ab initio sequencing within the DING proteins family

International Nuclear Information System (INIS)

Elias, Mikael; Liebschner, Dorothee; Gotthard, Guillaume; Chabriere, Eric

2011-01-01

DING proteins constitute a recently discovered protein family that is ubiquitous in eukaryotes. The structural insights and the physiological involvements of these intriguing proteins are hereby deciphered. DING proteins constitute an intriguing family of phosphate-binding proteins that was identified in a wide range of organisms, from prokaryotes and archae to eukaryotes. Despite their seemingly ubiquitous occurrence in eukaryotes, their encoding genes are missing from sequenced genomes. Such a lack has considerably hampered functional studies. In humans, these proteins have been related to several diseases, like atherosclerosis, kidney stones, inflammation processes and HIV inhibition. The human phosphate binding protein is a human representative of the DING family that was serendipitously discovered from human plasma. An original approach was developed to determine ab initio the complete and exact sequence of this 38 kDa protein by utilizing mass spectrometry and X-ray data in tandem. Taking advantage of this first complete eukaryotic DING sequence, a immunohistochemistry study was undertaken to check the presence of DING proteins in various mice tissues, revealing that these proteins are widely expressed. Finally, the structure of a bacterial representative from Pseudomonas fluorescens was solved at sub-angstrom resolution, allowing the molecular mechanism of the phosphate binding in these high-affinity proteins to be elucidated

Structural insights and ab initio sequencing within the DING proteins family

Energy Technology Data Exchange (ETDEWEB)

Elias, Mikael, E-mail: mikael.elias@weizmann.ac.il [Weizmann Institute of Science, Rehovot (Israel); Liebschner, Dorothee [CRM2, Nancy Université (France); Gotthard, Guillaume; Chabriere, Eric [AFMB, Université Aix-Marseille II (France)

2011-01-01

DING proteins constitute a recently discovered protein family that is ubiquitous in eukaryotes. The structural insights and the physiological involvements of these intriguing proteins are hereby deciphered. DING proteins constitute an intriguing family of phosphate-binding proteins that was identified in a wide range of organisms, from prokaryotes and archae to eukaryotes. Despite their seemingly ubiquitous occurrence in eukaryotes, their encoding genes are missing from sequenced genomes. Such a lack has considerably hampered functional studies. In humans, these proteins have been related to several diseases, like atherosclerosis, kidney stones, inflammation processes and HIV inhibition. The human phosphate binding protein is a human representative of the DING family that was serendipitously discovered from human plasma. An original approach was developed to determine ab initio the complete and exact sequence of this 38 kDa protein by utilizing mass spectrometry and X-ray data in tandem. Taking advantage of this first complete eukaryotic DING sequence, a immunohistochemistry study was undertaken to check the presence of DING proteins in various mice tissues, revealing that these proteins are widely expressed. Finally, the structure of a bacterial representative from Pseudomonas fluorescens was solved at sub-angstrom resolution, allowing the molecular mechanism of the phosphate binding in these high-affinity proteins to be elucidated.

Structural and dynamical insights into the membrane-bound α-synuclein.

Directory of Open Access Journals (Sweden)

Neha Jain

Full Text Available Membrane-induced disorder-to-helix transition of α-synuclein, a presynaptic protein, has been implicated in a number of important neuronal functions as well as in the etiology of Parkinson's disease. In order to obtain structural insights of membrane-bound α-synuclein at the residue-specific resolution, we took advantage of the fact that the protein is devoid of tryptophan and incorporated single tryptophan at various residue positions along the sequence. These tryptophans were used as site-specific markers to characterize the structural and dynamical aspects of α-synuclein on the negatively charged small unilamellar lipid vesicles. An array of site-specific fluorescence readouts, such as the spectral-shift, quenching efficiency and anisotropy, allowed us to discern various features of the conformational rearrangements occurring at different locations of α-synuclein on the lipid membrane. In order to define the spatial localization of various regions of the protein near the membrane surface, we utilized a unique and sensitive indicator, namely, red-edge excitation shift (REES, which originates when a fluorophore is located in a highly ordered micro-environment. The extent of REES observed at different residue positions allowed us to directly identify the residues that are localized at the membrane-water interface comprising a thin (∼ 15 Å layer of motionally restrained water molecules and enabled us to construct a dynamic hydration map of the protein. The combination of site-specific fluorescence readouts allowed us to unravel the intriguing molecular details of α-synuclein on the lipid membrane in a direct model-free fashion. Additionally, the combination of methodologies described here are capable of distinguishing subtle but important structural alterations of α-synuclein bound to different negatively charged lipids with varied head-group chemistry. We believe that the structural modulations of α-synuclein on the membrane could

PSI scientific highlights 2012

International Nuclear Information System (INIS)

Piwnicki, P.; Dury, T.

2013-05-01

This comprehensive report issued by the Paul Scherrer Institute (PSI) reviews research in various areas carried out by the institute in 2012. Also, the various facilities to be found at the institute are described. Research focus and highlights are discussed. These include work done using synchrotron light, neutrons and muons as well as work done in the particle physics, microtechnology and nanotechnology areas. Further areas of research include biomolecular research, radiopharmacy, radiochemistry and environmental chemistry. Other areas covered include general energy research and work done at the Competence Center for Energy and Mobility CCEM, work done on nuclear energy safety as well as systems analysis in the environmental and energy areas. The report is concluded with facts and figures on the PSI, its Advisory Board and its organisational structures

Structure and stability insights into tumour suppressor p53 evolutionary related proteins.

Directory of Open Access Journals (Sweden)

Bruno Pagano

Full Text Available The p53 family of genes and their protein products, namely, p53, p63 and p73, have over one billion years of evolutionary history. Advances in computational biology and genomics are enabling studies of the complexities of the molecular evolution of p53 protein family to decipher the underpinnings of key biological conditions spanning from cancer through to various metabolic and developmental disorders and facilitate the design of personalised medicines. However, a complete understanding of the inherent nature of the thermodynamic and structural stability of the p53 protein family is still lacking. This is due, to a degree, to the lack of comprehensive structural information for a large number of homologous proteins and to an incomplete knowledge of the intrinsic factors responsible for their stability and how these might influence function. Here we investigate the thermal stability, secondary structure and folding properties of the DNA-binding domains (DBDs of a range of proteins from the p53 family using biophysical methods. While the N- and the C-terminal domains of the p53 family show sequence diversity and are normally targets for post-translational modifications and alternative splicing, the central DBD is highly conserved. Together with data obtained from Molecular Dynamics simulations in solution and with structure based homology modelling, our results provide further insights into the molecular properties of evolutionary related p53 proteins. We identify some marked structural differences within the p53 family, which could account for the divergence in biological functions as well as the subtleties manifested in the oligomerization properties of this family.

ENC 2010 European nuclear congress - Conference highlights

Energy Technology Data Exchange (ETDEWEB)

Bonin, B. [European Nuclear Society (ENS), Bern (Switzerland)

2010-11-15

This synthetical paper presents the main progress, trends or achievements that have appeared through the 450 communications of this conference. The highlights are reported according to 11 issues: 1) general nuclear situation and policy, 2) life extension, 3) standardisation, 4) safety, 5) fuel cycle, 6) dismantling techniques and waste management, 7) research reactors, 8) fusion, 9) nuclear applications in life sciences, 10) education and training, 11) networks and research structures

Clinical insights into use of apomorphine in Parkinson's disease

DEFF Research Database (Denmark)

Henriksen, Tove

2014-01-01

is achieved a significant reduction of pre-existing levodopainduced dyskinesias is seen. The aim of this review is to give practical insight into apomorphine treatment, highlighting side effects, and complications and device-related problems are discussed with advice on how to prevent or handle these, should...

Structural insights into the anti-HIV activity of the Oscillatoria agardhii agglutinin homolog lectin family.

Science.gov (United States)

Koharudin, Leonardus M I; Kollipara, Sireesha; Aiken, Christopher; Gronenborn, Angela M

2012-09-28

Oscillatoria agardhii agglutinin homolog (OAAH) proteins belong to a recently discovered lectin family. All members contain a sequence repeat of ~66 amino acids, with the number of repeats varying among different family members. Apart from data for the founding member OAA, neither three-dimensional structures, information about carbohydrate binding specificities, nor antiviral activity data have been available up to now for any other members of the OAAH family. To elucidate the structural basis for the antiviral mechanism of OAAHs, we determined the crystal structures of Pseudomonas fluorescens and Myxococcus xanthus lectins. Both proteins exhibit the same fold, resembling the founding family member, OAA, with minor differences in loop conformations. Carbohydrate binding studies by NMR and x-ray structures of glycan-lectin complexes reveal that the number of sugar binding sites corresponds to the number of sequence repeats in each protein. As for OAA, tight and specific binding to α3,α6-mannopentaose was observed. All the OAAH proteins described here exhibit potent anti-HIV activity at comparable levels. Altogether, our results provide structural details of the protein-carbohydrate interaction for this novel lectin family and insights into the molecular basis of their HIV inactivation properties.

Insight and white matter fractional anisotropy in first-episode schizophrenia.

Science.gov (United States)

Asmal, Laila; du Plessis, Stefan; Vink, Matthijs; Fouche, Jean-Paul; Chiliza, Bonginkosi; Emsley, Robin

2017-05-01

Impaired insight is a hallmark feature of schizophrenia. Structural studies implicate predominantly prefrontal, cingulate, cuneus/precuneus, and inferior temporal brain regions. The cortical midline structures (CMS) are also implicated in functional studies primarily through self-reflective processing tasks. However, few studies have explored the relationship between white matter tracts and insight in schizophrenia, and none in first-episode schizophrenia (FES). Here, we examined for fractional anisotropy (FA) differences in 89 minimally treated FES patients and 98 matched controls, and identified those FA differences associated with impaired clinical insight in patients. We found widespread FA reduction in FES patients compared to controls. Poorer insight in patients was predicted by lower FA values in a number of white matter tracts with a predilection for tracts associated with cortical midline structures (fronto-occipital, cingulate, cingulate hippocampus, uncinate, anterior corona radiata), and more severe depressive symptoms. The association between FA abnormalities and insight was most robust for the awareness of symptoms and illness awareness domains. Our study implicates a network of tracts involved in impaired insight in schizophrenia with a predilection for the CMS. This study is a first step in delineating the white matter tracts involved in insight impairment in schizophrenia prior to chronicity. Copyright © 2016. Published by Elsevier B.V.

Structural characterisation of Tpx from Yersinia pseudotuberculosis reveals insights into the binding of salicylidene acylhydrazide compounds.

Directory of Open Access Journals (Sweden)

Mads Gabrielsen

Full Text Available Thiol peroxidase, Tpx, has been shown to be a target protein of the salicylidene acylhydrazide class of antivirulence compounds. In this study we present the crystal structures of Tpx from Y. pseudotuberculosis (ypTpx in the oxidised and reduced states, together with the structure of the C61S mutant. The structures solved are consistent with previously solved atypical 2-Cys thiol peroxidases, including that for "forced" reduced states using the C61S mutant. In addition, by investigating the solution structure of ypTpx using small angle X-ray scattering (SAXS, we have confirmed that reduced state ypTpx in solution is a homodimer. The solution structure also reveals flexibility around the dimer interface. Notably, the conformational changes observed between the redox states at the catalytic triad and at the dimer interface have implications for substrate and inhibitor binding. The structural data were used to model the binding of two salicylidene acylhydrazide compounds to the oxidised structure of ypTpx. Overall, the study provides insights into the binding of the salicylidene acylhydrazides to ypTpx, aiding our long-term strategy to understand the mode of action of this class of compounds.

Argonne National Laboratory Research Highlights 1988

International Nuclear Information System (INIS)

Anon.

1988-01-01

The research and development highlights are summarized. The world's brightest source of X-rays could revolutionize materials research. Test of a prototype insertion device, a key in achieving brilliant X-ray beams, have given the first glimpse of the machine's power. Superconductivity research focuses on the new materials' structure, economics and applications. Other physical science programs advance knowledge of material structures and properties, nuclear physics, molecular structure, and the chemistry and structure of coal. New programming approaches make advanced computers more useful. Innovative approaches to fighting cancer are being developed. More experiments confirm the passive safety of Argonne's Integral Fast Reactor concept. Device simplifies nuclear-waste processing. Advanced fuel cell could provide better mileage, more power than internal combustion engine. New instruments find leaks in underground pipe, measure sodium impurities in molten liquids, detect flaws in ceramics. New antibody findings may explain ability to fight many diseases. Cadmium in cigarettes linked to bone loss in women. Programs fight deforestation in Nepal. New technology could reduce acid rain, mitigate greenhouse effect, enhance oil recovery. Innovative approaches transfer Argonne-developed technology to private industry. Each year Argonne educational programs reach some 1200 students

Insight into Evolution, Processing and Performance of Multi-length-scale Structures in Planar Heterojunction Perovskite Solar Cells.

Science.gov (United States)

Huang, Yu-Ching; Tsao, Cheng-Si; Cho, Yi-Ju; Chen, Kuan-Chen; Chiang, Kai-Ming; Hsiao, Sheng-Yi; Chen, Chang-Wen; Su, Chun-Jen; Jeng, U-Ser; Lin, Hao-Wu

2015-09-04

The structural characterization correlated to the processing control of hierarchical structure of planar heterojunction perovskite layer is still incomplete due to the limitations of conventional microscopy and X-ray diffraction. This present study performed the simultaneously grazing-incidence small-angle scattering and wide-angle scattering (GISAXS/GIWAXS) techniques to quantitatively probe the hierarchical structure of the planar heterojunction perovskite solar cells. The result is complementary to the currently microscopic study. Correlation between the crystallization behavior, crystal orientation, nano- and meso-scale internal structure and surface morphology of perovskite film as functions of various processing control parameters is reported for the first time. The structural transition from the fractal pore network to the surface fractal can be tuned by the chloride percentage. The GISAXS/GIWAXS measurement provides the comprehensive understanding of concurrent evolution of the film morphology and crystallization correlated to the high performance. The result can provide the insight into formation mechanism and rational synthesis design.

Insight into Evolution, Processing and Performance of Multi-length-scale Structures in Planar Heterojunction Perovskite Solar Cells

Science.gov (United States)

Huang, Yu-Ching; Tsao, Cheng-Si; Cho, Yi-Ju; Chen, Kuan-Chen; Chiang, Kai-Ming; Hsiao, Sheng-Yi; Chen, Chang-Wen; Su, Chun-Jen; Jeng, U.-Ser; Lin, Hao-Wu

2015-09-01

The structural characterization correlated to the processing control of hierarchical structure of planar heterojunction perovskite layer is still incomplete due to the limitations of conventional microscopy and X-ray diffraction. This present study performed the simultaneously grazing-incidence small-angle scattering and wide-angle scattering (GISAXS/GIWAXS) techniques to quantitatively probe the hierarchical structure of the planar heterojunction perovskite solar cells. The result is complementary to the currently microscopic study. Correlation between the crystallization behavior, crystal orientation, nano- and meso-scale internal structure and surface morphology of perovskite film as functions of various processing control parameters is reported for the first time. The structural transition from the fractal pore network to the surface fractal can be tuned by the chloride percentage. The GISAXS/GIWAXS measurement provides the comprehensive understanding of concurrent evolution of the film morphology and crystallization correlated to the high performance. The result can provide the insight into formation mechanism and rational synthesis design.

New insight into atmospheric alteration of alkali-lime silicate glasses

International Nuclear Information System (INIS)

Alloteau, Fanny; Lehuédé, Patrice; Majérus, Odile; Biron, Isabelle; Dervanian, Anaïs; Charpentier, Thibault; Caurant, Daniel

2017-01-01

Highlights: •Glass silicate network hydrolysis is by far the predominant reaction at 80 °C. •Atmospheric conditions yield different altered layer structure than in immersion. •The altered layer bears about 10 wt% of water mainly as H-bonded SiOH groups. •Alkali ions stay embedded into the altered layer closed to SiOH and H 2 O species. -- Abstract: A mixed alkali lime silicate glass altered in atmospheric conditions (80 °C/85%RH, Relative Humidity) for various lengths of time was characterized at all scales. The altered glass forms a hydrated solid phase bearing about 10 wt% of H 2 O in the form of Si-OH groups and molecular water. No alkali depletion was observed after ageing tests. Structural results from 1 H, 23 Na and 29 Si MAS NMR point out the close proximity of Si-OH, H 2 O and Na + species. This study gives new insight into the mechanisms of the atmospheric alteration, essential to conservation strategies in industry and cultural heritage.

Highlights in emergency medicine medical education research: 2008.

Science.gov (United States)

Farrell, Susan E; Coates, Wendy C; Khun, Gloria J; Fisher, Jonathan; Shayne, Philip; Lin, Michelle

2009-12-01

The purpose of this article is to highlight medical education research studies published in 2008 that were methodologically superior and whose outcomes were pertinent to teaching and education in emergency medicine. Through a PubMed search of the English language literature in 2008, 30 medical education research studies were independently identified as hypothesis-testing investigations and measurements of educational interventions. Six reviewers independently rated and scored all articles based on eight anchors, four of which related to methodologic criteria. Articles were ranked according to their total rating score. A ranking agreement among the reviewers of 83% was established a priori as a minimum for highlighting articles in this review. Five medical education research studies met the a priori criteria for inclusion and are reviewed and summarized here. Four of these employed experimental or quasi-experimental methodology. Although technology was not a component of the structured literature search employed to identify the candidate articles for this review, 14 of the articles identified, including four of the five highlighted articles, employed or studied technology as a focus of the educational research. Overall, 36% of the reviewed studies were supported by funding; three of the highlighted articles were funded studies. This review highlights quality medical education research studies published in 2008, with outcomes of relevance to teaching and education in emergency medicine. It focuses on research methodology, notes current trends in the use of technology for learning in emergency medicine, and suggests future avenues for continued rigorous study in education.

Location and orientation of panel on the screen as a structural visual element to highlight text displayed

Science.gov (United States)

Léger, Laure; Chevalier, Aline

2017-07-01

Searching for information on the internet has become a daily activity. It is considered to be a complex cognitive activity that involves visual attention. Many studies have demonstrated that users' information search are affected both by the spatial configuration of words and the elements displayed on the screen: elements that are used to structure web pages. One of these elements, the web panel, contains information. Web panel is a rectangular area with a colored background that was used to highlighting content presented in this specific rectangular area. Our general hypothesis was that the presence of a panel on a web page would affect the structure of a word display, as a result, information search accuracy. We carried out an experiment in which we manipulated the presence vs. the absence of a panel, as well as its orientation on the screen (vertical vs. horizontal). Twenty participants were asked to answer questions while their eye movements were recorded. Results showed that the presence of a panel resulted in reduced accuracy and shorter response times. Panel orientation affected scanpaths, especially when they were orientated vertically. We discuss these findings and suggest ways in which this research could be developed further in future.

Insights on synergy of materials and structures in biomimetic platelet-matrix composites

Science.gov (United States)

Sakhavand, Navid; Shahsavari, Rouzbeh

2018-01-01

Hybrid materials such as biomimetic platelet-matrix composites are in high demand to confer low weight and multifunctional mechanical properties. This letter reports interfacial-bond regulated assembly of polymers on cement-an archetype model with significant infrastructure applications. We demonstrate a series of 20+ molecular dynamics studies on decoding and optimizing the complex interfacial interactions including the role and types of various heterogeneous, competing interfacial bonds that are key to adhesion and interfacial strength. Our results show an existence of an optimum overlap length scale (˜15 nm) between polymers and cement crystals, exhibiting the best balance of strength, toughness, stiffness, and ductility for the composite. This finding, combined with the fundamental insights into the nature of interfacial bonds, provides key hypotheses for selection and processing of constituents to deliberate the best synergy in the structure and materials of platelet-matrix composites.

Highlights of the 16th annual scientific sessions of the Society for Cardiovascular Magnetic Resonance.

Science.gov (United States)

Carpenter, John-Paul; Patel, Amit R; Fernandes, Juliano Lara

2013-07-19

The 16th Annual Scientific Sessions of the Society for Cardiovascular Magnetic Resonance (SCMR) took place in San Francisco, USA at the end of January 2013. With a faculty of experts from across the world, this congress provided a wealth of insight into cutting-edge research and technological development. This review article intends to provide a highlight of what represented the most significant advances in the field of cardiovascular magnetic resonance (CMR) during this year's meeting.

Kinetic and Structural Insights into the Mechanism of AMPylation by VopS Fic Domain*

Science.gov (United States)

Luong, Phi; Kinch, Lisa N.; Brautigam, Chad A.; Grishin, Nick V.; Tomchick, Diana R.; Orth, Kim

2010-01-01

The bacterial pathogen Vibrio parahemeolyticus manipulates host signaling pathways during infections by injecting type III effectors into the cytoplasm of the target cell. One of these effectors, VopS, blocks actin assembly by AMPylation of a conserved threonine residue in the switch 1 region of Rho GTPases. The modified GTPases are no longer able to interact with downstream effectors due to steric hindrance by the covalently linked AMP moiety. Herein we analyze the structure of VopS and its evolutionarily conserved catalytic residues. Steady-state analysis of VopS mutants provides kinetic understanding on the functional role of each residue for AMPylation activity by the Fic domain. Further mechanistic analysis of VopS with its two substrates, ATP and Cdc42, demonstrates that VopS utilizes a sequential mechanism to AMPylate Rho GTPases. Discovery of a ternary reaction mechanism along with structural insight provides critical groundwork for future studies for the family of AMPylators that modify hydroxyl-containing residues with AMP. PMID:20410310

Kinetic and Structural Insights into the Mechanism of AMPylation by VopS Fic Domain

Energy Technology Data Exchange (ETDEWEB)

Luong, Phi; Kinch, Lisa N.; Brautigam, Chad A.; Grishin, Nick V.; Tomchick, Diana R.; Orth, Kim (UTSMC)

2010-07-19

The bacterial pathogen Vibrio parahemeolyticus manipulates host signaling pathways during infections by injecting type III effectors into the cytoplasm of the target cell. One of these effectors, VopS, blocks actin assembly by AMPylation of a conserved threonine residue in the switch 1 region of Rho GTPases. The modified GTPases are no longer able to interact with downstream effectors due to steric hindrance by the covalently linked AMP moiety. Herein we analyze the structure of VopS and its evolutionarily conserved catalytic residues. Steady-state analysis of VopS mutants provides kinetic understanding on the functional role of each residue for AMPylation activity by the Fic domain. Further mechanistic analysis of VopS with its two substrates, ATP and Cdc42, demonstrates that VopS utilizes a sequential mechanism to AMPylate Rho GTPases. Discovery of a ternary reaction mechanism along with structural insight provides critical groundwork for future studies for the family of AMPylators that modify hydroxyl-containing residues with AMP.

Structural studies of Pseudomonas and Chromobacterium ω-aminotransferases provide insights into their differing substrate specificity

International Nuclear Information System (INIS)

Sayer, Christopher; Isupov, Michail N.; Westlake, Aaron; Littlechild, Jennifer A.

2013-01-01

The X-ray structures of two ω-aminotransferases from P. aeruginosa and C. violaceum in complex with an inhibitor offer the first detailed insight into the structural basis of the substrate specificity of these industrially important enzymes. The crystal structures and inhibitor complexes of two industrially important ω-aminotransferase enzymes from Pseudomonas aeruginosa and Chromobacterium violaceum have been determined in order to understand the differences in their substrate specificity. The two enzymes share 30% sequence identity and use the same amino acceptor, pyruvate; however, the Pseudomonas enzyme shows activity towards the amino donor β-alanine, whilst the Chromobacterium enzyme does not. Both enzymes show activity towards S-α-methylbenzylamine (MBA), with the Chromobacterium enzyme having a broader substrate range. The crystal structure of the P. aeruginosa enzyme has been solved in the holo form and with the inhibitor gabaculine bound. The C. violaceum enzyme has been solved in the apo and holo forms and with gabaculine bound. The structures of the holo forms of both enzymes are quite similar. There is little conformational difference observed between the inhibitor complex and the holoenzyme for the P. aeruginosa aminotransferase. In comparison, the crystal structure of the C. violaceum gabaculine complex shows significant structural rearrangements from the structures of both the apo and holo forms of the enzyme. It appears that the different rigidity of the protein scaffold contributes to the substrate specificity observed for the two ω-aminotransferases

The effects of gender and self-insight on early semantic processing.

Directory of Open Access Journals (Sweden)

Xu Xu

Full Text Available This event-related potential (ERP study explored individual differences associated with gender and level of self-insight in early semantic processing. Forty-eight Chinese native speakers completed a semantic judgment task with three different categories of words: abstract neutral words (e.g., logic, effect, concrete neutral words (e.g., teapot, table, and emotion words (e.g., despair, guilt. They then assessed their levels of self-insight. Results showed that women engaged in greater processing than did men. Gender differences also manifested in the relationship between level of self-insight and word processing. For women, level of self-insight was associated with level of semantic activation for emotion words and abstract neutral words, but not for concrete neutral words. For men, level of self-insight was related to processing speed, particularly in response to abstract and concrete neutral words. These findings provide electrophysiological evidence for the effects of gender and self-insight on semantic processing and highlight the need to take into consideration subject variables in related research.

Insight, Cognitive Insight and Sociodemographic Features in Obsessive Compulsive Disorder Presenting with Reactive and Autogeneus Features

Directory of Open Access Journals (Sweden)

Katre ÇAMLI

2012-03-01

Full Text Available Objective: The aim of the present study was to test hypothesis that obsessive compulsive disorder (OCD patients who have autogenous obsessions and reactive obsessions show different sociodemographic and clinical characteristics with different insight and cognitive insight levels. Method: Sixty-one patients diagnosed as OCD according to the Structured Clinical Interview for DSM-III-R (SCID-I are recruited. 31 patients had reactive obsessions and 30 had autogenous obsessions. The sociodemographic characteristics of patients and the symptomatology were evaluated using psychiatric scales including SCID-I, Yale Brown Obsessive- Compulsive Scale (YBOCS, Yale Brown Obsessive-Compulsive Scale-Symptom Checklist (YBOCS-SC and Beck Insight Scale. Results: The percentage of women in reactive obsessive group was higher and also this group had significantly less antipsychotic medication prescribed than the autogenous obsessive group. No significant difference was found for the other demographic variables. No significant difference was identified for the Beck Insight Self-Reflectiveness subscale but for the Self-Certainty subscale, reactive obsessives had higher scores. Although there was no significant difference for the composit index points, which is the subtraction of the two subscales, the p value was close to the limit. On the other hand YBOCS item- 11 scores which evaluates insight were higher in autogenous obsessives meaning low levels of insight. Conclusion: For the sociodemographic and clinical characteristics; there was no significant difference between the groups except gender distribution and antipsychotic medication. Our data about insight seems inconsistent but insight and cognitive insight can be different entities which show different levels of insight. Further investigation with different obsession types is needed.

BBG Highlights

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Broadcasting Board of Governors — BBG Highlights is a monthly summary of the BBG's accomplishments and news and developments affecting the Agency's work. Now, for the first time, this monthly update...

Structural Insights into DD-Fold Assembly and Caspase-9 Activation by the Apaf-1 Apoptosome.

Science.gov (United States)

Su, Tsung-Wei; Yang, Chao-Yu; Kao, Wen-Pin; Kuo, Bai-Jiun; Lin, Shan-Meng; Lin, Jung-Yaw; Lo, Yu-Chih; Lin, Su-Chang

2017-03-07

Death domain (DD)-fold assemblies play a crucial role in regulating the signaling to cell survival or death. Here we report the crystal structure of the caspase recruitment domain (CARD)-CARD disk of the human apoptosome. The structure surprisingly reveals that three 1:1 Apaf-1:procaspase-9 CARD protomers form a novel helical DD-fold assembly on the heptameric wheel-like platform of the apoptosome. The small-angle X-ray scattering and multi-angle light scattering data also support that three protomers could form an oligomeric complex similar to the crystal structure. Interestingly, the quasi-equivalent environment of CARDs could generate different quaternary CARD assemblies. We also found that the type II interaction is conserved in all DD-fold complexes, whereas the type I interaction is found only in the helical DD-fold assemblies. This study provides crucial insights into the caspase activation mechanism, which is tightly controlled by a sophisticated and highly evolved CARD assembly on the apoptosome, and also enables better understanding of the intricate DD-fold assembly. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tandem Mass Spectrometry and Ion Mobility Reveals Structural Insight into Eicosanoid Product Ion Formation.

Science.gov (United States)

Di Giovanni, James P; Barkley, Robert M; Jones, David N M; Hankin, Joseph A; Murphy, Robert C

2018-04-23

Ion mobility measurements of product ions were used to characterize the collisional cross section (CCS) of various complex lipid [M-H] - ions using traveling wave ion mobility mass spectrometry (TWIMS). TWIMS analysis of various product ions derived after collisional activation of mono- and dihydroxy arachidonate metabolites was found to be more complex than the analysis of intact molecular ions and provided some insight into molecular mechanisms involved in product ion formation. The CCS observed for the molecular ion [M-H] - and certain product ions were consistent with a folded ion structure, the latter predicted by the proposed mechanisms of product ion formation. Unexpectedly, product ions from [M-H-H 2 O-CO 2 ] - and [M-H-H 2 O] - displayed complex ion mobility profiles suggesting multiple mechanisms of ion formation. The [M-H-H 2 O] - ion from LTB 4 was studied in more detail using both nitrogen and helium as the drift gas in the ion mobility cell. One population of [M-H-H 2 O] - product ions from LTB 4 was consistent with formation of covalent ring structures, while the ions displaying a higher CCS were consistent with a more open-chain structure. Using molecular dynamics and theoretical CCS calculations, energy minimized structures of those product ions with the open-chain structures were found to have a higher CCS than a folded molecular ion structure. The measurement of product ion mobility can be an additional and unique signature of eicosanoids measured by LC-MS/MS techniques. Graphical Abstract ᅟ.

Tandem Mass Spectrometry and Ion Mobility Reveals Structural Insight into Eicosanoid Product Ion Formation

Science.gov (United States)

Di Giovanni, James P.; Barkley, Robert M.; Jones, David N. M.; Hankin, Joseph A.; Murphy, Robert C.

2018-04-01

Ion mobility measurements of product ions were used to characterize the collisional cross section (CCS) of various complex lipid [M-H]- ions using traveling wave ion mobility mass spectrometry (TWIMS). TWIMS analysis of various product ions derived after collisional activation of mono- and dihydroxy arachidonate metabolites was found to be more complex than the analysis of intact molecular ions and provided some insight into molecular mechanisms involved in product ion formation. The CCS observed for the molecular ion [M-H]- and certain product ions were consistent with a folded ion structure, the latter predicted by the proposed mechanisms of product ion formation. Unexpectedly, product ions from [M-H-H2O-CO2]- and [M-H-H2O]- displayed complex ion mobility profiles suggesting multiple mechanisms of ion formation. The [M-H-H2O]- ion from LTB4 was studied in more detail using both nitrogen and helium as the drift gas in the ion mobility cell. One population of [M-H-H2O]- product ions from LTB4 was consistent with formation of covalent ring structures, while the ions displaying a higher CCS were consistent with a more open-chain structure. Using molecular dynamics and theoretical CCS calculations, energy minimized structures of those product ions with the open-chain structures were found to have a higher CCS than a folded molecular ion structure. The measurement of product ion mobility can be an additional and unique signature of eicosanoids measured by LC-MS/MS techniques. [Figure not available: see fulltext.

AEB highlights

International Nuclear Information System (INIS)

1975-01-01

AEB HIGHLIGHTS is a half-yearly report reflecting the most important recent achievements of the various Research and Technical Divisions of the Atomic Energy Board. It appears alternately in English and Afrikaans [af

AEB highlights

International Nuclear Information System (INIS)

1977-01-01

AEB HIGHLIGHTS is a half yearly report reflecting the most important recent achievements of the various Research and Technical Divisions of the Atomic Energy Board. It appears alternately in English and Afrikaans [af

Density functional theory for field emission from carbon nano-structures

Energy Technology Data Exchange (ETDEWEB)

Li, Zhibing, E-mail: stslzb@mail.sysu.edu.cn

2015-12-15

Electron field emission is understood as a quantum mechanical many-body problem in which an electronic quasi-particle of the emitter is converted into an electron in vacuum. Fundamental concepts of field emission, such as the field enhancement factor, work-function, edge barrier and emission current density, will be investigated, using carbon nanotubes and graphene as examples. A multi-scale algorithm basing on density functional theory is introduced. We will argue that such a first principle approach is necessary and appropriate for field emission of nano-structures, not only for a more accurate quantitative description, but, more importantly, for deeper insight into field emission. - Highlights: • Applications of DFT to electron field emission of nano-structures are reviewed. • Fundamental concepts of field emission are re-visited with emphasis on the many-body effects. • New insights to field emission of nano-structures are obtained by multi-scale DFT calculations. • It is shown that the exchange–correlation effect on the emission barrier is significant. • Spontaneous symmetry breaking in field emission of CNT has been predicted.

Improved understanding of protein complex offers insight into DNA

Science.gov (United States)

Summer Science Writing Internship Improved understanding of protein complex offers insight into DNA clearer understanding of the origin recognition complex (ORC) - a protein complex that directs DNA replication - through its crystal structure offers new insight into fundamental mechanisms of DNA replication

Structural models of zebrafish (Danio rerio NOD1 and NOD2 NACHT domains suggest differential ATP binding orientations: insights from computational modeling, docking and molecular dynamics simulations.

Directory of Open Access Journals (Sweden)

Jitendra Maharana

Full Text Available Nucleotide-binding oligomerization domain-containing protein 1 (NOD1 and NOD2 are cytosolic pattern recognition receptors playing pivotal roles in innate immune signaling. NOD1 and NOD2 recognize bacterial peptidoglycan derivatives iE-DAP and MDP, respectively and undergoes conformational alternation and ATP-dependent self-oligomerization of NACHT domain followed by downstream signaling. Lack of structural adequacy of NACHT domain confines our understanding about the NOD-mediated signaling mechanism. Here, we predicted the structure of NACHT domain of both NOD1 and NOD2 from model organism zebrafish (Danio rerio using computational methods. Our study highlighted the differential ATP binding modes in NOD1 and NOD2. In NOD1, γ-phosphate of ATP faced toward the central nucleotide binding cavity like NLRC4, whereas in NOD2 the cavity was occupied by adenine moiety. The conserved 'Lysine' at Walker A formed hydrogen bonds (H-bonds and Aspartic acid (Walker B formed electrostatic interaction with ATP. At Sensor 1, Arg328 of NOD1 exhibited an H-bond with ATP, whereas corresponding Arg404 of NOD2 did not. 'Proline' of GxP motif (Pro386 of NOD1 and Pro464 of NOD2 interacted with adenine moiety and His511 at Sensor 2 of NOD1 interacted with γ-phosphate group of ATP. In contrast, His579 of NOD2 interacted with the adenine moiety having a relatively inverted orientation. Our findings are well supplemented with the molecular interaction of ATP with NLRC4, and consistent with mutagenesis data reported for human, which indicates evolutionary shared NOD signaling mechanism. Together, this study provides novel insights into ATP binding mechanism, and highlights the differential ATP binding modes in zebrafish NOD1 and NOD2.

Substrate analog interaction with MCR-1 offers insight into the rising threat of the plasmid-mediated transferable colistin resistance.

Science.gov (United States)

Wei, Pengcheng; Song, Guangji; Shi, Mengyang; Zhou, Yafei; Liu, Yang; Lei, Jun; Chen, Peng; Yin, Lei

2018-02-01

Colistin is considered a last-resort antibiotic against most gram-negative bacteria. Recent discoveries of a plasmid-mediated, transferable mobilized colistin-resistance gene ( mcr-1) on all continents have heralded the imminent emergence of pan-drug-resistant superbacteria. The inner-membrane protein MCR-1 can catalyze the transfer of phosphoethanolamine (PEA) to lipid A, resulting in colistin resistance. However, little is known about the mechanism, and few drugs exist to address this issue. We present crystal structures revealing the MCR-1 catalytic domain (cMCR-1) as a monozinc metalloprotein with ethanolamine (ETA) and d-glucose, respectively, thus highlighting 2 possible substrate-binding pockets in the MCR-1-catalyzed PEA transfer reaction. Mutation of the residues involved in ETA and d-glucose binding impairs colistin resistance in recombinant Escherichia coli containing full-length MCR-1. Partial analogs of the substrate are used for cocrystallization with cMCR-1, providing valuable information about the family of PEA transferases. One of the analogs, ETA, causes clear inhibition of polymyxin B resistance, highlighting its potential for drug development. These data demonstrate the crucial role of the PEA- and lipid A-binding pockets and provide novel insights into the structure-based mechanisms, important drug-target hot spots, and a drug template for further drug development to combat the urgent, rising threat of MCR-1-mediated antibiotic resistance.-Wei, P., Song, G., Shi, M., Zhou, Y., Liu, Y., Lei, J., Chen, P., Yin, L. Substrate analog interaction with MCR-1 offers insight into the rising threat of the plasmid-mediated transferable colistin resistance.

Genetic influences on insight problem solving: the role of catechol-O-methyltransferase (COMT) gene polymorphisms.

Science.gov (United States)

Jiang, Weili; Shang, Siyuan; Su, Yanjie

2015-01-01

People may experience an "aha" moment, when suddenly realizing a solution of a puzzling problem. This experience is called insight problem solving. Several findings suggest that catecholamine-related genes may contribute to insight problem solving, among which the catechol-O-methyltransferase (COMT) gene is the most promising candidate. The current study examined 753 healthy individuals to determine the associations between 7 candidate single nucleotide polymorphisms on the COMT gene and insight problem-solving performance, while considering gender differences. The results showed that individuals carrying A allele of rs4680 or T allele of rs4633 scored significantly higher on insight problem-solving tasks, and the COMT gene rs5993883 combined with gender interacted with correct solutions of insight problems, specifically showing that this gene only influenced insight problem-solving performance in males. This study presents the first investigation of the genetic impact on insight problem solving and provides evidence that highlights the role that the COMT gene plays in insight problem solving.

Model representations of kerogen structures: An insight from density functional theory calculations and spectroscopic measurements.

Science.gov (United States)

Weck, Philippe F; Kim, Eunja; Wang, Yifeng; Kruichak, Jessica N; Mills, Melissa M; Matteo, Edward N; Pellenq, Roland J-M

2017-08-01

Molecular structures of kerogen control hydrocarbon production in unconventional reservoirs. Significant progress has been made in developing model representations of various kerogen structures. These models have been widely used for the prediction of gas adsorption and migration in shale matrix. However, using density functional perturbation theory (DFPT) calculations and vibrational spectroscopic measurements, we here show that a large gap may still remain between the existing model representations and actual kerogen structures, therefore calling for new model development. Using DFPT, we calculated Fourier transform infrared (FTIR) spectra for six most widely used kerogen structure models. The computed spectra were then systematically compared to the FTIR absorption spectra collected for kerogen samples isolated from Mancos, Woodford and Marcellus formations representing a wide range of kerogen origin and maturation conditions. Limited agreement between the model predictions and the measurements highlights that the existing kerogen models may still miss some key features in structural representation. A combination of DFPT calculations with spectroscopic measurements may provide a useful diagnostic tool for assessing the adequacy of a proposed structural model as well as for future model development. This approach may eventually help develop comprehensive infrared (IR)-fingerprints for tracing kerogen evolution.

Structural Insights into Diversity and n-Alkane Biodegradation Mechanisms of Alkane Hydroxylases

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Yurui eJi

2013-03-01

Full Text Available Environmental microbes utilize four degradation pathways for the oxidation of n-alkanes. Although the enzymes degrading n-alkanes in different microbes may vary, enzymes functioning in the first step in the aerobic degradation of alkanes all belong to the alkane hydroxylases. Alkane hydroxylases are a class of enzymes that insert oxygen atoms derived from molecular oxygen into different sites of the alkane terminus (or termini depending on the type of enzymes. In this review, we summarize the different types of alkane hydroxylases, their degrading steps and compare typical enzymes from various classes with regard to their three dimensional structures, in order to provide insights into how the enzymes mediate their different roles in the degradation of n-alkanes and what determines their different substrate ranges. Through the above analyses, the degrading mechanisms of enzymes can be elucidated and molecular biological methods can be utilized to expand their catalytic roles in the petrochemical industry or in bioremediation of oil-contaminated environments.

Insight into the microscopic structure of an AdS black hole from a thermodynamical phase transition.

Science.gov (United States)

Wei, Shao-Wen; Liu, Yu-Xiao

2015-09-11

Comparing with an ordinary thermodynamic system, we investigate the possible microscopic structure of a charged anti-de Sitter black hole completely from the thermodynamic viewpoint. The number density of the black hole molecules is introduced to measure the microscopic degrees of freedom of the black hole. We found that the number density suffers a sudden change accompanied by a latent heat when the black hole system crosses the small-large black hole coexistence curve, while when the system passes the critical point, it encounters a second-order phase transition with a vanishing latent heat due to the continuous change of the number density. Moreover, the thermodynamic scalar curvature suggests that there is a weak attractive interaction between two black hole molecules. These phenomena might cast new insight into the underlying microscopic structure of a charged anti-de Sitter black hole.

Structure, dynamics, and function of the monooxygenase P450 BM-3: insights from computer simulations studies

International Nuclear Information System (INIS)

Roccatano, Danilo

2015-01-01

The monooxygenase P450 BM-3 is a NADPH-dependent fatty acid hydroxylase enzyme isolated from soil bacterium Bacillus megaterium. As a pivotal member of cytochrome P450 superfamily, it has been intensely studied for the comprehension of structure–dynamics–function relationships in this class of enzymes. In addition, due to its peculiar properties, it is also a promising enzyme for biochemical and biomedical applications. However, despite the efforts, the full understanding of the enzyme structure and dynamics is not yet achieved. Computational studies, particularly molecular dynamics (MD) simulations, have importantly contributed to this endeavor by providing new insights at an atomic level regarding the correlations between structure, dynamics, and function of the protein. This topical review summarizes computational studies based on MD simulations of the cytochrome P450 BM-3 and gives an outlook on future directions. (topical review)

Base pairing and structural insights into the 5-formylcytosine in RNA duplex

Science.gov (United States)

Wang, Rui; Luo, Zhipu; He, Kaizhang; Delaney, Michael O.; Chen, Doris; Sheng, Jia

2016-01-01

Abstract 5-Formylcytidine (f5C), a previously discovered natural nucleotide in the mitochondrial tRNA of many species including human, has been recently detected as the oxidative product of 5-methylcytidine (m5C) through 5-hydroxymethylcytidine (hm5C) in total RNA of mammalian cells. The discovery indicated that these cytosine derivatives in RNA might also play important epigenetic roles similar as in DNA, which has been intensively investigated in the past few years. In this paper, we studied the base pairing specificity of f5C in different RNA duplex contexts. We found that the 5-formyl group could increase duplex thermal stability and enhance base pairing specificity. We present three high-resolution crystal structures of an octamer RNA duplex [5′-GUA(f5C)GUAC-3′]2 that have been solved under three crystallization conditions with different buffers and pH values. Our results showed that the 5-formyl group is located in the same plane as the cytosine base and forms an intra-residue hydrogen bond with the amino group in the N4 position. In addition, this modification increases the base stacking between the f5C and the neighboring bases while not causing significant global and local structure perturbations. This work provides insights into the effects of 5-formylcytosine on RNA duplex. PMID:27079978

Neutron structures of the Helicobacter pylori 5'-methylthioadenosine nucleosidase highlight proton sharing and protonation states

Energy Technology Data Exchange (ETDEWEB)

Banco, Michael T.; Mishra, Vidhi; Ostermann, Andreas; Schrader, Tobias E.; Evans, Gary B.; Kovalevsky, Andrey; Ronning, Donald R.

2016-11-16

MTAN (5'-methylthioadenosine nucleosidase) catalyzes the hydrolysis of the N-ribosidic bond of a variety of adenosine-containing metabolites. The Helicobacter pylori MTAN (HpMTAN) hydrolyzes 6-amino-6-deoxyfutalosine in the second step of the alternative menaquinone biosynthetic pathway. Substrate binding of the adenine moiety is mediated almost exclusively by hydrogen bonds, and the proposed catalytic mechanism requires multiple proton-transfer events. Of particular interest is the protonation state of residue D198, which possesses a pKa above 8 and functions as a general acid to initiate the enzymatic reaction. In this study we present three corefined neutron/X-ray crystal structures of wild-type HpMTAN cocrystallized with S-adenosylhomocysteine (SAH), Formycin A (FMA), and (3R,4S)-4-(4-Chlorophenylthiomethyl)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxypyrrolidine (p-ClPh-Thio-DADMe-ImmA) as well as one neutron/X-ray crystal structure of an inactive variant (HpMTAN-D198N) cocrystallized with SAH. These results support a mechanism of D198 pKa elevation through the unexpected sharing of a proton with atom N7 of the adenine moiety possessing unconventional hydrogen-bond geometry. Additionally, the neutron structures also highlight active site features that promote the stabilization of the transition state and slight variations in these interactions that result in 100-fold difference in binding affinities between the DADMe-ImmA and ImmA analogs.

Revealing New Structural Insights from Surfactant Micelles through DLS, Microrheology and Raman Spectroscopy

Directory of Open Access Journals (Sweden)

Samiul Amin

2015-06-01

Full Text Available The correlation between molecular changes and microstructural evolution of rheological properties has been demonstrated for the first time in a mixed anionic/zwitterionic surfactant-based wormlike micellar system. Utilizing a novel combination of DLS-microrheology and Raman Spectroscopy, the effect of electrostatic screening on these properties of anionic (SLES and zwitterionic (CapB surfactant mixtures was studied by modulating the NaCl concentration. As Raman Spectroscopy delivers information about the molecular structure and DLS-microrheology characterizes viscoelastic properties, the combination of data delivered allows for a deeper understanding of the molecular changes underlying the viscoelastic ones. The high frequency viscoelastic response obtained through DLS-microrheology has shown the persistence of the Maxwell fluid response for low viscosity solutions at high NaCl concentrations. The intensity of the Raman band at 170 cm−1 exhibits very strong correlation with the viscosity variation. As this Raman band is assigned to hydrogen bonding, its variation with NaCl concentration additionally indicates differences in water structuring due to potential microstructural differences at low and high NaCl concentrations. The microstructural differences at low and high NaCl concentrations are further corroborated by persistence of a slow mode at the higher NaCl concentrations as seen through DLS measurements. The study illustrates the utility of the combined DLS, DLS-optical microrheology and Raman Spectroscopy in providing new molecular structural insights into the self-assembly process in complex fluids.

Insight into structural phase transitions from the decoupled anharmonic mode approximation.

Science.gov (United States)

Adams, Donat J; Passerone, Daniele

2016-08-03

We develop a formalism (decoupled anharmonic mode approximation, DAMA) that allows calculation of the vibrational free energy using density functional theory even for materials which exhibit negative curvature of the potential energy surface with respect to atomic displacements. We investigate vibrational modes beyond the harmonic approximation and approximate the potential energy surface with the superposition of the accurate potential along each normal mode. We show that the free energy can stabilize crystal structures at finite temperatures which appear dynamically unstable at T  =  0. The DAMA formalism is computationally fast because it avoids statistical sampling through molecular dynamics calculations, and is in principle completely ab initio. It is free of statistical uncertainties and independent of model parameters, but can give insight into the mechanism of a structural phase transition. We apply the formalism to the perovskite cryolite, and investigate the temperature-driven phase transition from the P21/n to the Immm space group. We calculate a phase transition temperature between 710 and 950 K, in fair agreement with the experimental value of 885 K. This can be related to the underestimation of the interaction of the vibrational states. We also calculate the main axes of the thermal ellipsoid and can explain the experimentally observed increase of its volume for the fluorine by 200-300% throughout the phase transition. Our calculations suggest the appearance of tunneling states in the high temperature phase. The convergence of the vibrational DOS and of the critical temperature with respect of reciprocal space sampling is investigated using the polarizable-ion model.

INSIGHT AGONISTES: A READING OF SOPHOCLES'S OEDIPUS THE KING.

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Mahon, Eugene J

2015-07-01

In this reading of Sophocles's Oedipus the King, the author suggests that insight can be thought of as the main protagonist of the tragedy. He personifies this depiction of insight, calling it Insight Agonistes, as if it were the sole conflicted character on the stage, albeit masquerading at times as several other characters, including gods, sphinxes, and oracles. This psychoanalytic reading of the text lends itself to an analogy between psychoanalytic process and Sophocles's tragic hero. The author views insight as always transgressing against, always at war with a conservative, societal, or intrapsychic chorus of structured elements. A clinical vignette is presented to illustrate this view of insight. © 2015 The Psychoanalytic Quarterly, Inc.

Structural insights into methanol-stable variants of lipase T6 from Geobacillus stearothermophilus.

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Dror, Adi; Kanteev, Margarita; Kagan, Irit; Gihaz, Shalev; Shahar, Anat; Fishman, Ayelet

2015-11-01

Enzymatic production of biodiesel by transesterification of triglycerides and alcohol, catalyzed by lipases, offers an environmentally friendly and efficient alternative to the chemically catalyzed process while using low-grade feedstocks. Methanol is utilized frequently as the alcohol in the reaction due to its reactivity and low cost. However, one of the major drawbacks of the enzymatic system is the presence of high methanol concentrations which leads to methanol-induced unfolding and inactivation of the biocatalyst. Therefore, a methanol-stable lipase is of great interest for the biodiesel industry. In this study, protein engineering was applied to substitute charged surface residues with hydrophobic ones to enhance the stability in methanol of a lipase from Geobacillus stearothermophilus T6. We identified a methanol-stable variant, R374W, and combined it with a variant found previously, H86Y/A269T. The triple mutant, H86Y/A269T/R374W, had a half-life value at 70 % methanol of 324 min which reflects an 87-fold enhanced stability compared to the wild type together with elevated thermostability in buffer and in 50 % methanol. This variant also exhibited an improved biodiesel yield from waste chicken oil compared to commercial Lipolase 100L® and Novozyme® CALB. Crystal structures of the wild type and the methanol-stable variants provided insights regarding structure-stability correlations. The most prominent features were the extensive formation of new hydrogen bonds between surface residues directly or mediated by structural water molecules and the stabilization of Zn and Ca binding sites. Mutation sites were also characterized by lower B-factor values calculated from the X-ray structures indicating improved rigidity.

Quantum-Chemical Insights into the Self-Assembly of Carbon-Based Supramolecular Complexes

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Joaquín Calbo

2018-01-01

Full Text Available Understanding how molecular systems self-assemble to form well-organized superstructures governed by noncovalent interactions is essential in the field of supramolecular chemistry. In the nanoscience context, the self-assembly of different carbon-based nanoforms (fullerenes, carbon nanotubes and graphene with, in general, electron-donor molecular systems, has received increasing attention as a means of generating potential candidates for technological applications. In these carbon-based systems, a deep characterization of the supramolecular organization is crucial to establish an intimate relation between supramolecular structure and functionality. Detailed structural information on the self-assembly of these carbon-based nanoforms is however not always accessible from experimental techniques. In this regard, quantum chemistry has demonstrated to be key to gain a deep insight into the supramolecular organization of molecular systems of high interest. In this review, we intend to highlight the fundamental role that quantum-chemical calculations can play to understand the supramolecular self-assembly of carbon-based nanoforms through a limited selection of supramolecular assemblies involving fullerene, fullerene fragments, nanotubes and graphene with several electron-rich π-conjugated systems.

Outsourcing/Offshoring Insights

DEFF Research Database (Denmark)

Tate, Wendy; Bals, Lydia

2017-01-01

Findings: Both the geographical and governance dimensions are part of the rightshoring decision which is an important conceptual foundation for this special issue, as it invited insightful pieces on all of these phenomena (e.g. outsourcing, insourcing, offshoring, reshoring), acknowledging...... for future research out of the six papers are summarized in Table III. There is ample opportunity to further shed light on these suggestions as well as to cover parts of the “rightshoring” framework presented, that remain less covered here (e.g. insourcing and/or reshoring). Practical implications: The array...... of potential “rightshoring” options fosters clarity about the phenomena studied and their implications. The main practical implications of the six papers are summarized in Table II. Originality/value: The overall conceptual framework highlights the positioning of the final papers included into the special...

Deep transcriptome sequencing provides new insights into the structural and functional organization of the wheat genome.

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Pingault, Lise; Choulet, Frédéric; Alberti, Adriana; Glover, Natasha; Wincker, Patrick; Feuillet, Catherine; Paux, Etienne

2015-02-10

Because of its size, allohexaploid nature, and high repeat content, the bread wheat genome is a good model to study the impact of the genome structure on gene organization, function, and regulation. However, because of the lack of a reference genome sequence, such studies have long been hampered and our knowledge of the wheat gene space is still limited. The access to the reference sequence of the wheat chromosome 3B provided us with an opportunity to study the wheat transcriptome and its relationships to genome and gene structure at a level that has never been reached before. By combining this sequence with RNA-seq data, we construct a fine transcriptome map of the chromosome 3B. More than 8,800 transcription sites are identified, that are distributed throughout the entire chromosome. Expression level, expression breadth, alternative splicing as well as several structural features of genes, including transcript length, number of exons, and cumulative intron length are investigated. Our analysis reveals a non-monotonic relationship between gene expression and structure and leads to the hypothesis that gene structure is determined by its function, whereas gene expression is subject to energetic cost. Moreover, we observe a recombination-based partitioning at the gene structure and function level. Our analysis provides new insights into the relationships between gene and genome structure and function. It reveals mechanisms conserved with other plant species as well as superimposed evolutionary forces that shaped the wheat gene space, likely participating in wheat adaptation.

Structural and molecular insights into novel surface-exposed mucus adhesins from Lactobacillus reuteri human strains.

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Etzold, Sabrina; MacKenzie, Donald A; Jeffers, Faye; Walshaw, John; Roos, Stefan; Hemmings, Andrew M; Juge, Nathalie

2014-05-01

The mucus layer covering the gastrointestinal tract is the first point of contact of the intestinal microbiota with the host. Cell surface macromolecules are critical for adherence of commensal bacteria to mucus but structural information is scarce. Here we report the first molecular and structural characterization of a novel cell-surface protein, Lar_0958 from Lactobacillus reuteri JCM 1112(T) , mediating adhesion of L. reuteri human strains to mucus. Lar_0958 is a modular protein of 133 kDa containing six repeat domains, an N-terminal signal sequence and a C-terminal anchoring motif (LPXTG). Lar_0958 homologues are expressed on the cell-surface of L. reuteri human strains, as shown by flow-cytometry and immunogold microscopy. Adhesion of human L. reuteri strains to mucus in vitro was significantly reduced in the presence of an anti-Lar_0958 antibody and Lar_0958 contribution to adhesion was further confirmed using a L. reuteri ATCC PTA 6475 lar_0958 KO mutant (6475-KO). The X-ray crystal structure of a single Lar_0958 repeat, determined at 1.5 Å resolution, revealed a divergent immunoglobulin (Ig)-like β-sandwich fold, sharing structural homology with the Ig-like inter-repeat domain of internalins of the food borne pathogen Listeria monocytogenes. These findings provide unique structural insights into cell-surface protein repeats involved in adhesion of Gram-positive bacteria to the intestine. © 2014 John Wiley & Sons Ltd.

An Insight into the Pharmacophores of Phosphodiesterase-5 Inhibitors from Synthetic and Crystal Structural Studies

Energy Technology Data Exchange (ETDEWEB)

Chen,G.; Wang, H.; Robinson, H.; Cai, J.; Wan, Y.; Ke, H.

2008-01-01

Selective inhibitors of cyclic nucleotide phosphodiesterase-5 (PDE5) have been used as drugs for treatment of male erectile dysfunction and pulmonary hypertension. An insight into the pharmacophores of PDE5 inhibitors is essential for development of second generation of PDE5 inhibitors, but has not been completely illustrated. Here we report the synthesis of a new class of the sildenafil derivatives and a crystal structure of the PDE5 catalytic domain in complex with 5-(2-ethoxy-5-(sulfamoyl)-3-thienyl)-1-methyl-3-propyl-1, 6-dihydro-7H-pyrazolo[4, 3-d]pyrimidin-7-one (12). Inhibitor 12 induces conformational change of the H-loop (residues 660-683), which is different from any of the known PDE5 structures. The pyrazolopyrimidinone groups of 12 and sildenafil are well superimposed, but their sulfonamide groups show a positional difference of as much as 1.5 Angstroms . The structure-activity analysis suggests that a small hydrophobic pocket and the H-loop of PDE5 are important for the inhibitor affinity, in addition to two common elements for binding of almost all the PDE inhibitors: the stack against the phenylalanine and the hydrogen bond with the invariant glutamine. However, the PDE5-12 structure does not provide a full explanation to affinity changes of the inhibitors. Thus alternatives such as conformational change of the M-loop are open and further structural study is required.

Class I Cytokine Receptors: Structure and function in the Membrane

DEFF Research Database (Denmark)

Bugge, Katrine Østergaard

bilayer via structural characterizations of TMD representatives. To enable structural studies of these domains, an organic-extraction based strategy for efficient production of isotope-labeled TMDs with or without short intrinsically disordered regions was developed. This strategy successfully provided...... of these challenging domains. Supplemented by a review of the current collection of TMD structures from single-pass transmembrane receptors, the thesis as a whole provides important insights on the structure and function in the membrane as well as highlight the open questions to be addressed in the years to come.......Class I cytokine receptors are involved in important biological functions of both physiological and pathological nature in mammals. However, the molecular details of the cross-membrane signal transduction through these receptors remain obscure. One of the major reasons for this is the lack...

Silicon Graphics' IRIS InSight: An SGML Success Story.

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Glushko, Robert J.; Kershner, Ken

1993-01-01

Offers a case history of the development of the Silicon Graphics "IRIS InSight" system, a system for viewing on-line documentation using Standard Generalized Markup Language. Notes that SGML's explicit encoding of structure and separation of structure and presentation make possible structure-based search, alternative structural views of…

Toward the fourth dimension of membrane protein structure: insight into dynamics from spin-labeling EPR spectroscopy.

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McHaourab, Hassane S; Steed, P Ryan; Kazmier, Kelli

2011-11-09

Trapping membrane proteins in the confines of a crystal lattice obscures dynamic modes essential for interconversion between multiple conformations in the functional cycle. Moreover, lattice forces could conspire with detergent solubilization to stabilize a minor conformer in an ensemble thus confounding mechanistic interpretation. Spin labeling in conjunction with electron paramagnetic resonance (EPR) spectroscopy offers an exquisite window into membrane protein dynamics in the native-like environment of a lipid bilayer. Systematic application of spin labeling and EPR identifies sequence-specific secondary structures, defines their topology and their packing in the tertiary fold. Long range distance measurements (60 Å-80 Å) between pairs of spin labels enable quantitative analysis of equilibrium dynamics and triggered conformational changes. This review highlights the contribution of spin labeling to bridging structure and mechanism. Efforts to develop methods for determining structures from EPR restraints and to increase sensitivity and throughput promise to expand spin labeling applications in membrane protein structural biology. Copyright © 2011 Elsevier Ltd. All rights reserved.

Assessing cognitive insight in nonpsychiatric individuals and outpatients with schizophrenia in Taiwan: an investigation using the Beck Cognitive Insight Scale

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Lu Chien-Wen

2011-10-01

Full Text Available Abstract Background The Beck Cognitive Insight Scale (BCIS was designed for the assessment of the cognitive processes involved in self-reflection and the ability to modify erroneous beliefs and misinterpretations. Studies investigating the factor structure of the BCIS have indicated a two-factor model in the psychotic population. The factor structure of the BCIS, however, has not received much consideration in the nonpsychiatric population. The present study examined the factor structure and validity of the BCIS and compared its scores between nonpsychiatric individuals and outpatients with psychosis. Method The Taiwanese version of the BCIS was administered to 507 nonpsychiatric individuals and 118 outpatients with schizophrenia. The psychometric properties of the BCIS were examined through the following analyses: exploratory and confirmatory factor analyses, reliability, correlation analyses, and discriminative validity. Results The BCIS showed adequate internal consistency and stability over time. Exploratory and confirmatory factor analyses on the 15-item measure indicated a two-factor solution that supported the two dimensions of the Taiwanese BCIS, which was also observed with the original BCIS. Following the construct validation, we obtained a composite index (self-reflectiveness minus self-certainty of the Taiwanese BCIS that reflected cognitive insight. Consistent with previous studies, our results indicated that psychosis is associated with low self-reflectiveness and high self-certainty, which possibly reflect lower cognitive insight. Our results also showed that better cognitive insight is related to worse depression in patients with schizophrenia spectrum disorders, but not in nonpsychiatric individuals. The receiver operating characteristic (ROC analyses revealed that the area under the curve (AUC was 0.731. A composite index of 3 was a good limit, with a sensitivity of 87% and a specificity of 51%. Conclusion The BCIS proved to be

Insights into Watson–Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m1A

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Sathyamoorthy, Bharathwaj; Shi, Honglue; Zhou, Huiqing; Xue, Yi; Rangadurai, Atul; Merriman, Dawn K.

2017-01-01

Abstract In the canonical DNA double helix, Watson–Crick (WC) base pairs (bps) exist in dynamic equilibrium with sparsely populated (∼0.02–0.4%) and short-lived (lifetimes ∼0.2–2.5 ms) Hoogsteen (HG) bps. To gain insights into transient HG bps, we used solution-state nuclear magnetic resonance spectroscopy, including measurements of residual dipolar couplings and molecular dynamics simulations, to examine how a single HG bp trapped using the N1-methylated adenine (m1A) lesion affects the structural and dynamic properties of two duplexes. The solution structure and dynamic ensembles of the duplexes reveals that in both cases, m1A forms a m1A•T HG bp, which is accompanied by local and global structural and dynamic perturbations in the double helix. These include a bias toward the BI backbone conformation; sugar repuckering, major-groove directed kinking (∼9°); and local melting of neighboring WC bps. These results provide atomic insights into WC/HG breathing dynamics in unmodified DNA duplexes as well as identify structural and dynamic signatures that could play roles in m1A recognition and repair. PMID:28369571

Crystal structure of the Epithiospecifier Protein, ESP from Arabidopsis thaliana provides insights into its product specificity.

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Zhang, Weiwei; Wang, Wenhe; Liu, Zihe; Xie, Yongchao; Wang, Hao; Mu, Yajuan; Huang, Yao; Feng, Yue

2016-09-16

Specifier proteins are important components of the glucosinolate-myrosinase system, which mediate plant defense against herbivory and pathogen attacks. Upon tissue disruption, glucosinolates are hydrolyzed to instable aglucones by myrosinases, and then aglucones will rearrange to form defensive isothiocyanates. Specifier proteins can redirect this reaction to form other products, such as simple nitriles, epithionitriles and organic thiocyanates instead of isothiocyanates based on the side chain structure of glucosinolate and the type of the specifier proteins. Nevertheless, the molecular mechanism underlying the different product spectrums of various specifier proteins was not fully understood. Here in this study, we solved the crystal structure of the Epithiospecifier Protein, ESP from Arabidopsis thaliana (AtESP) at 2.3 Å resolution. Structural comparisons with the previously solved structure of thiocyanate forming protein, TFP from Thlaspi arvense (TaTFP) reveal that AtESP shows a dimerization pattern different from TaTFP. Moreover, AtESP harbors a slightly larger active site pocket than TaTFP and several residues around the active site are different between the two proteins, which might account for the different product spectrums of the two proteins. Together, our structural study provides important insights into the molecular mechanisms of specifier proteins and shed light on the basis of their different product spectrums. Copyright © 2016 Elsevier Inc. All rights reserved.

Insight into the biological effects of acupuncture points by X-ray absorption fine structure.

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Liu, Chenglin; Liu, Qinghua; Zhang, Dongming; Liu, Wei; Yan, Xiaohui; Zhang, Xinyi; Oyanagi, Hiroyuki; Pan, Zhiyun; Hu, Fengchun; Wei, Shiqiang

2018-06-02

Exploration of the biological effects of transition metal ions in acupuncture points is essential to clarify the functional mechanism of acupuncture treatment. Here we show that in the SP6 acupuncture point (Sanyinjiao) the Fe ions are in a high-spin state of approximately t 2g 4.5 e g 1.5 in an Fe-N(O) octahedral crystal field. The Fe K-edge synchrotron radiation X-ray absorption fine structure results reveal that the Fe-N and Fe-O bond lengths in the SP6 acupuncture point are 2.05 and 2.13 Å, respectively, and are 0.05-0.10 Å longer than those in the surrounding tissue. The distorted atomic structure reduces the octahedral symmetry and weakens the crystal field around the Fe ions by approximately 0.3 eV, leading to the high-spin configuration of the Fe ions, which is favorable for strengthening the magnetotransport and oxygen transportation properties in the acupuncture point by the enhanced spin coherence. This finding might provide some insight into the microscopic effect of the atomic and electronic interactions of transition metal ions in the acupuncture point. Graphical Abstract ᅟ.

Insights into the role of protein molecule size and structure on interfacial properties using designed sequences

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Dwyer, Mirjana Dimitrijev; He, Lizhong; James, Michael; Nelson, Andrew; Middelberg, Anton P. J.

2013-01-01

Mixtures of a large, structured protein with a smaller, unstructured component are inherently complex and hard to characterize at interfaces, leading to difficulties in understanding their interfacial behaviours and, therefore, formulation optimization. Here, we investigated interfacial properties of such a mixed system. Simplicity was achieved using designed sequences in which chemical differences had been eliminated to isolate the effect of molecular size and structure, namely a short unstructured peptide (DAMP1) and its longer structured protein concatamer (DAMP4). Interfacial tension measurements suggested that the size and bulk structuring of the larger molecule led to much slower adsorption kinetics. Neutron reflectometry at equilibrium revealed that both molecules adsorbed as a monolayer to the air–water interface (indicating unfolding of DAMP4 to give a chain of four connected DAMP1 molecules), with a concentration ratio equal to that in the bulk. This suggests the overall free energy of adsorption is equal despite differences in size and bulk structure. At small interfacial extensional strains, only molecule packing influenced the stress response. At larger strains, the effect of size became apparent, with DAMP4 registering a higher stress response and interfacial elasticity. When both components were present at the interface, most stress-dissipating movement was achieved by DAMP1. This work thus provides insights into the role of proteins' molecular size and structure on their interfacial properties, and the designed sequences introduced here can serve as effective tools for interfacial studies of proteins and polymers. PMID:23303222

First-principles insights on electron transport in V{sub 2}O{sub 5} nanostructures

Energy Technology Data Exchange (ETDEWEB)

Srivastava, Anurag [Advanced Materials Research Group, Computational Nanoscience and Technology Laboratory, Atal Bihari Vajpayee-Indian Institute of Information Technology and Management, Gwalior, Madhya Pradesh 474015 (India); Chandiramouli, R., E-mail: rcmoulii@gmail.com [School of Electrical and Electronics Engineering, Shanmugha Arts Science Technology and Research Academy (SASTRA) University, Tirumalaisamudram, Thanjavur, Tamil Nadu 613 401 (India)

2015-11-15

Graphical abstract: - Highlights: • Band structure and electron transport in V{sub 2}O{sub 5} nanostructure are investigated using density functional theory. • V{sub 2}O{sub 5} nanostructure exhibits semiconducting behavior. • The electron density is observed to be more in oxygen sites than in vanadium sites. • The electron transport in V{sub 2}O{sub 5} molecular device can be tuned with the applied bias voltage. - Abstract: The present report is on the electron transport properties of V{sub 2}O{sub 5} nanostructures, investigated using density functional theory. As the band structure of V{sub 2}O{sub 5} exhibits semiconducting nature, the V{sub 2}O{sub 5} nanostructures are designed as molecular device and the transport properties are studied. The density of electrons is found to be more in the oxygen sites than in vanadium sites. The device density of states shows that the density of electrons in the energy intervals depends on the applied bias voltage. The transmission spectrum gives the insight on the transport property of V{sub 2}O{sub 5} molecular device. The bias voltage drives the electrons across V{sub 2}O{sub 5} scattering region, where the transmission along V{sub 2}O{sub 5} molecular device mainly depends on the bias voltage. The findings of the present work give insights to fine-tune the transport property of V{sub 2}O{sub 5} molecular device upon varying the bias voltage.

The narrative structure as a way to gain insight into peoples' experiences: one methodological approach.

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Rejnö, Åsa; Berg, Linda; Danielson, Ella

2014-09-01

The narrative method is used in healthcare research, mostly in data collection but also in the analysis. Narrative approaches draw attention to how people tell about and create meaning of experiences. The aim of the article was to examine the narrative structure, the elements in the structure and their function and how these can be used in research to gain insights into experiences. Examples are taken from a material of narratives from a study where next of kin were asked to narrate their experiences of sudden and unexpected death from stroke. The narratives had a clear beginning, midpoint and ending. In the beginning, orientation of the narrated events was given. The narrated events were told to have a turning point constituted of complicating actions that lead to a resolution that solved the narrated event. The narratives were built up by multiple recaps into the narrated events and also consisted of asides - side narratives and flashbacks - events back in time. Use of a narrative structure can contribute with valuable information that might be missed with other analysis. The analysis can be used on its own, as a complement to other narrative analysis or even as a complement to other qualitative analysis. © 2013 Nordic College of Caring Science.

Insights into Caco-2 cell culture structure using coherent anti-Stokes Raman scattering (CARS) microscopy.

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Saarinen, Jukka; Sözeri, Erkan; Fraser-Miller, Sara J; Peltonen, Leena; Santos, Hélder A; Isomäki, Antti; Strachan, Clare J

2017-05-15

We have used coherent anti-Stokes Raman scattering (CARS) microscopy as a novel and rapid, label-free and non-destructive imaging method to gain structural insights into live intestinal epithelial cell cultures used for drug permeability testing. Specifically we have imaged live Caco-2 cells in (bio)pharmaceutically relevant conditions grown on membrane inserts. Imaging conditions were optimized, including evaluation of suitable membrane materials and media solutions, as well as tolerable laser powers for non-destructive imaging of the live cells. Lipid structures, in particular lipid droplets, were imaged within the cells on the insert membranes. The size of the individual lipid droplets increased substantially over the 21-day culturing period up to approximately 10% of the volume of the cross section of individual cells. Variation in lipid content has important implications for intestinal drug permeation testing during drug development but has received limited attention to date due to a lack of suitable analytical techniques. CARS microscopy was shown to be well suited for such analysis with the potential for in situ imaging of the same individual cell-cultures that are used for permeation studies. Overall, the method may be used to provide important information about cell monolayer structure to better understand drug permeation results. Copyright © 2017 Elsevier B.V. All rights reserved.

X-ray structure reveals a new class and provides insight into evolution of alkaline phosphatases.

Directory of Open Access Journals (Sweden)

Subhash C Bihani

Full Text Available The alkaline phosphatase (AP is a bi-metalloenzyme of potential applications in biotechnology and bioremediation, in which phosphate monoesters are nonspecifically hydrolysed under alkaline conditions to yield inorganic phosphate. The hydrolysis occurs through an enzyme intermediate in which the catalytic residue is phosphorylated. The reaction, which also requires a third metal ion, is proposed to proceed through a mechanism of in-line displacement involving a trigonal bipyramidal transition state. Stabilizing the transition state by bidentate hydrogen bonding has been suggested to be the reason for conservation of an arginine residue in the active site. We report here the first crystal structure of alkaline phosphatase purified from the bacterium Sphingomonas. sp. Strain BSAR-1 (SPAP. The crystal structure reveals many differences from other APs: 1 the catalytic residue is a threonine instead of serine, 2 there is no third metal ion binding pocket, and 3 the arginine residue forming bidentate hydrogen bonding is deleted in SPAP. A lysine and an aspargine residue, recruited together for the first time into the active site, bind the substrate phosphoryl group in a manner not observed before in any other AP. These and other structural features suggest that SPAP represents a new class of APs. Because of its direct contact with the substrate phosphoryl group, the lysine residue is proposed to play a significant role in catalysis. The structure is consistent with a mechanism of in-line displacement via a trigonal bipyramidal transition state. The structure provides important insights into evolutionary relationships between members of AP superfamily.

Structure of EspB from the ESX-1 type VII secretion system and insights into its export mechanism.

Science.gov (United States)

Solomonson, Matthew; Setiaputra, Dheva; Makepeace, Karl A T; Lameignere, Emilie; Petrotchenko, Evgeniy V; Conrady, Deborah G; Bergeron, Julien R; Vuckovic, Marija; DiMaio, Frank; Borchers, Christoph H; Yip, Calvin K; Strynadka, Natalie C J

2015-03-03

Mycobacterium tuberculosis (Mtb) uses the ESX-1 type VII secretion system to export virulence proteins across its lipid-rich cell wall, which helps permeabilize the host's macrophage phagosomal membrane, facilitating the escape and cell-to-cell spread of Mtb. ESX-1 membranolytic activity depends on a set of specialized secreted Esp proteins, the structure and specific roles of which are not currently understood. Here, we report the X-ray and electron microscopic structures of the ESX-1-secreted EspB. We demonstrate that EspB adopts a PE/PPE-like fold that mediates oligomerization with apparent heptameric symmetry, generating a barrel-shaped structure with a central pore that we propose contributes to the macrophage killing functions of EspB. Our structural data also reveal unexpected direct interactions between the EspB bipartite secretion signal sequence elements that form a unified aromatic surface. These findings provide insight into how specialized proteins encoded within the ESX-1 locus are targeted for secretion, and for the first time indicate an oligomerization-dependent role for Esp virulence factors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structural Insights into Arl1-Mediated Targeting of the Arf-GEF BIG1 to the trans-Golgi

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Antonio Galindo

2016-07-01

Full Text Available The GTPase Arf1 is the major regulator of vesicle traffic at both the cis- and trans-Golgi. Arf1 is activated at the cis-Golgi by the guanine nucleotide exchange factor (GEF GBF1 and at the trans-Golgi by the related GEF BIG1 or its paralog, BIG2. The trans-Golgi-specific targeting of BIG1 and BIG2 depends on the Arf-like GTPase Arl1. We find that Arl1 binds to the dimerization and cyclophilin binding (DCB domain in BIG1 and report a crystal structure of human Arl1 bound to this domain. Residues in the DCB domain that bind Arl1 are required for BIG1 to locate to the Golgi in vivo. DCB domain-binding residues in Arl1 have a distinct conformation from those in known Arl1-effector complexes, and this plasticity allows Arl1 to interact with different effectors of unrelated structure. The findings provide structural insight into how Arf1 GEFs, and hence active Arf1, achieve their correct subcellular distribution.

Structural and functional insights into the malaria parasite moving junction complex.

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Brigitte Vulliez-Le Normand

Full Text Available Members of the phylum Apicomplexa, which include the malaria parasite Plasmodium, share many features in their invasion mechanism in spite of their diverse host cell specificities and life cycle characteristics. The formation of a moving junction (MJ between the membranes of the invading apicomplexan parasite and the host cell is common to these intracellular pathogens. The MJ contains two key parasite components: the surface protein Apical Membrane Antigen 1 (AMA1 and its receptor, the Rhoptry Neck Protein (RON complex, which is targeted to the host cell membrane during invasion. In particular, RON2, a transmembrane component of the RON complex, interacts directly with AMA1. Here, we report the crystal structure of AMA1 from Plasmodium falciparum in complex with a peptide derived from the extracellular region of PfRON2, highlighting clear specificities of the P. falciparum RON2-AMA1 interaction. The receptor-binding site of PfAMA1 comprises the hydrophobic groove and a region that becomes exposed by displacement of the flexible Domain II loop. Mutations of key contact residues of PfRON2 and PfAMA1 abrogate binding between the recombinant proteins. Although PfRON2 contacts some polymorphic residues, binding studies with PfAMA1 from different strains show that these have little effect on affinity. Moreover, we demonstrate that the PfRON2 peptide inhibits erythrocyte invasion by P. falciparum merozoites and that this strong inhibitory potency is not affected by AMA1 polymorphisms. In parallel, we have determined the crystal structure of PfAMA1 in complex with the invasion-inhibitory peptide R1 derived by phage display, revealing an unexpected structural mimicry of the PfRON2 peptide. These results identify the key residues governing the interactions between AMA1 and RON2 in P. falciparum and suggest novel approaches to antimalarial therapeutics.

Structural insights into RISC assembly facilitated by dsRNA-binding domains of human RNA helicase A (DHX9).

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Fu, Qinqin; Yuan, Y Adam

2013-03-01

Intensive research interest has focused on small RNA-processing machinery and the RNA-induced silencing complex (RISC), key cellular machines in RNAi pathways. However, the structural mechanism regarding RISC assembly, the primary step linking small RNA processing and RNA-mediated gene silencing, is largely unknown. Human RNA helicase A (DHX9) was reported to function as an RISC-loading factor, and such function is mediated mainly by its dsRNA-binding domains (dsRBDs). Here, we report the crystal structures of human RNA helicase A (RHA) dsRBD1 and dsRBD2 domains in complex with dsRNAs, respectively. Structural analysis not only reveals higher siRNA duplex-binding affinity displayed by dsRBD1, but also identifies a crystallographic dsRBD1 pair of physiological significance in cooperatively recognizing dsRNAs. Structural observations are further validated by isothermal titration calorimetric (ITC) assay. Moreover, co-immunoprecipitation (co-IP) assay coupled with mutagenesis demonstrated that both dsRBDs are required for RISC association, and such association is mediated by dsRNA. Hence, our structural and functional efforts have revealed a potential working model for siRNA recognition by RHA tandem dsRBDs, and together they provide direct structural insights into RISC assembly facilitated by RHA.

Insights into Watson-Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m1A.

Science.gov (United States)

Sathyamoorthy, Bharathwaj; Shi, Honglue; Zhou, Huiqing; Xue, Yi; Rangadurai, Atul; Merriman, Dawn K; Al-Hashimi, Hashim M

2017-05-19

In the canonical DNA double helix, Watson-Crick (WC) base pairs (bps) exist in dynamic equilibrium with sparsely populated (∼0.02-0.4%) and short-lived (lifetimes ∼0.2-2.5 ms) Hoogsteen (HG) bps. To gain insights into transient HG bps, we used solution-state nuclear magnetic resonance spectroscopy, including measurements of residual dipolar couplings and molecular dynamics simulations, to examine how a single HG bp trapped using the N1-methylated adenine (m1A) lesion affects the structural and dynamic properties of two duplexes. The solution structure and dynamic ensembles of the duplexes reveals that in both cases, m1A forms a m1A•T HG bp, which is accompanied by local and global structural and dynamic perturbations in the double helix. These include a bias toward the BI backbone conformation; sugar repuckering, major-groove directed kinking (∼9°); and local melting of neighboring WC bps. These results provide atomic insights into WC/HG breathing dynamics in unmodified DNA duplexes as well as identify structural and dynamic signatures that could play roles in m1A recognition and repair. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Structure and petroleum plays of the St. Lawrence Platform and Appalachians in southern Quebec : insights from interpretation of MRNQ seismic reflection data

Energy Technology Data Exchange (ETDEWEB)

Castonguay, S.; Lavoie, D. [Natural Resources Canada, Quebec, PQ (Canada). Geological Survey of Canada, Quebec Division; Dietrich, J. [Natural Resources Canada, Calgary, AB (Canada). Geological Survey of Canada; Laliberte, J.Y. [Ministere des Ressources naturelles et de la Faune du Quebec, Charlesbourg, QC (Canada). Direction generale des hydrocarbures et des biocarburants

2010-09-15

This paper presented the results of a study in which 3 regional seismic reflection lines originally acquired in 1978 were reprocessed and reinterpreted using current techniques and methodologies. The profiles cross the Chambly-Fortierville syncline and provide images of the St. Lawrence Platform and the Appalachian foreland thrust belt of southern Quebec, including one that spans the entire width of the southern Quebec Appalachians. Post-stack seismic data processing and time migration were used to improve the quality of the original seismic sections, allowing interpretations that provide new information on subsurface geology, such as the recognition of complex structural patterns in platform and foreland units, the presence of a triangle zone at the structural front, and the geometry of thrust slices of platform units and Appalachian thrust beds, as well as images of the internal Humber Zone, including back-thrust faults and mega thrust wedges. The Saint-Flavien natural gas-field and other potential targets in the St. Lawrence Platform and Appalachian Foreland are imaged in the seismic profiles. The study provided new insights into the structure, geological evolution, and petroleum potential of the St. Lawrence Platform and the Appalachian foreland thrust belt of southern Quebec, including a potential, previously unrecognized Ordovician hydrothermal dolomite play. The new subsurface interpretations give a clearer view of the major structure affecting the Utica Shale, providing new insights into the limits of the unconventional shale gas play in the St. Lawrence Platform. 53 refs., 8 figs.

Atmospheric Research 2011 Technical Highlights

Science.gov (United States)

2012-01-01

The 2011 Technical Highlights describes the efforts of all members of Atmospheric Research. Their dedication to advancing Earth Science through conducting research, developing and running models, designing instruments, managing projects, running field campaigns, and numerous other activities, is highlighted in this report.

Enhanced dewaterability of sludge during anaerobic digestion with thermal hydrolysis pretreatment: New insights through structure evolution.

Science.gov (United States)

Zhang, Jingsi; Li, Ning; Dai, Xiaohu; Tao, Wenquan; Jenkinson, Ian R; Li, Zhuo

2017-12-19

Comprehensive insights into the sludge digestate dewaterability were gained through porous network structure of sludge. We measured the evolution of digestate dewaterability, represented by the solid content of centrifugally dewatered cake, in high-solids sequencing batch digesters with and without thermal hydrolysis pretreatment (THP). The results show that the dewaterability of the sludge after digestion was improved by 3.5% (±0.5%) for unpretreated sludge and 5.1% (±0.4%) for thermally hydrolyzed sludge. Compared to the unpretreated sludge digestate, thermal hydrolysis pretreatment eventually resulted in an improvement of dewaterability by 4.6% (±0.5%). Smaller particle size and larger surface area of sludge were induced by thermal hydrolysis and anaerobic digestion treatments. The structure strength and compactness of sludge, represented by elastic modulus and fractal dimension respectively, decreased with increase of digestion time. The porous network structure was broken up by thermal hydrolysis pretreatment and was further weakened during anaerobic digestion, which correspondingly improved the dewaterability of digestates. The logarithm of elastic modulus increased linearly with fractal dimension regardless of the pretreatment. Both fractal dimension and elastic modulus showed linear relationship with dewaterability. The rheological characterization combined with the analysis of fractal dimension of sewage sludge porous network structure was found applicable in quantitative evaluation of sludge dewaterability, which depended positively on both thermal hydrolysis and anaerobic digestion. Copyright © 2017 Elsevier Ltd. All rights reserved.

Brookhaven highlights

International Nuclear Information System (INIS)

Rowe, M.S.; Belford, M.; Cohen, A.; Greenberg, D.; Seubert, L.

1993-01-01

This report highlights the research activities of Brookhaven National Laboratory during the period dating from October 1, 1992 through September 30, 1993. There are contributions to the report from different programs and departments within the laboratory. These include technology transfer, RHIC, Alternating Gradient Synchrotron, physics, biology, national synchrotron light source, applied science, medical science, advanced technology, chemistry, reactor physics, safety and environmental protection, instrumentation, and computing and communications

Structures of parasite calreticulins provide insights into their flexibility and dual carbohydrate/peptide-binding properties.

Science.gov (United States)

Moreau, Christophe; Cioci, Gianluca; Iannello, Marina; Laffly, Emmanuelle; Chouquet, Anne; Ferreira, Arturo; Thielens, Nicole M; Gaboriaud, Christine

2016-11-01

Calreticulin (CRT) is a multifaceted protein, initially discovered as an endoplasmic reticulum (ER) chaperone protein, that is essential in calcium metabolism. Various implications in cancer, early development and immunology have been discovered more recently for CRT, as well as its role as a dominant 'eat-me' prophagocytic signal. Intriguingly, cell-surface exposure/secretion of CRT is among the infective strategies used by parasites such as Trypanosoma cruzi , Entamoeba histolytica , Taenia solium , Leishmania donovani and Schistosoma mansoni . Because of the inherent flexibility of CRTs, their analysis by X-ray crystallography requires the design of recombinant constructs suitable for crystallization, and thus only the structures of two very similar mammalian CRT lectin domains are known. With the X-ray structures of two distant parasite CRTs, insights into species structural determinants that might be harnessed to fight against the parasites without affecting the functions of the host CRT are now provided. Moreover, although the hypothesis that CRT can exhibit both open and closed conformations has been proposed in relation to its chaperone function, only the open conformation has so far been observed in crystal structures. The first evidence is now provided of a complex conformational transition with the junction reoriented towards P-domain closure. SAXS experiments also provided additional information about the flexibility of T. cruzi CRT in solution, thus complementing crystallographic data on the open conformation. Finally, regarding the conserved lectin-domain structure and chaperone function, evidence is provided of its dual carbohydrate/protein specificity and a new scheme is proposed to interpret such unusual substrate-binding properties. These fascinating features are fully consistent with previous experimental observations, as discussed considering the broad spectrum of CRT sequence conservations and differences.

Silver vanadium diphosphate Ag2VP2O8: Electrochemistry and characterization of reduced material providing mechanistic insights

International Nuclear Information System (INIS)

Takeuchi, Esther S.; Lee, Chia-Ying; Cheng, Po-Jen; Menard, Melissa C.; Marschilok, Amy C.; Takeuchi, Kenneth J.

2013-01-01

Silver vanadium phosphorous oxides (Ag w V x P y O z ) are notable battery cathode materials due to their high energy density and demonstrated ability to form in-situ Ag metal nanostructured electrically conductive networks within the cathode. While analogous silver vanadium diphosphate materials have been prepared, electrochemical evaluations of these diphosphate based materials have been limited. We report here the first electrochemical study of a silver vanadium diphosphate, Ag 2 VP 2 O 8 , where the structural differences associated with phosphorous oxides versus diphosphates profoundly affect the associated electrochemistry. Reminiscent of Ag 2 VO 2 PO 4 reduction, in-situ formation of silver metal nanoparticles was observed with reduction of Ag 2 VP 2 O 8 . However, counter to Ag 2 VO 2 PO 4 reduction, Ag 2 VP 2 O 8 demonstrates a significant decrease in conductivity upon continued electrochemical reduction. Structural analysis contrasting the crystallography of the parent Ag 2 VP 2 O 8 with that of the proposed Li 2 VP 2 O 8 reduction product is employed to gain insight into the observed electrochemical reduction behavior, where the structural rigidity associated with the diphosphate anion may be associated with the observed particle fracturing upon deep electrochemical reduction. Further, the diphosphate anion structure may be associated with the high thermal stability of the partially reduced Ag 2 VP 2 O 8 materials, which bodes well for enhanced safety of batteries incorporating this material. - Graphical abstract: Structure and galvanostatic intermittent titration-type test data for silver vanadium diphosphate, Ag 2 VP 2 O 8 . Highlights: ► First electrochemical study of a silver vanadium diphosphate, Ag 2 VP 2 O 8 . ► In-situ formation of Ag 0 nanoparticles was observed upon electrochemical reduction. ► Structural analysis used to provide insight of the electrochemical behavior

Functional Diversity of Haloacid Dehalogenase Superfamily Phosphatases from Saccharomyces cerevisiae: BIOCHEMICAL, STRUCTURAL, AND EVOLUTIONARY INSIGHTS.

Science.gov (United States)

Kuznetsova, Ekaterina; Nocek, Boguslaw; Brown, Greg; Makarova, Kira S; Flick, Robert; Wolf, Yuri I; Khusnutdinova, Anna; Evdokimova, Elena; Jin, Ke; Tan, Kemin; Hanson, Andrew D; Hasnain, Ghulam; Zallot, Rémi; de Crécy-Lagard, Valérie; Babu, Mohan; Savchenko, Alexei; Joachimiak, Andrzej; Edwards, Aled M; Koonin, Eugene V; Yakunin, Alexander F

2015-07-24

The haloacid dehalogenase (HAD)-like enzymes comprise a large superfamily of phosphohydrolases present in all organisms. The Saccharomyces cerevisiae genome encodes at least 19 soluble HADs, including 10 uncharacterized proteins. Here, we biochemically characterized 13 yeast phosphatases from the HAD superfamily, which includes both specific and promiscuous enzymes active against various phosphorylated metabolites and peptides with several HADs implicated in detoxification of phosphorylated compounds and pseudouridine. The crystal structures of four yeast HADs provided insight into their active sites, whereas the structure of the YKR070W dimer in complex with substrate revealed a composite substrate-binding site. Although the S. cerevisiae and Escherichia coli HADs share low sequence similarities, the comparison of their substrate profiles revealed seven phosphatases with common preferred substrates. The cluster of secondary substrates supporting significant activity of both S. cerevisiae and E. coli HADs includes 28 common metabolites that appear to represent the pool of potential activities for the evolution of novel HAD phosphatases. Evolution of novel substrate specificities of HAD phosphatases shows no strict correlation with sequence divergence. Thus, evolution of the HAD superfamily combines the conservation of the overall substrate pool and the substrate profiles of some enzymes with remarkable biochemical and structural flexibility of other superfamily members. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Electron Microscopy Structural Insights into CPAP Oligomeric Behavior

DEFF Research Database (Denmark)

Alvarez-Cabrera, Ana L; Delgado, Sandra; Gil-Carton, David

2017-01-01

Centrosomal P4.1-associated protein (CPAP) is a cell cycle regulated protein fundamental for centrosome assembly and centriole elongation. In humans, the region between residues 897-1338 of CPAP mediates interactions with other proteins and includes a homodimerization domain. CPAP mutations cause...... into clearly different regular 3D maps (putatively corresponding to dimers and tetramers) and direct observation of individual images representing other complexes of HsCPAP(897-1338) (i.e., putative flexible monomers and higher-order multimers), we report a dynamic oligomeric behavior of this protein, where...... of different oligomers of CPAP, suggesting further insights to understand how this protein works, contributing to the elucidation of control mechanisms for centriole biogenesis....

Identification and characterisation of a novel acylpeptide hydrolase from Sulfolobus solfataricus: structural and functional insights.

Directory of Open Access Journals (Sweden)

Marta Gogliettino

Full Text Available A novel acylpeptide hydrolase, named APEH-3(Ss, was isolated from the hypertermophilic archaeon Sulfolobus solfataricus. APEH is a member of the prolyl oligopeptidase family which catalyzes the removal of acetylated amino acid residues from the N terminus of oligopeptides. The purified enzyme shows a homotrimeric structure, unique among the associate partners of the APEH cluster and, in contrast to the archaeal APEHs which show both exo/endo peptidase activities, it appears to be a "true" aminopeptidase as exemplified by its mammalian counterparts, with which it shares a similar substrate specificity. Furthermore, a comparative study on the regulation of apeh gene expression, revealed a significant but divergent alteration in the expression pattern of apeh-3(Ss and apeh(Ss (the gene encoding the previously identified APEH(Ss from S. solfataricus, which is induced in response to various stressful growth conditions. Hence, both APEH enzymes can be defined as stress-regulated proteins which play a complementary role in enabling the survival of S. solfataricus cells under different conditions. These results provide new structural and functional insights into S. solfataricus APEH, offering a possible explanation for the multiplicity of this enzyme in Archaea.

Heavy Vehicle Propulsion Materials Program: Progress and Highlights

International Nuclear Information System (INIS)

D. Ray Johnson; Sidney Diamond

2000-01-01

The Heavy Vehicle Propulsion Materials Program was begun in 1997 to support the enabling materials needs of the DOE Office of Heavy Vehicle Technologies (OHVT). The technical agenda for the program grew out of the technology roadmap for the OHVT and includes efforts in materials for: fuel systems, exhaust aftertreatment, valve train, air handling, structural components, electrochemical propulsion, natural gas storage, and thermal management. A five-year program plan was written in early 2000, following a stakeholders workshop. The technical issues and planned and ongoing projects are discussed. Brief summaries of several technical highlights are given

State of the art in the insight into experimentally observed mesons and baryons predicted by current fundamental models of particle physics

International Nuclear Information System (INIS)

Bednar, M.; Hron, J.

2001-01-01

Current insight into mesons and baryons is highlighted, their classification is given, and their arrangement into multiplets is described. A brief chronological overview of discoveries of the most important mesons and baryons is presented, followed by a description of the attempts to find fundamental particles between mesons and baryons, which could be composed of other mesons and baryons (Fermi-Yang model, Sakata model, Ikea-Ohnuki-Ogawa model). The attempts ultimately led to the formulation of the quark model. The quark structure of some mesons and baryons is presented. The quark model foresees the existence of mesons and baryons that have not yet been discovered. (Z.J.)

Symposium Highlights

International Nuclear Information System (INIS)

Owen-Whitred, K.

2015-01-01

Overview/Highlights: To begin, I'd like to take a moment to highlight some of the novel elements of this Symposium as compared to those that have been held in the past. For the first time ever, this Symposium was organized around five concurrent sessions, covering over 300 papers and presentations. These sessions were complemented by an active series of exhibits put on by vendors, universities, ESARDA, INMM, and Member State Support Programmes. We also had live demonstrations throughout the week on everything from software to destructive analysis to instrumentation, which provided the participants the opportunity to see recent developments that are ready for implementation. I'm sure you all had a chance to observe - and, more importantly, interact with - the electronic Poster, or ePoster format used this past week. This technology was used here for the first time ever by the IAEA, and I'm sure was a first for many of us as well. The ePoster format allowed participants to interact with the subject matter, and the subject matter experts, in a dynamic, engaging way. In addition to the novel technology used here, I have to say that having the posters strategically embedded in the sessions on the same topic, by having each poster author introduce his or her topic to the assembled group in order to lure us to the poster area during the breaks, was also a novel and highly effective technique. A final highlight I'd like to touch on in terms of the Symposium organization is the diversity of participation. This chart shows the breakdown by geographical distribution for the Symposium, in terms of participants. There are no labels, so don't try to read any, I simply wanted to demonstrate that we had great representation in terms of both the Symposium participants in general and the session chairs more specifically-and on that note, I would just mention here that 59 Member States participated in the Symposium. But what I find especially interesting and

Insights into carbon nanotube and graphene formation mechanisms from molecular simulations: a review

International Nuclear Information System (INIS)

Page, A J; Ding, F; Irle, S; Morokuma, K

2015-01-01

The discovery of carbon nanotubes (CNTs) and graphene over the last two decades has heralded a new era in physics, chemistry and nanotechnology. During this time, intense efforts have been made towards understanding the atomic-scale mechanisms by which these remarkable nanostructures grow. Molecular simulations have made significant contributions in this regard; indeed, they are responsible for many of the key discoveries and advancements towards this goal. Here we review molecular simulations of CNT and graphene growth, and in doing so we highlight the many invaluable insights gained from molecular simulations into these complex nanoscale self-assembly processes. This review highlights an often-overlooked aspect of CNT and graphene formation—that the two processes, although seldom discussed in the same terms, are in fact remarkably similar. Both can be viewed as a 0D → 1D → 2D transformation, which converts carbon atoms (0D) to polyyne chains (1D) to a complete sp 2 -carbon network (2D). The difference in the final structure (CNT or graphene) is determined only by the curvature of the catalyst and the strength of the carbon–metal interaction. We conclude our review by summarizing the present shortcomings of CNT/graphene growth simulations, and future challenges to this important area. (review article)

Mechanistic insights into validoxylamine A 7'-phosphate synthesis by VldE using the structure of the entire product complex.

Directory of Open Access Journals (Sweden)

Michael C Cavalier

Full Text Available The pseudo-glycosyltransferase VldE catalyzes non-glycosidic C-N coupling between an unsaturated cyclitol and a saturated aminocyclitol with the conservation of the stereochemical configuration of the substrates to form validoxylamine A 7'-phosphate, the biosynthetic precursor of the antibiotic validamycin A. To study the molecular basis of its mechanism, the three-dimensional structures of VldE from Streptomyces hygroscopicus subsp. limoneus was determined in apo form, in complex with GDP, in complex with GDP and validoxylamine A 7'-phosphate, and in complex with GDP and trehalose. The structure of VldE with the catalytic site in both an "open" and "closed" conformation is also described. With these structures, the preferred binding of the guanine moiety by VldE, rather than the uracil moiety as seen in OtsA could be explained. The elucidation of the VldE structure in complex with the entirety of its products provides insight into the internal return mechanism by which catalysis occurs with a net retention of the stereochemical configuration of the donated cyclitol.

Structural insights into transcription complexes

NARCIS (Netherlands)

Berger, I.; Blanco, A.G.; Boelens, R.; Cavarelli, J.; Coll, M.; Folkers, G.E.; Nie, Y.; Pogenberg, V.; Schultz, P.; Wilmanns, M.; Moras, D.; Poterszman, A.

2011-01-01

Control of transcription allows the regulation of cell activity in response to external stimuli and research in the field has greatly benefited from efforts in structural biology. In this review, based on specific examples from the European SPINE2-COMPLEXES initiative, we illustrate the impact of

The sights and insights of examiners in objective structured clinical examinations

Directory of Open Access Journals (Sweden)

Lauren Chong

2017-12-01

Full Text Available Purpose The objective structured clinical examination (OSCE is considered to be one of the most robust methods of clinical assessment. One of its strengths lies in its ability to minimise the effects of examiner bias due to the standardisation of items and tasks for each candidate. However, OSCE examiners’ assessment scores are influenced by several factors that may jeopardise the assumed objectivity of OSCEs. To better understand this phenomenon, the current review aims to determine and describe important sources of examiner bias and the factors affecting examiners’ assessments. Methods We performed a narrative review of the medical literature using Medline. All articles meeting the selection criteria were reviewed, with salient points extracted and synthesised into a clear and comprehensive summary of the knowledge in this area. Results OSCE examiners’ assessment scores are influenced by factors belonging to 4 different domains: examination context, examinee characteristics, examinee-examiner interactions, and examiner characteristics. These domains are composed of several factors including halo, hawk/dove and OSCE contrast effects; the examiner’s gender and ethnicity; training; lifetime experience in assessing; leadership and familiarity with students; station type; and site effects. Conclusion Several factors may influence the presumed objectivity of examiners’ assessments, and these factors need to be addressed to ensure the objectivity of OSCEs. We offer insights into directions for future research to better understand and address the phenomenon of examiner bias.

Comparison of NMR and crystal structures highlights conformational isomerism in protein active sites

International Nuclear Information System (INIS)

Serrano, Pedro; Pedrini, Bill; Geralt, Michael; Jaudzems, Kristaps; Mohanty, Biswaranjan; Horst, Reto; Herrmann, Torsten; Elsliger, Marc-André; Wilson, Ian A.; Wüthrich, Kurt

2010-01-01

Tools for systematic comparisons of NMR and crystal structures developed by the JCSG were applied to two proteins with known functions: the T. maritima anti-σ factor antagonist TM1081 and the mouse γ-glutamylamine cyclotransferase A2LD1 (gi:13879369). In an attempt to exploit the complementarity of crystal and NMR data, the combined use of the two structure-determination techniques was explored for the initial steps in the challenge of searching proteins of unknown functions for putative active sites. The JCSG has recently developed a protocol for systematic comparisons of high-quality crystal and NMR structures of proteins. In this paper, the extent to which this approach can provide function-related information on the two functionally annotated proteins TM1081, a Thermotoga maritima anti-σ factor antagonist, and A2LD1 (gi:13879369), a mouse γ-glutamylamine cyclotransferase, is explored. The NMR structures of the two proteins have been determined in solution at 313 and 298 K, respectively, using the current JCSG protocol based on the software package UNIO for extensive automation. The corresponding crystal structures were solved by the JCSG at 100 K and 1.6 Å resolution and at 100 K and 1.9 Å resolution, respectively. The NMR and crystal structures of the two proteins share the same overall molecular architectures. However, the precision of the structure determination along the amino-acid sequence varies over a significantly wider range in the NMR structures than in the crystal structures. Thereby, in each of the two NMR structures about 65% of the residues have displacements below the average and in both proteins the less well ordered residues include large parts of the active sites, in addition to some highly solvent-exposed surface areas. Whereas the latter show increased disorder in the crystal and in solution, the active-site regions display increased displacements only in the NMR structures, where they undergo local conformational exchange on the

Structures of parasite calreticulins provide insights into their flexibility and dual carbohydrate/peptide-binding properties

Directory of Open Access Journals (Sweden)

Christophe Moreau

2016-11-01

Full Text Available Calreticulin (CRT is a multifaceted protein, initially discovered as an endoplasmic reticulum (ER chaperone protein, that is essential in calcium metabolism. Various implications in cancer, early development and immunology have been discovered more recently for CRT, as well as its role as a dominant `eat-me' prophagocytic signal. Intriguingly, cell-surface exposure/secretion of CRT is among the infective strategies used by parasites such as Trypanosoma cruzi, Entamoeba histolytica, Taenia solium, Leishmania donovani and Schistosoma mansoni. Because of the inherent flexibility of CRTs, their analysis by X-ray crystallography requires the design of recombinant constructs suitable for crystallization, and thus only the structures of two very similar mammalian CRT lectin domains are known. With the X-ray structures of two distant parasite CRTs, insights into species structural determinants that might be harnessed to fight against the parasites without affecting the functions of the host CRT are now provided. Moreover, although the hypothesis that CRT can exhibit both open and closed conformations has been proposed in relation to its chaperone function, only the open conformation has so far been observed in crystal structures. The first evidence is now provided of a complex conformational transition with the junction reoriented towards P-domain closure. SAXS experiments also provided additional information about the flexibility of T. cruzi CRT in solution, thus complementing crystallographic data on the open conformation. Finally, regarding the conserved lectin-domain structure and chaperone function, evidence is provided of its dual carbohydrate/protein specificity and a new scheme is proposed to interpret such unusual substrate-binding properties. These fascinating features are fully consistent with previous experimental observations, as discussed considering the broad spectrum of CRT sequence conservations and differences.

Editorial highlighting and highly cited papers

Science.gov (United States)

Antonoyiannakis, Manolis

Editorial highlighting-the process whereby journal editors select, at the time of publication, a small subset of papers that are ostensibly of higher quality, importance or interest-is by now a widespread practice among major scientific journal publishers. Depending on the venue, and the extent to which editorial resources are invested in the process, highlighted papers appear as News & Views, Research Highlights, Perspectives, Editors' Choice, IOP Select, Editors' Summary, Spotlight on Optics, Editors' Picks, Viewpoints, Synopses, Editors' Suggestions, etc. Here, we look at the relation between highlighted papers and highly influential papers, which we define at two levels: having received enough citations to be among the (i) top few percent of their journal, and (ii) top 1% of all physics papers. Using multiple linear regression and multilevel regression modeling we examine the parameters associated with highly influential papers. We briefly comment on cause and effect relationships between citedness and highlighting of papers.

Extended and structurally supported insights into extracellular hormone binding, signal transduction and organization of the thyrotropin receptor.

Directory of Open Access Journals (Sweden)

Gerd Krause

Full Text Available The hormone thyrotropin (TSH and its receptor (TSHR are crucial for the growth and function of the thyroid gland. The TSHR is evolutionary linked with the receptors of follitropin (FSHR and lutropin/choriogonadotropin (LHR and their sequences and structures are similar. The extracellular region of TSHR contains more than 350 amino acids and binds hormone and antibodies. Several important questions related to functions and mechanisms of TSHR are still not comprehensively understood. One major reason for these open questions is the lack of any structural information about the extracellular segment of TSHR that connects the N-terminal leucine-rich repeat domain (LRRD with the transmembrane helix (TMH 1, the hinge region. It has been shown experimentally that this segment is important for fine tuning of signaling and ligand interactions. A new crystal structure containing most of the extracellular hFSHR region in complex with hFSH has recently been published. Now, we have applied these new structural insights to the homologous TSHR and have generated a structural model of the TSHR LRRD/hinge-region/TSH complex. This structural model is combined and evaluated with experimental data including hormone binding (bTSH, hTSH, thyrostimulin, super-agonistic effects, antibody interactions and signaling regulation. These studies and consideration of significant and non-significant amino acids have led to a new description of mechanisms at the TSHR, including ligand-induced displacements of specific hinge region fragments. This event triggers conformational changes at a convergent center of the LRRD and the hinge region, activating an "intramolecular agonistic unit" close to the transmembrane domain.

Extended and structurally supported insights into extracellular hormone binding, signal transduction and organization of the thyrotropin receptor.

Science.gov (United States)

Krause, Gerd; Kreuchwig, Annika; Kleinau, Gunnar

2012-01-01

The hormone thyrotropin (TSH) and its receptor (TSHR) are crucial for the growth and function of the thyroid gland. The TSHR is evolutionary linked with the receptors of follitropin (FSHR) and lutropin/choriogonadotropin (LHR) and their sequences and structures are similar. The extracellular region of TSHR contains more than 350 amino acids and binds hormone and antibodies. Several important questions related to functions and mechanisms of TSHR are still not comprehensively understood. One major reason for these open questions is the lack of any structural information about the extracellular segment of TSHR that connects the N-terminal leucine-rich repeat domain (LRRD) with the transmembrane helix (TMH) 1, the hinge region. It has been shown experimentally that this segment is important for fine tuning of signaling and ligand interactions. A new crystal structure containing most of the extracellular hFSHR region in complex with hFSH has recently been published. Now, we have applied these new structural insights to the homologous TSHR and have generated a structural model of the TSHR LRRD/hinge-region/TSH complex. This structural model is combined and evaluated with experimental data including hormone binding (bTSH, hTSH, thyrostimulin), super-agonistic effects, antibody interactions and signaling regulation. These studies and consideration of significant and non-significant amino acids have led to a new description of mechanisms at the TSHR, including ligand-induced displacements of specific hinge region fragments. This event triggers conformational changes at a convergent center of the LRRD and the hinge region, activating an "intramolecular agonistic unit" close to the transmembrane domain.

Using Highlighting to Train Attentional Expertise.

Science.gov (United States)

Roads, Brett; Mozer, Michael C; Busey, Thomas A

2016-01-01

Acquiring expertise in complex visual tasks is time consuming. To facilitate the efficient training of novices on where to look in these tasks, we propose an attentional highlighting paradigm. Highlighting involves dynamically modulating the saliency of a visual image to guide attention along the fixation path of a domain expert who had previously viewed the same image. In Experiment 1, we trained naive subjects via attentional highlighting on a fingerprint-matching task. Before and after training, we asked subjects to freely inspect images containing pairs of prints and determine whether the prints matched. Fixation sequences were automatically scored for the degree of expertise exhibited using a Bayesian discriminative model of novice and expert gaze behavior. Highlighted training causes gaze behavior to become more expert-like not only on the trained images but also on transfer images, indicating generalization of learning. In Experiment 2, to control for the possibility that the increase in expertise is due to mere exposure, we trained subjects via highlighting of fixation sequences from novices, not experts, and observed no transition toward expertise. In Experiment 3, to determine the specificity of the training effect, we trained subjects with expert fixation sequences from images other than the one being viewed, which preserves coarse-scale statistics of expert gaze but provides no information about fine-grain features. Observing at least a partial transition toward expertise, we obtain only weak evidence that the highlighting procedure facilitates the learning of critical local features. We discuss possible improvements to the highlighting procedure.

Using Highlighting to Train Attentional Expertise.

Directory of Open Access Journals (Sweden)

Brett Roads

Full Text Available Acquiring expertise in complex visual tasks is time consuming. To facilitate the efficient training of novices on where to look in these tasks, we propose an attentional highlighting paradigm. Highlighting involves dynamically modulating the saliency of a visual image to guide attention along the fixation path of a domain expert who had previously viewed the same image. In Experiment 1, we trained naive subjects via attentional highlighting on a fingerprint-matching task. Before and after training, we asked subjects to freely inspect images containing pairs of prints and determine whether the prints matched. Fixation sequences were automatically scored for the degree of expertise exhibited using a Bayesian discriminative model of novice and expert gaze behavior. Highlighted training causes gaze behavior to become more expert-like not only on the trained images but also on transfer images, indicating generalization of learning. In Experiment 2, to control for the possibility that the increase in expertise is due to mere exposure, we trained subjects via highlighting of fixation sequences from novices, not experts, and observed no transition toward expertise. In Experiment 3, to determine the specificity of the training effect, we trained subjects with expert fixation sequences from images other than the one being viewed, which preserves coarse-scale statistics of expert gaze but provides no information about fine-grain features. Observing at least a partial transition toward expertise, we obtain only weak evidence that the highlighting procedure facilitates the learning of critical local features. We discuss possible improvements to the highlighting procedure.

Expression of recombinant glycoproteins in mammalian cells: towards an integrative approach to structural biology.

Science.gov (United States)

Aricescu, A Radu; Owens, Raymond J

2013-06-01

Mammalian cells are rapidly becoming the system of choice for the production of recombinant glycoproteins for structural biology applications. Their use has enabled the structural investigation of a whole new set of targets including large, multi-domain and highly glycosylated eukaryotic cell surface receptors and their supra-molecular assemblies. We summarize the technical advances that have been made in mammalian expression technology and highlight some of the structural insights that have been obtained using these methods. Looking forward, it is clear that mammalian cell expression will provide exciting and unique opportunities for an integrative approach to the structural study of proteins, especially of human origin and medically relevant, by bridging the gap between the purified state and the cellular context. Copyright © 2013 Elsevier Ltd. All rights reserved.

Structural, mechanistic and functional insight into gliotoxin bis-thiomethylation in Aspergillus fumigatus.

Science.gov (United States)

Dolan, Stephen K; Bock, Tobias; Hering, Vanessa; Owens, Rebecca A; Jones, Gary W; Blankenfeldt, Wulf; Doyle, Sean

2017-02-01

Gliotoxin is an epipolythiodioxopiperazine (ETP) class toxin, contains a disulfide bridge that mediates its toxic effects via redox cycling and is produced by the opportunistic fungal pathogen Aspergillus fumigatus Self-resistance against gliotoxin is effected by the gliotoxin oxidase GliT, and attenuation of gliotoxin biosynthesis is catalysed by gliotoxin S -methyltransferase GtmA. Here we describe the X-ray crystal structures of GtmA-apo (1.66 Å), GtmA complexed to S -adenosylhomocysteine (1.33 Å) and GtmA complexed to S -adenosylmethionine (2.28 Å), providing mechanistic insights into this important biotransformation. We further reveal that simultaneous elimination of the ability of A. fumigatus to dissipate highly reactive dithiol gliotoxin, via deletion of GliT and GtmA, results in the most significant hypersensitivity to exogenous gliotoxin observed to date. Indeed, quantitative proteomic analysis of Δ gliT ::Δ gtmA reveals an uncontrolled over-activation of the gli -cluster upon gliotoxin exposure. The data presented herein reveal, for the first time, the extreme risk associated with intracellular dithiol gliotoxin biosynthesis-in the absence of an efficient dismutation capacity. Significantly, a previously concealed protective role for GtmA and functionality of ETP bis -thiomethylation as an ancestral protection strategy against dithiol compounds is now evident. © 2017 The Authors.

Key insights on the structural characterization of textured Er2O3–ZrO2 nano-oxides prepared by a surfactant-free solvothermal route

International Nuclear Information System (INIS)

Julián-López, Beatriz; Luz, Verónica de la; Gonell, Francisco; Cordoncillo, Eloisa; López-Haro, Miguel; Calvino, Jose J.; Escribano, Purificación

2012-01-01

Highlights: ► Structural resolution of fluorite vs. pyrochlore in small nanocrystals. ► Simple template-free solvothermal synthesis of Er 2 O 3 –ZrO 2 nanooxides. ► Good control over size, morphology and surface properties (280 m 2 g −1 ). - Abstract: Zirconia-mixed oxides can exhibit cubic fluorite and pyrochlore structure. Their discrimination is not easy in nanooxides with a crystal size close to that of a few unit cells. In this work, high resolution transmission electron microscopy (HRTEM) has been employed to provide key insights on the structural characterization of a nanometric and porous mixed Er 2 O 3 –ZrO 2 oxide. The material was prepared by a simple template-free solvothermal route that provided nanocrystalline powders at low temperature (170 °C) with spherical morphology, and high surface area (∼280 m 2 g −1 ). The porosity was mainly originated from the assembling of organic complexing agents used in the synthesis to limit the crystal growth and to control hydrolysis and condensation reaction rates. The samples were characterized by thermal analysis, X-ray diffraction, scanning electron microscopy and N 2 adsorption measurements. A detailed study by HRTEM was conducted on microtomed samples. It was observed that the material was made of nanocrystals packed into spherical agglomerates. HRTEM simulations indicated that it is not possible to identify the pyrochlore phase in nanoparticles with diameter below 2 nm. In our samples, the analysis of the HRTEM lattice images by means of fast Fourier transform (FFT) techniques revealed well defined spots that can be assigned to different planes of a cubic fluorite-type phase, even in the raw material. Raman spectroscopy was also a powerful technique to elucidate the crystalline phase of the materials with the smallest nanoparticles. HREM and Raman results evidenced that the material is constituted, irrespective of the temperature of the final calcination step, by an ensemble of randomly

Structural insights into the metabolism of 2-chlorodibenzofuran by an evolved biphenyl dioxygenase

International Nuclear Information System (INIS)

Kumar, Pravindra; Mohammadi, Mahmood; Dhindwal, Sonali; Pham, Thi Thanh My; Bolin, Jeffrey T.; Sylvestre, Michel

2012-01-01

Highlights: ► Regiospecificity of BphAE RR41 toward dibenzofuran and 2-chlorodibenzofuran differs. ► We compared the structures of the substrate-bound forms of the enzyme with both substrates. ► Dibenzofuran is compelled to move during the catalytic reaction. ► Ser283 contact with 2-chlorodibenzofuran helps prevent substrate movement during the reaction. -- Abstract: The biphenyl dioxygenase of Burkholderia xenovorans LB400 (BphAE LB400 ) is a Rieske-type oxygenase that catalyzes the stereospecific oxygenation of many heterocyclic aromatics including dibenzofuran. In a previous work, we evolved BphAE LB400 and obtained BphAE RR41 . This variant metabolizes dibenzofuran and 2-chlorodibenzofuran more efficiently than BphAE LB400 . However, the regiospecificity of BphAE RR41 toward these substrates differs. Dibenzofuran is metabolized principally through a lateral dioxygenation whereas 2-chlorodibenzofuran is metabolized principally through an angular dioxygenation. In order to explain this difference, we examined the crystal structures of both substrate-bound forms of BphAE RR41 obtained under anaerobic conditions. This structure analysis, in combination with biochemical data for a Ser283Gly mutant provided evidences that the substrate is compelled to move after oxygen-binding in BphAE RR41 :dibenzofuran. In BphAE RR41 :2-chlorodibenzofuran, the chlorine atom is close to the side chain of Ser283. This contact is missing in the BphAE RR41 :dibenzofuran, and strong enough in the BphAE RR41 :2-chlorodibenzofuran to help prevent substrate movement during the catalytic reaction.

Determining criminal responsibility: How relevant are insight and personal attitudes to mock jurors?

Science.gov (United States)

Jung, Sandy

2015-01-01

High levels of insight are interpreted as indications of a treatment compliance and good outcome by clinical professionals. However, it is unclear whether a defendant's insight plays a role in the decision-making of jurors when determining criminal responsibility. It may be the case that personal biases and attitudes toward the mentally ill and the insanity defense are more relevant in such decisions. This study examines the influence of two core dimensions of insight and personal attitudes on juror decision-making. Participants read trial scenarios describing a defendant who is accused of a violent crime and is diagnosed with schizophrenia. Assigning a verdict of not criminally responsible to the defendant was not influenced by insight, but instead, by supportive attitudes of the insanity defense and higher attributions of blame to external factors and to psychological factors. These findings highlight the need for continued investigation in the area of extra-legal factors that guide legal decision-making when defendants have a mental disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mentalization, insightfulness, and therapeutic action. The importance of mental organization.

Science.gov (United States)

Sugarman, Alan

2006-08-01

Continuing debates over the relative importance of the role of interpretation leading to insight versus the relationship with the analyst as contributing to structural change are based on traditional definitions of insight as gaining knowledge of unconscious content. This definition inevitably privileges verbal interpretation as self-knowledge becomes equated with understanding the contents of the mind. It is suggested that a way out of this debate is to redefine insight as a process, one that is called insightfulness. This term builds on concepts such as mentalization, or theory of mind, and suggests that patients present with difficulties being able to fully mentalize. Awareness of repudiated content will usually accompany the attainment of insightfulness. But the point of insightfulness is to regain access to inhibited or repudiated mentalization, not to specific content, per se. Emphasizing the process of insightfulness integrates the importance of the relationship with the analyst with the facilitation of insightfulness. A variety of interventions help patients gain the capacity to reflect upon and become aware of the intricate workings of their minds, of which verbal interpretation is only one. For example, often it seems less important to focus on a particular conflict than to show interest in our patients' minds. Furthermore, analysands develop insightfulness by becoming interested in and observing our minds in action. Because the mind originates in bodily experience, mental functioning will always fluctuate between action modes of experiencing and expressing and verbal, symbolic modes. The analyst's role becomes making the patient aware of regressions to action modes, understanding the reasons for doing so, and subordinating this tendency to the verbal, symbolic mode. All mental functions work better and facilitate greater self-regulation when they work in abstract, symbolic ways. Psychopathology can be understood as failing to develop or losing the

Insights into structural and dynamical features of water at halloysite interfaces probed by DFT and classical molecular dynamics simulations.

Science.gov (United States)

Presti, Davide; Pedone, Alfonso; Mancini, Giordano; Duce, Celia; Tiné, Maria Rosaria; Barone, Vincenzo

2016-01-21

Density functional theory calculations and classical molecular dynamics simulations have been used to investigate the structure and dynamics of water molecules on kaolinite surfaces and confined in the interlayer of a halloysite model of nanometric dimension. The first technique allowed us to accurately describe the structure of the tetrahedral-octahedral slab of kaolinite in vacuum and in interaction with water molecules and to assess the performance of two widely employed empirical force fields to model water/clay interfaces. Classical molecular dynamics simulations were used to study the hydrogen bond network structure and dynamics of water adsorbed on kaolinite surfaces and confined in the halloysite interlayer. The results are in nice agreement with the few experimental data available in the literature, showing a pronounced ordering and reduced mobility of water molecules at the hydrophilic octahedral surfaces of kaolinite and confined in the halloysite interlayer, with respect to water interacting with the hydrophobic tetrahedral surfaces and in the bulk. Finally, this investigation provides new atomistic insights into the structural and dynamical properties of water-clay interfaces, which are of fundamental importance for both natural processes and industrial applications.

Structural Insights into the Mechanisms of Action of Short-Peptide HIV-1 Fusion Inhibitors Targeting the Gp41 Pocket

Directory of Open Access Journals (Sweden)

Xiujuan Zhang

2018-02-01

Full Text Available The deep hydrophobic pocket of HIV-1 gp41 has been considered a drug target, but short-peptides targeting this site usually lack potent antiviral activity. By applying the M-T hook structure, we previously generated highly potent short-peptide fusion inhibitors that specifically targeted the pocket site, such as MT-SC22EK, HP23L, and LP-11. Here, the crystal structures of HP23L and LP-11 bound to the target mimic peptide N36 demonstrated the critical intrahelical and interhelical interactions, especially verifying that the hook-like conformation was finely adopted while the methionine residue was replaced by the oxidation-less prone residue leucine, and that addition of an extra glutamic acid significantly enhanced the binding and inhibitory activities. The structure of HP23L bound to N36 with two mutations (E49K and L57R revealed the critical residues and motifs mediating drug resistance and provided new insights into the mechanism of action of inhibitors. Therefore, the present data help our understanding for the structure-activity relationship (SAR of HIV-1 fusion inhibitors and facilitate the development of novel antiviral drugs.

Molecular details of secretory phospholipase A2 from flax (Linum usitatissimum L.) provide insight into its structure and function.

Science.gov (United States)

Gupta, Payal; Dash, Prasanta K

2017-09-11

Secretory phospholipase A 2 (sPLA 2 ) are low molecular weight proteins (12-18 kDa) involved in a suite of plant cellular processes imparting growth and development. With myriad roles in physiological and biochemical processes in plants, detailed analysis of sPLA 2 in flax/linseed is meagre. The present work, first in flax, embodies cloning, expression, purification and molecular characterisation of two distinct sPLA 2 s (I and II) from flax. PLA 2 activity of the cloned sPLA 2 s were biochemically assayed authenticating them as bona fide phospholipase A 2 . Physiochemical properties of both the sPLA 2 s revealed they are thermostable proteins requiring di-valent cations for optimum activity.While, structural analysis of both the proteins revealed deviations in the amino acid sequence at C- & N-terminal regions; hydropathic study revealed LusPLA 2 I as a hydrophobic protein and LusPLA 2 II as a hydrophilic protein. Structural analysis of flax sPLA 2 s revealed that secondary structure of both the proteins are dominated by α-helix followed by random coils. Modular superimposition of LusPLA 2 isoforms with rice sPLA 2 confirmed monomeric structural preservation among plant phospholipase A 2 and provided insight into structure of folded flax sPLA 2 s.

Mechanistic Insights into Validoxylamine A 7'-Phosphate Synthesis by VldE Using the Structure of the Entire Product Complex

Energy Technology Data Exchange (ETDEWEB)

Cavalier, Michael C.; Yim, Young-Sun; Asamizu, Shumpei; Neau, David; Almabruk, Khaled H.; Mahmud, Taifo; Lee, Yong-Hwan [Oregon State U.; (Cornell); (LSU)

2013-09-09

The pseudo-glycosyltransferase VldE catalyzes non-glycosidic C-N coupling between an unsaturated cyclitol and a saturated aminocyclitol with the conservation of the stereochemical configuration of the substrates to form validoxylamine A 7'-phosphate, the biosynthetic precursor of the antibiotic validamycin A. To study the molecular basis of its mechanism, the three-dimensional structures of VldE from Streptomyces hygroscopicus subsp. limoneus was determined in apo form, in complex with GDP, in complex with GDP and validoxylamine A 7'-phosphate, and in complex with GDP and trehalose. The structure of VldE with the catalytic site in both an “open” and “closed” conformation is also described. With these structures, the preferred binding of the guanine moiety by VldE, rather than the uracil moiety as seen in OtsA could be explained. The elucidation of the VldE structure in complex with the entirety of its products provides insight into the internal return mechanism by which catalysis occurs with a net retention of the stereochemical configuration of the donated cyclitol.

Cryo-EM structures of two bovine adenovirus type 3 intermediates

International Nuclear Information System (INIS)

Cheng, Lingpeng; Huang, Xiaoxing; Li, Xiaomin; Xiong, Wei; Sun, Wei; Yang, Chongwen; Zhang, Kai; Wang, Ying; Liu, Hongrong; Huang, Xiaojun; Ji, Gang; Sun, Fei; Zheng, Congyi; Zhu, Ping

2014-01-01

Adenoviruses (Ads) infect hosts from all vertebrate species and have been investigated as vaccine vectors. We report here near-atomic structures of two bovine Ad type 3 (BAd3) intermediates obtained by cryo-electron microscopy. A comparison between the two intermediate structures reveals that the differences are localized in the fivefold vertex region, while their facet structures are identical. The overall facet structure of BAd3 exhibits a similar structure to human Ads; however, BAd3 protein IX has a unique conformation. Mass spectrometry and cryo-electron tomography analyses indicate that one intermediate structure represents the stage during DNA encapsidation, whilst the other intermediate structure represents a later stage. These results also suggest that cleavage of precursor protein VI occurs during, rather than after, the DNA encapsidation process. Overall, our results provide insights into the mechanism of Ad assembly, and allow the first structural comparison between human and nonhuman Ads at backbone level. - Highlights: • First structure of bovine adenovirus type 3. • Some channels are located at the vertex of intermediate during DNA encapsidation. • Protein IX exhibits a unique conformation of trimeric coiled–coiled structure. • Cleavage of precursor protein VI occurs during the DNA encapsidation process

Cryo-EM structures of two bovine adenovirus type 3 intermediates

Energy Technology Data Exchange (ETDEWEB)

Cheng, Lingpeng; Huang, Xiaoxing; Li, Xiaomin [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Xiong, Wei [State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Luo-jia-shan, Wuhan, Hubei 430072 (China); Sun, Wei; Yang, Chongwen; Zhang, Kai; Wang, Ying [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Liu, Hongrong [College of Physics and Information Science, Hunan Normal University, Changsha, Hunan 410081 (China); Huang, Xiaojun; Ji, Gang; Sun, Fei [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Zheng, Congyi, E-mail: cctcc202@whu.edu.cn [State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Luo-jia-shan, Wuhan, Hubei 430072 (China); Zhu, Ping, E-mail: zhup@ibp.ac.cn [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China)

2014-02-15

Adenoviruses (Ads) infect hosts from all vertebrate species and have been investigated as vaccine vectors. We report here near-atomic structures of two bovine Ad type 3 (BAd3) intermediates obtained by cryo-electron microscopy. A comparison between the two intermediate structures reveals that the differences are localized in the fivefold vertex region, while their facet structures are identical. The overall facet structure of BAd3 exhibits a similar structure to human Ads; however, BAd3 protein IX has a unique conformation. Mass spectrometry and cryo-electron tomography analyses indicate that one intermediate structure represents the stage during DNA encapsidation, whilst the other intermediate structure represents a later stage. These results also suggest that cleavage of precursor protein VI occurs during, rather than after, the DNA encapsidation process. Overall, our results provide insights into the mechanism of Ad assembly, and allow the first structural comparison between human and nonhuman Ads at backbone level. - Highlights: • First structure of bovine adenovirus type 3. • Some channels are located at the vertex of intermediate during DNA encapsidation. • Protein IX exhibits a unique conformation of trimeric coiled–coiled structure. • Cleavage of precursor protein VI occurs during the DNA encapsidation process.

Research and technology highlights, 1993

Science.gov (United States)

1994-01-01

This report contains highlights of the major accomplishments and applications that have been made by Langley researchers and by our university and industry colleagues during the past year. The highlights illustrate both the broad range of the research and technology activities supported by NASA Langley Research Center and the contributions of this work toward maintaining United States leadership in aeronautics and space research. This report also describes some of the Center's most important research and testing facilities.

Enter the Matrix: Building Creative Industry through Delivering Insights in Comics

Directory of Open Access Journals (Sweden)

Hafiz Ahmad Aziz

2014-10-01

Full Text Available Comic is a media which delivers its content through visual sequence. This media has negative preference in Indonesia’s community because viewed as mild entertainment for children. Yet in modern society, comics observed and researched as one of media which could penetrate deep within its reader’s mind. In re-create cultural insight through comic, the content must encrypt into visual and sequential mode which form a matrix of insight. This matrix will encompasses the effective transformation of cultural content in comic and also other visual media through media linkage strategy. The media linkage strategy is to surround the children’s access of information and visual entertainment in order to build certain knowledge and understanding. It’s a system that crystallized from global marketing practices of visual media industry over decades. This paper urges to highlight the visual communication design study in creating a matrix of cultural insight in translating cultures of Archipelago and media linkage strategy in order to strengthen cultural understanding among children.

Highlighting micrographic structures of uranium-zirconium alloys with 6 per cent of weight of Zr; Mise en evidence des structures micrographiques des alliages uranium-zirconium a 6 pour cent en poids de Zr

Energy Technology Data Exchange (ETDEWEB)

Bouleau, Maurice

1961-01-17

In order to study the transformation kinetics of U-Zr alloys with a Zr content of 6 per cent in weight, the authors searched for a slow enough electrolytic polishing bath, and for an attack and examination method to highlight martensite structures produced by austempering and water tempering, and ultra-fine decomposition structures obtained by austempering. The authors explain the choice of a perchloric-butyl glycol polishing bath, of an examination under polarized light or normal light after appropriate attacks. These studies are reported for annealed alloys, and for processed alloys with martensite or ultra-fine decomposition structures [French] L'etude de la cinetique de transformation des alliages U-Zr a 6 pc en poids de Zr a necessite la recherche d'un bain de polissage electrolytique assez lent et de methodes d'attaque et d'examen qui permettent la mise en evidence des structures martensitiques (provenant de trempes etagees ou de trempes a l'eau) et des structures de decomposition ultrafines (obtenues par trempes etagees). Nous nous sommes arretes dans notre choix: - sur un bain de polissage perchlorique-butyl glycol; sur des examens en lumiere polarisee ou en lumiere normale apres attaques appropriees (en cellule dans le meme electrolyte ou au tampon dans un bain phosphorique ethylene glycol). (auteur)

ATLAS Outreach Highlights

CERN Document Server

Cheatham, Susan; The ATLAS collaboration

2016-01-01

The ATLAS outreach team is very active, promoting particle physics to a broad range of audiences including physicists, general public, policy makers, students and teachers, and media. A selection of current outreach activities and new projects will be presented. Recent highlights include the new ATLAS public website and ATLAS Open Data, the very recent public release of 1 fb-1 of ATLAS data.

Difference between highlight and object colors enhances glossiness.

Science.gov (United States)

Hanada, Mitsuhiko

2012-06-01

The effect of highlight and object colors on perception of glossiness was examined. Ten participants rated glossiness of object images. The color coordinates of objects and highlights were varied while luminance of each pixel was unchanged. Four colors were used for objects and highlights. Objects were perceived as glossier when the highlight color was different from the object color than when they were the same. Objects with some unnatural combinations of highlight and object colors were perceived to be as glossy as those with natural color combinations. The results suggested that differences between highlight and object colors enhance perceived glossiness and that perceived glossiness does not depend on naturalness of color combination for highlights and objects.

A study of poor insight in social anxiety disorder.

Science.gov (United States)

Vigne, Paula; de Menezes, Gabriela B; Harrison, Ben J; Fontenelle, Leonardo F

2014-11-30

We investigated levels of insight among patients with Social Anxiety Disorder (SAD) as compared to patients with Obsessive-Compulsive Disorder (OCD) and evaluated whether levels of insight in SAD were related to specific sociodemographic and/or clinical features. Thirty-seven SAD patients and 51 OCD patients attending a tertiary obsessive-compulsive and anxiety disorders clinic were assessed with a sociodemographic and clinical questionnaire, a structured diagnostic interview, the Brown Assessment of Beliefs Scale (BABS), the Social Phobia Inventory (SPIN), the Beck Depression Inventory (BDI), the Sheehan Disability Scale (SDS), and the Treatment Adherence Survey-patient version (TAS-P). According to the BABS, SAD patients exhibited insight levels that were as low as those exhibited by OCD patients, with up to 29.7% of them being described as "poor insight" SAD. Although poor insight SAD patients were more frequently married, less depressed and displayed a statistical trend towards greater rates of early drop-out from cognitive-behavioral therapy, their insight levels were not associated with other variables of interest, including sex, age, employment, age at onset, duration of illness, associated psychiatric disorders, SPIN and SDS scores. Patients with poor insight SAD might perceive their symptoms as being less distressful and thus report fewer depressive symptoms and high rates of treatment non-adherence. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Insights into the structure and function of fungal β-mannosidases from glycoside hydrolase family 2 based on multiple crystal structures of the Trichoderma harzianum enzyme.

Science.gov (United States)

Nascimento, Alessandro S; Muniz, Joao Renato C; Aparício, Ricardo; Golubev, Alexander M; Polikarpov, Igor

2014-09-01

Hemicellulose is an important part of the plant cell wall biomass, and is relevant to cellulosic ethanol technologies. β-Mannosidases are enzymes capable of cleaving nonreducing residues of β-d-mannose from β-d-mannosides and hemicellulose mannose-containing polysaccharides, such as mannans and galactomannans. β-Mannosidases are distributed between glycoside hydrolase (GH) families 1, 2, and 5, and only a handful of the enzymes have been structurally characterized to date. The only published X-ray structure of a GH family 2 mannosidase is that of the bacterial Bacteroides thetaiotaomicron enzyme. No structures of eukaryotic mannosidases of this family are currently available. To fill this gap, we set out to solve the structure of Trichoderma harzianum GH family 2 β-mannosidase and to refine it to 1.9-Å resolution. Structural comparisons of the T. harzianum GH2 β-mannosidase highlight similarities in its structural architecture with other members of GH family 2, reveal the molecular mechanism of β-mannoside binding and recognition, and shed light on its putative galactomannan-binding site. Coordinates and observed structure factor amplitudes have been deposited with the Protein Data Bank (4CVU and 4UOJ). The T. harzianum β-mannosidase 2A nucleotide sequence has GenBank accession number BankIt1712036 GeneMark.hmm KJ624918. © 2014 FEBS.

Energy transitions research: Insights and cautionary tales

International Nuclear Information System (INIS)

Grubler, Arnulf

2012-01-01

This short essay first reviews the pioneers of energy transition research both in terms of data as well as theories. Three major insights that have emerged from this nascent research fields are summarized highlighting the importance of energy end-use and services, the lengthy process of transitions, as well as the patterns that characterize successful scale up of technologies and industries that drive historical energy transitions. The essay concludes with cautionary notes also derived from historical experience. In order to trigger a next energy transition policies and innovation efforts need to be persistent and continuous, aligned, as well as balanced. It is argued that current policy frameworks in place invariably do not meet these criteria and need to change in order to successfully trigger a next energy transition towards sustainability. - Highlights: ► Includes the first literature review of early energy transition research. ► Summarizes three major research findings from the literature. ► Reviews policy implications of recent case studies of energy technology innovation. ► Argues that current policy frameworks are deficient in view of above lessons.

Structural insights into the metabolism of 2-chlorodibenzofuran by an evolved biphenyl dioxygenase

Energy Technology Data Exchange (ETDEWEB)

Kumar, Pravindra [Department of Biological Sciences and Center for Cancer Research, Purdue University, West Lafayette, IN 47907 (United States); Department of Biotechnology, Indian Institute of Technology, Roorkee 247667 (India); Mohammadi, Mahmood [Institut National de la Recherche Scientifique (INRS-Institut Armand-Frappier), Laval, QC, Canada H7V 1B7 (Canada); Dhindwal, Sonali [Department of Biotechnology, Indian Institute of Technology, Roorkee 247667 (India); Pham, Thi Thanh My [Institut National de la Recherche Scientifique (INRS-Institut Armand-Frappier), Laval, QC, Canada H7V 1B7 (Canada); Bolin, Jeffrey T. [Department of Biological Sciences and Center for Cancer Research, Purdue University, West Lafayette, IN 47907 (United States); Sylvestre, Michel, E-mail: Michel.Sylvestre@iaf.inrs.ca [Institut National de la Recherche Scientifique (INRS-Institut Armand-Frappier), Laval, QC, Canada H7V 1B7 (Canada)

2012-05-18

Highlights: Black-Right-Pointing-Pointer Regiospecificity of BphAE{sub RR41} toward dibenzofuran and 2-chlorodibenzofuran differs. Black-Right-Pointing-Pointer We compared the structures of the substrate-bound forms of the enzyme with both substrates. Black-Right-Pointing-Pointer Dibenzofuran is compelled to move during the catalytic reaction. Black-Right-Pointing-Pointer Ser283 contact with 2-chlorodibenzofuran helps prevent substrate movement during the reaction. -- Abstract: The biphenyl dioxygenase of Burkholderia xenovorans LB400 (BphAE{sub LB400}) is a Rieske-type oxygenase that catalyzes the stereospecific oxygenation of many heterocyclic aromatics including dibenzofuran. In a previous work, we evolved BphAE{sub LB400} and obtained BphAE{sub RR41}. This variant metabolizes dibenzofuran and 2-chlorodibenzofuran more efficiently than BphAE{sub LB400}. However, the regiospecificity of BphAE{sub RR41} toward these substrates differs. Dibenzofuran is metabolized principally through a lateral dioxygenation whereas 2-chlorodibenzofuran is metabolized principally through an angular dioxygenation. In order to explain this difference, we examined the crystal structures of both substrate-bound forms of BphAE{sub RR41} obtained under anaerobic conditions. This structure analysis, in combination with biochemical data for a Ser283Gly mutant provided evidences that the substrate is compelled to move after oxygen-binding in BphAE{sub RR41}:dibenzofuran. In BphAE{sub RR41}:2-chlorodibenzofuran, the chlorine atom is close to the side chain of Ser283. This contact is missing in the BphAE{sub RR41}:dibenzofuran, and strong enough in the BphAE{sub RR41}:2-chlorodibenzofuran to help prevent substrate movement during the catalytic reaction.

Using qualitative problem-solving strategies to highlight the role of conceptual knowledge in solving problems

Science.gov (United States)

Leonard, William J.; Dufresne, Robert J.; Mestre, Jose P.

1996-12-01

We report on the use of qualitative problem-solving strategies in teaching an introductory, calculus-based physics course as a means of highlighting the role played by conceptual knowledge in solving problems. We found that presenting strategies during lectures and in homework solutions provides an excellent opportunity to model for students the type of concept-based, qualitative reasoning that is valued in our profession, and that student-generated strategies serve a diagnostic function by providing instructors with insights on students' conceptual understanding and reasoning. Finally, we found strategies to be effective pedagogical tools for helping students both to identify principles that could be applied to solve specific problems, as well as to recall the major principles covered in the course months after it was over.

The structural flexibility of the human copper chaperone Atox1: Insights from combined pulsed EPR studies and computations.

Science.gov (United States)

Levy, Ariel R; Turgeman, Meital; Gevorkyan-Aiapetov, Lada; Ruthstein, Sharon

2017-08-01

Metallochaperones are responsible for shuttling metal ions to target proteins. Thus, a metallochaperone's structure must be sufficiently flexible both to hold onto its ion while traversing the cytoplasm and to transfer the ion to or from a partner protein. Here, we sought to shed light on the structure of Atox1, a metallochaperone involved in the human copper regulation system. Atox1 shuttles copper ions from the main copper transporter, Ctr1, to the ATP7b transporter in the Golgi apparatus. Conventional biophysical tools such as X-ray or NMR cannot always target the various conformational states of metallochaperones, owing to a requirement for crystallography or low sensitivity and resolution. Electron paramagnetic resonance (EPR) spectroscopy has recently emerged as a powerful tool for resolving biological reactions and mechanisms in solution. When coupled with computational methods, EPR with site-directed spin labeling and nanoscale distance measurements can provide structural information on a protein or protein complex in solution. We use these methods to show that Atox1 can accommodate at least four different conformations in the apo state (unbound to copper), and two different conformations in the holo state (bound to copper). We also demonstrate that the structure of Atox1 in the holo form is more compact than in the apo form. Our data provide insight regarding the structural mechanisms through which Atox1 can fulfill its dual role of copper binding and transfer. © 2017 The Protein Society.

Structure-based analysis of CysZ-mediated cellular uptake of sulfate

Science.gov (United States)

Assur Sanghai, Zahra; Liu, Qun; Clarke, Oliver B; Belcher-Dufrisne, Meagan; Wiriyasermkul, Pattama; Giese, M Hunter; Leal-Pinto, Edgar; Kloss, Brian; Tabuso, Shantelle; Love, James; Punta, Marco; Banerjee, Surajit; Rajashankar, Kanagalaghatta R; Rost, Burkhard; Logothetis, Diomedes; Quick, Matthias; Hendrickson, Wayne A

2018-01-01

Sulfur, most abundantly found in the environment as sulfate (SO42-), is an essential element in metabolites required by all living cells, including amino acids, co-factors and vitamins. However, current understanding of the cellular delivery of SO42- at the molecular level is limited. CysZ has been described as a SO42- permease, but its sequence family is without known structural precedent. Based on crystallographic structure information, SO42- binding and flux experiments, we provide insight into the molecular mechanism of CysZ-mediated translocation of SO42- across membranes. CysZ structures from three different bacterial species display a hitherto unknown fold and have subunits organized with inverted transmembrane topology. CysZ from Pseudomonas denitrificans assembles as a trimer of antiparallel dimers and the CysZ structures from two other species recapitulate dimers from this assembly. Mutational studies highlight the functional relevance of conserved CysZ residues. PMID:29792261

An overview of structure-activity relationship studies of curcumin analogs as antioxidant and anti-inflammatory agents.

Science.gov (United States)

Arshad, Laiba; Haque, Md Areeful; Abbas Bukhari, Syed Nasir; Jantan, Ibrahim

2017-04-01

Curcumin, extracted mainly from Curcuma longa rhizomes, has been reported to possess potent anti-inflammatory and anti-oxidant activities. Although safe at higher doses and exhibiting multiple biological activities, curcumin still has the problem of poor bioavailability which has been an attractive area of research over the last few years. A number of efforts have been made by modifying structural features of curcumin. This review highlights the structurally modified and more stable newly synthesized curcumin analogs that have been screened against antioxidant and anti-inflammatory activities. Also the structure-activity relationship to gain insight into future guidelines for scheming new compounds has been discussed, and further these analogs being more stable may serve as promising agents for use in different pathological conditions.

Relationships between structural complexity, coral traits, and reef fish assemblages

Science.gov (United States)

Darling, Emily S.; Graham, Nicholas A. J.; Januchowski-Hartley, Fraser A.; Nash, Kirsty L.; Pratchett, Morgan S.; Wilson, Shaun K.

2017-06-01

With the ongoing loss of coral cover and the associated flattening of reef architecture, understanding the links between coral habitat and reef fishes is of critical importance. Here, we investigate whether considering coral traits and functional diversity provides new insights into the relationship between structural complexity and reef fish communities, and whether coral traits and community composition can predict structural complexity. Across 157 sites in Seychelles, Maldives, the Chagos Archipelago, and Australia's Great Barrier Reef, we find that structural complexity and reef zone are the strongest and most consistent predictors of reef fish abundance, biomass, species richness, and trophic structure. However, coral traits, diversity, and life histories provided additional predictive power for models of reef fish assemblages, and were key drivers of structural complexity. Our findings highlight that reef complexity relies on living corals—with different traits and life histories—continuing to build carbonate skeletons, and that these nuanced relationships between coral assemblages and habitat complexity can affect the structure of reef fish assemblages. Seascape-level estimates of structural complexity are rapid and cost effective with important implications for the structure and function of fish assemblages, and should be incorporated into monitoring programs.

Highlights on distinctive structural and functional properties of HTLV Tax proteins

Science.gov (United States)

Romanelli, Maria Grazia; Diani, Erica; Bergamo, Elisa; Casoli, Claudio; Ciminale, Vincenzo; Bex, Françoise; Bertazzoni, Umberto

2013-01-01

Human T cell leukemia viruses (HTLVs) are complex human retroviruses of the Deltaretrovirus genus. Four types have been identified thus far, with HTLV-1 and HTLV-2 much more prevalent than HTLV-3 or HTLV-4. HTLV-1 and HTLV-2 possess strictly related genomic structures, but differ significantly in pathogenicity, as HTLV-1 is the causative agent of adult T cell leukemia and of HTLV-associated myelopathy/tropical spastic paraparesis, whereas HTLV-2 is not associated with neoplasia. HTLVs code for a protein named Tax that is responsible for enhancing viral expression and drives cell transformation. Much effort has been invested to dissect the impact of Tax on signal transduction pathways and to identify functional differences between the HTLV Tax proteins that may explain the distinct oncogenic potential of HTLV-1 and HTLV-2. This review summarizes our current knowledge of Tax-1 and Tax-2 with emphasis on their structure, role in activation of the NF-κB (nuclear factor kappa-B) pathway, and interactions with host factors. PMID:24058363

Magnetic alloy nanowire arrays with different lengths: Insights into the crossover angle of magnetization reversal process

Energy Technology Data Exchange (ETDEWEB)

Samanifar, S.; Alikhani, M. [Department of Physics, University of Kashan, Kashan 87317-51167 (Iran, Islamic Republic of); Almasi Kashi, M., E-mail: almac@kashanu.ac.ir [Department of Physics, University of Kashan, Kashan 87317-51167 (Iran, Islamic Republic of); Institute of Nanoscience and Nanotechnology, University of Kashan, Kashan 87317-51167 (Iran, Islamic Republic of); Ramazani, A. [Department of Physics, University of Kashan, Kashan 87317-51167 (Iran, Islamic Republic of); Institute of Nanoscience and Nanotechnology, University of Kashan, Kashan 87317-51167 (Iran, Islamic Republic of); Montazer, A.H. [Institute of Nanoscience and Nanotechnology, University of Kashan, Kashan 87317-51167 (Iran, Islamic Republic of)

2017-05-15

Nanoscale magnetic alloy wires are being actively investigated, providing fundamental insights into tuning properties in magnetic data storage and processing technologies. However, previous studies give trivial information about the crossover angle of magnetization reversal process in alloy nanowires (NWs). Here, magnetic alloy NW arrays with different compositions, composed of Fe, Co and Ni have been electrochemically deposited into hard-anodic aluminum oxide templates with a pore diameter of approximately 150 nm. Under optimized conditions of alumina barrier layer and deposition bath concentrations, the resulting alloy NWs with aspect ratio and saturation magnetization (M{sub s}) up to 550 and 1900 emu cm{sup −3}, respectively, are systematically investigated in terms of composition, crystalline structure and magnetic properties. Using angular dependence of coercivity extracted from hysteresis loops, the reversal processes are evaluated, indicating non-monotonic behavior. The crossover angle (θ{sub c}) is found to depend on NW length and M{sub s}. At a constant M{sub s}, increasing NW length decreases θ{sub c}, thereby decreasing the involvement of vortex mode during the magnetization reversal process. On the other hand, decreasing M{sub s} decreases θ{sub c} in large aspect ratio (>300) alloy NWs. Phenomenologically, it is newly found that increasing Ni content in the composition decreases θ{sub c}. The angular first-order reversal curve (AFORC) measurements including the irreversibility of magnetization are also investigated to gain a more detailed insight into θ{sub c}. - Highlights: • Magnetic alloy NWs with aspect ratios up to 550 were fabricated into hard-AAO templates. • Morphology, composition, crystal structure and magnetic properties were investigated. • Angular dependence of coercivity was used to describe the magnetization reversal process. • The crossover angle of magnetization reversal was found to depend on NW length and M{sub s}. �

Leishmania naiffi and Leishmania guyanensis reference genomes highlight genome structure and gene evolution in the Viannia subgenus.

Science.gov (United States)

Coughlan, Simone; Taylor, Ali Shirley; Feane, Eoghan; Sanders, Mandy; Schonian, Gabriele; Cotton, James A; Downing, Tim

2018-04-01

The unicellular protozoan parasite Leishmania causes the neglected tropical disease leishmaniasis, affecting 12 million people in 98 countries. In South America, where the Viannia subgenus predominates, so far only L. ( Viannia ) braziliensis and L. ( V. ) panamensis have been sequenced, assembled and annotated as reference genomes. Addressing this deficit in molecular information can inform species typing, epidemiological monitoring and clinical treatment. Here, L. ( V. ) naiffi and L. ( V. ) guyanensis genomic DNA was sequenced to assemble these two genomes as draft references from short sequence reads. The methods used were tested using short sequence reads for L. braziliensis M2904 against its published reference as a comparison. This assembly and annotation pipeline identified 70 additional genes not annotated on the original M2904 reference. Phylogenetic and evolutionary comparisons of L. guyanensis and L. naiffi with 10 other Viannia genomes revealed four traits common to all Viannia : aneuploidy, 22 orthologous groups of genes absent in other Leishmania subgenera, elevated TATE transposon copies and a high NADH-dependent fumarate reductase gene copy number. Within the Viannia , there were limited structural changes in genome architecture specific to individual species: a 45 Kb amplification on chromosome 34 was present in all bar L. lainsoni , L. naiffi had a higher copy number of the virulence factor leishmanolysin, and laboratory isolate L. shawi M8408 had a possible minichromosome derived from the 3' end of chromosome 34 . This combination of genome assembly, phylogenetics and comparative analysis across an extended panel of diverse Viannia has uncovered new insights into the origin and evolution of this subgenus and can help improve diagnostics for leishmaniasis surveillance.

Biochemical and Structural Analysis of Hormone-sensitive Lipase Homolog EstE7: Insight into the Stabilized Dimerization of HSL-Homolog Proteins

International Nuclear Information System (INIS)

Nam, Ki Hyun; Park, Sung Ha; Lee, Won Ho; Hwang, Kwang Yeon

2010-01-01

Hormone sensitive lipase (HSL) plays a major role in energy homeostasis and lipid metabolism. Several crystal structures of HSL-homolog proteins have been identified, which has led to a better understanding of its molecular function. HSLhomolog proteins exit as both monomer and dimer, but the biochemical and structural basis for such oligomeric states has not been successfully elucidated. Therefore, we determined the crystal structure of HSL-homolog protein EstE7 from a metagenome library at 2.2 A resolution and characterized the oligomeric states of EstE7 both structurally and biochemically. EstE7 protein prefers the dimeric state in solution, which is supported by its higher enzymatic activity in the dimeric state. In the crystal form, EstE7 protein shows two-types of dimeric interface. Specifically, dimerization via the external β8-strand occurred through tight association between two pseudosymmetric folds via salt bridges, hydrogen bonds and van der Waals interactions. This dimer formation was similar to that of other HSL-homolog protein structures such as AFEST, BEFA, and EstE1. We anticipate that our results will provide insight into the oligomeric state of HSLhomolog proteins

Unraveling interrelationships among psychopathology symptoms, cognitive domains and insight dimensions in chronic schizophrenia.

Science.gov (United States)

Xavier, Rose Mary; Pan, Wei; Dungan, Jennifer R; Keefe, Richard S E; Vorderstrasse, Allison

2018-03-01

Insight in schizophrenia is long known to have a complex relationship with psychopathology symptoms and cognition. However, very few studies have examined models that explain these interrelationships. In a large sample derived from the NIMH Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial (N=1391), we interrogated these interrelationships for potential causal pathways using structural equation modeling. Using the NIMH consensus model, latent variables were constructed for psychopathology symptom dimensions, including positive, negative, disorganized, excited and depressed from the Positive and Negative Syndrome Scale (PANSS) items. Neurocognitive variables were created from five predefined domains of working memory, verbal memory, reasoning, vigilance and processing speed. Illness insight and treatment insight were tested using latent variables constructed from the Illness and Treatment Attitude Questionnaire (ITAQ). Disorganized symptoms had the strongest effect on insight. Illness insight mediated the relationship of positive, depressed, and disorganized symptoms with treatment insight. Neurocognition mediated the relationship between disorganized and treatment insight and depressed symptoms and treatment insight. There was no effect of negative symptoms on either illness insight or treatment insight. Taken together, our results indicate overlapping and unique relational paths for illness and treatment insight dimensions, which could suggest differences in causal mechanisms and potential interventions to improve insight. Copyright © 2017 Elsevier B.V. All rights reserved.

New insights into the structure of Om Ali-Thelepte basin, central Tunisia, inferred from gravity data: Hydrogeological implications

Science.gov (United States)

Harchi, Mongi; Gabtni, Hakim; El Mejri, Hatem; Dassi, Lassaad; Mammou, Abdallah Ben

2016-08-01

This work presents new results from gravity data analyses and interpretation within the Om Ali-Thelepte (OAT) basin, central Tunisia. It focuses on the hydrogeological implication, using several qualitative and quantitative techniques such as horizontal gradient, upward continuation and Euler deconvolution on boreholes log data, seismic reflection data and electrical conductivity measurements. The structures highlighted using the filtering techniques suggest that the Miocene aquifer of OAT basin is cut by four major fault systems that trend E-W, NE-SW, NW-SE and NNE-SSW. In addition, a NW-SE gravity model established shows the geometry of the Miocene sandstone reservoir and the Upper Cretaceous limestone rocks. Moreover, the superimposition of the electrical conductivity and the structural maps indicates that the low conductivity values of sampled water from boreholes are located around main faults.

Brookhaven highlights, 1986-1987

International Nuclear Information System (INIS)

Rowe, M.S.

1988-01-01

The highlights of research conducted between October 1985 and September 1987 at Brookhaven National Laboratory are reviewed in this publication. Also covered are the administrative and financial status of the laboratory and a brief mention of meetings held and honors received. (FI)

Key insights on the structural characterization of textured Er{sub 2}O{sub 3}-ZrO{sub 2} nano-oxides prepared by a surfactant-free solvothermal route

Energy Technology Data Exchange (ETDEWEB)

Julian-Lopez, Beatriz, E-mail: julian@qio.uji.es [Departamento de Quimica Inorganica y Organica, Universitat Jaume I, Avda. Vicente Sos Baynat s/n, 12071 Castellon (Spain); Luz, Veronica de la; Gonell, Francisco; Cordoncillo, Eloisa [Departamento de Quimica Inorganica y Organica, Universitat Jaume I, Avda. Vicente Sos Baynat s/n, 12071 Castellon (Spain); Lopez-Haro, Miguel; Calvino, Jose J. [Departamento de Ciencia de los Materiales e Ingenieria Metalurgica y Quimica Inorganica, Facultad de Ciencias, Universidad de Cadiz, Campus Rio San Pedro, Puerto Real, 11510 Cadiz (Spain); Escribano, Purificacion [Departamento de Quimica Inorganica y Organica, Universitat Jaume I, Avda. Vicente Sos Baynat s/n, 12071 Castellon (Spain)

2012-04-05

Highlights: Black-Right-Pointing-Pointer Structural resolution of fluorite vs. pyrochlore in small nanocrystals. Black-Right-Pointing-Pointer Simple template-free solvothermal synthesis of Er{sub 2}O{sub 3}-ZrO{sub 2} nanooxides. Black-Right-Pointing-Pointer Good control over size, morphology and surface properties (280 m{sup 2} g{sup -1}). - Abstract: Zirconia-mixed oxides can exhibit cubic fluorite and pyrochlore structure. Their discrimination is not easy in nanooxides with a crystal size close to that of a few unit cells. In this work, high resolution transmission electron microscopy (HRTEM) has been employed to provide key insights on the structural characterization of a nanometric and porous mixed Er{sub 2}O{sub 3}-ZrO{sub 2} oxide. The material was prepared by a simple template-free solvothermal route that provided nanocrystalline powders at low temperature (170 Degree-Sign C) with spherical morphology, and high surface area ({approx}280 m{sup 2} g{sup -1}). The porosity was mainly originated from the assembling of organic complexing agents used in the synthesis to limit the crystal growth and to control hydrolysis and condensation reaction rates. The samples were characterized by thermal analysis, X-ray diffraction, scanning electron microscopy and N{sub 2} adsorption measurements. A detailed study by HRTEM was conducted on microtomed samples. It was observed that the material was made of nanocrystals packed into spherical agglomerates. HRTEM simulations indicated that it is not possible to identify the pyrochlore phase in nanoparticles with diameter below 2 nm. In our samples, the analysis of the HRTEM lattice images by means of fast Fourier transform (FFT) techniques revealed well defined spots that can be assigned to different planes of a cubic fluorite-type phase, even in the raw material. Raman spectroscopy was also a powerful technique to elucidate the crystalline phase of the materials with the smallest nanoparticles. HREM and Raman results evidenced

The relationship between theory of mind and insight in obsessive-compulsive disorder.

Science.gov (United States)

Tulacı, Rıza Gökçer; Cankurtaran, Eylem Şahin; Özdel, Kadir; Öztürk, Nefise; Kuru, Erkan; Özdemir, İlker

2018-02-09

It is known that obsessive-compulsive disorder (OCD) patients with poor insight display more severe neuropsychological impairments than other patients with OCD. There are limited studies of OCD and theory of mind (ToM). To investigate ToM skills in patients with OCD and the relationship between insight and ToM skills by comparing OCD patients with good and poor insight. Eighty patients with OCD and 80 healthy controls completed the structured clinical interview for DSM-IV axis I disorders, the Yale Brown Obsessive-Compulsive Scale, the Beck Anxiety and Beck Depression Inventories, and the Brown Assessment of Beliefs Scale. To assess ToM skills, first- and second-order false-belief tests, a hinting test, a faux pas test, a reading the mind in the eyes test, and a double-bluff test were administered. Patients with OCD had poorer ToM abilities than healthy controls. All ToM scores were significantly lower in the poor insight group than in the good insight group (p insight than in OCD with good insight may contribute to the idea of OCD with poor insight being a subtype with different clinical and neuropsychological characteristics.

Studies Highlight Biodiesel's Benefits

Science.gov (United States)

, Colo., July 6, 1998 — Two new studies highlight the benefits of biodiesel in reducing overall air Energy's National Renewable Energy Laboratory (NREL) conducted both studies: An Overview of Biodiesel and Petroleum Diesel Life Cycles and Biodiesel Research Progress, 1992-1997. Biodiesel is a renewable diesel

Structural insights of the ssDNA binding site in the multifunctional endonuclease AtBFN2 from Arabidopsis thaliana.

Directory of Open Access Journals (Sweden)

Tsung-Fu Yu

Full Text Available The multi S1/P1 nuclease AtBFN2 (EC 3.1.30.1 encoded by the Arabidopsis thaliana At1g68290 gene is a glycoprotein that digests RNA, ssDNA, and dsDNA. AtBFN2 depends on three zinc ions for cleaving DNA and RNA at 3'-OH to yield 5'-nucleotides. In addition, AtBFN2's enzymatic activity is strongly glycan dependent. Plant Zn(2+-dependent endonucleases present a unique fold, and belong to the Phospholipase C (PLC/P1 nuclease superfamily. In this work, we present the first complete, ligand-free, AtBFN2 crystal structure, along with sulfate, phosphate and ssDNA co-crystal structures. With these, we were able to provide better insight into the glycan structure and possible enzymatic mechanism. In comparison with other nucleases, the AtBFN2/ligand-free and AtBFN2/PO4 models suggest a similar, previously proposed, catalytic mechanism. Our data also confirm that the phosphate and vanadate can inhibit the enzyme activity by occupying the active site. More importantly, the AtBFN2/A5T structure reveals a novel and conserved secondary binding site, which seems to be important for plant Zn(2+-dependent endonucleases. Based on these findings, we propose a rational ssDNA binding model, in which the ssDNA wraps itself around the protein and the attached surface glycan, in turn, reinforces the binding complex.

How Different Insights from a Variety of Theories Might Help Ethical Decision-Making in Educational Counselling

Science.gov (United States)

Tveit, Anne Dorthe; Sunde, Annikken Louise

2016-01-01

The purpose of this paper is to explore how different insights from a variety of theories might help ethical decision making in educational counselling and highlight the need for reflection. A framework for ethical decision making based on basic features of counselling, namely the interlocutors' practice or "acts", is proposed. There are…

Structural and dynamical properties of the porins OmpF and OmpC: insights from molecular simulations

International Nuclear Information System (INIS)

Kumar, Amit; Hajjar, Eric; Ruggerone, Paolo; Ceccarelli, Matteo

2010-01-01

In this paper we investigate the structural and dynamical properties of the two major porins (OmpF and OmpC) in Escherichia coli, using molecular dynamics (MD) simulations. In particular we characterized the atomic fluctuations, correlated motions, temperature dependence, solvent-accessible cross-sectional area and water dynamics in the key regions of the two channels. Our in-depth analysis allows us to highlight the importance of both the key conserved and substituted residues between OmpF and OmpC. The latter is characterized by a narrower and longer constriction region with respect to OmpF. OmpC also showed a higher stability upon increasing temperature. We then present the results of transport properties by using accelerated MD simulations to probe the diffusion of norfloxacin (a fluoroquinolone antibiotic) through the two porins OmpF/OmpC. Our study constitutes a step forward towards understanding the structure-function relationship of the two porins' channels. This will benefit the research of antibacterials with improved permeation properties and nanopores that aim to use these porins as sensing systems.

Seeking Structural Specificity: Direct Modulation of Pentameric Ligand-Gated Ion Channels by Alcohols and General Anesthetics

Science.gov (United States)

Trudell, James R.; Harris, R. Adron

2014-01-01

Alcohols and other anesthetic agents dramatically alter neurologic function in a wide range of organisms, yet their molecular sites of action remain poorly characterized. Pentameric ligand-gated ion channels, long implicated in important direct effects of alcohol and anesthetic binding, have recently been illuminated in renewed detail thanks to the determination of atomic-resolution structures of several family members from lower organisms. These structures provide valuable models for understanding and developing anesthetic agents and for allosteric modulation in general. This review surveys progress in this field from function to structure and back again, outlining early evidence for relevant modulation of pentameric ligand-gated ion channels and the development of early structural models for ion channel function and modulation. We highlight insights and challenges provided by recent crystal structures and resulting simulations, as well as opportunities for translation of these newly detailed models back to behavior and therapy. PMID:24515646

Crystal Structure of the FGFR4/LY2874455 Complex Reveals Insights into the Pan-FGFR Selectivity of LY2874455.

Science.gov (United States)

Wu, Daichao; Guo, Ming; Philips, Michael A; Qu, Lingzhi; Jiang, Longying; Li, Jun; Chen, Xiaojuan; Chen, Zhuchu; Chen, Lin; Chen, Yongheng

2016-01-01

Aberrant FGFR4 signaling has been documented abundantly in various human cancers. The majority of FGFR inhibitors display significantly reduced potency toward FGFR4 compared to FGFR1-3. However, LY2874455 has similar inhibition potency for FGFR1-4 with IC50 less than 6.4 nM. To date, there is no published crystal structure of LY2874455 in complex with any kinase. To better understand the pan-FGFR selectivity of LY2874455, we have determined the crystal structure of the FGFR4 kinase domain bound to LY2874455 at a resolution of 2.35 Å. LY2874455, a type I inhibitor for FGFR4, binds to the ATP-binding pocket of FGFR4 in a DFG-in active conformation with three hydrogen bonds and a number of van der Waals contacts. After alignment of the kinase domain sequence of 4 FGFRs, and superposition of the ATP binding pocket of 4 FGFRs, our structural analyses reveal that the interactions of LY2874455 to FGFR4 are largely conserved in 4 FGFRs, explaining at least partly, the broad inhibitory activity of LY2874455 toward 4 FGFRs. Consequently, our studies reveal new insights into the pan-FGFR selectivity of LY2874455 and provide a structural basis for developing novel FGFR inhibitors that target FGFR1-4 broadly.

Giga-Voxel Structural Optimization

DEFF Research Database (Denmark)

Aage, Niels; Andreassen, Erik; Lazarov, Boyan Stefanov

2017-01-01

The optimal topology of large structural systems has until now been concerned with the design of individual parts and not that of complete assemblies. However, due to recent advances in numerical algorithms tailored for large scale structural optimization this limitation can now be circumvented....... In this work we present several examplesdisplaying how high resolution topology optimization can be used to obtain new, as well as already known, insight within the field of structural optimization. To demonstrate the capabilities of the developed framework we apply it to the design of the supporting structure...... topology optimization provides new insight and possible weight savings forfuture aircraft designs....

Primed for Discovery: Atomic-Resolution Cryo-EM Structure of a Reovirus Entry Intermediate

Directory of Open Access Journals (Sweden)

Shane D. Trask

2010-06-01

Full Text Available A recently solved structure of the aquareovirus virion (Zhang, X; Jin, L.; Fang, Q; Hui, W.H.; Zhou Z.H. 3.3 Å Cryo-EM Structure of a Nonenveloped Virus Reveals a Priming Mechanism for Cell Entry. Cell 2010, 141, 472-482 [1] provides new insights into the order of entry events, as well as confirming and refining several aspects of the entry mechanism, for aquareovirus and the related orthoreovirus. In particular, the structure provides evidence of a defined order for the progressive proteolytic cleavages of myristoylated penetration protein VP5 that prime the virion for membrane penetration. These observations reinforce the concept that, much like enveloped viruses, nonenveloped virions often undergo priming events that lead to a meta-stable state, preparing the virus for membrane penetration under the appropriate circumstances. In addition, this and other recent studies highlight the increasing power of electron cryomicroscopy to analyze large, geometrically regular structures, such as icosahedral viruses, at atomic resolution.

Theory of mind correlates with clinical insight but not cognitive insight in patients with schizophrenia.

Science.gov (United States)

Zhang, Qi; Li, Xu; Parker, Giverny J; Hong, Xiao-Hong; Wang, Yi; Lui, Simon S Y; Neumann, David L; Cheung, Eric F C; Shum, David H K; Chan, Raymond C K

2016-03-30

Research on the relationship between insight and social cognition, in particular Theory of Mind (ToM), in schizophrenia has yielded mixed findings to date. Very few studies, however, have assessed both clinical insight and cognitive insight when examining their relationships with ToM in schizophrenia. The current study thus investigated the relationship between clinical insight, cognitive insight, and ToM in a sample of 56 patients with schizophrenia and 30 healthy controls. Twenty-seven patients were classified as low in clinical insight according to their scores on the 'insight' item (G12) of the Positive and Negative Syndrome Scale (PANSS). Moreover, cognitive insight and ToM were assessed with the Beck Cognitive Insight Scale (BCIS) and the Yoni task, respectively. The results indicated that patients with poor clinical insight performed worse on tasks of second-order cognitive and affective ToM, while the ToM performance of patients with high clinical insight was equivalent to that of healthy controls. Furthermore, while clinical insight was correlated with ToM and clinical symptoms, cognitive insight did not correlate with clinical insight, ToM, or clinical symptoms. Clinical insight thus appears to be an important factor related to ToM in schizophrenia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Photon science 2010. Highlights and HASYLAB annual report

Energy Technology Data Exchange (ETDEWEB)

NONE

2010-12-15

The following topics are dealt with: Silicon melts in two steps, 3D-imaging at FLASH, femtosecond snapshots of magnetic domains, shooting an ultrafast electronic movie, Thomson scattering at FLASH, delaying sample destruction in FLASH experiments, periodic dislocations in thin PbSe films, formation of 2D crystals on water, advancing of the carbon age in nanoelectronics by rhodium, delocalized excitons in amorphous solids, aquatic - paraffin coated -pentacene transistors for biosensing, putting the squeeze on cuprate superconductors, X-ray audit of DNA replication licensing, structural insights into the regulation of protein kinases, X-ray superradiance and the collective Lamb shift, defect imaging with coherent X-rays, X-radiation damage in biological samples, the light sources DORIS III, FLASH, PETRA III, and the European XFEL, a fast switching mirror unit at FLASH, a high-precision on-line grating spectrometer, a working prototype of the adaptive gain integrating pixel detector, undulators at the PETRA III light source, development of multilayer optics at DESY, longitudinal coherence studies of FLASH radiation. (HSI)

Photon science 2010. Highlights and HASYLAB annual report

International Nuclear Information System (INIS)

2010-12-01

The following topics are dealt with: Silicon melts in two steps, 3D-imaging at FLASH, femtosecond snapshots of magnetic domains, shooting an ultrafast electronic movie, Thomson scattering at FLASH, delaying sample destruction in FLASH experiments, periodic dislocations in thin PbSe films, formation of 2D crystals on water, advancing of the carbon age in nanoelectronics by rhodium, delocalized excitons in amorphous solids, aquatic - paraffin coated -pentacene transistors for biosensing, putting the squeeze on cuprate superconductors, X-ray audit of DNA replication licensing, structural insights into the regulation of protein kinases, X-ray superradiance and the collective Lamb shift, defect imaging with coherent X-rays, X-radiation damage in biological samples, the light sources DORIS III, FLASH, PETRA III, and the European XFEL, a fast switching mirror unit at FLASH, a high-precision on-line grating spectrometer, a working prototype of the adaptive gain integrating pixel detector, undulators at the PETRA III light source, development of multilayer optics at DESY, longitudinal coherence studies of FLASH radiation. (HSI)

Dissection of protein interactomics highlights microRNA synergy.

Science.gov (United States)

Zhu, Wenliang; Zhao, Yilei; Xu, Yingqi; Sun, Yong; Wang, Zhe; Yuan, Wei; Du, Zhimin

2013-01-01

Despite a large amount of microRNAs (miRNAs) have been validated to play crucial roles in human biology and disease, there is little systematic insight into the nature and scale of the potential synergistic interactions executed by miRNAs themselves. Here we established an integrated parameter synergy score to determine miRNA synergy, by combining the two mechanisms for miRNA-miRNA interactions, miRNA-mediated gene co-regulation and functional association between target gene products, into one single parameter. Receiver operating characteristic (ROC) analysis indicated that synergy score accurately identified the gene ontology-defined miRNA synergy (AUC = 0.9415, psynergy, implying poor expectancy of widespread synergy. However, targeting more key genes made two miRNAs more likely to act synergistically. Compared to other miRNAs, miR-21 was a highly exceptional case due to frequent appearance in the top synergistic miRNA pairs. This result highlighted its essential role in coordinating or strengthening physiological and pathological functions of other miRNAs. The synergistic effect of miR-21 and miR-1 were functionally validated for their significant influences on myocardial apoptosis, cardiac hypertrophy and fibrosis. The novel approach established in this study enables easy and effective identification of condition-restricted potent miRNA synergy simply by concentrating the available protein interactomics and miRNA-target interaction data into a single parameter synergy score. Our results may be important for understanding synergistic gene regulation by miRNAs and may have significant implications for miRNA combination therapy of cardiovascular disease.

Capital structure in LNG infrastructures and gas pipelines projects: Empirical evidences and methodological issues

International Nuclear Information System (INIS)

Pierru, Axel; Roussanaly, Simon; Sabathier, Jérôme

2013-01-01

This paper provides new empirical insights on the capital structure of project-financed LNG infrastructures and gas pipeline projects, by using data relating to projects whose financial close occurred between June 2004 and March 2011. Most results are consistent with the basic view of risk-averse funds suppliers. Especially, the projects located in risky countries and larger projects tend to exhibit lower debt ratios and less-concentrated equity ownerships. In addition, regasification projects appear to have a more diluted equity ownership. Methodological issues raised by the financing of these projects are also examined from a capital-budgeting perspective. In particular, the equity residual method, usually used by industrial practitioners to value these projects, should be adjusted. - Highlights: • This paper provides new empirical insights on the capital structure of project-financed LNG and gas pipeline infrastructures. • Most of our results are consistent with the basic view of risk-averse funds suppliers. • Projects located in risky countries exhibit lower debt ratios and less-concentrated equity ownerships. • Larger projects and regasification projects also have less concentrated equity ownerships. • From a capital-budgeting viewpoint, we examine methodological issues raised by the financing of these projects

Structural insights into the interaction of human IgG1 with FcγRI: no direct role of glycans in binding

Energy Technology Data Exchange (ETDEWEB)

Oganesyan, Vaheh, E-mail: oganesyanv@medimmune.com; Mazor, Yariv; Yang, Chunning; Cook, Kimberly E.; Woods, Robert M. [MedImmune LLC, 1 MedImmune Way, Gaithersburg, MD 20878 (United States); Ferguson, Andrew [AstraZeneca Pharmaceuticals, 35 Gatehouse Drive, Mailstop E3, Waltham, MA 02451 (United States); Bowen, Michael A.; Martin, Tom; Zhu, Jie; Wu, Herren; Dall’Acqua, William F., E-mail: oganesyanv@medimmune.com [MedImmune LLC, 1 MedImmune Way, Gaithersburg, MD 20878 (United States)

2015-10-31

In an effort to identify the critical structural features responsible for the high-affinity interaction of IgG1 Fc with FcγRI, the structure of the corresponding complex was solved at a resolution of 2.4 Å. The three-dimensional structure of a human IgG1 Fc fragment bound to wild-type human FcγRI is reported. The structure of the corresponding complex was solved at a resolution of 2.4 Å using molecular replacement; this is the highest resolution achieved for an unmutated FcγRI molecule. This study highlights the critical structural and functional role played by the second extracellular subdomain of FcγRI. It also explains the long-known major energetic contribution of the Fc ‘LLGG’ motif at positions 234–237, and particularly of Leu235, via a ‘lock-and-key’ mechanism. Finally, a previously held belief is corrected and a differing view is offered on the recently proposed direct role of Fc carbohydrates in the corresponding interaction. Structural evidence is provided that such glycan-related effects are strictly indirect.

Simultaneous Determination of Structure and Event Location Using Body and Surface Wave Measurements at a Single Station: Preparation for Mars Data from the InSight Mission

Science.gov (United States)

Panning, M. P.; Banerdt, W. B.; Beucler, E.; Blanchette-Guertin, J. F.; Boese, M.; Clinton, J. F.; Drilleau, M.; James, S. R.; Kawamura, T.; Khan, A.; Lognonne, P. H.; Mocquet, A.; van Driel, M.

2015-12-01

An important challenge for the upcoming InSight mission to Mars, which will deliver a broadband seismic station to Mars along with other geophysical instruments in 2016, is to accurately determine event locations with the use of a single station. Locations are critical for the primary objective of the mission, determining the internal structure of Mars, as well as a secondary objective of measuring the activity of distribution of seismic events. As part of the mission planning process, a variety of techniques have been explored for location of marsquakes and inversion of structure, and preliminary procedures and software are already under development as part of the InSight Mars Quake and Mars Structure Services. One proposed method, involving the use of recordings of multiple-orbit surface waves, has already been tested with synthetic data and Earth recordings. This method has the strength of not requiring an a priori velocity model of Mars for quake location, but will only be practical for larger events. For smaller events where only first orbit surface waves and body waves are observable, other methods are required. In this study, we implement a transdimensional Bayesian inversion approach to simultaneously invert for basic velocity structure and location parameters (epicentral distance and origin time) using only measurements of body wave arrival times and dispersion of first orbit surface waves. The method is tested with synthetic data with expected Mars noise and Earth data for single events and groups of events and evaluated for errors in both location and structural determination, as well as tradeoffs between resolvable parameters and the effect of 3D crustal variations.

Insights into Modern Human Prehistory Using Ancient Genomes.

Science.gov (United States)

Yang, Melinda A; Fu, Qiaomei

2018-03-01

The genetic relationship of past modern humans to today's populations and each other was largely unknown until recently, when advances in ancient DNA sequencing allowed for unprecedented analysis of the genomes of these early people. These ancient genomes reveal new insights into human prehistory not always observed studying present-day populations, including greater details on the genetic diversity, population structure, and gene flow that characterized past human populations, particularly in early Eurasia, as well as increased insight on the relationship between archaic and modern humans. Here, we review genetic studies on ∼45000- to 7500-year-old individuals associated with mainly preagricultural cultures found in Eurasia, the Americas, and Africa. Copyright © 2017 Elsevier Ltd. All rights reserved.

BARC highlights '88

International Nuclear Information System (INIS)

1989-01-01

Highlights of research and development activities of the Bhabha Atomic Research Centre (BARC), Bombay during 1988 are presented in chapters entitled: Physical Sciences, Chemical Sciences, Materials and Materials Sciences, Radioisotopes, Reactors, Fuel Cycle, Radiological Safety and Protection, Electronics and Instrumentation, Engineering Services, and Life Sciences. Main thrust of the R and D activities of BARC is on nuclear power reactor technology and all stages of nuclear fuel cycle. Some activities are also in the frontier areas such as high temperature superconductivity and inertial confinement fusion. (M.G.B.). figs., tabs., coloured ills

A structural insight into the P1S1 binding mode of diaminoethylphosphonic and phosphinic acids, selective inhibitors of alanine aminopeptidases

Energy Technology Data Exchange (ETDEWEB)

Węglarz-Tomczak, Ewelina; Berlicki, Łukasz; Pawełczak, Małgorzata; Nocek, Bogusław; Joachimiak, Andrzej; Mucha, Artur

2016-07-01

N0 -substituted 1,2-diaminoethylphosphonic acids and 1,2-diaminoethylphosphinic dipeptides were explored to unveil the structural context of the unexpected selectivity of these inhibitors of M1 alanine aminopeptidases (APNs) versus M17 leucine aminopeptidase (LAP). The diaminophosphonic acids were obtained via aziridines in an improved synthetic procedure that was further expanded for the phosphinic pseudodipeptide system. The inhibitory activity, measured for three M1 and one M17 metalloaminopeptidases of different sources (bacterial, human and porcine), revealed several potent compounds (e.g., Ki ¼ 65 nM of 1u for HsAPN). Two structures of an M1 representative (APN from Neisseria meningitidis) in complex with N-benzyl-1,2-diaminoethylphosphonic acid and N-cyclohexyl-1,2- diaminoethylphosphonic acid were determined by the X-ray crystallography. The analysis of these structures and the models of the phosphonic acid complexes of the human ortholog provided an insight into the role of the additional amino group and the hydrophobic substituents of the ligands within the S1 active site region.

Insight in bipolar mania: evaluation of its heterogeneity and correlation with clinical symptoms.

Science.gov (United States)

Silva, Rafael de Assis da; Mograbi, Daniel C; Bifano, Jaqueline; Santana, Cristina M T; Cheniaux, Elie

2016-07-15

Studies on insight in bipolar mania are not numerous and usually consider insight as a unitary construct. Evaluate how different facets of insight are affected in bipolar mania and investigate correlations between insight for each specific object in bipolar disorder and manic symptomatology. A group of 165 bipolar patients were followed during a year, with 51 patients having manic episodes according to DSM-IV-TR criteria. Patients underwent a clinical assessment and insight was evaluated through the Insight Scale for Affective Disorders. The study found that insight regarding symptoms is worse than insight of having bipolar disorder, social relationships and self esteem. Moreover, poor global insight (total ISAD) correlates with more severe changes in mood, speech and thought structure, with worse insight about symptoms correlating with the same alterations and also with more severe symptoms of agitation/energy. Although a large sample of bipolar patients was followed up, the final sample composed of patients with at least one manic episode was relatively smaller. Moreover, the fact that the study was performed in a university hospital may have led to selection biases. Results suggest that patients with BD are reasonably capable of identifying that their condition implies consequences but have more impaired awareness of their energy and activity levels. A lower level of insight specifically about symptoms correlates with more severe symptoms of agitation/energy, which suggests a psychomotor nucleus able to impair insight in mania. Copyright © 2016 Elsevier B.V. All rights reserved.

Structural Insights into the HWE Histidine Kinase Family: The Brucella Blue Light-Activated Histidine Kinase Domain.

Science.gov (United States)

Rinaldi, Jimena; Arrar, Mehrnoosh; Sycz, Gabriela; Cerutti, María Laura; Berguer, Paula M; Paris, Gastón; Estrín, Darío Ariel; Martí, Marcelo Adrián; Klinke, Sebastián; Goldbaum, Fernando Alberto

2016-03-27

In response to light, as part of a two-component system, the Brucella blue light-activated histidine kinase (LOV-HK) increases its autophosphorylation, modulating the virulence of this microorganism. The Brucella histidine kinase (HK) domain belongs to the HWE family, for which there is no structural information. The HWE family is exclusively present in proteobacteria and usually coupled to a wide diversity of light sensor domains. This work reports the crystal structure of the Brucella HK domain, which presents two different dimeric assemblies in the asymmetric unit: one similar to the already described canonical parallel homodimers (C) and the other, an antiparallel non-canonical (NC) dimer, each with distinct relative subdomain orientations and dimerization interfaces. Contrary to these crystallographic structures and unlike other HKs, in solution, the Brucella HK domain is monomeric and still active, showing an astonishing instability of the dimeric interface. Despite this instability, using cross-linking experiments, we show that the C dimer is the functionally relevant species. Mutational analysis demonstrates that the autophosphorylation activity occurs in cis. The different relative subdomain orientations observed for the NC and C states highlight the large conformational flexibility of the HK domain. Through the analysis of these alternative conformations by means of molecular dynamics simulations, we also propose a catalytic mechanism for Brucella LOV-HK. Copyright © 2016 Elsevier Ltd. All rights reserved.

Vacuum arc localization in CLIC prototype radio frequency accelerating structures

CERN Document Server

AUTHOR|(CDS)2091976; Koivunen, Visa

2016-04-04

A future linear collider capable of reaching TeV collision energies should support accelerating gradients beyond 100 MV/m. At such high fields, the occurrence of vacuum arcs have to be mitigated through conditioning, during which an accelerating structure’s resilience against breakdowns is slowly increased through repeated radio frequency pulsing. Conditioning is very time and resource consuming, which is why developing more efficient procedures is desirable. At CERN, conditioning related research is conducted at the CLIC high-power X-band test stands. Breakdown localization is an important diagnostic tool of accelerating structure tests. Abnormal position distributions highlight issues in structure design, manufacturing or operation and may consequently help improve these processes. Additionally, positioning can provide insight into the physics of vacuum arcs. In this work, two established positioning methods based on the time-difference-ofarrival of radio frequency waves are extended. The first method i...

Adsorption and structure of water on kaolinite surfaces: possible insight into ice nucleation from grand canonical monte carlo calculations.

Science.gov (United States)

Croteau, T; Bertram, A K; Patey, G N

2008-10-30

Grand canonical Monte Carlo calculations are used to determine water adsorption and structure on defect-free kaolinite surfaces as a function of relative humidity at 235 K. This information is then used to gain insight into ice nucleation on kaolinite surfaces. Results for both the SPC/E and TIP5P-E water models are compared and demonstrate that the Al-surface [(001) plane] and both protonated and unprotonated edges [(100) plane] strongly adsorb at atmospherically relevant relative humidities. Adsorption on the Al-surface exhibits properties of a first-order process with evidence of collective behavior, whereas adsorption on the edges is essentially continuous and appears dominated by strong water lattice interactions. For the protonated and unprotonated edges no structure that matches hexagonal ice is observed. For the Al-surface some of the water molecules formed hexagonal rings. However, the a o lattice parameter for these rings is significantly different from the corresponding constant for hexagonal ice ( Ih). A misfit strain of 14.0% is calculated between the hexagonal pattern of water adsorbed on the Al-surface and the basal plane of ice Ih. Hence, the ring structures that form on the Al-surface are not expected to be good building-blocks for ice nucleation due to the large misfit strain.

The structure of psychological life satisfaction: insights from farmers and a general community sample in Australia

Science.gov (United States)

2012-01-01

Background Psychological life satisfaction is a robust predictor of wellbeing. Public health measures to improve wellbeing would benefit from an understanding of how overall life satisfaction varies as a function of satisfaction with multiple life domains, an area that has been little explored. We examine a sample of drought-affected Australian farmers and a general community sample of Australians to investigate how domain satisfaction combines to form psychological satisfaction. In particular, we introduce a way of statistically testing for the presence of “supra-domains” of satisfaction to propose a novel way of examining the composition of psychological life satisfaction to gain insights for health promotion and policy. Methods Covariance between different perceptions of life domain satisfaction was identified by conducting correlation, regression, and exploratory factor analyses on responses to the Personal Wellbeing Index. Structural equations modelling was then used to (a) validate satisfaction supra-domain constructs emerging from different perceptions of life domain satisfaction, and (b) model relationships between supra-domains and an explicit measure of psychological life satisfaction. Results Perceived satisfaction with eight different life domains loaded onto a single unitary satisfaction construct adequately in each sample. However, in both samples, different domains better loaded onto two separate but correlated constructs (‘supra-domains’): “satisfaction with connectedness” and “satisfaction with efficacy”. Modelling reciprocal pathways between these supra-domains and an explicit measure of psychological life satisfaction revealed that efficacy mediated the link between connectedness and psychological satisfaction. Conclusions If satisfaction with connectedness underlies satisfaction with efficacy (and thus psychological satisfaction), a novel insight for health policy emerges: psychological life satisfaction, a vital part of

The structure of psychological life satisfaction: insights from farmers and a general community sample in Australia

Directory of Open Access Journals (Sweden)

OBrien Léan V

2012-11-01

Full Text Available Abstract Background Psychological life satisfaction is a robust predictor of wellbeing. Public health measures to improve wellbeing would benefit from an understanding of how overall life satisfaction varies as a function of satisfaction with multiple life domains, an area that has been little explored. We examine a sample of drought-affected Australian farmers and a general community sample of Australians to investigate how domain satisfaction combines to form psychological satisfaction. In particular, we introduce a way of statistically testing for the presence of “supra-domains” of satisfaction to propose a novel way of examining the composition of psychological life satisfaction to gain insights for health promotion and policy. Methods Covariance between different perceptions of life domain satisfaction was identified by conducting correlation, regression, and exploratory factor analyses on responses to the Personal Wellbeing Index. Structural equations modelling was then used to (a validate satisfaction supra-domain constructs emerging from different perceptions of life domain satisfaction, and (b model relationships between supra-domains and an explicit measure of psychological life satisfaction. Results Perceived satisfaction with eight different life domains loaded onto a single unitary satisfaction construct adequately in each sample. However, in both samples, different domains better loaded onto two separate but correlated constructs (‘supra-domains’: “satisfaction with connectedness” and “satisfaction with efficacy”. Modelling reciprocal pathways between these supra-domains and an explicit measure of psychological life satisfaction revealed that efficacy mediated the link between connectedness and psychological satisfaction. Conclusions If satisfaction with connectedness underlies satisfaction with efficacy (and thus psychological satisfaction, a novel insight for health policy emerges: psychological life satisfaction

Thermal behavior of spatial structures under solar irradiation

International Nuclear Information System (INIS)

Liu, Hongbo; Liao, Xiangwei; Chen, Zhihua; Zhang, Qian

2015-01-01

The temperature, particularly the non-uniform temperature under solar irradiation, is the main load for large-span steel structures. Due the shortage of in-site temperature test in previous studies, an in-site test was conducted on the large-span steel structures under solar irradiation, which was covered by glass roof and light roof, to gain insight into the temperature distribution of steel members under glass roof or light roof. A numerical method also was presented and verified to forecast the temperature of steel member under glass roof or light roof. Based on the on-site measurement and numerical analyses conducted, the following conclusions were obtained: 1) a remarkable temperature difference exists between the steel member under glass roof and that under light roof, 2) solar irradiation has a significant effect on the temperature distribution and thermal behavior of large-span spatial structures, 3) negative thermal load is the controlling factor for member stress, and the positive thermal load is the controlling factor for nodal displacement. - Highlights: • Temperature was measured for a steel structures under glass roof and light roof. • Temperature simulation method was presented and verified. • The thermal behavior of steel structures under glass or light roof was presented

Insight Is Not in the Problem: Investigating Insight in Problem Solving across Task Types.

Science.gov (United States)

Webb, Margaret E; Little, Daniel R; Cropper, Simon J

2016-01-01

The feeling of insight in problem solving is typically associated with the sudden realization of a solution that appears obviously correct (Kounios et al., 2006). Salvi et al. (2016) found that a solution accompanied with sudden insight is more likely to be correct than a problem solved through conscious and incremental steps. However, Metcalfe (1986) indicated that participants would often present an inelegant but plausible (wrong) answer as correct with a high feeling of warmth (a subjective measure of closeness to solution). This discrepancy may be due to the use of different tasks or due to different methods in the measurement of insight (i.e., using a binary vs. continuous scale). In three experiments, we investigated both findings, using many different problem tasks (e.g., Compound Remote Associates, so-called classic insight problems, and non-insight problems). Participants rated insight-related affect (feelings of Aha-experience, confidence, surprise, impasse, and pleasure) on continuous scales. As expected we found that, for problems designed to elicit insight, correct solutions elicited higher proportions of reported insight in the solution compared to non-insight solutions; further, correct solutions elicited stronger feelings of insight compared to incorrect solutions.

The biological and structural characterization of Mycobacterium tuberculosis UvrA provides novel insights into its mechanism of action.

Science.gov (United States)

Rossi, Franca; Khanduja, Jasbeer Singh; Bortoluzzi, Alessio; Houghton, Joanna; Sander, Peter; Güthlein, Carolin; Davis, Elaine O; Springer, Burkhard; Böttger, Erik C; Relini, Annalisa; Penco, Amanda; Muniyappa, K; Rizzi, Menico

2011-09-01

Mycobacterium tuberculosis is an extremely well adapted intracellular human pathogen that is exposed to multiple DNA damaging chemical assaults originating from the host defence mechanisms. As a consequence, this bacterium is thought to possess highly efficient DNA repair machineries, the nucleotide excision repair (NER) system amongst these. Although NER is of central importance to DNA repair in M. tuberculosis, our understanding of the processes in this species is limited. The conserved UvrABC endonuclease represents the multi-enzymatic core in bacterial NER, where the UvrA ATPase provides the DNA lesion-sensing function. The herein reported genetic analysis demonstrates that M. tuberculosis UvrA is important for the repair of nitrosative and oxidative DNA damage. Moreover, our biochemical and structural characterization of recombinant M. tuberculosis UvrA contributes new insights into its mechanism of action. In particular, the structural investigation reveals an unprecedented conformation of the UvrB-binding domain that we propose to be of functional relevance. Taken together, our data suggest UvrA as a potential target for the development of novel anti-tubercular agents and provide a biochemical framework for the identification of small-molecule inhibitors interfering with the NER activity in M. tuberculosis.

Structural-Functional Features of the Thyrotropin Receptor: A Class A G-Protein-Coupled Receptor at Work.

Science.gov (United States)

Kleinau, Gunnar; Worth, Catherine L; Kreuchwig, Annika; Biebermann, Heike; Marcinkowski, Patrick; Scheerer, Patrick; Krause, Gerd

2017-01-01

The thyroid-stimulating hormone receptor (TSHR) is a member of the glycoprotein hormone receptors, a sub-group of class A G-protein-coupled receptors (GPCRs). TSHR and its endogenous ligand thyrotropin (TSH) are of essential importance for growth and function of the thyroid gland and proper function of the TSH/TSHR system is pivotal for production and release of thyroid hormones. This receptor is also important with respect to pathophysiology, such as autoimmune (including ophthalmopathy) or non-autoimmune thyroid dysfunctions and cancer development. Pharmacological interventions directly targeting the TSHR should provide benefits to disease treatment compared to currently available therapies of dysfunctions associated with the TSHR or the thyroid gland. Upon TSHR activation, the molecular events conveying conformational changes from the extra- to the intracellular side of the cell across the membrane comprise reception, conversion, and amplification of the signal. These steps are highly dependent on structural features of this receptor and its intermolecular interaction partners, e.g., TSH, antibodies, small molecules, G-proteins, or arrestin. For better understanding of signal transduction, pathogenic mechanisms such as autoantibody action and mutational modifications or for developing new pharmacological strategies, it is essential to combine available structural data with functional information to generate homology models of the entire receptor. Although so far these insights are fragmental, in the past few decades essential contributions have been made to investigate in-depth the involved determinants, such as by structure determination via X-ray crystallography. This review summarizes available knowledge (as of December 2016) concerning the TSHR protein structure, associated functional aspects, and based on these insights we suggest several receptor complex models. Moreover, distinct TSHR properties will be highlighted in comparison to other class A GPCRs to

Coated Particle and Deep Burn Fuels Monthly Highlights December 2010

International Nuclear Information System (INIS)

Snead, Lance Lewis; Bell, Gary L.; Besmann, Theodore M.

2011-01-01

During FY 2011 the CP and DB Program will report Highlights on a monthly basis, but will no longer produce Quarterly Progress Reports. Technical details that were previously included in the quarterly reports will be included in the appropriate Milestone Reports that are submitted to FCRD Program Management. These reports will also be uploaded to the Deep Burn website. The Monthly Highlights report for November 2010, ORNL/TM-2010/323, was distributed to program participants on December 9, 2010. The final Quarterly for FY 2010, Deep Burn Program Quarterly Report for July - September 2010, ORNL/TM-2010/301, was announced to program participants and posted to the website on December 28, 2010. This report discusses the following: (1) Thermochemical Data and Model Development - (a) Thermochemical Modeling, (b) Core Design Optimization in the HTR (high temperature helium-cooled reactor) Pebble Bed Design (INL), (c) Radiation Damage and Properties; (2) TRISO (tri-structural isotropic) Development - (a) TRU (transuranic elements) Kernel Development, (b) Coating Development; (3) LWR Fully Ceramic Fuel - (a) FCM Fabrication Development, (b) FCM Irradiation Testing (ORNL); (4) Fuel Performance and Analytical Analysis - Fuel Performance Modeling (ORNL).

Self-stigma and its relationship with insight, demoralization, and clinical outcome among people with schizophrenia spectrum disorders.

Science.gov (United States)

Cavelti, Marialuisa; Kvrgic, Sara; Beck, Eva-Marina; Rüsch, Nicolas; Vauth, Roland

2012-07-01

Paradoxically, insight is associated with positive outcomes, such as better treatment adherence and recovery, and negative outcomes, such as depression, hopelessness, low self-esteem, and quality of life. Self-stigma as a moderating variable can be decisive whether more insight leads to better or worse outcome. On the other hand, self-stigma can act as a mediator between insight and outcomes. We therefore examined self-stigma both as a moderator and a mediator. Insight, self-stigma, demoralization, symptoms, and functioning were assessed among 145 outpatients with schizophrenia spectrum disorders using questionnaires and structured interviews. Structural equation modeling was used to analyze the cross-sectional data. Results confirmed self-stigma as a moderator: The association of insight and demoralization was stronger as self-stigma increased. Self-stigma also partially mediated the positive relationship between insight and demoralization. Moreover, demoralization fully mediated the adverse associations of self-stigma with psychotic symptoms and global functioning. Given the decisive role of self-stigma regarding the detrimental consequences of insight, interventions should address self-stigma, particularly if psychoeducational or other interventions have increased insight. Therapeutic implications for changes of dysfunctional beliefs related to illness and self and change of self-concept in the context of recovery at the level of narrative identity are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

A General Procedure to Assess the Internal Structure of a Noncognitive Measure--The Student360 Insight Program (S360) Time Management Scale. Research Report. ETS RR-11-42

Science.gov (United States)

Ling, Guangming; Rijmen, Frank

2011-01-01

The factorial structure of the Time Management (TM) scale of the Student 360: Insight Program (S360) was evaluated based on a national sample. A general procedure with a variety of methods was introduced and implemented, including the computation of descriptive statistics, exploratory factor analysis (EFA), and confirmatory factor analysis (CFA).…

Structures of minute virus of mice replication initiator protein N-terminal domain: Insights into DNA nicking and origin binding

International Nuclear Information System (INIS)

Tewary, Sunil K.; Liang, Lingfei; Lin, Zihan; Lynn, Annie; Cotmore, Susan F.; Tattersall, Peter; Zhao, Haiyan; Tang, Liang

2015-01-01

Members of the Parvoviridae family all encode a non-structural protein 1 (NS1) that directs replication of single-stranded viral DNA, packages viral DNA into capsid, and serves as a potent transcriptional activator. Here we report the X-ray structure of the minute virus of mice (MVM) NS1 N-terminal domain at 1.45 Å resolution, showing that sites for dsDNA binding, ssDNA binding and cleavage, nuclear localization, and other functions are integrated on a canonical fold of the histidine-hydrophobic-histidine superfamily of nucleases, including elements specific for this Protoparvovirus but distinct from its Bocaparvovirus or Dependoparvovirus orthologs. High resolution structural analysis reveals a nickase active site with an architecture that allows highly versatile metal ligand binding. The structures support a unified mechanism of replication origin recognition for homotelomeric and heterotelomeric parvoviruses, mediated by a basic-residue-rich hairpin and an adjacent helix in the initiator proteins and by tandem tetranucleotide motifs in the replication origins. - Highlights: • The structure of a parvovirus replication initiator protein has been determined; • The structure sheds light on mechanisms of ssDNA binding and cleavage; • The nickase active site is preconfigured for versatile metal ligand binding; • The binding site for the double-stranded replication origin DNA is identified; • A single domain integrates multiple functions in virus replication

Structures of minute virus of mice replication initiator protein N-terminal domain: Insights into DNA nicking and origin binding

Energy Technology Data Exchange (ETDEWEB)

Tewary, Sunil K.; Liang, Lingfei; Lin, Zihan; Lynn, Annie [Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045 (United States); Cotmore, Susan F. [Departments of Laboratory Medicine, Yale University Medical School, New Haven, CT 06510 (United States); Tattersall, Peter [Departments of Laboratory Medicine, Yale University Medical School, New Haven, CT 06510 (United States); Departments of Genetics, Yale University Medical School, New Haven, CT 06510 (United States); Zhao, Haiyan, E-mail: zhaohy@ku.edu [Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045 (United States); Tang, Liang, E-mail: tangl@ku.edu [Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045 (United States)

2015-02-15

Members of the Parvoviridae family all encode a non-structural protein 1 (NS1) that directs replication of single-stranded viral DNA, packages viral DNA into capsid, and serves as a potent transcriptional activator. Here we report the X-ray structure of the minute virus of mice (MVM) NS1 N-terminal domain at 1.45 Å resolution, showing that sites for dsDNA binding, ssDNA binding and cleavage, nuclear localization, and other functions are integrated on a canonical fold of the histidine-hydrophobic-histidine superfamily of nucleases, including elements specific for this Protoparvovirus but distinct from its Bocaparvovirus or Dependoparvovirus orthologs. High resolution structural analysis reveals a nickase active site with an architecture that allows highly versatile metal ligand binding. The structures support a unified mechanism of replication origin recognition for homotelomeric and heterotelomeric parvoviruses, mediated by a basic-residue-rich hairpin and an adjacent helix in the initiator proteins and by tandem tetranucleotide motifs in the replication origins. - Highlights: • The structure of a parvovirus replication initiator protein has been determined; • The structure sheds light on mechanisms of ssDNA binding and cleavage; • The nickase active site is preconfigured for versatile metal ligand binding; • The binding site for the double-stranded replication origin DNA is identified; • A single domain integrates multiple functions in virus replication.

AEB-highlights. January - June 1977

International Nuclear Information System (INIS)

1977-01-01

AEB Highlights is a half-yearly report reflecting the most important recent achievements of the various Research and Technical divisions of the Atomic Energy Board. It appears alternatively in English and Afrikaans [af

IGC highlights 1988

International Nuclear Information System (INIS)

1989-01-01

The major thrust of the research and development (R and D) activities of the Indira Gandhi Centre for Atomic Research (IGCAR), Kalpakkam is oriented towards mastering fast breeder reactor (FBR) technology. Towards this end, its current R and D activities are carried out in a wide variety of disciplines. Highlights of its R and D activities during 1988 are summarised under the headings: Reactor Engineering and Design, Reactor Physics and Safety, Materials Science and Technology, Sodium Chemistry and Technology, Fuel Reprocessing and Electronics and Instrumentation. The text is illustrated with a number of figures, graphs and coloured pictures. (M.G.B.). figs., tabs

Speech perception under adverse conditions: Insights from behavioral, computational and neuroscience research

Directory of Open Access Journals (Sweden)

Sara eGuediche

2014-01-01

Full Text Available Adult speech perception reflects the long-term regularities of the native language, but it is also flexible such that it accommodates and adapts to adverse listening conditions and short-term deviations from native-language norms. The purpose of this review article is to examine how the broader neuroscience literature can inform and advance research efforts in understanding the neural basis of flexibility and adaptive plasticity in speech perception. In particular, we consider several domains of neuroscience research that offer insight into how perception can be adaptively tuned to short-term deviations while also maintaining without affecting the long-term learned regularities for mapping sensory input. We review several literatures to highlight the potential role of learning algorithms that rely on prediction error signals and discuss specific neural structures that are likely to contribute to such learning. Already, a few studies have alluded to a potential role of these mechanisms in adaptive plasticity in speech perception. Better understanding the application and limitations of these algorithms for the challenges of flexible speech perception under adverse conditions promises to inform theoretical models of speech.

Biochemical and Structural Insights into the Preference of Nairoviral DeISGylases for Interferon-Stimulated Gene Product 15 Originating from Certain Species

Energy Technology Data Exchange (ETDEWEB)

Deaton, M. K.; Dzimianski, J. V.; Daczkowski, C. M.; Whitney, G. K.; Mank, N. J.; Parham, M. M.; Bergeron, E.; Pegan, S. D.; Perlman, S.

2016-07-13

The regulation of the interferon type I (IFN-I) response has been shown to rely on posttranslational modification by ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15) to stabilize, or activate, a variety of IFN-I signaling and downstream effector proteins. Unlike Ub, which is almost perfectly conserved among eukaryotes, ISG15 is highly divergent, even among mammals. Since zoonotic viruses rely on viral proteins to recognize, or cleave, ISG15 conjugates in order to evade, or suppress, innate immunity, the impact of ISG15 biodiversity on deISGylating proteases of the ovarian tumor family (vOTU) from nairoviruses was evaluated. The enzymatic activities of vOTUs originating from the Crimean-Congo hemorrhagic fever virus, Erve virus, and Nairobi sheep disease virus were tested against ISG15s from humans, mice, shrews, sheep, bats, and camels, which are mammalian species known to be infected by nairoviruses. This along with investigation of binding by isothermal titration calorimetry illustrated significant differences in the abilities of nairovirus deISGylases to accommodate certain species of ISG15. To investigate the molecular underpinnings of species preferences of these vOTUs, a structure was determined to 2.5 Å for a complex of Erve virus vOTU protease and a mouse ISG15 domain. This structure revealed the molecular basis of Erve virus vOTU's preference for ISG15 over Ub and the first structural insight into a nonhuman ISG15. This structure also revealed key interactions, or lack thereof, surrounding three amino acids that may drive a viral deISgylase to prefer an ISG15 from one species over that of another.

IMPORTANCEViral ovarian tumor domain proteases (vOTUs) are one of the two principal classes of viral proteases observed to reverse posttranslational modification of host proteins by ubiquitin and interferon-stimulated gene product 15 (ISG15), subsequently facilitating downregulation of

Energy Policy. Highlights. 2013 Edition

Energy Technology Data Exchange (ETDEWEB)

NONE

2013-07-01

Energy Policy Highlights showcases recent developments in energy policies among all 28 IEA member countries. Each contribution underscores the changing nature of both global and domestic energy challenges, as well as the commonality of energy concerns among member countries. The policies highlighted in this publication identify an urgent need to reduce greenhouse gas (GHG) emissions as a clear policy objective. Electricity, enhancing energy efficiency and increasing the share of renewables in the energy mix in a cost effective manner are likewise areas of common focus. On the end-user side, increasing public awareness of domestic energy policies through improved transparency and engagement is an important facet of policy support among IEA member countries. The successful implementation of policies and other initiatives benefitted from efforts to inform the public.

Structural Insights into the Methylation of C1402 in 16S rRNA by Methyltransferase RsmI.

Directory of Open Access Journals (Sweden)

Mohan Zhao

Full Text Available RsmI and RsmH are conserved S-Adenosylmethionine (AdoMet-dependent methyltransferases (MTases that are responsible for the 2'-O-methylation and N4-methylation of C1402 in bacterial 16S rRNA, respectively. Methylation of m4Cm1402 plays a role in fine-tuning the shape and functions of the P-site to increase the decoding fidelity, and was recently found to contribute to the virulence of Staphylococcus aureus in host animals. Here we report the 2.20-Å crystal structure of homodimeric RsmI from Escherichia coli in complex with the cofactor AdoMet. RsmI consists of an N-terminal putative RNA-binding domain (NTD and a C-terminal catalytic domain (CTD with a Rossmann-like fold, and belongs to the class III MTase family. AdoMet is specifically bound into a negatively charged deep pocket formed by both domains by making extensive contacts. Structure-based mutagenesis and isothermal titration calorimetry (ITC assays revealed Asp100 and Ala124 are vital for AdoMet-binding. Although the overall fold of RsmI shows remarkable similarities to the characterized MTases involved in vitamin B12 biosynthesis, it exhibits a distinct charge distribution especially around the AdoMet-binding pocket because of different substrate specificity. The docking model of RsmI-AdoMet-RNA ternary complex suggested a possible base-flipping mechanism of the substrate RNA that has been observed in several known RNA MTases. Our structural and biochemical studies provide novel insights into the catalytic mechanism of C1402 methylation in 16S rRNA.

Structural and functional insight into the carbohydrate receptor binding of F4 fimbriae-producing enterotoxigenic Escherichia coli.

Science.gov (United States)

Moonens, Kristof; Van den Broeck, Imke; De Kerpel, Maia; Deboeck, Francine; Raymaekers, Hanne; Remaut, Han; De Greve, Henri

2015-03-27

Enterotoxigenic Escherichia coli (ETEC) strains are important causes of intestinal disease in humans and lead to severe production losses in animal farming. A range of fimbrial adhesins in ETEC strains determines host and tissue tropism. ETEC strains expressing F4 fimbriae are associated with neonatal and post-weaning diarrhea in piglets. Three naturally occurring variants of F4 fimbriae (F4ab, F4ac, and F4ad) exist that differ in the primary sequence of their major adhesive subunit FaeG, and each features a related yet distinct receptor binding profile. Here the x-ray structure of FaeGad bound to lactose provides the first structural insight into the receptor specificity and mode of binding by the poly-adhesive F4 fimbriae. A small D'-D″-α1-α2 subdomain grafted on the immunoglobulin-like core of FaeG hosts the carbohydrate binding site. Two short amino acid stretches Phe(150)-Glu(152) and Val(166)-Glu(170) of FaeGad bind the terminal galactose in the lactosyl unit and provide affinity and specificity to the interaction. A hemagglutination-based assay with E. coli expressing mutant F4ad fimbriae confirmed the elucidated co-complex structure. Interestingly, the crucial D'-α1 loop that borders the FaeGad binding site adopts a different conformation in the two other FaeG variants and hints at a heterogeneous binding pocket among the FaeG serotypes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Structures of Life: The Role of Molecular Structures in Scientists' Work

NARCIS (Netherlands)

Vyas, Dhaval; Kulyk, Olga Anatoliyivna; van der Vet, P.E.; Nijholt, Antinus; van der Veer, Gerrit C.; Jorge, J

2008-01-01

The visual and multidimensional representations like images and graphical structures related to biology provide great insights into understanding the complexities of different organisms. Especially, life scientists use different representations of molecular structures to answer biological questions

Coated Particle Fuel and Deep Burn Program Monthly Highlights May 2011

International Nuclear Information System (INIS)

Snead, Lance Lewis; Bell, Gary L.; Besmann, Theodore M.

2011-01-01

During FY 2011 the CP and DB Program will report Highlights on a monthly basis, but will no longer produce Quarterly Progress Reports. Technical details that were previously included in the quarterly reports will be included in the appropriate Milestone Reports that are submitted to FCRD Program Management. These reports will also be uploaded to the Deep Burn website. The Monthly Highlights report for April 2011, ORNL/TM-2011/125, was distributed to program participants on May 10, 2011. As reported previously, the final Quarterly for FY 2010, Deep Burn Program Quarterly Report for July - September 2010, ORNL/TM-2010/301, was announced to program participants and posted to the website on December 28, 2010. This report discusses the following: (1) Fuel Performance Modeling - Fuel Performance Analysis; (2) Thermochemical Data and Model Development - (a) Thermochemical Modeling, (b) Thermomechanical Modeling, (c) Actinide and Fission Product Transport; (3) TRU (transuranic elements) TRISO (tri-structural isotropic) Development - (a) TRU Kernel Development, (b) Coating Development; and (4) LWR Fully Ceramic Fuel - (a) FCM Fabrication Development, (b) FCM Irradiation Testing.

Coated Particle Fuel and Deep Burn Program Monthly Highlights June 2011

International Nuclear Information System (INIS)

Snead, Lance Lewis; Bell, Gary L.; Besmann, Theodore M.

2011-01-01

During FY 2011 the CP and DB Program will report Highlights on a monthly basis, but will no longer produce Quarterly Progress Reports. Technical details that were previously included in the quarterly reports will be included in the appropriate Milestone Reports that are submitted to FCRD Program Management. These reports will also be uploaded to the Deep Burn website. The Monthly Highlights report for May 2011, ORNL/TM-2011/126, was distributed to program participants on June 9, 2011. As reported previously, the final Quarterly for FY 2010, Deep Burn Program Quarterly Report for July - September 2010, ORNL/TM-2010/301, was announced to program participants and posted to the website on December 28, 2010. This report discusses the following: (1) Fuel Performance Modeling - Fuel Performance Analysis; (2) Thermochemical Data and Model Development - (a) Thermochemical Behavior, (b) Thermomechanical Modeling, (c) Actinide and Fission Product Transport; (3) TRU (transuranic elements) TRISO (tri-structural isotropic) Development - (a) TRU Kernel Development, (b) Coating Development; and (4) LWR Fully Ceramic Fuel - (a) FCM Fabrication Development, (b) FCM Irradiation Testing.

Structural and Functional Studies of H. seropedicae RecA Protein - Insights into the Polymerization of RecA Protein as Nucleoprotein Filament.

Directory of Open Access Journals (Sweden)

Wellington C Leite

Full Text Available The bacterial RecA protein plays a role in the complex system of DNA damage repair. Here, we report the functional and structural characterization of the Herbaspirillum seropedicae RecA protein (HsRecA. HsRecA protein is more efficient at displacing SSB protein from ssDNA than Escherichia coli RecA protein. HsRecA also promotes DNA strand exchange more efficiently. The three dimensional structure of HsRecA-ADP/ATP complex has been solved to 1.7 Å resolution. HsRecA protein contains a small N-terminal domain, a central core ATPase domain and a large C-terminal domain, that are similar to homologous bacterial RecA proteins. Comparative structural analysis showed that the N-terminal polymerization motif of archaeal and eukaryotic RecA family proteins are also present in bacterial RecAs. Reconstruction of electrostatic potential from the hexameric structure of HsRecA-ADP/ATP revealed a high positive charge along the inner side, where ssDNA is bound inside the filament. The properties of this surface may explain the greater capacity of HsRecA protein to bind ssDNA, forming a contiguous nucleoprotein filament, displace SSB and promote DNA exchange relative to EcRecA. Our functional and structural analyses provide insight into the molecular mechanisms of polymerization of bacterial RecA as a helical nucleoprotein filament.

Structural and Functional Studies of H. seropedicae RecA Protein - Insights into the Polymerization of RecA Protein as Nucleoprotein Filament.

Science.gov (United States)

Leite, Wellington C; Galvão, Carolina W; Saab, Sérgio C; Iulek, Jorge; Etto, Rafael M; Steffens, Maria B R; Chitteni-Pattu, Sindhu; Stanage, Tyler; Keck, James L; Cox, Michael M

2016-01-01

The bacterial RecA protein plays a role in the complex system of DNA damage repair. Here, we report the functional and structural characterization of the Herbaspirillum seropedicae RecA protein (HsRecA). HsRecA protein is more efficient at displacing SSB protein from ssDNA than Escherichia coli RecA protein. HsRecA also promotes DNA strand exchange more efficiently. The three dimensional structure of HsRecA-ADP/ATP complex has been solved to 1.7 Å resolution. HsRecA protein contains a small N-terminal domain, a central core ATPase domain and a large C-terminal domain, that are similar to homologous bacterial RecA proteins. Comparative structural analysis showed that the N-terminal polymerization motif of archaeal and eukaryotic RecA family proteins are also present in bacterial RecAs. Reconstruction of electrostatic potential from the hexameric structure of HsRecA-ADP/ATP revealed a high positive charge along the inner side, where ssDNA is bound inside the filament. The properties of this surface may explain the greater capacity of HsRecA protein to bind ssDNA, forming a contiguous nucleoprotein filament, displace SSB and promote DNA exchange relative to EcRecA. Our functional and structural analyses provide insight into the molecular mechanisms of polymerization of bacterial RecA as a helical nucleoprotein filament.

Insights on Forest Structure and Composition from Long-Term Research in the Luquillo Mountains

Directory of Open Access Journals (Sweden)

Tamara Heartsill Scalley

2017-06-01

Full Text Available The science of ecology fundamentally aims to understand species and their relation to the environment. At sites where hurricane disturbance is part of the environmental context, permanent forest plots are critical to understand ecological vegetation dynamics through time. An overview of forest structure and species composition from two of the longest continuously measured tropical forest plots is presented. Long-term measurements, 72 years at the leeward site, and 25 years at windward site, of stem density are similar to initial and pre-hurricane values at both sites. For 10 years post-hurricane Hugo (1989, stem density increased at both sites. Following that increase period, stem density has remained at 1400 to 1600 stems/ha in the leeward site, and at 1200 stems/ha in the windward site. The forests had similar basal area values before hurricane Hugo in 1989, but these sites are following different patterns of basal area accumulation. The leeward forest site continues to accumulate and increase basal area with each successive measurement, currently above 50 m2/ha. The windward forest site maintains its basal area values close to an asymptote of 35 m2/ha. Currently, the most abundant species at both sites is the sierra palm. Ordinations to explore variation in tree species composition through time present the leeward site with a trajectory of directional change, while at the windward site, the composition of species seems to be converging to pre-hurricane conditions. The observed differences in forest structure and composition from sites differently affected by hurricane disturbance provide insight into how particular forest characteristics respond at shorter or longer time scales in relation to previous site conditions and intensity of disturbance effects.

Gas/vapour separation using ultra-microporous metal–organic frameworks: insights into the structure/separation relationship

KAUST Repository

Adil, Karim; Belmabkhout, Youssef; Pillai, Renjith S.; Cadiau, Amandine; Bhatt, Prashant; Assen, Ayalew Hussen Assen; Maurin, Guillaume; Eddaoudi, Mohamed

2017-01-01

The separation of related molecules with similar physical/chemical properties is of prime industrial importance and practically entails a substantial energy penalty, typically necessitating the operation of energy-demanding low temperature fractional distillation techniques. Certainly research efforts, in academia and industry alike, are ongoing with the main aim to develop advanced functional porous materials to be adopted as adsorbents for the effective and energy-efficient separation of various important commodities. Of special interest is the subclass of metal-organic frameworks (MOFs) with pore aperture sizes below 5-7 Å, namely ultra-microporous MOFs, which in contrast to conventional zeolites and activated carbons show great prospects for addressing key challenges in separations pertaining to energy and environmental sustainability, specifically materials for carbon capture and separation of olefin/paraffin, acetylene/ethylene, linear/branched alkanes, xenon/krypton, etc. In this tutorial review we discuss the latest developments in ultra-microporous MOF adsorbents and their use as separating agents via thermodynamics and/or kinetics and molecular sieving. Appreciably, we provide insights into the distinct microscopic mechanisms governing the resultant separation performances, and suggest a plausible correlation between the inherent structural features/topology of MOFs and the associated gas/vapour separation performance.

Gas/vapour separation using ultra-microporous metal–organic frameworks: insights into the structure/separation relationship

KAUST Repository

Adil, Karim

2017-05-30

The separation of related molecules with similar physical/chemical properties is of prime industrial importance and practically entails a substantial energy penalty, typically necessitating the operation of energy-demanding low temperature fractional distillation techniques. Certainly research efforts, in academia and industry alike, are ongoing with the main aim to develop advanced functional porous materials to be adopted as adsorbents for the effective and energy-efficient separation of various important commodities. Of special interest is the subclass of metal-organic frameworks (MOFs) with pore aperture sizes below 5-7 Å, namely ultra-microporous MOFs, which in contrast to conventional zeolites and activated carbons show great prospects for addressing key challenges in separations pertaining to energy and environmental sustainability, specifically materials for carbon capture and separation of olefin/paraffin, acetylene/ethylene, linear/branched alkanes, xenon/krypton, etc. In this tutorial review we discuss the latest developments in ultra-microporous MOF adsorbents and their use as separating agents via thermodynamics and/or kinetics and molecular sieving. Appreciably, we provide insights into the distinct microscopic mechanisms governing the resultant separation performances, and suggest a plausible correlation between the inherent structural features/topology of MOFs and the associated gas/vapour separation performance.

Similar but Different: Dynamic Social Network Analysis Highlights Fundamental Differences between the Fission-Fusion Societies of Two Equid Species, the Onager and Grevy's Zebra.

Directory of Open Access Journals (Sweden)

Daniel I Rubenstein

Full Text Available Understanding why animal societies take on the form that they do has benefited from insights gained by applying social network analysis to patterns of individual associations. Such analyses typically aggregate data over long time periods even though most selective forces that shape sociality have strong temporal elements. By explicitly incorporating the temporal signal in social interaction data we re-examine the network dynamics of the social systems of the evolutionarily closely-related Grevy's zebras and wild asses that show broadly similar social organizations. By identifying dynamic communities, previously hidden differences emerge: Grevy's zebras show more modularity than wild asses and in wild asses most communities consist of solitary individuals; and in Grevy's zebras, lactating females show a greater propensity to switch communities than non-lactating females and males. Both patterns were missed by static network analyses and in general, adding a temporal dimension provides insights into differences associated with the size and persistence of communities as well as the frequency and synchrony of their formation. Dynamic network analysis provides insights into the functional significance of these social differences and highlights the way dynamic community analysis can be applied to other species.

Fluid-structure interaction of submerged structures

International Nuclear Information System (INIS)

Tang, H.T.; Becker, E.B.; Taylor, L.M.

1979-01-01

The purpose of the paper is to investigate fluid-structure interaction (FSI) of submerged structures in a confined fluid-structure system. Our particular interest is the load experienced by a rigid submerged structure subject to a pressure excitation in a fluid domain bounded by a structure which is either flexible or rigid. The objective is to see whether the load experienced by the submerged structure will be influenced by its confinement conditions. This investigation is intended to provide insight into the characteristics of FSI and answer the question as to whether one can obtain FSI independent data by constructing a small scale rigid submerged structure inside a flexible fluid-structure system. (orig.)

Structural insight into catalytic mechanism of PET hydrolase

OpenAIRE

Han, Xu; Liu, Weidong; Huang, Jian-Wen; Ma, Jiantao; Zheng, Yingying; Ko, Tzu-Ping; Xu, Limin; Cheng, Ya-Shan; Chen, Chun-Chi; Guo, Rey-Ting

2017-01-01

PET hydrolase (PETase), which hydrolyzes polyethylene terephthalate (PET) into soluble building blocks, provides an attractive avenue for the bioconversion of plastics. Here we present the structures of a novel PETase from the PET-consuming microbe Ideonella sakaiensis in complex with substrate and product analogs. Through structural analyses, mutagenesis, and activity measurements, a substrate-binding mode is proposed, and several features critical for catalysis are elucidated.

Structural insight into catalytic mechanism of PET hydrolase.

Science.gov (United States)

Han, Xu; Liu, Weidong; Huang, Jian-Wen; Ma, Jiantao; Zheng, Yingying; Ko, Tzu-Ping; Xu, Limin; Cheng, Ya-Shan; Chen, Chun-Chi; Guo, Rey-Ting

2017-12-13

PET hydrolase (PETase), which hydrolyzes polyethylene terephthalate (PET) into soluble building blocks, provides an attractive avenue for the bioconversion of plastics. Here we present the structures of a novel PETase from the PET-consuming microbe Ideonella sakaiensis in complex with substrate and product analogs. Through structural analyses, mutagenesis, and activity measurements, a substrate-binding mode is proposed, and several features critical for catalysis are elucidated.

Crystal Structures of the Tetratricopeptide Repeat Domains of Kinesin Light Chains: Insight into Cargo Recognition Mechanisms

Energy Technology Data Exchange (ETDEWEB)

Zhu, Haizhong; Lee, Han Youl; Tong, Yufeng; Hong, Bum-Soo; Kim, Kyung-Phil; Shen, Yang; Lim, Kyung Jik; Mackenzie, Farrell; Tempel, Wolfram; Park, Hee-Won (SGC-Toronto); (PPCS); (Toronto)

2012-10-23

Kinesin-1 transports various cargos along the axon by interacting with the cargos through its light chain subunit. Kinesin light chains (KLC) utilize its tetratricopeptide repeat (TPR) domain to interact with over 10 different cargos. Despite a high sequence identity between their TPR domains (87%), KLC1 and KLC2 isoforms exhibit differential binding properties towards some cargos. We determined the structures of human KLC1 and KLC2 tetratricopeptide repeat (TPR) domains using X-ray crystallography and investigated the different mechanisms by which KLCs interact with their cargos. Using isothermal titration calorimetry, we attributed the specific interaction between KLC1 and JNK-interacting protein 1 (JIP1) cargo to residue N343 in the fourth TRP repeat. Structurally, the N343 residue is adjacent to other asparagines and lysines, creating a positively charged polar patch within the groove of the TPR domain. Whereas, KLC2 with the corresponding residue S328 did not interact with JIP1. Based on these finding, we propose that N343 of KLC1 can form 'a carboxylate clamp' with its neighboring asparagine to interact with JIP1, similar to that of HSP70/HSP90 organizing protein-1's (HOP1) interaction with heat shock proteins. For the binding of cargos shared by KLC1 and KLC2, we propose a different site located within the groove but not involving N343. We further propose a third binding site on KLC1 which involves a stretch of polar residues along the inter-TPR loops that may form a network of hydrogen bonds to JIP3 and JIP4. Together, these results provide structural insights into possible mechanisms of interaction between KLC TPR domains and various cargo proteins.

Structures of foot and mouth disease virus pentamers: Insight into capsid dissociation and unexpected pentamer reassociation.

Directory of Open Access Journals (Sweden)

Nayab Malik

2017-09-01

Full Text Available Foot-and-mouth disease virus (FMDV belongs to the Aphthovirus genus of the Picornaviridae, a family of small, icosahedral, non-enveloped, single-stranded RNA viruses. It is a highly infectious pathogen and is one of the biggest hindrances to the international trade of animals and animal products. FMDV capsids (which are unstable below pH6.5 release their genome into the host cell from an acidic compartment, such as that of an endosome, and in the process dissociate into pentamers. Whilst other members of the family (enteroviruses have been visualized to form an expanded intermediate capsid with holes from which inner capsid proteins (VP4, N-termini (VP1 and RNA can be released, there has been no visualization of any such state for an aphthovirus, instead the capsid appears to simply dissociate into pentamers. Here we present the 8-Å resolution structure of isolated dissociated pentamers of FMDV, lacking VP4. We also found these pentamers to re-associate into a rigid, icosahedrally symmetric assembly, which enabled their structure to be solved at higher resolution (5.2 Å. In this assembly, the pentamers unexpectedly associate 'inside out', but still with their exposed hydrophobic edges buried. Stabilizing interactions occur between the HI loop of VP2 and its symmetry related partners at the icosahedral 3-fold axes, and between the BC and EF loops of VP3 with the VP2 βB-strand and the CD loop at the 2-fold axes. A relatively extensive but subtle structural rearrangement towards the periphery of the dissociated pentamer compared to that in the mature virus provides insight into the mechanism of dissociation of FMDV and the marked difference in antigenicity.

Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance

KAUST Repository

Phelan, Jody

2016-03-23

Background Combating the spread of drug resistant tuberculosis is a global health priority. Whole genome association studies are being applied to identify genetic determinants of resistance to anti-tuberculosis drugs. Protein structure and interaction modelling are used to understand the functional effects of putative mutations and provide insight into the molecular mechanisms leading to resistance. Methods To investigate the potential utility of these approaches, we analysed the genomes of 144 Mycobacterium tuberculosis clinical isolates from The Special Programme for Research and Training in Tropical Diseases (TDR) collection sourced from 20 countries in four continents. A genome-wide approach was applied to 127 isolates to identify polymorphisms associated with minimum inhibitory concentrations for first-line anti-tuberculosis drugs. In addition, the effect of identified candidate mutations on protein stability and interactions was assessed quantitatively with well-established computational methods. Results The analysis revealed that mutations in the genes rpoB (rifampicin), katG (isoniazid), inhA-promoter (isoniazid), rpsL (streptomycin) and embB (ethambutol) were responsible for the majority of resistance observed. A subset of the mutations identified in rpoB and katG were predicted to affect protein stability. Further, a strong direct correlation was observed between the minimum inhibitory concentration values and the distance of the mutated residues in the three-dimensional structures of rpoB and katG to their respective drugs binding sites. Conclusions Using the TDR resource, we demonstrate the usefulness of whole genome association and convergent evolution approaches to detect known and potentially novel mutations associated with drug resistance. Further, protein structural modelling could provide a means of predicting the impact of polymorphisms on drug efficacy in the absence of phenotypic data. These approaches could ultimately lead to novel resistance

Highlights of nuclear chemistry 1995

International Nuclear Information System (INIS)

1996-07-01

In this report 9 topics of the work of the Nuclear Chemistry Group in 1995 are highlighted. A list of publications and an overview of the international cooperation is given. (orig.). 19 refs., 19 figs., 2 tabs., 2 app

Highlights of nuclear chemistry 1995

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-07-01

In this report 9 topics of the work of the Nuclear Chemistry Group in 1995 are highlighted. A list of publications and an overview of the international cooperation is given. (orig.). 19 refs., 19 figs., 2 tabs., 2 app.

LAMA Preconference and Program Highlights.

Science.gov (United States)

Library Administration & Management, 1988

1988-01-01

Highlights events of the Library Administration and Management Association 1988 conference, including presentation of awards and programs on: (1) transfer of training; (2) hiring; (3) mentoring; (4) acquisitions automation; (5) library building consultation; and (6) managing shared systems. (MES)

Influence of heme environment structure on dioxygen affinity for the dual function Amphitrite ornata hemoglobin/dehaloperoxidase. Insights into the evolutional structure-function adaptations

Energy Technology Data Exchange (ETDEWEB)

Sun, Shengfang; Sono, Masanori; Wang, Chunxue; Du, Jing; Lebioda, Lukasz; Dawson, John H. [SC

2014-05-15

Sea worm, Amphitrite ornata, has evolved its globin (an O₂ carrier) also to serves as a dehaloperoxidase (DHP) to detoxify haloaromatic pollutants generated by competing species. A previous mutagenesis study by our groups on both DHP and sperm whale myoglobin (SW Mb) revealed some structural factors that influence the dehaloperoxidase activities (significantly lower for Mb) of both proteins. Using an isocyanide/O₂ partition constant measurement method in this study, we have examined the effects of these structural factors on the O₂ equilibrium constants (K_O2) of DHP, SW Mb, and their mutants. A clear trend of decreasing O₂ affinity and increasing catalytic activity along with the increase in the distal His N^ε–heme iron distance is observed. An H93K/T95H Mb double mutant mimicking the DHP proximal His positioning exhibited markedly enhanced O₂ affinity, confirming the essential effect of proximal His rotation on the globin function of DHP. For DHP, the L100F, T56G and M86E variants showed the effects of distal volume, distal His flexibility and proximal electronic push, respectively, on the O₂ affinity. This study provides insights into how DHP has evolved its heme environment to gain significantly enhanced peroxidase capability without compromising its primary function as an O₂ carrier.

Photon science 2008. Highlights and HASYLAB annual report

Energy Technology Data Exchange (ETDEWEB)

NONE

2009-07-01

The following topics are dealt with: A femtosecond X-ray/optical cross-correlator, ultrafast movies of nanoscale dynamics, massively parallel X-ray holography, clusters in super intense FLASH pulses, a chemical driven insulator-metal transition, tough silk, insight into the reactivity, the many faces of molecular assemblies in electronic devices, cooperative or self-centred electrons, visualizing a lost painting by Vincent van Gogh, metal contaminations in small water fleas, small-angle X-ray scattering as complement of crystallography, mapping the protein world, how metallic iron eats its own native oxide, hard X-ray diffraction imaging, the centre for free-electron laser science CFEL, the Hamburg EMBL unit, the Max-Planck unit for structural molecular biology, the GKSS Research Centre Geesthacht, the GFZ Helmholtz Centre Potsdam, the University of Hamburg on the DESY site, the light sources DORIS III, FLASH, PETRA III, and the European XFEL project, beamline enhancements and photon diagnostics at FLASH, undulator development for the European XFEL, special X-ray monochromators for PETRA III, high-power photon slits and shutters, the generation of brilliant beams, undulator demagnetization in LINAC based FELs, the control of experiments, advanced detection. (HSI)

Photon science 2008. Highlights and HASYLAB annual report

International Nuclear Information System (INIS)

2009-01-01

The following topics are dealt with: A femtosecond X-ray/optical cross-correlator, ultrafast movies of nanoscale dynamics, massively parallel X-ray holography, clusters in super intense FLASH pulses, a chemical driven insulator-metal transition, tough silk, insight into the reactivity, the many faces of molecular assemblies in electronic devices, cooperative or self-centred electrons, visualizing a lost painting by Vincent van Gogh, metal contaminations in small water fleas, small-angle X-ray scattering as complement of crystallography, mapping the protein world, how metallic iron eats its own native oxide, hard X-ray diffraction imaging, the centre for free-electron laser science CFEL, the Hamburg EMBL unit, the Max-Planck unit for structural molecular biology, the GKSS Research Centre Geesthacht, the GFZ Helmholtz Centre Potsdam, the University of Hamburg on the DESY site, the light sources DORIS III, FLASH, PETRA III, and the European XFEL project, beamline enhancements and photon diagnostics at FLASH, undulator development for the European XFEL, special X-ray monochromators for PETRA III, high-power photon slits and shutters, the generation of brilliant beams, undulator demagnetization in LINAC based FELs, the control of experiments, advanced detection. (HSI)

Tracking coherent structures in massively-separated and turbulent flows

Science.gov (United States)

Rockwood, Matthew; Huang, Yangzi; Green, Melissa

2018-01-01

Coherent vortex structures are tracked in simulations of massively-separated and turbulent flows. Topological Lagrangian saddle points are found using intersections of the positive and negative finite-time Lyapunov exponent ridges, and these points are then followed in order to track individual coherent structure motion both in a complex interacting three-dimensional flow (turbulent channel) and during vortex formation (two-dimensional bluff body shedding). For a simulation of wall-bounded turbulence in a channel flow, tracking Lagrangian saddles shows that the average structure convection speed exhibits a similar trend as a previously published result based on velocity and pressure correlations, giving validity to the method. When this tracking method is applied in a study of a circular cylinder in cross-flow it shows that Lagrangian saddles rapidly accelerate away from the cylinder surface as the vortex sheds. This saddle behavior is compared with the time-resolved static pressure distribution on the circular cylinder, yielding locations on a cylinder surface where common sensors could detect this phenomenon, which is not available from force measurements or vortex circulation calculations. The current method of tracking coherent structures yields insight into the behavior of the coherent structures in both of the diverse flows presented, highlighting the breadth of its potential application.

Functional and structural insights revealed by molecular dynamics simulations of an essential RNA editing ligase in Trypanosoma brucei.

Directory of Open Access Journals (Sweden)

Rommie E Amaro

2007-11-01

Full Text Available RNA editing ligase 1 (TbREL1 is required for the survival of both the insect and bloodstream forms of Trypanosoma brucei, the parasite responsible for the devastating tropical disease African sleeping sickness. The type of RNA editing that TbREL1 is involved in is unique to the trypanosomes, and no close human homolog is known to exist. In addition, the high-resolution crystal structure revealed several unique features of the active site, making this enzyme a promising target for structure-based drug design. In this work, two 20 ns atomistic molecular dynamics (MD simulations are employed to investigate the dynamics of TbREL1, both with and without the ATP substrate present. The flexibility of the active site, dynamics of conserved residues and crystallized water molecules, and the interactions between TbREL1 and the ATP substrate are investigated and discussed in the context of TbREL1's function. Differences in local and global motion upon ATP binding suggest that two peripheral loops, unique to the trypanosomes, may be involved in interdomain signaling events. Notably, a significant structural rearrangement of the enzyme's active site occurs during the apo simulations, opening an additional cavity adjacent to the ATP binding site that could be exploited in the development of effective inhibitors directed against this protozoan parasite. Finally, ensemble averaged electrostatics calculations over the MD simulations reveal a novel putative RNA binding site, a discovery that has previously eluded scientists. Ultimately, we use the insights gained through the MD simulations to make several predictions and recommendations, which we anticipate will help direct future experimental studies and structure-based drug discovery efforts against this vital enzyme.

Narrative insight in psychosis: The relationship with spiritual and religious explanatory frameworks.

Science.gov (United States)

Marriott, Michael R; Thompson, Andrew R; Cockshutt, Graham; Rowse, Georgina

2018-03-25

When considering psychosis, the concept of narrative insight has been offered as an alternative to clinical insight in determining individuals' responses to their difficulties, as it allows for a more holistic and person-centred framework to be embraced within professional practice. This study aims to explore the validity of the narrative insight construct within a group of people who have experienced psychosis. Inductive qualitative methods were used to explore how eight participants utilized spiritual or religious explanatory frameworks for their experiences of psychosis and to consider these in relation to the construct of narrative insight. Semi-structured interviews were undertaken with individuals who identified themselves as interested in spiritual or religious ideas and whose self-reported experiences which were identified as akin to psychosis by experienced academic clinicians. Transcriptions from these interviews were subject to interpretative phenomenological analysis within a broader research question; a selection of themes and data from the resultant phenomenological structure are explored here for their relevance to narrative insight. Participants discussed spiritual and biological explanations for their experiences and were able to hold alternative potential explanations alongside each other. They were reflective regarding the origins of their explanations and would describe a process of testing and proof in relation to them. These findings suggest that the narrative insight construct has the potential to be a valid approach to understanding experiences of psychosis, and challenge the dominance of the clinical insight construct within clinical practice. Clinicians should value the explanatory framework for experiences which are provided by individuals experiencing psychosis, and encourage them to develop a framework which is coherent to their own world view rather than predominantly pursuing a biomedical explanation. Assessments of psychosis should

Operating experience insights supporting ageing assessments

International Nuclear Information System (INIS)

Nitoi, M.

2013-01-01

Be effective in ageing management means looking at the right aspects, with the right techniques, and one of the most effective tool which could be used for that purpose is the analysis of operating experience. The paper has as objective to perform a review of available operating experience, with the aim to provide a better picture about the impact of ageing effects. The IAEA International Reporting System and NRC Licensee Event Reports were chosen as reference databases, both databases being internationally recognized as important sources of information about events occurrences in the nuclear power plants. The ageing related events identified in the selected time window were analyzed in detail, and the contributions of each major degradation mechanisms that have induced the ageing related events (specific to each defined group of components) was represented and discussed. The paper demonstrates the possibility to use operating experience insights in highlighting the ageing effects. (authors)

Single-crystal structure determination of hydrous minerals and insights into a wet deep lower mantle

Science.gov (United States)

Zhang, L.; Yuan, H.; Meng, Y.; Popov, D.

2017-12-01

Water enters the Earth's interior through hydrated subducting slabs. How deep within the lower mantle (670-2900 km depth) can water be transported down and stored depends upon the availability of hydrous phases that is thermodynamically stable under the high P-T conditions and have a sufficiently high density to sink through the lower mantle. Phase H [MgSiH2O4] (1) and the δ-AlOOH (2) form solid solutions that are stable in the deep lower mantle (3), but the solid solution phase is 10% lighter than the corresponding lower mantle. Recent experimental discoveries of the pyrite (Py) structured FeO2 and FeOOH (4-6) suggest that these Fe-enriched phases can be transported to the deepest lower mantle owing to their high density. We have further discovered a very dense hydrous phase in (Fe,Al)OOH with a previously unknown hexagonal symmetry and this phase is stable relative to the Py-phase under extreme high P-T conditions in the deep lower mantle. Through in situ multigrain analysis (7) and single-crystal structure determination of the hydrous minerals at P-Tconditions of the deep lower mantle, we can obtain detailed structure information of the hydrous phases and therefore provide insights into the hydration mechanism in the deep lower mantle. These highly stable hydrous minerals extend the water cycle at least to the depth of 2900 km. 1. M. Nishi et al., Nature Geoscience 7, 224-227 (2014). 2. E. Ohtani, K. Litasov, A. Suzuki, T. Kondo, Geophysical Research Letters 28, 3991-3993 (2001). 3. I. Ohira et al., Earth and Planetary Science Letters 401, 12-17 (2014). 4. Q. Hu et al., Proceedings of the National Academy of Sciences of the United States of America 114, 1498-1501 (2017). 5. M. Nishi, Y. Kuwayama, J. Tsuchiya, T. Tsuchiya, Nature 547, 205-208 (2017). 6. Q. Hu et al., Nature 534, 241-244 (2016). 7. L. Zhang et al., American Mineralogist 101, 231-234 (2016).

The structure of cytomegalovirus immune modulator UL141 highlights structural Ig-fold versatility for receptor binding

Energy Technology Data Exchange (ETDEWEB)

Nemčovičová, Ivana [La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037 (United States); Slovak Academy of Sciences, Dúbravská cesta 9, SK 84505 Bratislava (Slovakia); Zajonc, Dirk M., E-mail: dzajonc@liai.org [La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037 (United States)

2014-03-01

The crystal structure of Human cytomegalovirus immune modulator UL141 was solved at 3.25 Å resolution. Here, a detailed analysis of its intimate dimerization interface and the biophysical properties of its receptor (TRAIL-R2 and CD155) binding interactions are presented. Natural killer (NK) cells are critical components of the innate immune system as they rapidly detect and destroy infected cells. To avoid immune recognition and to allow long-term persistence in the host, Human cytomegalovirus (HCMV) has evolved a number of genes to evade or inhibit immune effector pathways. In particular, UL141 can inhibit cell-surface expression of both the NK cell-activating ligand CD155 as well as the TRAIL death receptors (TRAIL-R1 and TRAIL-R2). The crystal structure of unliganded HCMV UL141 refined to 3.25 Å resolution allowed analysis of its head-to-tail dimerization interface. A ‘dimerization-deficient’ mutant of UL141 (ddUL141) was further designed, which retained the ability to bind to TRAIL-R2 or CD155 while losing the ability to cross-link two receptor monomers. Structural comparison of unliganded UL141 with UL141 bound to TRAIL-R2 further identified a mobile loop that makes intimate contacts with TRAIL-R2 upon receptor engagement. Superposition of the Ig-like domain of UL141 on the CD155 ligand T-cell immunoreceptor with Ig and ITIM domains (TIGIT) revealed that UL141 can potentially engage CD155 similar to TIGIT by using the C′C′′ and GF loops. Further mutations in the TIGIT binding site of CD155 (Q63R and F128R) abrogated UL141 binding, suggesting that the Ig-like domain of UL141 is a viral mimic of TIGIT, as it targets the same binding site on CD155 using similar ‘lock-and-key’ interactions. Sequence alignment of the UL141 gene and its orthologues also showed conservation in this highly hydrophobic (L/A)X{sub 6}G ‘lock’ motif for CD155 binding as well as conservation of the TRAIL-R2 binding patches, suggesting that these host�

The structure of cytomegalovirus immune modulator UL141 highlights structural Ig-fold versatility for receptor binding

International Nuclear Information System (INIS)

Nemčovičová, Ivana; Zajonc, Dirk M.

2014-01-01

The crystal structure of Human cytomegalovirus immune modulator UL141 was solved at 3.25 Å resolution. Here, a detailed analysis of its intimate dimerization interface and the biophysical properties of its receptor (TRAIL-R2 and CD155) binding interactions are presented. Natural killer (NK) cells are critical components of the innate immune system as they rapidly detect and destroy infected cells. To avoid immune recognition and to allow long-term persistence in the host, Human cytomegalovirus (HCMV) has evolved a number of genes to evade or inhibit immune effector pathways. In particular, UL141 can inhibit cell-surface expression of both the NK cell-activating ligand CD155 as well as the TRAIL death receptors (TRAIL-R1 and TRAIL-R2). The crystal structure of unliganded HCMV UL141 refined to 3.25 Å resolution allowed analysis of its head-to-tail dimerization interface. A ‘dimerization-deficient’ mutant of UL141 (ddUL141) was further designed, which retained the ability to bind to TRAIL-R2 or CD155 while losing the ability to cross-link two receptor monomers. Structural comparison of unliganded UL141 with UL141 bound to TRAIL-R2 further identified a mobile loop that makes intimate contacts with TRAIL-R2 upon receptor engagement. Superposition of the Ig-like domain of UL141 on the CD155 ligand T-cell immunoreceptor with Ig and ITIM domains (TIGIT) revealed that UL141 can potentially engage CD155 similar to TIGIT by using the C′C′′ and GF loops. Further mutations in the TIGIT binding site of CD155 (Q63R and F128R) abrogated UL141 binding, suggesting that the Ig-like domain of UL141 is a viral mimic of TIGIT, as it targets the same binding site on CD155 using similar ‘lock-and-key’ interactions. Sequence alignment of the UL141 gene and its orthologues also showed conservation in this highly hydrophobic (L/A)X 6 G ‘lock’ motif for CD155 binding as well as conservation of the TRAIL-R2 binding patches, suggesting that these host–receptor interactions

STRUCTURAL INSIGHTS INTO SUBSTRATE BINDING AND STEREOSELECTIVITY OF GIARDIA FRUCTOSE-1,6-BISPHOSPHATE ALDOLASE*

Science.gov (United States)

Galkin, Andrey; Li, Zhimin; Li, Ling; Kulakova, Liudmila; Pal, Lipika R.; Dunaway-Mariano, Debra; Herzberg, Osnat

2009-01-01

does not cleave TBP. The active sites of FBPAs contain an aspartate residue equivalent to Asp255 of glFBPA, whereas tagatose-1,6-bisphosphate aldolase contains an alanine in this position. We and others hypothesized that this aspartic acid is a likely determinant of FBP vs. TBP specificity. Replacement of Asp255 by an alanine resulted in an enzyme that possesses double specificity, now cleaving TBP (albeit with low efficacy; kcat/Km = 80 M−1s−1) while maintaining activity towards FBP at 50-fold lower catalytic efficacy compared with the wild type FBPA. The collection of structures and sequence analyses highlighted additional residues that may be involved in substrate discrimination. PMID:19236002

Impaired insight into illness and cognitive insight in schizophrenia spectrum disorders: Resting state functional connectivity

Science.gov (United States)

Gerretsen, Philip; Menon, Mahesh; Mamo, David C.; Fervaha, Gagan; Remington, Gary; Pollock, Bruce G.; Graff-Guerrero, Ariel

2015-01-01

Background Impaired insight into illness (clinical insight) in schizophrenia has negative effects on treatment adherence and clinical outcomes. Schizophrenia is described as a disorder of disrupted brain connectivity. In line with this concept, resting state networks (RSNs) appear differentially affected in persons with schizophrenia. Therefore, impaired clinical, or the related construct of cognitive insight (which posits that impaired clinical insight is a function of metacognitive deficits), may reflect alterations in RSN functional connectivity (fc). Based on our previous research, which showed that impaired insight into illness was associated with increased left hemisphere volume relative to right, we hypothesized that impaired clinical insight would be associated with increased connectivity in the DMN with specific left hemisphere brain regions. Methods Resting state MRI scans were acquired for participants with schizophrenia or schizoaffective disorder (n = 20). Seed-to-voxel and ROI-to-ROI fc analyses were performed using the CONN-fMRI fc toolbox v13 for established RSNs. Clinical and cognitive insight were measured with the Schedule for the Assessment of Insight—Expanded Version and Beck Cognitive Insight Scale, respectively, and included as the regressors in fc analyses. Results As hypothesized, impaired clinical insight was associated with increased connectivity in the default mode network (DMN) with the left angular gyrus, and also in the self-referential network (SRN) with the left insula. Cognitive insight was associated with increased connectivity in the dorsal attention network (DAN) with the right inferior frontal cortex (IFC) and left anterior cingulate cortex (ACC). Conclusion Increased connectivity in DMN and SRN with the left angular gyrus and insula, respectively, may represent neural correlates of impaired clinical insight in schizophrenia spectrum disorders, and is consistent with the literature attributing impaired insight to left

Cell Secretion: Current Structural and Biochemical Insights

Directory of Open Access Journals (Sweden)

Saurabh Trikha

2010-01-01

Full Text Available Essential physiological functions in eukaryotic cells, such as release of hormones and digestive enzymes, neurotransmission, and intercellular signaling, are all achieved by cell secretion. In regulated (calcium-dependent secretion, membrane-bound secretory vesicles dock and transiently fuse with specialized, permanent, plasma membrane structures, called porosomes or fusion pores. Porosomes are supramolecular, cup-shaped lipoprotein structures at the cell plasma membrane that mediate and control the release of vesicle cargo to the outside of the cell. The sizes of porosomes range from 150nm in diameter in acinar cells of the exocrine pancreas to 12nm in neurons. In recent years, significant progress has been made in our understanding of the porosome and the cellular activities required for cell secretion, such as membrane fusion and swelling of secretory vesicles. The discovery of the porosome complex and the molecular mechanism of cell secretion are summarized in this article.

Proofs that Develop Insight

Science.gov (United States)

Weber, Keith

2010-01-01

Many mathematics educators have noted that mathematicians do not only read proofs to gain conviction but also to obtain insight. The goal of this article is to discuss what this insight is from mathematicians' perspective. Based on interviews with nine research-active mathematicians, two sources of insight are discussed. The first is reading a…

New insights into innate immune control of systemic candidiasis

Science.gov (United States)

Lionakis, Michail S.

2014-01-01

Systemic infection caused by Candida species is the fourth leading cause of nosocomial bloodstream infection in modern hospitals and carries high morbidity and mortality despite antifungal therapy. A recent surge of immunological studies in the mouse models of systemic candidiasis and the parallel discovery and phenotypic characterization of inherited genetic disorders in antifungal immune factors that are associated with enhanced susceptibility or resistance to the infection have provided new insights into the cellular and molecular basis of protective innate immune responses against Candida. In this review, the new developments in our understanding of how the mammalian immune system responds to systemic Candida challenge are synthesized and important future research directions are highlighted. PMID:25023483

Top Mysteries of the Mind: Insights From the Default Space Model of Consciousness

Directory of Open Access Journals (Sweden)

Ravinder Jerath

2018-04-01

Full Text Available Aside from the nature of consciousness itself, there are still many unsolved problems in the neurosciences. Despite the vast and quickly growing body of work in this field, we still find ourselves perplexed at seemingly simple qualities of our mental being such as why we need to sleep. The neurosciences are at least beginning to take a hold on these mysteries and are working toward solving them. We hold a perspective that metastable consciousness models, specifically the Default Space Model (DSM, provide insights into these mysteries. In this perspective article, we explore some of these curious questions in order to elucidate the interesting points they bring up. The DSM is a dynamic, global theory of consciousness that involves the maintenance of an internal, 3D simulation of the external, physical world which is the foundation and structure of consciousness. This space is created and filled by multiple frequencies of membrane potential oscillations throughout the brain and body which are organized, synchronized and harmonized by the thalamus. The veracity of the DSM is highlighted here in its ability to further understanding of some of the most puzzling problems in neuroscience.

Highlighting Entanglement of Cultures via Ranking of Multilingual Wikipedia Articles

Science.gov (United States)

Eom, Young-Ho; Shepelyansky, Dima L.

2013-01-01

How different cultures evaluate a person? Is an important person in one culture is also important in the other culture? We address these questions via ranking of multilingual Wikipedia articles. With three ranking algorithms based on network structure of Wikipedia, we assign ranking to all articles in 9 multilingual editions of Wikipedia and investigate general ranking structure of PageRank, CheiRank and 2DRank. In particular, we focus on articles related to persons, identify top 30 persons for each rank among different editions and analyze distinctions of their distributions over activity fields such as politics, art, science, religion, sport for each edition. We find that local heroes are dominant but also global heroes exist and create an effective network representing entanglement of cultures. The Google matrix analysis of network of cultures shows signs of the Zipf law distribution. This approach allows to examine diversity and shared characteristics of knowledge organization between cultures. The developed computational, data driven approach highlights cultural interconnections in a new perspective. Dated: June 26, 2013 PMID:24098338

Highlighting entanglement of cultures via ranking of multilingual Wikipedia articles.

Directory of Open Access Journals (Sweden)

Young-Ho Eom

Full Text Available How different cultures evaluate a person? Is an important person in one culture is also important in the other culture? We address these questions via ranking of multilingual Wikipedia articles. With three ranking algorithms based on network structure of Wikipedia, we assign ranking to all articles in 9 multilingual editions of Wikipedia and investigate general ranking structure of PageRank, CheiRank and 2DRank. In particular, we focus on articles related to persons, identify top 30 persons for each rank among different editions and analyze distinctions of their distributions over activity fields such as politics, art, science, religion, sport for each edition. We find that local heroes are dominant but also global heroes exist and create an effective network representing entanglement of cultures. The Google matrix analysis of network of cultures shows signs of the Zipf law distribution. This approach allows to examine diversity and shared characteristics of knowledge organization between cultures. The developed computational, data driven approach highlights cultural interconnections in a new perspective. Dated: June 26, 2013.

Structural integrity for DEMO: An opportunity to close the gap from materials science to engineering needs

Energy Technology Data Exchange (ETDEWEB)

Porton, M., E-mail: michael.porton@ccfe.ac.uk [CCFE, Culham Science Centre, Abingdon, Oxon OX14 3DB (United Kingdom); Wynne, B.P. [CCFE, Culham Science Centre, Abingdon, Oxon OX14 3DB (United Kingdom); University of Sheffield, Sheffield, South Yorkshire S10 2TN (United Kingdom); Bamber, R.; Hardie, C.D.; Kalsey, M. [CCFE, Culham Science Centre, Abingdon, Oxon OX14 3DB (United Kingdom)

2016-11-01

Highlights: • Key shortfalls in the current approaches to verification of structural integrity are outlined. • Case studies for high integrity applications in other demanding environments are examined. • Relevant lessons are drawn from fission and space for the design stage and through service life. • Future efforts are suggested to align materials and engineering for DEMO structural integrity. - Abstract: It is clear that fusion demonstration devices offer unique challenges due to the myriad, interacting material degradation effects and the numerous, conflicting requirements that must be addressed in order for in-vessel components to deliver satisfactory performance over the required lifetime. The link between mechanical engineering and materials science is pivotal to assure the timely realisation and exploitation of successful fusion power. A key aspect of this link is the verification of structural integrity, achieved at the design stage via structural design criteria against which designs are judged to be sufficiently resilient (or not) to failure, for a given set of loading conditions and desired lifetime. As various demonstration power plant designs progress through their current conceptual design phases, this paper seeks to highlight key shortfalls in this vital link between engineering needs and materials science, offering a perspective on where future attention can be prioritised to maximise impact. Firstly, issues in applying existing structural design criteria to demonstration power plant designs are identified. Whilst fusion offers particular challenges, there are significant insights to be gained from attempts to address such issues for high performance, high integrity applications in other demanding environments. Therefore case studies from beyond fusion are discussed. These offer examples where similar shortfalls have been successfully addressed, via approaches at the design stage and through service lifetime in order to deliver significant

Cyanuric acid hydrolase from Azorhizobium caulinodans ORS 571: crystal structure and insights into a new class of Ser-Lys dyad proteins.

Directory of Open Access Journals (Sweden)

Seunghee Cho

Full Text Available Cyanuric acid hydrolase (CAH catalyzes the hydrolytic ring-opening of cyanuric acid (2,4,6-trihydroxy-1,3,5-triazine, an intermediate in s-triazine bacterial degradation and a by-product from disinfection with trichloroisocyanuric acid. In the present study, an X-ray crystal structure of the CAH-barbituric acid inhibitor complex from Azorhizobium caulinodans ORS 571 has been determined at 2.7 Å resolution. The CAH protein fold consists of three structurally homologous domains forming a β-barrel-like structure with external α-helices that result in a three-fold symmetry, a dominant feature of the structure and active site that mirrors the three-fold symmetrical shape of the substrate cyanuric acid. The active site structure of CAH is similar to that of the recently determined AtzD with three pairs of active site Ser-Lys dyads. In order to determine the role of each Ser-Lys dyad in catalysis, a mutational study using a highly sensitive, enzyme-coupled assay was conducted. The 10⁹-fold loss of activity by the S226A mutant was at least ten times lower than that of the S79A and S333A mutants. In addition, bioinformatics analysis revealed the Ser226/Lys156 dyad as the only absolutely conserved dyad in the CAH/barbiturase family. These data suggest that Lys156 activates the Ser226 nucleophile which can then attack the substrate carbonyl. Our combination of structural, mutational, and bioinformatics analyses differentiates this study and provides experimental data for mechanistic insights into this unique protein family.

Insight in schizophrenia: a review.

Science.gov (United States)

Dam, Jesper

2006-01-01

The issue of insight in schizophrenia must be assumed to be one of the most important aspects of the clinical examination. Comprehensive studies have shown that between 50% and 80% of all patients suffering from schizophrenia do not believe that they have a disorder. In recent years, poor insight in schizophrenia has been the subject of increasing interest, as manifested in a number of studies discussed in the present review. Some of these studies focus on insight correlated to various parameters such as psychopathology, neuropsychology, clinical relevance and compliance. Other studies refer to more theoretical implications, among these the issue of defining the concept of insight: whether insight can be seen as a "primary" phenomenon in schizophrenia, and whether insight may be graduated, dimensioned or increased. Several authors have developed rating scales in an attempt to obtain a measure for the degree or dimension of insight. Here, the range of parameters employed gives an excellent impression of the complexity of the concept of insight. In the concluding discussion, a phenomenological aspect is brought in, in an attempt to place the concept of insight in relation to disturbances of the self in schizophrenia and to primary symptoms in schizophrenia, amongst these autism.

FY 2016 Research Highlights

Energy Technology Data Exchange (ETDEWEB)

2017-03-23

This fact sheet summarizes the research highlights for the Clean Energy Manufacturing Analysis Center (CEMAC) for Fiscal Year 2106. Topics covered include additive manufacturing for the wind industry, biomass-based chemicals substitutions, carbon fiber manufacturing facility siting, geothermal power plant turbines, hydrogen refueling stations, hydropower turbines, LEDs and lighting, light-duty automotive lithium-ion cells, magnetocaloric refrigeration, silicon carbide power electronics for variable frequency motor drives, solar photovoltaics, and wide bandgap semiconductor opportunities in power electronics.

Insights into the chicken IgY with emphasis on the generation and applications of chicken recombinant monoclonal antibodies.

Science.gov (United States)

Lee, Warren; Syed Atif, Ali; Tan, Soo Choon; Leow, Chiuan Herng

2017-08-01

The advantages of chicken (Gallus gallus domesticus) antibodies as immunodiagnostic and immunotherapeutic biomolecules has only been recently recognized. Even so, chicken antibodies remain less-well characterized than their mammalian counterparts. This review aims at providing a current overview of the structure, function, development and generation of chicken antibodies. Additionally, brief but comprehensive insights into current knowledge pertaining to the immunogenetic framework and diversity-generation of the chicken immunoglobulin repertoire which have contributed to the establishment of recombinant chicken mAb-generating methods are discussed. Focus is provided on the current methods used to generate antibodies from chickens with added emphasis on the generation of recombinant chicken mAbs and its derivative formats. The advantages and limitations of established protocols for the generation of chicken mAbs are highlighted. The various applications of recombinant chicken mAbs and its derivative formats in immunodiagnostics and immunotherapy are further detailed. Copyright © 2017 Elsevier B.V. All rights reserved.

Structural and Functional Studies of H. seropedicae RecA Protein – Insights into the Polymerization of RecA Protein as Nucleoprotein Filament

Energy Technology Data Exchange (ETDEWEB)

Leite, Wellington C.; Galvão, Carolina W.; Saab, Sérgio C.; Iulek, Jorge; Etto, Rafael M.; Steffens, Maria B.R.; Chitteni-Pattu, Sindhu; Stanage, Tyler; Keck, James L.; Cox, Michael M. (UW); (UW-MED); (Ponta Grossa)

2016-07-22

The bacterial RecA protein plays a role in the complex system of DNA damage repair. Here, we report the functional and structural characterization of the Herbaspirillum seropedicae RecA protein (HsRecA). HsRecA protein is more efficient at displacing SSB protein from ssDNA than Escherichia coli RecA protein. HsRecA also promotes DNA strand exchange more efficiently. The three dimensional structure of HsRecA-ADP/ATP complex has been solved to 1.7 Å resolution. HsRecA protein contains a small N-terminal domain, a central core ATPase domain and a large C-terminal domain, that are similar to homologous bacterial RecA proteins. Comparative structural analysis showed that the N-terminal polymerization motif of archaeal and eukaryotic RecA family proteins are also present in bacterial RecAs. Reconstruction of electrostatic potential from the hexameric structure of HsRecA-ADP/ATP revealed a high positive charge along the inner side, where ssDNA is bound inside the filament. The properties of this surface may explain the greater capacity of HsRecA protein to bind ssDNA, forming a contiguous nucleoprotein filament, displace SSB and promote DNA exchange relative to EcRecA. In conclusion, our functional and structural analyses provide insight into the molecular mechanisms of polymerization of bacterial RecA as a helical nucleoprotein filament.

Structural and Functional Studies of H. seropedicae RecA Protein – Insights into the Polymerization of RecA Protein as Nucleoprotein Filament

Science.gov (United States)

Galvão, Carolina W.; Saab, Sérgio C.; Iulek, Jorge; Etto, Rafael M.; Steffens, Maria B. R.; Chitteni-Pattu, Sindhu; Stanage, Tyler; Keck, James L.; Cox, Michael M.

2016-01-01

The bacterial RecA protein plays a role in the complex system of DNA damage repair. Here, we report the functional and structural characterization of the Herbaspirillum seropedicae RecA protein (HsRecA). HsRecA protein is more efficient at displacing SSB protein from ssDNA than Escherichia coli RecA protein. HsRecA also promotes DNA strand exchange more efficiently. The three dimensional structure of HsRecA-ADP/ATP complex has been solved to 1.7 Å resolution. HsRecA protein contains a small N-terminal domain, a central core ATPase domain and a large C-terminal domain, that are similar to homologous bacterial RecA proteins. Comparative structural analysis showed that the N-terminal polymerization motif of archaeal and eukaryotic RecA family proteins are also present in bacterial RecAs. Reconstruction of electrostatic potential from the hexameric structure of HsRecA-ADP/ATP revealed a high positive charge along the inner side, where ssDNA is bound inside the filament. The properties of this surface may explain the greater capacity of HsRecA protein to bind ssDNA, forming a contiguous nucleoprotein filament, displace SSB and promote DNA exchange relative to EcRecA. Our functional and structural analyses provide insight into the molecular mechanisms of polymerization of bacterial RecA as a helical nucleoprotein filament. PMID:27447485

Canadian insights: The challenges of an integrated environmental assessment framework

International Nuclear Information System (INIS)

McCaig, Karen

2005-01-01

The paper draws results from a review of literature to examine the strengths and weaknesses of the integrated environmental assessment framework in Canada with respect to the inclusion of health impact assessment. Insights include the legislative nature, rigid structure and priority for the natural environment that may restrict progress and the pool of government agencies that need to be convinced of the benefits of health impact assessment that may provide a strong structure for compliance in the long term

Small Drinking Water Systems Communication and Outreach Highlights

Science.gov (United States)

As part of our small drinking water systems efforts, this poster highlights several communications and outreach highlights that EPA's Office of Research and Development and Office of Water have been undertaking in collaboration with states and the Association of State Drinking Wa...

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

Science.gov (United States)

Arking, Dan E.; Pulit, Sara L.; Crotti, Lia; van der Harst, Pim; Munroe, Patricia B.; Koopmann, Tamara T.; Sotoodehnia, Nona; Rossin, Elizabeth J.; Morley, Michael; Wang, Xinchen; Johnson, Andrew D.; Lundby, Alicia; Gudbjartsson, Daníel F.; Noseworthy, Peter A.; Eijgelsheim, Mark; Bradford, Yuki; Tarasov, Kirill V.; Dörr, Marcus; Müller-Nurasyid, Martina; Lahtinen, Annukka M.; Nolte, Ilja M.; Smith, Albert Vernon; Bis, Joshua C.; Isaacs, Aaron; Newhouse, Stephen J.; Evans, Daniel S.; Post, Wendy S.; Waggott, Daryl; Lyytikäinen, Leo-Pekka; Hicks, Andrew A.; Eisele, Lewin; Ellinghaus, David; Hayward, Caroline; Navarro, Pau; Ulivi, Sheila; Tanaka, Toshiko; Tester, David J.; Chatel, Stéphanie; Gustafsson, Stefan; Kumari, Meena; Morris, Richard W.; Naluai, Åsa T.; Padmanabhan, Sandosh; Kluttig, Alexander; Strohmer, Bernhard; Panayiotou, Andrie G.; Torres, Maria; Knoflach, Michael; Hubacek, Jaroslav A.; Slowikowski, Kamil; Raychaudhuri, Soumya; Kumar, Runjun D.; Harris, Tamara B.; Launer, Lenore J.; Shuldiner, Alan R.; Alonso, Alvaro; Bader, Joel S.; Ehret, Georg; Huang, Hailiang; Kao, W.H. Linda; Strait, James B.; Macfarlane, Peter W.; Brown, Morris; Caulfield, Mark J.; Samani, Nilesh J.; Kronenberg, Florian; Willeit, Johann; Smith, J. Gustav; Greiser, Karin H.; zu Schwabedissen, Henriette Meyer; Werdan, Karl; Carella, Massimo; Zelante, Leopoldo; Heckbert, Susan R.; Psaty, Bruce M.; Rotter, Jerome I.; Kolcic, Ivana; Polašek, Ozren; Wright, Alan F.; Griffin, Maura; Daly, Mark J.; Arnar, David O.; Hólm, Hilma; Thorsteinsdottir, Unnur; Denny, Joshua C.; Roden, Dan M.; Zuvich, Rebecca L.; Emilsson, Valur; Plump, Andrew S.; Larson, Martin G.; O'Donnell, Christopher J.; Yin, Xiaoyan; Bobbo, Marco; D'Adamo, Adamo P.; Iorio, Annamaria; Sinagra, Gianfranco; Carracedo, Angel; Cummings, Steven R.; Nalls, Michael A.; Jula, Antti; Kontula, Kimmo K.; Marjamaa, Annukka; Oikarinen, Lasse; Perola, Markus; Porthan, Kimmo; Erbel, Raimund; Hoffmann, Per; Jöckel, Karl-Heinz; Kälsch, Hagen; Nöthen, Markus M.; consortium, HRGEN; den Hoed, Marcel; Loos, Ruth J.F.; Thelle, Dag S.; Gieger, Christian; Meitinger, Thomas; Perz, Siegfried; Peters, Annette; Prucha, Hanna; Sinner, Moritz F.; Waldenberger, Melanie; de Boer, Rudolf A.; Franke, Lude; van der Vleuten, Pieter A.; Beckmann, Britt Maria; Martens, Eimo; Bardai, Abdennasser; Hofman, Nynke; Wilde, Arthur A.M.; Behr, Elijah R.; Dalageorgou, Chrysoula; Giudicessi, John R.; Medeiros-Domingo, Argelia; Barc, Julien; Kyndt, Florence; Probst, Vincent; Ghidoni, Alice; Insolia, Roberto; Hamilton, Robert M.; Scherer, Stephen W.; Brandimarto, Jeffrey; Margulies, Kenneth; Moravec, Christine E.; Fabiola Del, Greco M.; Fuchsberger, Christian; O'Connell, Jeffrey R.; Lee, Wai K.; Watt, Graham C.M.; Campbell, Harry; Wild, Sarah H.; El Mokhtari, Nour E.; Frey, Norbert; Asselbergs, Folkert W.; Leach, Irene Mateo; Navis, Gerjan; van den Berg, Maarten P.; van Veldhuisen, Dirk J.; Kellis, Manolis; Krijthe, Bouwe P.; Franco, Oscar H.; Hofman, Albert; Kors, Jan A.; Uitterlinden, André G.; Witteman, Jacqueline C.M.; Kedenko, Lyudmyla; Lamina, Claudia; Oostra, Ben A.; Abecasis, Gonçalo R.; Lakatta, Edward G.; Mulas, Antonella; Orrú, Marco; Schlessinger, David; Uda, Manuela; Markus, Marcello R.P.; Völker, Uwe; Snieder, Harold; Spector, Timothy D.; Ärnlöv, Johan; Lind, Lars; Sundström, Johan; Syvänen, Ann-Christine; Kivimaki, Mika; Kähönen, Mika; Mononen, Nina; Raitakari, Olli T.; Viikari, Jorma S.; Adamkova, Vera; Kiechl, Stefan; Brion, Maria; Nicolaides, Andrew N.; Paulweber, Bernhard; Haerting, Johannes; Dominiczak, Anna F.; Nyberg, Fredrik; Whincup, Peter H.; Hingorani, Aroon; Schott, Jean-Jacques; Bezzina, Connie R.; Ingelsson, Erik; Ferrucci, Luigi; Gasparini, Paolo; Wilson, James F.; Rudan, Igor; Franke, Andre; Mühleisen, Thomas W.; Pramstaller, Peter P.; Lehtimäki, Terho J.; Paterson, Andrew D.; Parsa, Afshin; Liu, Yongmei; van Duijn, Cornelia; Siscovick, David S.; Gudnason, Vilmundur; Jamshidi, Yalda; Salomaa, Veikko; Felix, Stephan B.; Sanna, Serena; Ritchie, Marylyn D.; Stricker, Bruno H.; Stefansson, Kari; Boyer, Laurie A.; Cappola, Thomas P.; Olsen, Jesper V.; Lage, Kasper; Schwartz, Peter J.; Kääb, Stefan; Chakravarti, Aravinda; Ackerman, Michael J.; Pfeufer, Arne; de Bakker, Paul I.W.; Newton-Cheh, Christopher

2014-01-01

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal Mendelian Long QT Syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals we identified 35 common variant QT interval loci, that collectively explain ∼8-10% of QT variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 novel QT loci in 298 unrelated LQTS probands identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode for proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies novel candidate genes for ventricular arrhythmias, LQTS,and SCD. PMID:24952745

Secondary School Students' Epistemic Insight into the Relationships Between Science and Religion—A Preliminary Enquiry

Science.gov (United States)

Billingsley, Berry; Taber, Keith; Riga, Fran; Newdick, Helen

2013-08-01

A number of previous studies have shown that there is a widespread view among young people that science and religion are opposed. In this paper, we suggest that it requires a significant level of what can be termed "epistemic insight" to access the idea that some people see science and religion as compatible while others do not. To explore this further, we draw on previous work to devise a methodology to discover students' thinking about apparent contradictions between scientific and religious explanations of the origins of the universe. In our discussion of the findings, we highlight that students' epistemic insight in this context does seem in many cases to be limited and we outline some of the issues emerging from the study that seem to boost or limit students' progress in this area.

Illness Insight and Recovery: How Important is Illness Insight in Peoples’ Recovery Process?

DEFF Research Database (Denmark)

Korsbek, Lisa

2013-01-01

. Sources Used:The writing is based on research literature related to illness insight and on personal recovery experiences.Conclusions and Implications for Practice: It is helpful to consider the integration of the issue of illness insight when addressing the questions and consequences of diagnosis......Topic: This account reflects on the topic of illness insight and recovery. Purpose: The purpose of the account is to clarify our understanding about the importance of illness insight in peoples’ recovery process, especially when relating the question of illness insight to the question of identity......, and to assist individuals to work through the false analogy between illness and identity while supporting the transformation from patient to person. It is also necessary for clinicians to develop a clear understanding of peoples’ actual needs and gain more knowledge about peoples’ own views and experiences...

Cognitive insight: A systematic review.

Science.gov (United States)

Van Camp, L S C; Sabbe, B G C; Oldenburg, J F E

2017-07-01

Cognitive insight is the ability to re-evaluate thoughts and beliefs in order to make thoughtful conclusions. It differs from clinical insight, as it focuses on more general metacognitive processes. Therefore, it could be relevant to diverse disorders and non-clinical subjects. There is a growing body of research on cognitive insight in individuals with and without psychosis. This review has summarised the current state of the art regarding this topic. We conclude that while cognitive insight in its current form seems valid for use in individuals with psychosis, it is less so for individuals without psychosis. Additionally, higher cognitive insight not always leads to better psychological functioning. For instance, higher levels of self-reflection are often associated with depressive mood. We therefore recommend the sub-components of cognitive insight to be studied separately. Also, it is unclear what position cognitive insight takes within the spectrum of metacognitive processes and how it relates to other self-related concepts that have been defined previously in literature. Combining future and past research on cognitive insight and its analogue concepts will help in the formation of a uniform definition that fits all subjects discussed here. Copyright © 2017. Published by Elsevier Ltd.

Flow-mediated dilation: can new approaches provide greater mechanistic insight into vascular dysfunction in preeclampsia and other diseases?

Science.gov (United States)

Weissgerber, Tracey L

2014-11-01

Endothelial dysfunction is a key feature of preeclampsia and may contribute to increased cardiovascular disease risk years after pregnancy. Flow-mediated dilation (FMD) is a non-invasive endothelial function test that predicts cardiovascular event risk. New protocols allow researchers to measure three components of the FMD response: FMD, low flow-mediated constriction, and shear stimulus. This review encourages researchers to think beyond "low FMD" by examining how these three components may provide additional insights into the mechanisms and location of vascular dysfunction. The review then examines what FMD studies reveal about vascular dysfunction in preeclampsia while highlighting opportunities to gain greater mechanistic insight from new protocols. Studies using traditional protocols show that FMD is low in mid-pregnancy prior to preeclampsia, at diagnosis, and for 3 years post-partum. However, FMD returns to normal by 10 years post-partum. Studies using new protocols are needed to gain more mechanistic insight.

Insights into Conifer Giga-Genomes1

Science.gov (United States)

De La Torre, Amanda R.; Birol, Inanc; Bousquet, Jean; Ingvarsson, Pär K.; Jansson, Stefan; Jones, Steven J.M.; Keeling, Christopher I.; MacKay, John; Nilsson, Ove; Ritland, Kermit; Street, Nathaniel; Yanchuk, Alvin; Zerbe, Philipp; Bohlmann, Jörg

2014-01-01

Insights from sequenced genomes of major land plant lineages have advanced research in almost every aspect of plant biology. Until recently, however, assembled genome sequences of gymnosperms have been missing from this picture. Conifers of the pine family (Pinaceae) are a group of gymnosperms that dominate large parts of the world’s forests. Despite their ecological and economic importance, conifers seemed long out of reach for complete genome sequencing, due in part to their enormous genome size (20–30 Gb) and the highly repetitive nature of their genomes. Technological advances in genome sequencing and assembly enabled the recent publication of three conifer genomes: white spruce (Picea glauca), Norway spruce (Picea abies), and loblolly pine (Pinus taeda). These genome sequences revealed distinctive features compared with other plant genomes and may represent a window into the past of seed plant genomes. This Update highlights recent advances, remaining challenges, and opportunities in light of the publication of the first conifer and gymnosperm genomes. PMID:25349325

Clinical highlights from Amsterdam

Directory of Open Access Journals (Sweden)

Jouke T. Annema

2016-07-01

Full Text Available This article contains highlights and a selection of the scientific advances from the Clinical Assembly that were presented at the 2015 European Respiratory Society International Congress in Amsterdam, the Netherlands. The most relevant topics for clinicians will be discussed, covering a wide range of areas including interventional pulmonology, rehabilitation and chronic care, thoracic imaging, diffuse and parenchymal lung diseases, and general practice and primary care. In this comprehensive review, exciting novel data will be discussed and put into perspective.

Highlights from CMS

CERN Document Server

Autermann, Christian

2018-01-01

This article summarizes the latest highlights from the CMS experiment as presented at the Lepton Photon conference 2017 in Guangzhou, China. A selection of the latest physics results, the latest detector upgrades, and the current detector status are discussed. CMS has analyzed the full dataset of proton-proton collision data delivered by the LHC in 2016 at a center-of-mass energy of $13$\\,TeV corresponding to an integrated luminosity of $40$\\,fb$^{-1}$. The leap in center-of-mass energy and in luminosity with respect to the $7$ and $8$\\,TeV runs enabled interesting and relevant new physics results. A new silicon pixel tracking detector was installed during the LHC shutdown 2016/17 and has successfully started operation.

Electric transport in the Netherlands. Highlights 2012; Elektrisch vervoer in Nederland. Highlights 2012

Energy Technology Data Exchange (ETDEWEB)

NONE

2013-03-15

Businesses, social and educational institutions and governmental institutes work together to accelerate electric transport and to discover and exploit economic opportunities. In 2012, many activities were carried out and results achieved, of which the highlights are presented in this brochure [Dutch] Bedrijfsleven, maatschappelijke- en kennisinstellingen en overheden werken samen aan versnelling van elektrisch vervoer en het ontdekken en benutten van economische kansen. In 2012 werden veel activiteiten uitgevoerd en resultaten geboekt, waarvan in deze brochure verslag wordt gedaan.

CYANOMETHANIMINE ISOMERS IN COLD INTERSTELLAR CLOUDS: INSIGHTS FROM ELECTRONIC STRUCTURE AND KINETIC CALCULATIONS

Energy Technology Data Exchange (ETDEWEB)

Vazart, Fanny; Latouche, Camille; Skouteris, Dimitrios; Barone, Vincenzo [Scuola Normale Superiore, Piazza dei Cavalieri 7, I-56125 Pisa (Italy); Balucani, Nadia [Dipartimento di Chimica, Biologia e Biotecnologie, Universitá degli Studi di Perugia, Via Elce di Sotto 8, I-06123 Perugia (Italy)

2015-09-10

New insights into the formation of interstellar cyanomethanimine, a species of great relevance in prebiotic chemistry, are provided by electronic structure and kinetic calculations for the reaction CN + CH{sub 2} = NH. This reaction is a facile formation route of Z,E-C-cyanomethanimine, even under the extreme conditions of density and temperature typical of cold interstellar clouds. E-C-cyanomethanimine has been recently identified in Sgr B2(N) in the Green Bank Telescope (GBT) PRIMOS survey by P. Zaleski et al. and no efficient formation routes have been envisaged so far. The rate coefficient expression for the reaction channel leading to the observed isomer E-C-cyanomethanimine is 3.15 × 10-10 × (T/300){sup 0.152} × e{sup (−0.0948/T)}. According to the present study, the more stable Z-C-cyanomethanimine isomer is formed with a slightly larger yield (4.59 × 10{sup −10} × (T/300){sup 0.153} × e{sup (−0.0871/T)}. As the detection of E-isomer is favored due to its larger dipole moment, the missing detection of the Z-isomer can be due to the sensitivity limit of the GBT PRIMOS survey and the detection of the Z-isomer should be attempted with more sensitive instrumentation. The CN + CH{sub 2} = NH reaction can also play a role in the chemistry of the upper atmosphere of Titan where the cyanomethanimine products can contribute to the buildup of the observed nitrogen-rich organic aerosols that cover the moon.

3D-structured illumination microscopy provides novel insight into architecture of human centrosomes

Directory of Open Access Journals (Sweden)

Katharina F. Sonnen

2012-08-01

Centrioles are essential for the formation of cilia and flagella. They also form the core of the centrosome, which organizes microtubule arrays important for cell shape, polarity, motility and division. Here, we have used super-resolution 3D-structured illumination microscopy to analyse the spatial relationship of 18 centriole and pericentriolar matrix (PCM components of human centrosomes at different cell cycle stages. During mitosis, PCM proteins formed extended networks with interspersed γ-Tubulin. During interphase, most proteins were arranged at specific distances from the walls of centrioles, resulting in ring staining, often with discernible density masses. Through use of site-specific antibodies, we found the C-terminus of Cep152 to be closer to centrioles than the N-terminus, illustrating the power of 3D-SIM to study protein disposition. Appendage proteins showed rings with multiple density masses, and the number of these masses was strongly reduced during mitosis. At the proximal end of centrioles, Sas-6 formed a dot at the site of daughter centriole assembly, consistent with its role in cartwheel formation. Plk4 and STIL co-localized with Sas-6, but Cep135 was associated mostly with mother centrioles. Remarkably, Plk4 formed a dot on the surface of the mother centriole before Sas-6 staining became detectable, indicating that Plk4 constitutes an early marker for the site of nascent centriole formation. Our study provides novel insights into the architecture of human centrosomes and illustrates the power of super-resolution microscopy in revealing the relative localization of centriole and PCM proteins in unprecedented detail.

Modeling Double Subjectivity for Gaining Programmable Insights: Framing the Case of Uber

Directory of Open Access Journals (Sweden)

Loretta Henderson Cheeks

2017-09-01

Full Text Available The Internet is the premier platform that enable the emergence of new technologies. Online news is unstructured narrative text that embeds facts, frames, and amplification that can influence society attitudes about technology adoption. Online news sources are carriers of voluminous amounts of news for reaching significantly large audience and have no geographical or time boundaries. The interplay of complex and dynamical forces among authors and readers allow for progressive emergent and latent properties to exhibit. Our concept of “Double subjectivity” provides a new paradigm for exploring complementary programmable insights of deeply buried meanings in a system. The ability to understand internal embeddedness in a large collection of related articles are beyond the reach of existing computational tools, and are hence left to human readers with unscalable results. This paper uncovers the potential to utilize advanced machine learning in a new way to automate the understanding of implicit structures and their associated latent meanings to give an early human-level insight into emergent technologies, with a concrete example of “Uber”. This paper establishes the new concept of double subjectivity as an instrument for large-scale machining of unstructured text and introduces a social influence model for the discovery of distinct pathways into emerging technology, and hence an insight. The programmable insight reveals early spatial and temporal opinion shift monitoring in complex networks in a structured way for computational treatment and visualization.

Highlights on the IAEA project QUATRO

International Nuclear Information System (INIS)

Milano, F.

2012-01-01

The success of radiotherapy in term of prob- ability of local control of the tumor and the limiting factor in treatments in term of probability of complications are strictly depending on the accuracy and precision of the pa- tient treatment. An overall Quality Assurance programme (QAP) has been recognized as an essential tool to assure that the goals of radiotherapy are achieved. As part of a comprehensive approach to QAP an independent external audit is considered a very effective method of checking that the quality of activities in an Institution permits to achieve the required objectives. Since many years the International Atomic Energy Agency (IAEA) has audited Member States for radiotherapy dosimetry, for educating and training radio- therapy professionals and for reviewing the radiotherapy process. Recently a new approach has been developed and named ''Quality Assurance Team for Radiation Oncology (QUATRO)''. The principal aim of QUATRO is to review all the radiotherapy process, including organization, infra- structure, clinical and medical physics aspects of the radio- therapy services. It also includes a review of the hospital's professional competence with a view to quality improve- ment. The aim of this paper is to introduce and to highlight the QUATRO methodology describing its effectiveness on improving either the quality of the radiotherapy treatments and in general the management of the patient.

Dreaming and insight

Science.gov (United States)

Edwards, Christopher L.; Ruby, Perrine M.; Malinowski, Josie E.; Bennett, Paul D.; Blagrove, Mark T.

2013-01-01

This paper addresses claims that dreams can be a source of personal insight. Whereas there has been anecdotal backing for such claims, there is now tangential support from findings of the facilitative effect of sleep on cognitive insight, and of REM sleep in particular on emotional memory consolidation. Furthermore, the presence in dreams of metaphorical representations of waking life indicates the possibility of novel insight as an emergent feature of such metaphorical mappings. In order to assess whether personal insight can occur as a result of the consideration of dream content, 11 dream group discussion sessions were conducted which followed the Ullman Dream Appreciation technique, one session for each of 11 participants (10 females, 1 male; mean age = 19.2 years). Self-ratings of deepened self-perception and personal gains from participation in the group sessions showed that the Ullman technique is an effective procedure for establishing connections between dream content and recent waking life experiences, although wake life sources were found for only 14% of dream report text. The mean Exploration-Insight score on the Gains from Dream Interpretation questionnaire was very high and comparable to outcomes from the well-established Hill (1996) therapist-led dream interpretation method. This score was associated between-subjects with pre-group positive Attitude Toward Dreams (ATD). The need to distinguish “aha” experiences as a result of discovering a waking life source for part of a dream, from “aha” experiences of personal insight as a result of considering dream content, is discussed. Difficulties are described in designing a control condition to which the dream report condition can be compared. PMID:24550849

Unicystic plexiform ameloblastoma: An insight for pediatric dentists

Directory of Open Access Journals (Sweden)

Yavagal C

2009-03-01

Full Text Available Ameloblastomas have been categorized broadly into three biologic variants: cystic (unicystic, solid, and peripheral. The term plexiform unicystic ameloblastoma refers to a pattern of epithelial proliferation that has been described in cystic lesions of the jaws. Although the histology suggests that cystic ameloblastomas follow a biologically low-grade course, recent evidence suggests that they may often behave clinically as biologically aggressive tumors. This is supported by the high incidence of cortical perforation, tooth resorption, lesion size, bony destruction, and a high rate of recurrence after simple enucleation. This article tries to provide an insight for pediatric dentists regarding this biologically distinct entity. A literature review on the topic has been added along with a case report highlighting the state-of-the-art approach and management of such ameloblastomas, in pediatric patients.

New functional insights into the internal architecture of the laminated anchor spicules of Euplectella aspergillum.

Science.gov (United States)

Monn, Michael A; Weaver, James C; Zhang, Tianyang; Aizenberg, Joanna; Kesari, Haneesh

2015-04-21

To adapt to a wide range of physically demanding environmental conditions, biological systems have evolved a diverse variety of robust skeletal architectures. One such example, Euplectella aspergillum, is a sediment-dwelling marine sponge that is anchored into the sea floor by a flexible holdfast apparatus consisting of thousands of anchor spicules (long, hair-like glassy fibers). Each spicule is covered with recurved barbs and has an internal architecture consisting of a solid core of silica surrounded by an assembly of coaxial silica cylinders, each of which is separated by a thin organic layer. The thickness of each silica cylinder progressively decreases from the spicule's core to its periphery, which we hypothesize is an adaptation for redistributing internal stresses, thus increasing the overall strength of each spicule. To evaluate this hypothesis, we created a spicule structural mechanics model, in which we fixed the radii of the silica cylinders such that the force transmitted from the surface barbs to the remainder of the skeletal system was maximized. Compared with measurements of these parameters in the native sponge spicules, our modeling results correlate remarkably well, highlighting the beneficial nature of this elastically heterogeneous lamellar design strategy. The structural principles obtained from this study thus provide potential design insights for the fabrication of high-strength beams for load-bearing applications through the modification of their internal architecture, rather than their external geometry.

Barriers and impediments to transformational government : Insights from literature and practice

NARCIS (Netherlands)

Van Veenstra, A.F.; Klievink, B.; Janssen, M.F.W.H.A.

2011-01-01

Transformational government (t-government) has been introduced as a new stage of e-government aimed at realising structural changes and greater benefits in the public sector. Yet, there are many impediments blocking transformation, and there is limited insight in these barriers. In this paper,

A genome-wide analysis of the RNA-guided silencing pathway in coffee reveals insights into its regulatory mechanisms.

Directory of Open Access Journals (Sweden)

Christiane Noronha Fernandes-Brum

Full Text Available microRNAs (miRNAs are derived from self-complementary hairpin structures, while small-interfering RNAs (siRNAs are derived from double-stranded RNA (dsRNA or hairpin precursors. The core mechanism of sRNA production involves DICER-like (DCL in processing the smallRNAs (sRNAs and ARGONAUTE (AGO as effectors of silencing, and siRNA biogenesis also involves action of RNA-Dependent RNA Polymerase (RDR, Pol IV and Pol V in biogenesis. Several other proteins interact with the core proteins to guide sRNA biogenesis, action, and turnover. We aimed to unravel the components and functions of the RNA-guided silencing pathway in a non-model plant species of worldwide economic relevance. The sRNA-guided silencing complex members have been identified in the Coffea canephora genome, and they have been characterized at the structural, functional, and evolutionary levels by computational analyses. Eleven AGO proteins, nine DCL proteins (which include a DCL1-like protein that was not previously annotated, and eight RDR proteins were identified. Another 48 proteins implicated in smallRNA (sRNA pathways were also identified. Furthermore, we identified 235 miRNA precursors and 317 mature miRNAs from 113 MIR families, and we characterized ccp-MIR156, ccp-MIR172, and ccp-MIR390. Target prediction and gene ontology analyses of 2239 putative targets showed that significant pathways in coffee are targeted by miRNAs. We provide evidence of the expansion of the loci related to sRNA pathways, insights into the activities of these proteins by domain and catalytic site analyses, and gene expression analysis. The number of MIR loci and their targeted pathways highlight the importance of miRNAs in coffee. We identified several roles of sRNAs in C. canephora, which offers substantial insight into better understanding the transcriptional and post-transcriptional regulation of this major crop.

New OprM structure highlighting the nature of the N-terminal anchor

Directory of Open Access Journals (Sweden)

Laura eMONLEZUN

2015-07-01

Full Text Available Among the different mechanisms used by bacteria to resist antibiotics, active efflux plays a major role. In gram-negative bacteria, active efflux is carried out by tripartite efflux pumps that form a macromolecular assembly spanning both membranes of the cellular wall. At the outer membrane level, a well-conserved Outer Membrane Factor (OMF protein acts as an exit duct, but its sequence varies greatly among different species. The OMFs share a similar tri-dimensional structure that includes a beta-barrel pore domain that stabilizes the channel within the membrane. In addition, OMFs are often subjected to different N-terminal post-translational modifications, such as an acylation with a lipid. The role of additional N-terminal anchors is all the more intriguing since it is not always required among the OMFs family. Understanding this optional post-translational modification could open new research lines in the field of antibiotics resistance. In E. coli, it has been shown that CusC is modified with a tri-acylated lipid, whereas TolC does not show any. In the case of OprM from Pseudomonas aeruginosa, the N-terminal modification remains a matter of debate, therefore, we used several approaches to investigate this issue. As definitive evidence, we present a new X ray structure at 3.8Å resolution that was solved in a new space group, making it possible to model the N-terminal residue as a palmitylated cysteine.

Magnetotelluric 2D Modelling Provides Insight on the Structural Characteristics of the Guadalajara (Mexico) Triple Junction Domains

Science.gov (United States)

Arboleda Zapata, M. D. J., Sr.; Arzate-Flores, J.; Guevara Betancourt, R. E., Sr.

2017-12-01

The Jalisco Block is a continental microplate produced by the extension along three large structures: the Tepic-Zacoalco rift (TZR), the Colima rift (CR) and the Chapala rift that converge in a triple junction 50 km southwest of Guadalajara, Mexico, with orientation NW-SE, N-S, and E-W respectively. The present study focuses on investigating the deep structure of the north Colima and eastern Zacoalco grabens close to the Guadalajara triple junction (GTJ). This is a first study of its type that provide insight on the grabens structures and crustal characteristics underneath. We measured along two magnetotellurics (MT) profiles that cut perpendicularly the TZR (profile ZAC), and the northern CR (profile SAY) comprising a total of 24 broad band MT soundings. The ZAC profile has 11 stations and has a NE orientation, and the SAY profile has 14 station aligned E-W. Standard processing and editing procedures were completed, and distortion analysis was applied to the data set in order to define the dimensionality and electric strike of the separated profiles. Static shift was corrected using geology information to distinguish the different types of soundings and later averaging for those soundings located over the same lithology. The Bahr dimensionality parameters showed that the medium is mainly 3D for the SAY profile and 2D for the ZAC profile; furthermore, the regional geoelectric strike azimuth calculated with Bahr methodology were -4° and -48° respectively, with good concordance with the main surface structures. The tipper analysis permitted validated these results, as the real induction vectors were nearly perpendicular to main fault structures. All soundings were rotated to the respective regional strike and a 2D simultaneous inversion of the transverse electric (TE) mode, the transvers magnetic (TM) mode and the Tipper was completed. The RMS fitting error yield 3.2% for ZAC profile and 3.7% for SAY profile. Both profiles show a shallow conductive zone at north of

Human astrocytes: structure and functions in the healthy brain.

Science.gov (United States)

Vasile, Flora; Dossi, Elena; Rouach, Nathalie

2017-07-01

Data collected on astrocytes' physiology in the rodent have placed them as key regulators of synaptic, neuronal, network, and cognitive functions. While these findings proved highly valuable for our awareness and appreciation of non-neuronal cell significance in brain physiology, early structural and phylogenic investigations of human astrocytes hinted at potentially different astrocytic properties. This idea sparked interest to replicate rodent-based studies on human samples, which have revealed an analogous but enhanced involvement of astrocytes in neuronal function of the human brain. Such evidence pointed to a central role of human astrocytes in sustaining more complex information processing. Here, we review the current state of our knowledge of human astrocytes regarding their structure, gene profile, and functions, highlighting the differences with rodent astrocytes. This recent insight is essential for assessment of the relevance of findings using animal models and for comprehending the functional significance of species-specific properties of astrocytes. Moreover, since dysfunctional astrocytes have been described in many brain disorders, a more thorough understanding of human-specific astrocytic properties is crucial for better-adapted translational applications.

Automatic Online Lecture Highlighting Based on Multimedia Analysis

Science.gov (United States)

Che, Xiaoyin; Yang, Haojin; Meinel, Christoph

2018-01-01

Textbook highlighting is widely considered to be beneficial for students. In this paper, we propose a comprehensive solution to highlight the online lecture videos in both sentence- and segment-level, just as is done with paper books. The solution is based on automatic analysis of multimedia lecture materials, such as speeches, transcripts, and…

Evolution of Parallel Spindles Like genes in plants and highlight of unique domain architecture#

Directory of Open Access Journals (Sweden)

Consiglio Federica M

2011-03-01

Full Text Available Abstract Background Polyploidy has long been recognized as playing an important role in plant evolution. In flowering plants, the major route of polyploidization is suggested to be sexual through gametes with somatic chromosome number (2n. Parallel Spindle1 gene in Arabidopsis thaliana (AtPS1 was recently demonstrated to control spindle orientation in the 2nd division of meiosis and, when mutated, to induce 2n pollen. Interestingly, AtPS1 encodes a protein with a FHA domain and PINc domain putatively involved in RNA decay (i.e. Nonsense Mediated mRNA Decay. In potato, 2n pollen depending on parallel spindles was described long time ago but the responsible gene has never been isolated. The knowledge derived from AtPS1 as well as the availability of genome sequences makes it possible to isolate potato PSLike (PSL and to highlight the evolution of PSL family in plants. Results Our work leading to the first characterization of PSLs in potato showed a greater PSL complexity in this species respect to Arabidopsis thaliana. Indeed, a genomic PSL locus and seven cDNAs affected by alternative splicing have been cloned. In addition, the occurrence of at least two other PSL loci in potato was suggested by the sequence comparison of alternatively spliced transcripts. Phylogenetic analysis on 20 Viridaeplantae showed the wide distribution of PSLs throughout the species and the occurrence of multiple copies only in potato and soybean. The analysis of PSLFHA and PSLPINc domains evidenced that, in terms of secondary structure, a major degree of variability occurred in PINc domain respect to FHA. In terms of specific active sites, both domains showed diversification among plant species that could be related to a functional diversification among PSL genes. In addition, some specific active sites were strongly conserved among plants as supported by sequence alignment and by evidence of negative selection evaluated as difference between non-synonymous and

Self-evaluation in schizophrenia: an fMRI study with implications for the understanding of insight

Directory of Open Access Journals (Sweden)

Bedford Nicholas J

2012-08-01

Full Text Available Abstract Background Lack of insight is a core feature of schizophrenia and is associated with structural brain abnormalities. The functional neuroanatomy of insight has only recently been investigated. When people evaluate their personality traits compared to those of another, activation is seen in central midline structures (CMS of the brain. This study set out to compare cerebral activation in schizophrenia patients versus controls during a self-evaluation task which included positive and negative traits as well as mental and physical illness terms. Methods Eleven schizophrenia patients and 8 healthy controls, matched for age were studied. Insight was assessed using the Schedule for the Assessment of Insight-expanded version (SAI-E. FMRI data were obtained with a 1.5 Tesla GE system and interactions between participant group, self versus other, significant at the cluster level, were recorded. Results Significant hypoactivation in the medial superior frontal gyrus (dorsomedial prefrontal cortex was observed in patients vs. controls during self-evaluation of all traits combined. A second cluster of hypoactivation in the posterior cingulate was also detected. When the response to individual traits was explored, underactivation in other frontal regions plus right inferior parietal lobule emerged and this tended to correlate, albeit weakly with lower insight scores. Further, there were areas of hyperactivation relative to controls in anterior cingulate, frontal and parietal regions (especially precuneus which showed moderate inverse correlations with insight scores. Conclusions We have demonstrated that the CMS, identified as a key system underpinning self-evaluation, is dysfunctional in patients with schizophrenia, particularly dorso-medial PFC. This may have implications for lack of insight in schizophrenia. Hypofunction within the dorsomedial prefrontal region seems to be particularly important although other posterior and lateral cortical

Palliativedrugs.com therapeutic highlights: gabapentin

Directory of Open Access Journals (Sweden)

Twycross Robert

2003-01-01

Full Text Available This is the second in a series of highlights drawn from the www.palliativedrugs.com website. The website provides free access to the Palliative Care Formulary, a monthly newsletter and a bulletin board for advice to be given and received. With almost 10,000 professional members it is the largest palliative care resource of its kind.

Genetic structure of Octopus vulgaris (Cephalopoda, Octopodidae) in the central Mediterranean Sea inferred from the mitochondrial COIII gene.

Science.gov (United States)

Fadhlaoui-Zid, Karima; Knittweis, Leyla; Aurelle, Didier; Nafkha, Chaala; Ezzeddine, Soufia; Fiorentino, Fabio; Ghmati, Hisham; Ceriola, Luca; Jarboui, Othman; Maltagliati, Ferruccio

2012-01-01

The polymorphism of the mitochondrial gene cytochrome oxidase III was studied in the Mediterranean octopus, Octopus vulgaris Cuvier, 1797. A total of 202 specimens from seven sampling sites were analysed with the aim of elucidating patterns of genetic structure in the central Mediterranean Sea and to give an insight into the phylogeny of the Octopus genus. Phylogenetic analyses showed that individuals from the central Mediterranean belong to the O. vulgaris species whose limits should nevertheless be clarified. Concerning genetic structure, two high-frequency haplotypes were present in all locations. The overall genetic divergence (Φ(ST)=0.05, P<0.05) indicated a significant genetic structuring in the study area and an AMOVA highlighted a significant break between western and eastern Mediterranean basins (Φ(CT)=0.094, P<0.05). Possible explanations for the observed patterns of genetic structuring are discussed with reference to their relevance for fisheries management. Copyright © 2012. Published by Elsevier SAS.

Cobalt 60 gamma irradiation current status, trends and insights

International Nuclear Information System (INIS)

Corley, John T.

1998-01-01

This paper discusses the current status, trends and insights into the continued, safe use of cobalt 60 gamma irradiation. Also presented are some of the many initiatives undertaken at MDS Nordion. Topics covered include our investment for the future supply of raw materials and the latest news from source production. Briefly presented are the tasks associated with the safe transport of cobalt 60 around the world. Discussed is cobalt 60 usage at the customer site; more specifically maintaining source integrity, source utilization and irradiator design trends. Highlighted are industry trends for North America, Europe and the rest of the world. Finally presented are the challenges and opportunities for the industry. Stressed in the paper is the need to work together

Highlights in the hadron electromagnetic structure

Directory of Open Access Journals (Sweden)

Tomasi-Gustafsson Egle

2017-01-01

Full Text Available In frame of a general view of proton electromagnetic form factors, two recent findings related to reanalyses of data are presented. Recent experiments in the scattering and in the annihilation region provided us with more precise data and/or extending the kinematical region, allowing a deeper analysis and a common view of these fundamental quantities. We will discuss two issues: the discrepancy between the form factors extracted from unpolarized and polarized ep elastic scattering experiments, in connection with the commonly used dipole parametrization; peculiar oscillations in e+e− → p̄p(γ annihilation cross section, that become periodical when plotted as a function of the 3-momentum of the relative motion of the final proton and antiproton, after subtraction of a smooth function.

Wake structure of a single vertical axis wind turbine

International Nuclear Information System (INIS)

Posa, Antonio; Parker, Colin M.; Leftwich, Megan C.; Balaras, Elias

2016-01-01

Highlights: • The wake structure of an isolated Vertical Axis Wind Turbine is studied by both Particle Imaging Velocimetry and Large Eddy Simulation. • The wake structure is investigated for two values of tip speed ratio, TSR_1=1.35 and TSR_2=2.21. • A displacement of the momentum deficit towards the windward side is verified in the wake. • Higher turbulence and coherence is observed on the leeward side of the wake, due to the upwind stall of the blades. • Coherence in the wake core, associated to the downwind stall, decays quickly downstream. - Abstract: The wake structure behind a vertical axis wind turbine (VAWT) is both measured in a wind tunnel using particle imaging velocimetry (PIV) and computed with large-eddy simulation (LES). Geometric and dynamic conditions are closely matched to typical applications of VAWTs (Re_D ∼ 1.8 × 10"5). The experiments and computations were highly coordinated with continuous two-way feedback to produce the most insightful results. Good qualitative agreement is seen between the computational and experimental results. The dependence of the wake structure on the tip speed ratio, TSR, is investigated, showing higher asymmetry and larger vortices at the lower rotational speed, due to stronger dynamic stall phenomena. Instantaneous, ensemble-averaged and phase-averaged fields are discussed, as well as the dynamics of coherent structures in the rotor region and downstream wake.

Automated detection of structural alerts (chemical fragments in (ecotoxicology

Directory of Open Access Journals (Sweden)

Ronan Bureau

2013-02-01

Full Text Available This mini-review describes the evolution of different algorithms dedicated to the automated discovery of chemical fragments associated to (ecotoxicological endpoints. These structural alerts correspond to one of the most interesting approach of in silico toxicology due to their direct link with specific toxicological mechanisms. A number of expert systems are already available but, since the first work in this field which considered a binomial distribution of chemical fragments between two datasets, new data miners were developed and applied with success in chemoinformatics. The frequency of a chemical fragment in a dataset is often at the core of the process for the definition of its toxicological relevance. However, recent progresses in data mining provide new insights into the automated discovery of new rules. Particularly, this review highlights the notion of Emerging Patterns that can capture contrasts between classes of data.

AUTOMATED DETECTION OF STRUCTURAL ALERTS (CHEMICAL FRAGMENTS IN (ECOTOXICOLOGY

Directory of Open Access Journals (Sweden)

Alban Lepailleur

2013-02-01

Full Text Available This mini-review describes the evolution of different algorithms dedicated to the automated discovery of chemical fragments associated to (ecotoxicological endpoints. These structural alerts correspond to one of the most interesting approach of in silico toxicology due to their direct link with specific toxicological mechanisms. A number of expert systems are already available but, since the first work in this field which considered a binomial distribution of chemical fragments between two datasets, new data miners were developed and applied with success in chemoinformatics. The frequency of a chemical fragment in a dataset is often at the core of the process for the definition of its toxicological relevance. However, recent progresses in data mining provide new insights into the automated discovery of new rules. Particularly, this review highlights the notion of Emerging Patterns that can capture contrasts between classes of data.

Composition of the mitochondrial electron transport chain in acanthamoeba castellanii: structural and evolutionary insights.

Science.gov (United States)

Gawryluk, Ryan M R; Chisholm, Kenneth A; Pinto, Devanand M; Gray, Michael W

2012-11-01

The mitochondrion, derived in evolution from an α-proteobacterial progenitor, plays a key metabolic role in eukaryotes. Mitochondria house the electron transport chain (ETC) that couples oxidation of organic substrates and electron transfer to proton pumping and synthesis of ATP. The ETC comprises several multiprotein enzyme complexes, all of which have counterparts in bacteria. However, mitochondrial ETC assemblies from animals, plants and fungi are generally more complex than their bacterial counterparts, with a number of 'supernumerary' subunits appearing early in eukaryotic evolution. Little is known, however, about the ETC of unicellular eukaryotes (protists), which are key to understanding the evolution of mitochondria and the ETC. We present an analysis of the ETC proteome from Acanthamoeba castellanii, an ecologically, medically and evolutionarily important member of Amoebozoa (sister to Opisthokonta). Data obtained from tandem mass spectrometric (MS/MS) analyses of purified mitochondria as well as ETC complexes isolated via blue native polyacrylamide gel electrophoresis are combined with the results of bioinformatic queries of sequence databases. Our bioinformatic analyses have identified most of the ETC subunits found in other eukaryotes, confirming and extending previous observations. The assignment of proteins as ETC subunits by MS/MS provides important insights into the primary structures of ETC proteins and makes possible, through the use of sensitive profile-based similarity searches, the identification of novel constituents of the ETC along with the annotation of highly divergent but phylogenetically conserved ETC subunits. © 2012 Elsevier B.V. All rights reserved.

ITALIAN LOCAL PUBLIC SERVICES: SOME GOVERNANCE HIGHLIGHTS FROM THE LARGER CITIES’ EXPERIENCE

Directory of Open Access Journals (Sweden)

DE MATTEIS Fabio

2013-06-01

Full Text Available Entrusting most local public services to local government entities has led to proliferation of public groups and, consistently, to greater complexity of the governance dynamics of local authorities. Differently from Anglo-Saxon countries, the Italian local public services provision has been characterized by a hybrid externalization process where local entities are legally autonomous but owned by the local government. This leads to a peculiar governance complexity source represented by the dual role (stakeholder and customer assumed by the local authority. Considering these elements (hybrid externalization and governance structure, this work tries to investigate some governance issues of public groups, basing on the two most populous Italian municipalities. The empirical findings highlight a gap between the presence of the conditions for defining a group governance structure and the adoption of a group approach by the parent local government. The authors try to suggest how to bridge this gap.

New Insights on the Structure of Electrochemically Deposited Lithium Metal and Its Solid Electrolyte Interphases via Cryogenic TEM

Energy Technology Data Exchange (ETDEWEB)

Wang, Xuefeng; Zhang, Minghao; Alvarado, Judith; Wang, Shen; Sina, Mahsa; Lu, Bingyu; Bouwer, James; Xu, Wu [Energy; Xiao, Jie [Energy; Zhang, Ji-Guang [Energy; Liu, Jun [Energy; Meng, Ying Shirley

2017-11-02

Lithium metal has been considered as the “holy grail” anode material for rechargeable batteries though the dendritic growth and low Coulombic efficiency (CE) have crippled its practical use for decades. Its high chemical reactivity and low stability make it difficult to explore the intrinsic chemical and physical properties of the electrochemically deposited lithium (EDLi) and its accompanied solid electrolyte interphase (SEI). To prevent the dendritic growth and enhance the electrochemical reversibility, it is crucial to understand the nano- and meso- structures of EDLi. However, Li metal is very sensitive to beam damage and has low contrast for commonly used characterization techniques such as electron microscopy. Inspired by biological imaging techniques, this work demonstrates the power of cryogenic (cryo)- electron microscopy to reveal the detailed structure of EDLi and the SEI composition at the nano scale while minimizing beam damage during imaging. Surprisingly, the results show that the nucleation dominated EDLi (five minutes at 0.5 mA cm-2) is amorphous while there is some crystalline LiF present in the SEI. The EDLi grown from various electrolytes with different additives exhibits distinctive surface properties. Consequently, these results highlight the importance of the SEI and its relationship with the CE. Our findings not only illustrate the capabilities of cryogenic microscopy for beam (thermal)-sensitive materials, but it yields crucial structural information of the EDLi evolution with and without electrolyte additives.

New Insight into Carbon Nanotube Electronic Structure Selectivity

Energy Technology Data Exchange (ETDEWEB)

Sumpter, Bobby G [ORNL; Meunier, Vincent [ORNL; Jiang, Deen [ORNL

2009-01-01

The fundamental role of aryl diazonium salts for post synthesis selectivity of carbon nanotubes is investigated using extensive electronic structure calculations. The resulting understanding for diazonium salt based selective separation of conducting and semiconducting carbon nanotubes shows how the primary contributions come from the interplay between the intrinsic electronic structure of the carbon nanotubes and that of the anion of the salt. We demonstrate how the electronic transport properties change upon the formation of charge transfer complexes and upon their conversion into covalently attached functional groups. Our results are found to correlate well with experiments and provide for the first time an atomistic description for diazonium salt based chemical separation of carbon nanotubes

Structural and Mechanistic Insights into Hemoglobin-catalyzed Hydrogen Sulfide Oxidation and the Fate of Polysulfide Products

Energy Technology Data Exchange (ETDEWEB)

Vitvitsky, Victor; Yadav, Pramod K.; An, Sojin; Seravalli, Javier; Cho, Uhn-Soo; Banerjee, Ruma (Michigan-Med); (UNL)

2017-02-17

Hydrogen sulfide is a cardioprotective signaling molecule but is toxic at elevated concentrations. Red blood cells can synthesize H2S but, lacking organelles, cannot dispose of H2S via the mitochondrial sulfide oxidation pathway. We have recently shown that at high sulfide concentrations, ferric hemoglobin oxidizes H2S to a mixture of thiosulfate and iron-bound polysulfides in which the latter species predominates. Here, we report the crystal structure of human hemoglobin containing low spin ferric sulfide, the first intermediate in heme-catalyzed sulfide oxidation. The structure provides molecular insights into why sulfide is susceptible to oxidation in human hemoglobin but is stabilized against it in HbI, a specialized sulfide-carrying hemoglobin from a mollusk adapted to life in a sulfide-rich environment. We have also captured a second sulfide bound at a postulated ligand entry/exit site in the α-subunit of hemoglobin, which, to the best of our knowledge, represents the first direct evidence for this site being used to access the heme iron. Hydrodisulfide, a postulated intermediate at the junction between thiosulfate and polysulfide formation, coordinates ferric hemoglobin and, in the presence of air, generated thiosulfate. At low sulfide/heme iron ratios, the product distribution between thiosulfate and iron-bound polysulfides was approximately equal. The iron-bound polysulfides were unstable at physiological glutathione concentrations and were reduced with concomitant formation of glutathione persulfide, glutathione disulfide, and H2S. Hence, although polysulfides are unlikely to be stable in the reducing intracellular milieu, glutathione persulfide could serve as a persulfide donor for protein persulfidation, a posttranslational modification by which H2S is postulated to signal.

Tourette syndrome research highlights 2015

Science.gov (United States)

Richards, Cheryl A.; Black, Kevin J.

2016-01-01

We present selected highlights from research that appeared during 2015 on Tourette syndrome and other tic disorders. Topics include phenomenology, comorbidities, developmental course, genetics, animal models, neuroimaging, electrophysiology, pharmacology, and treatment. We briefly summarize articles whose results we believe may lead to new treatments, additional research or modifications in current models of TS. PMID:27429744

Progress in the structural understanding of voltage-gated calcium channel (CaV) function and modulation.

Science.gov (United States)

Minor, Daniel L; Findeisen, Felix

2010-01-01

Voltage-gated calcium channels (CaVs) are large, transmembrane multiprotein complexes that couple membrane depolarization to cellular calcium entry. These channels are central to cardiac action potential propagation, neurotransmitter and hormone release, muscle contraction, and calcium-dependent gene transcription. Over the past six years, the advent of high-resolution structural studies of CaV components from different isoforms and CaV modulators has begun to reveal the architecture that underlies the exceptionally rich feedback modulation that controls CaV action. These descriptions of CaV molecular anatomy have provided new, structure-based insights into the mechanisms by which particular channel elements affect voltage-dependent inactivation (VDI), calcium‑dependent inactivation (CDI), and calcium‑dependent facilitation (CDF). The initial successes have been achieved through structural studies of soluble channel domains and modulator proteins and have proven most powerful when paired with biochemical and functional studies that validate ideas inspired by the structures. Here, we review the progress in this growing area and highlight some key open challenges for future efforts.

Is Domain Highlighting Actually Helpful in Identifying Phishing Web Pages?

Science.gov (United States)

Xiong, Aiping; Proctor, Robert W; Yang, Weining; Li, Ninghui

2017-06-01

To evaluate the effectiveness of domain highlighting in helping users identify whether Web pages are legitimate or spurious. As a component of the URL, a domain name can be overlooked. Consequently, browsers highlight the domain name to help users identify which Web site they are visiting. Nevertheless, few studies have assessed the effectiveness of domain highlighting, and the only formal study confounded highlighting with instructions to look at the address bar. We conducted two phishing detection experiments. Experiment 1 was run online: Participants judged the legitimacy of Web pages in two phases. In Phase 1, participants were to judge the legitimacy based on any information on the Web page, whereas in Phase 2, they were to focus on the address bar. Whether the domain was highlighted was also varied. Experiment 2 was conducted similarly but with participants in a laboratory setting, which allowed tracking of fixations. Participants differentiated the legitimate and fraudulent Web pages better than chance. There was some benefit of attending to the address bar, but domain highlighting did not provide effective protection against phishing attacks. Analysis of eye-gaze fixation measures was in agreement with the task performance, but heat-map results revealed that participants' visual attention was attracted by the highlighted domains. Failure to detect many fraudulent Web pages even when the domain was highlighted implies that users lacked knowledge of Web page security cues or how to use those cues. Potential applications include development of phishing prevention training incorporating domain highlighting with other methods to help users identify phishing Web pages.

Cellulases from Thermophilic Fungi: Recent Insights and Biotechnological Potential

Directory of Open Access Journals (Sweden)

Duo-Chuan Li

2011-01-01

Full Text Available Thermophilic fungal cellulases are promising enzymes in protein engineering efforts aimed at optimizing industrial processes, such as biomass degradation and biofuel production. The cloning and expression in recent years of new cellulase genes from thermophilic fungi have led to a better understanding of cellulose degradation in these species. Moreover, crystal structures of thermophilic fungal cellulases are now available, providing insights into their function and stability. The present paper is focused on recent progress in cloning, expression, regulation, and structure of thermophilic fungal cellulases and the current research efforts to improve their properties for better use in biotechnological applications.

New Insights into HTLV-1 Particle Structure, Assembly, and Gag-Gag Interactions in Living Cells

Directory of Open Access Journals (Sweden)

Jolene L. Johnson

2011-06-01

Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 has a reputation for being extremely difficult to study in cell culture. The challenges in propagating HTLV-1 has prevented a rigorous analysis of how these viruses replicate in cells, including the detailed steps involved in virus assembly. The details for how retrovirus particle assembly occurs are poorly understood, even for other more tractable retroviral systems. Recent studies on HTLV-1 using state-of-the-art cryo-electron microscopy and fluorescence-based biophysical approaches explored questions related to HTLV-1 particle size, Gag stoichiometry in virions, and Gag-Gag interactions in living cells. These results provided new and exciting insights into fundamental aspects of HTLV-1 particle assembly—which are distinct from those of other retroviruses, including HIV-1. The application of these and other novel biophysical approaches promise to provide exciting new insights into HTLV-1 replication.

Structural setting of the Metán Basin (NW Argentina): new insights from 2D seismic profiles

Science.gov (United States)

Conti, Alessia; Maffucci, Roberta; Bigi, Sabina; Corrado, Sveva; Giordano, Guido; Viramonte, José G.

2017-04-01

The Metán Basin is located in the sub-Andean foreland, in the southernmost portion of the Santa Barbara system structural province (NW Argentina). The upper crust in this region shows a strong segmentation due to inherited stratigraphic and structural discontinuities, related to a Palaeozoic orogenic event and to a Cretaceous to Paleogene rifting event (Kley et al., 1999; Iaffa et al., 2011). This study seeks to unravel the deep structural setting of the basin, in order to better understand the tectonic evolution of the area. Different seismic sections are analysed, located in the Metán basin and acquired by YPF (Yacimientos Petrolíferos Fiscales, former national oil company of Argentina) in different surveys during the '70s - '80s. Stratigraphic control for the seismic interpretation is provided by petroleum exploratory wells drilled in the basin; they show a stratigraphic succession of syn-rift and post-rift deposits, mainly constituted by a continental succession of red beds, with minor limestone intercalations (Salta Group), overlain by a thick continental foreland basin succession (Orán Group) (Salfity et al., 1981). From a structural point of view, the Metán basin is characterized by a variety of structural trends, with thrust faults and related folds mainly trending N-S, NE-SW and NNE-SSW. Different mechanism can be responsible for the folding of the sedimentary cover; hangingwall anticlines are represented both by high angle thrust faults produced by inversion of Cretaceous extensional faults (Maffucci et al., 2015), and by fault propagation folds formed during the Andean shortening event. The study of the interaction between the older reactivated faults and the newly generated ones could provide new insights to unravel the complex structural setting of the area. References Iaffa D. N., Sàbat, F., Muñoz, J.A., Mon, R., Gutierrez, A.A., 2011. The role of inherited structures in a foreland basin evolution. The Metán Basin in NW Argentina. Journal of

Combining microsatellite, otolith shape and parasites community analyses as a holistic approach to assess population structure of Dentex dentex

Science.gov (United States)

Marengo, M.; Baudouin, M.; Viret, A.; Laporte, M.; Berrebi, P.; Vignon, M.; Marchand, B.; Durieux, E. D. H.

2017-10-01

The common dentex, Dentex dentex, is an iconic marine coastal fish of the Mediterranean Sea. Despite its economic and ecological importance, data on the population structure of this species are still very limited. The aim of this study was to identify the stock structure of the common dentex at relatively fine spatial scale around Corsica Island, using a combination of markers that have different spatial and temporal scales of integration: microsatellite DNA markers, otolith shape analysis and parasites communities. Microsatellite analysis indicated that there was no significant genetic differentiation in D. dentex between the four sampling sites around Corsica. Otolith shape analysis suggests one potential distinct population unit of D. dentex centered in one site (Cap Corse) varying in their degree of differentiation from those in the other zones. Multivariate analysis on parasite abundance data highlights to a lower extent two sites (Bonifacio and Galeria) with some connectivity between adjacent zones. The combination of these three markers together highlights the resulting three sites while giving complementary insights and an opportunity to compare their utility and potential to understand population interactions. A complex population structure around Corsican coasts is then proposed, providing a new perspective on common dentex fishery stock conservation and management strategies.

Highlights of the Annual Congress of the European Association of Nuclear Medicine, Helsinki 2004, and a dash of horizon scanning

International Nuclear Information System (INIS)

Ell, Peter J.

2005-01-01

The Annual Congress of the European Association of Nuclear Medicine represents the major scientific and professional event in the field of nuclear medicine in Europe. Specialists from all allied professions meet to discuss the latest findings and discoveries. A very large industrial exhibition demonstrates the latest technological innovations and developments. This Highlights Lecture summarises the scientific and medical advances discussed at this important gathering. The lecture covers a significant proportion of the data presented and/or discussed in up-to-date reviews, and places some of the trends encountered in the context of the evolution of the field as a whole. There is much food for thought in most areas of nuclear medicine: advances in instrumentation and data processing, progress in radiochemistry and pharmacy, novel diagnostics and therapeutics, and new insights in known areas of clinical application such as neurology and psychiatry, cardiology, oncology, endocrine disorders, paediatrics, nephro-urology and musculoskeletal disorders. This Highlights Lecture is, however, only a brief resume of the vast amount of data discussed, which can be found in much greater detail in the Congress Proceedings, published as volume 31, supplement 2 of Eur J Nucl Med Mol Imagingin August 2004. (orig.)

Particle swarm optimization of the stable structure of tetrahexahedral Pt-based bimetallic nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Liu, Tun-Dong; Fan, Tian-E [Center for Cloud Computing and Big Data, Department of Automation, Xiamen University, Xiamen 361005 (China); Shao, Gui-Fang, E-mail: gfshao@xmu.edu.cn [Center for Cloud Computing and Big Data, Department of Automation, Xiamen University, Xiamen 361005 (China); Zheng, Ji-Wen [Center for Cloud Computing and Big Data, Department of Automation, Xiamen University, Xiamen 361005 (China); Wen, Yu-Hua [Institute of Theoretical Physics and Astrophysics, Department of Physics, Xiamen University, Xiamen 361005 (China)

2014-08-14

Bimetallic nanoparticles, enclosed by high-index facets, have great catalytic activity and selectivity owing to the synergy effects of high-index facets and the electronic structures of alloy. In this paper, a discrete particle swarm optimization algorithm was employed to systematically investigate the structural stability and features of tetrahexahedral Pt-based bimetallic nanoparticles with high-index facets. Different Pt/Ag, Pt/Cu, Pt/Pd atom ratios and particle sizes were considered in this work. The simulation results reveal that these alloy nanoparticles exhibit considerably different structural characteristics. Pt–Ag nanoparticles tend to form Pt–Ag core–shell structure. Pt–Cu nanoparticles are preferred to take multi-shell structure with Cu on the outer surface while Pt–Pd nanoparticles present a mixing structure in the interior and Pd-dominated surface. Atomic distribution and bonding characteristics were applied to further characterize the structural features of Pt-based nanoparticles. This study provides an important insight into the structural stability and features of Pt-based nanoparticles with different alloys. - Highlights: • We explore the structural stability of Pt-based alloy NPs by a discrete PSO. • Our study discovers the different structural characteristics for Pt-based NPs. • Alloy composition and size have important effects on the surface segregation. • Our work shows strong phase separation for Pt–Ag NPs while weak for Pt–Pd NPs.

Particle swarm optimization of the stable structure of tetrahexahedral Pt-based bimetallic nanoparticles

International Nuclear Information System (INIS)

Liu, Tun-Dong; Fan, Tian-E; Shao, Gui-Fang; Zheng, Ji-Wen; Wen, Yu-Hua

2014-01-01

Bimetallic nanoparticles, enclosed by high-index facets, have great catalytic activity and selectivity owing to the synergy effects of high-index facets and the electronic structures of alloy. In this paper, a discrete particle swarm optimization algorithm was employed to systematically investigate the structural stability and features of tetrahexahedral Pt-based bimetallic nanoparticles with high-index facets. Different Pt/Ag, Pt/Cu, Pt/Pd atom ratios and particle sizes were considered in this work. The simulation results reveal that these alloy nanoparticles exhibit considerably different structural characteristics. Pt–Ag nanoparticles tend to form Pt–Ag core–shell structure. Pt–Cu nanoparticles are preferred to take multi-shell structure with Cu on the outer surface while Pt–Pd nanoparticles present a mixing structure in the interior and Pd-dominated surface. Atomic distribution and bonding characteristics were applied to further characterize the structural features of Pt-based nanoparticles. This study provides an important insight into the structural stability and features of Pt-based nanoparticles with different alloys. - Highlights: • We explore the structural stability of Pt-based alloy NPs by a discrete PSO. • Our study discovers the different structural characteristics for Pt-based NPs. • Alloy composition and size have important effects on the surface segregation. • Our work shows strong phase separation for Pt–Ag NPs while weak for Pt–Pd NPs

The Association of Insight and Change in Insight with Clinical Symptoms in Depressed Inpatients.

Science.gov (United States)

He, Hongbo; Chang, Qing; Ma, Yarong

2018-04-25

Lack of insight has been extensively studied and was found to be adversely correlated with impaired treatment compliance and worse long term clinical outcomes among patients with schizophrenia, while not much is known about this phenonmenon in patients with severe depression. To explore the correlates of insight and its relation to symptom changes among the most seriously ill patients with affective disorders, those who require hospitalization. Patients hospitalized in a large psychiatric hospital in south China with either major depressive disorder (MDD)(N=55) or bipolar depression (BD) (N=85) based on ICD-10 diagnostic criteria were assessed with the Insight and Treatment Attitudes Questionnaire (ITAQ) one week after admission and at the time of discharge. Clinical symptoms were measured at the same time with the Hamilton Rating Scale for Depression (HAMD-17) and the Depression subscale of the Symptom Check list-90 (SCL-90). Length of stay (LOS), duration of illness, duration of untreated mood disorder, number of previous episodes of depression and previous admissions for depression were documented during interviews with patients and their families and from a review of medical records. Bivariate correlations and multiple regression analysis were used to examine the relationship of sociodemographic characteristics, clinical symptomatology and clinical history, to insight at the time of admission. The relationships between change in clinical symptoms and change in insight from admission to discharge were also examined. Stepwise multiple regression models suggested that any previous admissions for depression and higher anxiety factor scores on the HAMD-17 are significant independent predictors of insight accounting for 22.9% of the variance. Multiple regression analysis residual change scores (change scores adjusted for baseline values) on the ITAQ showed that improved insight over average stays of 51 days were inversely related to the residual psychomotor

Insights from 20 years of bacterial genome sequencing

DEFF Research Database (Denmark)

Land, Miriam; Hauser, Loren; Jun, Se-Ran

2015-01-01

Since the first two complete bacterial genome sequences were published in 1995, the science of bacteria has dramatically changed. Using third-generation DNA sequencing, it is possible to completely sequence a bacterial genome in a few hours and identify some types of methylation sites along...... the genome as well. Sequencing of bacterial genome sequences is now a standard procedure, and the information from tens of thousands of bacterial genomes has had a major impact on our views of the bacterial world. In this review, we explore a series of questions to highlight some insights that comparative...... genomics has produced. To date, there are genome sequences available from 50 different bacterial phyla and 11 different archaeal phyla. However, the distribution is quite skewed towards a few phyla that contain model organisms. But the breadth is continuing to improve, with projects dedicated to filling...

Structural insight into the role of Streptococcus parasanguinis Fap1 within oral biofilm formation

Energy Technology Data Exchange (ETDEWEB)

Garnett, James A.; Simpson, Peter J.; Taylor, Jonathan; Benjamin, Stefi V.; Tagliaferri, Camille; Cota, Ernesto [Department of Biological Sciences, Centre for Structural Biology, Imperial College London, South Kensington, London SW7 2AZ (United Kingdom); Chen, Yi-Ywan M. [Department of Microbiology and Immunology, and Research Center for Pathogenic Bacteria, Chang Gung University, Tao-Yuan, Taiwan (China); Wu, Hui [Department of Pediatric Dentistry, University of Alabama at Birmingham, School of Dentistry, Birmingham, AL 35294 (United States); Matthews, Stephen, E-mail: s.j.matthews@imperial.ac.uk [Department of Biological Sciences, Centre for Structural Biology, Imperial College London, South Kensington, London SW7 2AZ (United Kingdom)

2012-01-06

Highlights: Black-Right-Pointing-Pointer Crystal structure of Streptococcus parasanguinis Fap1-NR{sub {alpha}} at pH 5.0. Black-Right-Pointing-Pointer pH-dependent conformational changes mediated through electrostatic potential of Fap1-NR{sub {alpha}}. Black-Right-Pointing-Pointer Fap1 facilitates pH-dependent biofilms. Black-Right-Pointing-Pointer We model inter-Fap1 biofilm interactions. -- Abstract: The fimbriae-associated protein 1 (Fap1) is a major adhesin of Streptococcus parasanguinis, a primary colonizer of the oral cavity that plays an important role in the formation of dental plaque. Fap1 is an extracellular adhesive surface fibre belonging to the serine-rich repeat protein (SRRP) family, which plays a central role in the pathogenesis of streptococci and staphylococci. The N-terminal adhesive region of Fap1 (Fap1-NR) is composed of two domains (Fap1-NR{sub {alpha}} and Fap1-NR{sub {beta}}) and is projected away from the bacterial surface via the extensive serine-rich repeat region, for adhesion to the salivary pellicle. The adhesive properties of Fap1 are modulated through a pH switch in which a reduction in pH results in a rearrangement between the Fap1-NR{sub {alpha}} and Fap1-NR{sub {beta}} domains, which assists in the survival of S. parasanguinis in acidic environments. We have solved the structure of Fap1-NR{sub {alpha}} at pH 5.0 at 3.0 A resolution and reveal how subtle rearrangements of the 3-helix bundle combined with a change in electrostatic potential mediates 'opening' and activation of the adhesive region. Further, we show that pH-dependent changes are critical for biofilm formation and present an atomic model for the inter-Fap1-NR interactions which have been assigned an important role in the biofilm formation.

Structural insight into the role of Streptococcus parasanguinis Fap1 within oral biofilm formation

International Nuclear Information System (INIS)

Garnett, James A.; Simpson, Peter J.; Taylor, Jonathan; Benjamin, Stefi V.; Tagliaferri, Camille; Cota, Ernesto; Chen, Yi-Ywan M.; Wu, Hui; Matthews, Stephen

2012-01-01

Highlights: ► Crystal structure of Streptococcus parasanguinis Fap1-NR α at pH 5.0. ► pH-dependent conformational changes mediated through electrostatic potential of Fap1-NR α . ► Fap1 facilitates pH-dependent biofilms. ► We model inter-Fap1 biofilm interactions. -- Abstract: The fimbriae-associated protein 1 (Fap1) is a major adhesin of Streptococcus parasanguinis, a primary colonizer of the oral cavity that plays an important role in the formation of dental plaque. Fap1 is an extracellular adhesive surface fibre belonging to the serine-rich repeat protein (SRRP) family, which plays a central role in the pathogenesis of streptococci and staphylococci. The N-terminal adhesive region of Fap1 (Fap1-NR) is composed of two domains (Fap1-NR α and Fap1-NR β ) and is projected away from the bacterial surface via the extensive serine-rich repeat region, for adhesion to the salivary pellicle. The adhesive properties of Fap1 are modulated through a pH switch in which a reduction in pH results in a rearrangement between the Fap1-NR α and Fap1-NR β domains, which assists in the survival of S. parasanguinis in acidic environments. We have solved the structure of Fap1-NR α at pH 5.0 at 3.0 A resolution and reveal how subtle rearrangements of the 3-helix bundle combined with a change in electrostatic potential mediates ‘opening’ and activation of the adhesive region. Further, we show that pH-dependent changes are critical for biofilm formation and present an atomic model for the inter-Fap1-NR interactions which have been assigned an important role in the biofilm formation.

Genetic correlates of insight in schizophrenia.

Science.gov (United States)

Xavier, Rose Mary; Vorderstrasse, Allison; Keefe, Richard S E; Dungan, Jennifer R

2018-05-01

Insight in schizophrenia is clinically important as it is associated with several adverse outcomes. Genetic contributions to insight are unknown. We examined genetic contributions to insight by investigating if polygenic risk scores (PRS) and candidate regions were associated with insight. Schizophrenia case-only analysis of the Clinical Antipsychotics Trials of Intervention Effectiveness trial. Schizophrenia PRS was constructed using Psychiatric Genomics Consortium (PGC) leave-one out GWAS as discovery data set. For candidate regions, we selected 105 schizophrenia-associated autosomal loci and 11 schizophrenia-related oligodendrocyte genes. We used regressions to examine PRS associations and set-based testing for candidate analysis. We examined data from 730 subjects. Best-fit PRS at p-threshold of 1e-07 was associated with total insight (R 2 =0.005, P=0.05, empirical P=0.054) and treatment insight (R 2 =0.005, P=0.048, empirical P=0.048). For models that controlled for neurocognition, PRS significantly predicted treatment insight but at higher p-thresholds (0.1 to 0.5) but did not survive correction. Patients with highest polygenic burden had 5.9 times increased risk for poor insight compared to patients with lowest burden. PRS explained 3.2% (P=0.002, empirical P=0.011) of variance in poor insight. Set-based analyses identified two variants associated with poor insight- rs320703, an intergenic variant (within-set P=6e-04, FDR P=0.046) and rs1479165 in SOX2-OT (within-set P=9e-04, FDR P=0.046). To the best of our knowledge, this is the first study examining genetic basis of insight. We provide evidence for genetic contributions to impaired insight. Relevance of findings and necessity for replication are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

U6+ minerals and inorganic compounds: insights into an expanded structural hierarchy of crystal structures

International Nuclear Information System (INIS)

Burns, P.C.

2005-01-01

The crystal structures of uranyl minerals and inorganic uranyl compounds are important for understanding the genesis of U deposits, the interaction of U mine and mill tailings with the environment, transport of actinides in soils and the vadose zone, the performance of geological repositories for nuclear waste, and for the development of advanced materials with novel applications. Over the past decade, the number of inorganic uranyl compounds (including minerals) with known structures has more than doubled, and reconsideration of the structural hierarchy of uranyl compounds is warranted. Here, 368 inorganic crystal structures that contain essential U 6+ are considered (of which 89 are minerals). They are arranged on the basis of the topological details of their structural units, which are formed by the polymerization of polyhedra containing higher-valence cations. Overarching structural categories correspond to those based upon isolated polyhedra (8), finite clusters (43), chains (57), sheets (204), and frameworks (56) of polyhedra. Within these categories, structures are organized and compared upon the basis of either their graphical representations, or in the case of sheets involving sharing of edges of polyhedra, upon the topological arrangement of anions within the sheets. (author)

Improving Student Retention in Online College Classes: Qualitative Insights from Faculty

Science.gov (United States)

Russo-Gleicher, Rosalie J.

2014-01-01

This article provides qualitative insights into addressing the issue of student retention in online classes in higher education. Semi-structured, in-depth interviews were conducted at random with 16 faculty who teach online courses at a large community college in the Northeast about how to improve online student retention. Qualitative analysis…

Brookhaven highlights, October 1979-September 1980

International Nuclear Information System (INIS)

1980-01-01

Highlights are given for the research areas of the Brookhaven National Laboratory. These areas include high energy physics, physics and chemistry, life sciences, applied energy science (energy and environment, and nuclear energy), and support activities (including mathematics, instrumentation, reactors, and safety)

Topographic attributes as a guide for automated detection or highlighting of geological features

Science.gov (United States)

Viseur, Sophie; Le Men, Thibaud; Guglielmi, Yves

2015-04-01

Photogrammetry or LIDAR technology combined with photography allow geoscientists to obtain 3D high-resolution numerical representations of outcrops, generally termed as Digital Outcrop Models (DOM). For over a decade, these 3D numerical outcrops serve as support for precise and accurate interpretations of geological features such as fracture traces or plans, strata, facies mapping, etc. These interpretations have the benefit to be directly georeferenced and embedded into the 3D space. They are then easily integrated into GIS or geomodeler softwares for modelling in 3D the subsurface geological structures. However, numerical outcrops generally represent huge data sets that are heavy to manipulate and hence to interpret. This may be particularly tedious as soon as several scales of geological features must be investigated or as geological features are very dense and imbricated. Automated tools for interpreting geological features from DOMs would be then a significant help to process these kinds of data. Such technologies are commonly used for interpreting seismic or medical data. However, it may be noticed that even if many efforts have been devoted to easily and accurately acquire 3D topographic point clouds and photos and to visualize accurate 3D textured DOMs, few attentions have been paid to the development of algorithms for automated detection of the geological structures from DOMs. The automatic detection of objects on numerical data generally assumes that signals or attributes computed from this data allows the recognition of the targeted object boundaries. The first step consists then in defining attributes that highlight the objects or their boundaries. For DOM interpretations, some authors proposed to use differential operators computed on the surface such as normal or curvatures. These methods generally extract polylines corresponding to fracture traces or bed limits. Other approaches rely on the PCA technology to segregate different topographic plans

Tracking the source of mineralisation in the Tampere Basin (southern Finland), insights from structure, sedimentology and geophysics studies

DEFF Research Database (Denmark)

Moreau, Julien; Torvela, Taija; Kalliomäki, Henrik

2013-01-01

The ancient basins are of a wide interest to geoscientists as they archive the early development of plate tectonics, life, and ore-bearing systems. Several basins, especially those involving volcanic-derived materials, contain ore and mineral deposits. The formation of these ores is often related...... marginal basin, and the mechanics of and strain distribution during its subsequent closure. In order to investigate the deposition, the tectonic deformation and the fluid migration, geological mapping of a key area of the basin has been performed. In addition, georadar reflection profiles have been...... covered. This study highlighted several sulphide-rich horizon within the basal succession of the basin infill. The sulphides are either in relation with tectonic structures or with genuinely clay-rich deposits. The studied succession shows a progressive deepening of the basin through time with facies...

Structural insight in the inhibition of adherence of F4 fimbriae producing enterotoxigenic Escherichia coli by llama single domain antibodies.

Science.gov (United States)

Moonens, Kristof; Van den Broeck, Imke; Okello, Emmanuel; Pardon, Els; De Kerpel, Maia; Remaut, Han; De Greve, Henri

2015-02-24

Enterotoxigenic Escherichia coli that cause neonatal and post-weaning diarrhea in piglets express F4 fimbriae to mediate attachment towards host receptors. Recently we described how llama single domain antibodies (VHHs) fused to IgA, produced in Arabidopsis thaliana seeds and fed to piglets resulted in a progressive decline in shedding of F4 positive ETEC bacteria. Here we present the structures of these inhibiting VHHs in complex with the major adhesive subunit FaeG. A conserved surface, distant from the lactose binding pocket, is targeted by these VHHs, highlighting the possibility of targeting epitopes on single-domain adhesins that are non-involved in receptor binding.

SDSL-ESR-based protein structure characterization

NARCIS (Netherlands)

Strancar, J.; Kavalenka, A.A.; Urbancic, I.; Ljubetic, A.; Hemminga, M.A.

2010-01-01

As proteins are key molecules in living cells, knowledge about their structure can provide important insights and applications in science, biotechnology, and medicine. However, many protein structures are still a big challenge for existing high-resolution structure-determination methods, as can be

University of Maryland MRSEC - Research: Highlights

Science.gov (United States)

-Engineering Program: Project Lead the Way Thinking Small: Nanoscale Informal Science Education (NISE Education Outreach Highlights NanoFabulous Greatest Show on Earth: Big Top Physics, USA Science and Perspective at UMD MRSEC Nanoscience Camp Annual Middle School Student Science Conference (SSC) Pre

Brookhaven highlights, October 1979-September 1980

Energy Technology Data Exchange (ETDEWEB)

1980-01-01

Highlights are given for the research areas of the Brookhaven National Laboratory. These areas include high energy physics, physics and chemistry, life sciences, applied energy science (energy and environment, and nuclear energy), and support activities (including mathematics, instrumentation, reactors, and safety). (GHT)

Brookhaven highlights - Brookhaven National Laboratory 1995

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-09-01

This report highlights research conducted at Brookhaven National Laboratory in the following areas: alternating gradient synchrotron; physics; biology; national synchrotron light source; department of applied science; medical; chemistry; department of advanced technology; reactor; safety and environmental protection; instrumentation; and computing and communications.

Cyclotide Evolution: Insights from the Analyses of Their Precursor Sequences, Structures and Distribution in Violets (Viola

Directory of Open Access Journals (Sweden)

Sungkyu Park

2017-12-01

Full Text Available Cyclotides are a family of plant proteins that are characterized by a cyclic backbone and a knotted disulfide topology. Their cyclic cystine knot (CCK motif makes them exceptionally resistant to thermal, chemical, and enzymatic degradation. By disrupting cell membranes, the cyclotides function as host defense peptides by exhibiting insecticidal, anthelmintic, antifouling, and molluscicidal activities. In this work, we provide the first insight into the evolution of this family of plant proteins by studying the Violaceae, in particular species of the genus Viola. We discovered 157 novel precursor sequences by the transcriptomic analysis of six Viola species: V. albida var. takahashii, V. mandshurica, V. orientalis, V. verecunda, V. acuminata, and V. canadensis. By combining these precursor sequences with the phylogenetic classification of Viola, we infer the distribution of cyclotides across 63% of the species in the genus (i.e., ~380 species. Using full precursor sequences from transcriptomes, we show an evolutionary link to the structural diversity of the cyclotides, and further classify the cyclotides by sequence signatures from the non-cyclotide domain. Also, transcriptomes were compared to cyclotide expression on a peptide level determined using liquid chromatography-mass spectrometry. Furthermore, the novel cyclotides discovered were associated with the emergence of new biological functions.

Highlights of nuclear chemistry 1994

International Nuclear Information System (INIS)

1994-12-01

Highlights were: 1. Fission product release: benchmark calculations for severe nuclear accidents; 2. Thermochemical data for reactor materials and fission products; 3. thermochemical calculations on fuel of the high-temperature gas-cooled reactor; 4. Formation of organic tellurides during nuclear accidents?; 5. Reaction of tellurium with Zircaloy-4; 6. Transmutation of fission products; 7. The thermal conductivity of high-burnup UO 2 fuel; 8. Tritium retention in graphite. (orig./HP)

Insights into the Structural Changes Occurring upon Photoconversion in the Orange Carotenoid Protein from Broadband Two-Dimensional Electronic Spectroscopy

Energy Technology Data Exchange (ETDEWEB)

De Re, Eleonora; Schlau-Cohen, Gabriela S.; Leverenz, Ryan L.; Huxter, Vanessa M.; Oliver, Thomas A. A.; Mathies, Richard A.; Fleming, Graham R.

2014-05-22

Carotenoids play an essential role in photoprotection, interacting with other pigments to safely dissipate excess absorbed energy as heat. In cyanobacteria, the short time scale photoprotective mechanisms involve the photoactive orange carotenoid protein (OCP), which binds a single carbonyl carotenoid. Blue-green light induces the photoswitching of OCP from its ground state form (OCPO) to a metastable photoproduct (OCPR). OCPR can bind to the phycobilisome antenna and induce fluorescence quenching. The photoswitching is accompanied by structural and functional changes at the level of the protein and of the bound carotenoid. In this study, we use broadband two-dimensional electronic spectroscopy to look at the differences in excited state dynamics of the carotenoid in the two forms of OCP. Our results provide insight into the origin of the pronounced vibrational lineshape and oscillatory dynamics observed in linear absorption and 2D electronic spectroscopy of OCPO and the large inhomogeneous broadening in OCPR, with consequences for the chemical function of the two forms.

The multitasking organ: recent insights into skin immune function.

Science.gov (United States)

Di Meglio, Paola; Perera, Gayathri K; Nestle, Frank O

2011-12-23

The skin provides the first line defense of the human body against injury and infection. By integrating recent findings in cutaneous immunology with fundamental concepts of skin biology, we portray the skin as a multitasking organ ensuring body homeostasis. Crosstalk between the skin and its microbial environment is also highlighted as influencing the response to injury, infection, and autoimmunity. The importance of the skin immune network is emphasized by the identification of several skin-resident cell subsets, each with its unique functions. Lessons learned from targeted therapy in inflammatory skin conditions, such as psoriasis, provide further insights into skin immune function. Finally, we look at the skin as an interacting network of immune signaling pathways exemplified by the development of a disease interactome for psoriasis. Copyright © 2011 Elsevier Inc. All rights reserved.

Reintegration upon return: insights from Ecuadorian returnees from Spain

OpenAIRE

Mercier, Marion; David, Anda; Mahia, Ramón; De Arce, Rafael

2016-01-01

Using the ECM2 survey data on Ecuadorian migrants returning from Spain, we investigate the determinants of reintegration upon return. We study how the migration experience, but also the before- and after-migration characteristics, correlate with migrants’ outcomes upon return. We adopt a broad conception of reintegration, considering jointly labour market-related outcomes that proxy for structural reintegration and subjective indicators that provide insights on sociocultural reintegration. Th...

Emulating a flexible space structure: Modeling

Science.gov (United States)

Waites, H. B.; Rice, S. C.; Jones, V. L.

1988-01-01

Control Dynamics, in conjunction with Marshall Space Flight Center, has participated in the modeling and testing of Flexible Space Structures. Through the series of configurations tested and the many techniques used for collecting, analyzing, and modeling the data, many valuable insights have been gained and important lessons learned. This paper discusses the background of the Large Space Structure program, Control Dynamics' involvement in testing and modeling of the configurations (especially the Active Control Technique Evaluation for Spacecraft (ACES) configuration), the results from these two processes, and insights gained from this work.

A holistic evolutionary and structural study of flaviviridae provides insights into the function and inhibition of HCV helicase

Directory of Open Access Journals (Sweden)

Dimitrios Vlachakis

2013-05-01

Full Text Available Viral RNA helicases are involved in duplex unwinding during the RNA replication of the virus. It is suggested that these helicases represent very promising antiviral targets. Viruses of the flaviviridae family are the causative agents of many common and devastating diseases, including hepatitis, yellow fever and dengue fever. As there is currently no available anti-Flaviviridae therapy, there is urgent need for the development of efficient anti-viral pharmaceutical strategies. Herein, we report the complete phylogenetic analysis across flaviviridae alongside a more in-depth evolutionary study that revealed a series of conserved and invariant amino acids that are predicted to be key to the function of the helicase. Structural molecular modelling analysis revealed the strategic significance of these residues based on their relative positioning on the 3D structures of the helicase enzymes, which may be used as pharmacological targets. We previously reported a novel series of highly potent HCV helicase inhibitors, and we now re-assess their antiviral potential using the 3D structural model of the invariant helicase residues. It was found that the most active compound of the series, compound C4, exhibited an IC50 in the submicromolar range, whereas its stereoisomer (compound C12 was completely inactive. Useful insights were obtained from molecular modelling and conformational search studies via molecular dynamics simulations. C12 tends to bend and lock in an almost “U” shape conformation, failing to establish vital interactions with the active site of HCV. On the contrary, C4 spends most of its conformational time in a straight, more rigid formation that allows it to successfully block the passage of the oligonucleotide in the ssRNA channel of the HCV helicase. This study paves the way and provides the necessary framework for the in-depth analysis required to enable the future design of new and potent anti-viral agents.

Insights into crustal structure of the Eastern North American Margin from community multichannel seismic and potential field data

Science.gov (United States)

Davis, J. K.; Becel, A.; Shillington, D. J.; Buck, W. R.

2017-12-01

In the fall of 2014, the R/V Marcus Langseth collected gravity, magnetic, and reflection seismic data as part of the Eastern North American Margin Community Seismic Experiment. The dataset covers a 500 km wide section of the Mid-Atlantic passive margin offshore North Carolina, which formed after the Mesozoic breakup of the supercontinent Pangaea. Using these seismic and potential field data, we present observations and interpretations along two cross margin and one along-margin profiles. Analyses and interpretations are conducted using pre-stack depth migrated reflection seismic profiles in conjunction with forward modeling of shipboard gravity and magnetic anomalies. Preliminary interpretations of the data reveal variations in basement character and structure across the entire transition between continental and oceanic domains. These interpretations help provide insight into the origin and nature of the prominent East Coast and Blake Spur magnetic anomalies, as well as the Inner Magnetic Quiet Zone which occupies the domain between the anomalies. Collectively, these observations can aid in deciphering the rift-to-drift transition during the breakup of North America and West Africa and formation of the Central Atlantic.

Adsorption studies of alcohol molecules on monolayer MoS_2 nanosheet—A first-principles insights

International Nuclear Information System (INIS)

Nagarajan, V.; Chandiramouli, R.

2017-01-01

Highlights: • The adsorption of methanol, ethanol & 1-propanol on MoS_2 nanosheet are studied. • The PDOS & band structure confirms adsorption of alcohol vapors on MoS_2 nanosheet. • The adsorption of 1-propanol vapor on MoS_2 nanosheet is more favorable. • The alcohol molecules adsorption on MoS_2 nanosheet is explored in atomistic level. - Abstract: The electronic and adsorption properties of three different alcohol molecules namely methanol, ethanol and 1-propanol vapors on MoS_2 nanosheet is investigated using DFT method. The structural stability of MoS_2 nanosheet is ascertained with formation energy. The adsorption properties of alcohol molecules on MoS_2 base material is discussed in terms of average energy gap variation, Mulliken charge transfer, energy band gap and adsorption energy. The prominent adsorption sites of methanol, ethanol and 1-propanol vapors on MoS_2 nanosheet are studied in atomistic level. The projected density of states (PDOS) spectrum gives the clear insights on the electronic properties of MoS_2 nanosheet. The PDOS and energy band structure confirmed the adsorption of alcohol vapors on MoS_2 nanosheet. The variation in the band structure and PDOS is noticed upon adsorption of methanol, ethanol and 1-propanol molecules on MoS_2 nanosheet. The PDOS spectrum also reveals the variation in peak maxima owing to transfer of electron between alcohol molecules and MoS_2 base material. The adsorption of 1-propanol vapor on MoS_2 nanosheet is observed to be more favorable than other alcohol molecules. The findings confirm that monolayer MoS_2 nanosheet can be used to detect the presence of alcohol vapors in the environment.

Insight into the Dzyaloshinskii-Moriya interaction through first-principles study of chiral magnetic structures

Science.gov (United States)

Sandratskii, L. M.

2017-07-01

The purpose of the paper is to gain deeper insight into microscopic formation of the Dzyaloshinskii-Moriya interaction (DMI). The paper aims at the development of the physical picture able to address apparently contradicting conclusions of recent studies concerning the location of the DMI energy in the real and reciprocal spaces as well as the relation between values of the atomic moments and the DMI strength. The main tools of our study are the first-principles calculations of the energies of the spiral magnetic states with opposite chiralities. We suggest a method of the calculation of the spiral structures with account for the spin-orbit coupling (SOC). It is based on the application of the generalized Bloch theorem and generalized Bloch functions and allows to reduce the consideration of arbitrary incommensurate spiral to small chemical unit cell. The method neglects the anisotropy in the plane orthogonal to the rotation axis of the spirals that does not influence importantly the DMI energy. For comparison, the supercell calculation with full account for the SOC is performed. The concrete calculations are performed for the Co/Pt bilayer. We consider the distribution of the DMI energy in both real and reciprocal spaces and the dependence of the DMI on the number of electrons. The results of the calculations reveal a number of energy compensations in the formation of the DMI. Thus, the partial atomic contributions as functions of the spiral wave vector q are nonmonotonic and have strongly varying slopes. However, in the total DMI energy these atom-related features compensate each other, resulting in a smooth q dependence. The reason for the peculiar form of the partial DMI contributions is a q -dependent difference in the charge distribution between q and -q spirals. The strongly q -dependent relation between atomic contributions shows that the real-space distribution of the DMI energy obtained for a selected q value cannot be considered as a general

Insights from simulations of star formation

International Nuclear Information System (INIS)

Larson, Richard B

2007-01-01

Although the basic physics of star formation is classical, numerical simulations have yielded essential insights into how stars form. They show that star formation is a highly nonuniform runaway process characterized by the emergence of nearly singular peaks in density, followed by the accretional growth of embryo stars that form at these density peaks. Circumstellar discs often form from the gas being accreted by the forming stars, and accretion from these discs may be episodic, driven by gravitational instabilities or by protostellar interactions. Star-forming clouds typically develop filamentary structures, which may, along with the thermal physics, play an important role in the origin of stellar masses because of the sensitivity of filament fragmentation to temperature variations. Simulations of the formation of star clusters show that the most massive stars form by continuing accretion in the dense cluster cores, and this again is a runaway process that couples star formation and cluster formation. Star-forming clouds also tend to develop hierarchical structures, and smaller groups of forming objects tend to merge into progressively larger ones, a generic feature of self-gravitating systems that is common to star formation and galaxy formation. Because of the large range of scales and the complex dynamics involved, analytic models cannot adequately describe many aspects of star formation, and detailed numerical simulations are needed to advance our understanding of the subject. 'The purpose of computing is insight, not numbers.' Richard W Hamming, in Numerical Methods for Scientists and Engineers (1962) 'There are more things in heaven and earth, Horatio, than are dreamt of in your philosophy.' William Shakespeare, in Hamlet, Prince of Denmark (1604) (key issues review)

Insights from simulations of star formation

Energy Technology Data Exchange (ETDEWEB)

Larson, Richard B [Department of Astronomy, Yale University, Box 208101, New Haven, CT 06520-8101 (United States)

2007-03-15

Although the basic physics of star formation is classical, numerical simulations have yielded essential insights into how stars form. They show that star formation is a highly nonuniform runaway process characterized by the emergence of nearly singular peaks in density, followed by the accretional growth of embryo stars that form at these density peaks. Circumstellar discs often form from the gas being accreted by the forming stars, and accretion from these discs may be episodic, driven by gravitational instabilities or by protostellar interactions. Star-forming clouds typically develop filamentary structures, which may, along with the thermal physics, play an important role in the origin of stellar masses because of the sensitivity of filament fragmentation to temperature variations. Simulations of the formation of star clusters show that the most massive stars form by continuing accretion in the dense cluster cores, and this again is a runaway process that couples star formation and cluster formation. Star-forming clouds also tend to develop hierarchical structures, and smaller groups of forming objects tend to merge into progressively larger ones, a generic feature of self-gravitating systems that is common to star formation and galaxy formation. Because of the large range of scales and the complex dynamics involved, analytic models cannot adequately describe many aspects of star formation, and detailed numerical simulations are needed to advance our understanding of the subject. 'The purpose of computing is insight, not numbers.' Richard W Hamming, in Numerical Methods for Scientists and Engineers (1962) 'There are more things in heaven and earth, Horatio, than are dreamt of in your philosophy.' William Shakespeare, in Hamlet, Prince of Denmark (1604) (key issues review)

Influences of the Living World on Architectural Structures: An Analytical Insight

Directory of Open Access Journals (Sweden)

Gülcan MİNSOLMAZ YELER

2015-01-01

Full Text Available Structures in the nature motivate innovation in architectural and engineering disciplines in termsof aesthetical, functional and structural advantages. Using efficient, lightweight structural forms similar tothose in nature reduces material and energy usage and waste amount. In this sense, it can be clearly seenthat based on learning from nature in relation to meeting gradually increasing and changing requirementsthrough limited resources and creating modern structural designs, biomimicry will provide much morecontribution on architecture and related fields. In this direction, in the study based on comprehensiveliterature research, lots of varying living organisms in the nature have been analyzed in terms of structure;architectural structures developed by inspiring from natural structures have been sampled and influencesof solutions inspired from nature on architectural environment have been focused.

Hanford Site Long-term Surface Barrier Development Program: Fiscal year 1994 highlights

International Nuclear Information System (INIS)

Petersen, K.L.; Link, S.O.; Gee, G.W.

1995-08-01

The Hanford Site Surface Barrier Development Program was organized in 1985 to test the effectiveness of various barrier designs in minimizing the effects of water infiltration; plant, animal and human intrusion; and wind and water erosion on buried wastes, plus preventing or minimizing the emanation of noxious gases. A team of scientists from the Pacific Northwest Laboratory (PNL) and engineers from Westinghouse Hanford Company (WHC) direct the barrier development effort. ICF Kaiser Hanford Company, in conjunction with WHC and PNL, developed design drawings and construction specifications for a 5-acre prototype barrier. The highlight of efforts in FY 1994 was the construction of the prototype barrier. The prototype barrier was constructed on the Hanford Site at the 200 BP-1 Operable Unit of the 200 East Area. Construction was completed in August 1994 and monitoring instruments are being installed so experiments on the prototype barrier can begin in FY 1995. The purpose of the prototype barrier is to provide insights and experience with issues regarding barrier design, construction, and performance that have not been possible with individual tests and experiments conducted to date. Additional knowledge and experience was gained in FY 1994 on erosion control, physical stability, water infiltration control, model testing, Resource Conservation and Recovery Act (RCRA) comparisons, biointrusion control, long-term performance, and technology transfer

New insights into the geodiversity of the southeast Indian Ocean seafloor revealed by Malaysia Airlines flight MH370 search data

Science.gov (United States)

Picard, K.; Brooke, B. B.; Harris, P. T.; Siwabessy, J. P. W.; Coffin, M. F.; Tran, M.; Spinoccia, M.; Weales, J.; Macmillan-Lawler, M.; Sullivan, J.

2017-12-01

A large multibeam echo sounder (MBES) dataset (710, 000 km2, inclusive of transit data) was acquired in the SE Indian Ocean to assist the search for Malaysia Airlines Flight 370 (MH370). Here, we present the results of a geomorphic analysis of this new data and compare with the Global Seafloor Geomorphic Features Map (GSFM) that is based on coarser resolution satellite-derived bathymetry data. The analyses show that abyssal plains and basins are significantly more rugged than their representation in the GSFM, with a 20% increase in the extent of hills and mountains. The new model also reveals four times more seamounts than presented in the GSFM, suggesting a greater number of these features than previously estimated for the broader region and indeed globally. This is important considering the potential ecological significance of these high-relief structures. Analyses of the new data also enabled knolls, fans, valleys, canyons, troughs and holes to be identified, doubling the number of discrete features mapped and revealing the true geodiversity of the deep ocean in this area. This high-resolution mapping of the seafloor also provides new insights into the geological evolution of the region, both in terms of structural, tectonic, and sedimentary processes. For example, sub-parallel ridges extend over approximately 20% of the area mapped and their form and alignment provide valuable insight into Southeast Indian Ridge seafloor spreading processes. Rifting is recorded along the Broken Ridge - Diamantina Escarpment, with rift blocks and well-bedded sedimentary bedrock exposures discernible down to 2,400 m water depth. Ocean floor sedimentary processes are represented in sediment mass transport features, especially along and north of Broken Ridge, and pockmarks (the finest-scale features mapped) south of Diamantina Trench. The new MBES data highlight the complexity of the search area and serve to demonstrate how little we know about the 85-90% of the ocean floor that

Insight into mitochondrial structure and function from electron tomography.

Science.gov (United States)

Frey, T G; Renken, C W; Perkins, G A

2002-09-10

In recent years, electron tomography has provided detailed three-dimensional models of mitochondria that have redefined our concept of mitochondrial structure. The models reveal an inner membrane consisting of two components, the inner boundary membrane (IBM) closely apposed to the outer membrane and the cristae membrane that projects into the matrix compartment. These two components are connected by tubular structures of relatively uniform size called crista junctions. The distribution of crista junction sizes and shapes is predicted by a thermodynamic model based upon the energy of membrane bending, but proteins likely also play a role in determining the conformation of the inner membrane. Results of structural studies of mitochondria during apoptosis demonstrate that cytochrome c is released without detectable disruption of the outer membrane or extensive swelling of the mitochondrial matrix, suggesting the formation of an outer membrane pore large enough to allow passage of holo-cytochrome c. The possible compartmentation of inner membrane function between the IBM and the cristae membrane is also discussed.

An insight into the nature of the relationship between migration and entrepreneurship

Directory of Open Access Journals (Sweden)

Alin Croitoru

2013-06-01

Full Text Available Having as starting point a research field within the Romanian immigrant community from Graz, this paper assumes two ambitious objectives. Firstly, the article highlights some of the features of Romanian migration to Austria, an under-researched country of destination. Secondly, the paper attempts to supply a brief introduction into a very broad topic, namely the relationship between migration and entrepreneurship. Here we also attempt an understanding of how individuals’ experience of international migration affects their propensity to entrepreneurial behaviors. The concept of entrepreneurship follows the lines described by Austrian economics which allows for a deeper insight into the individuals subjective perspectives on stimulating and inhibiting factors for entrepreneurship.

Structure-guided approach identifies a novel class of HIV-1 ribonuclease H inhibitors: binding mode insights through magnesium complexation and site-directed mutagenesis studies

DEFF Research Database (Denmark)

Poongavanam, Vasanthanathan; Corona, Angela; Steinmann, Casper

2018-01-01

is a long and expensive process that can be speeded up by in silico methods. In the present study, a structure-guided screening is coupled with a similarity-based search on the Specs database to identify a new class of HIV-1 RNase H inhibitors. Out of the 45 compounds selected for experimental testing, 15...... inhibited the RNase H function below 100 μM with three hits exhibiting IC50 values active compound, AA, inhibits HIV-1 RNase H with an IC50 of 5.1 μM and exhibits a Mg-independent mode of inhibition. Site-directed mutagenesis studies provide valuable insight into the binding mode of newly...

A cross-sectional study of insight and family accommodation in pediatric obsessive-compulsive disorder

Science.gov (United States)

2013-01-01

Background Factors predicting treatment outcome in pediatric patients with obsessive-compulsive disorder (OCD) include disease severity, functional impairment, comorbid disorders, insight, and family accommodation (FA). Treatment of pediatric OCD is often only partly successful as some of these predictors are not targeted with conventional therapy. Among these, insight and FA were identified to be modifiable predictors of special relevance to pediatric OCD. Despite their clinical relevance, insight and FA remain understudied in youth with OCD. This study examined the clinical correlates of insight and FA and determined whether FA mediates the relationship between symptom severity and functional impairment in pediatric OCD. Methods This was a cross-sectional, outpatient study. Thirty-five treatment-naive children and adolescentswith DSM-IV diagnosis of OCD (mean age: 13.11 ± 3.16; 54.3% males) were included. Standard questionnaires were administered for assessing the study variables. Insight and comorbidities were assessed based on clinician’s interview. Subjects were categorized as belonging to a high insight or a low insight group, and the differences between these two groups were analyzed using ANOVA. Pearson’s correlation coefficients were calculated for the remaining variables of interest. Mediation analysis was carried out using structural equation modeling. Results Relative to those in the high insight group, subjects in the low insight group were younger, had more severe disease and symptoms, and were accommodated to a greater extent by their families. In addition, comorbid depression was more frequent in subjects belonging to the low insight group. Family accommodation was positively related to disease severity, symptom severity, and functional impairment. Family accommodation totally mediated the relationship between symptom severity and functional impairment. Conclusions Results support the differences in the diagnostic criteria between adult and

Structural insights into the mycobacteria transcription initiation complex from analysis of X-ray crystal structures

Energy Technology Data Exchange (ETDEWEB)

Hubin, Elizabeth A.; Lilic, Mirjana; Darst, Seth A.; Campbell, Elizabeth A.

2017-07-13

The mycobacteria RNA polymerase (RNAP) is a target for antimicrobials against tuberculosis, motivating structure/function studies. Here we report a 3.2 Å-resolution crystal structure of a Mycobacterium smegmatis (Msm) open promoter complex (RPo), along with structural analysis of the Msm RPo and a previously reported 2.76 Å-resolution crystal structure of an Msm transcription initiation complex with a promoter DNA fragment. We observe the interaction of the Msm RNAP α-subunit C-terminal domain (αCTD) with DNA, and we provide evidence that the αCTD may play a role in Mtb transcription regulation. Our results reveal the structure of an Actinobacteria-unique insert of the RNAP β' subunit. Finally, our analysis reveals the disposition of the N-terminal segment of Msm σA, which may comprise an intrinsically disordered protein domain unique to mycobacteria. The clade-specific features of the mycobacteria RNAP provide clues to the profound instability of mycobacteria RPo compared with E. coli.

Nanomedicine highlights in atherosclerosis

International Nuclear Information System (INIS)

Karagkiozaki, Varvara

2013-01-01

Atherosclerosis is a multifactorial disease and many different approaches have been attempted for its accurate diagnosis and treatment. The disease is induced by a low-grade inflammatory process in the vascular wall, leading through a cascade of events to the eventual formation of atheromatous plaque and arterial stenosis. Different types of cells participate in the process making more difficult to recognize the potential cellular targets within the plaques for their effective treatment. The rise of nanomedicine over the last decade has provided new types of drug delivery nanosystems that are able to be delivered to a specific diseased site of the vessel for imaging while simultaneously act as therapeutic agents. In this paper, a review of the recent advances in nanomedicine that has provided novel insights to the disease diagnosis and treatment will be given in line with different nanotechnology-based approaches to advance the cardiovascular stents. The main complications of bare metal stents such as restenosis and of drug-eluting stents which is the late stent thrombosis are analyzed to comprehend the demand for emerging therapeutic strategies based on nanotechnology.

Nanomedicine highlights in atherosclerosis

Energy Technology Data Exchange (ETDEWEB)

Karagkiozaki, Varvara, E-mail: vakaragk@physics.auth.gr [Aristotle University of Thessaloniki, Nanomedicine Group, Laboratory for Thin Films-Nanosystems and Nanometrology (LTFN), Physics Department (Greece)

2013-04-15

Atherosclerosis is a multifactorial disease and many different approaches have been attempted for its accurate diagnosis and treatment. The disease is induced by a low-grade inflammatory process in the vascular wall, leading through a cascade of events to the eventual formation of atheromatous plaque and arterial stenosis. Different types of cells participate in the process making more difficult to recognize the potential cellular targets within the plaques for their effective treatment. The rise of nanomedicine over the last decade has provided new types of drug delivery nanosystems that are able to be delivered to a specific diseased site of the vessel for imaging while simultaneously act as therapeutic agents. In this paper, a review of the recent advances in nanomedicine that has provided novel insights to the disease diagnosis and treatment will be given in line with different nanotechnology-based approaches to advance the cardiovascular stents. The main complications of bare metal stents such as restenosis and of drug-eluting stents which is the late stent thrombosis are analyzed to comprehend the demand for emerging therapeutic strategies based on nanotechnology.

Approaching the Distinction between Intuition and Insight.

Science.gov (United States)

Zhang, Zhonglu; Lei, Yi; Li, Hong

2016-01-01

Intuition and insight share similar cognitive and neural basis. Though, there are still some essential differences between the two. Here in this short review, we discriminated between intuition, and insight in two aspects. First, intuition, and insight are toward different aspects of information processing. Whereas intuition involves judgment about "yes or no," insight is related to "what" is the solution. Second, tacit knowledge play different roles in between intuition and insight. On the one hand, tacit knowledge is conducive to intuitive judgment. On the other hand, tacit knowledge may first impede but later facilitate insight occurrence. Furthermore, we share theoretical, and methodological views on how to access the distinction between intuition and insight.

Probing the electronic structure of M-graphene oxide (M = Ni, Co, NiCo) catalysts for hydrolytic dehydrogenation of ammonia borane

Energy Technology Data Exchange (ETDEWEB)

Zhao, Binhua; Liu, Jinyin; Zhou, Litao [Soochow University-Western University Centre for Synchrotron Radiation Research, Institute of Functional Nano and Soft Material (FUNSOM) and Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou 215123 (China); Long, Dan, E-mail: legend_long@aliyun.com [Department of Radiology, Zhejiang Cancer Hospital, Hangzhou 310022 (China); Feng, Kun; Sun, Xuhui [Soochow University-Western University Centre for Synchrotron Radiation Research, Institute of Functional Nano and Soft Material (FUNSOM) and Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou 215123 (China); Zhong, Jun, E-mail: jzhong@suda.edu.cn [Soochow University-Western University Centre for Synchrotron Radiation Research, Institute of Functional Nano and Soft Material (FUNSOM) and Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou 215123 (China)

2016-01-30

Graphical abstract: An interaction between metal and graphene oxide was probed to enhance the hydrolysis efficiency of ammonia borane. - Highlights: • Various metal elements (M = Ni, Co, NiCo) were dispersed on graphene oxide (GO) for the hydrolysis of ammonia borane (AB). • The electronic structure of the hybrids has been probed by scanning transmission X-ray microscopy (STXM). • An interfacial interaction between metal and GO was observed which could be related to the hydrolysis performance. • The results provide new insight into the enhanced performance of the M-GO hybrids. - Abstract: Various metal elements (M = Ni, Co, NiCo) were dispersed on graphene oxide (GO) to form the M-GO hybrids by a facile way. The hybrids showed good catalytic activities in the hydrolytic dehydrogenation of ammonia borane (AB, NH{sub 3}BH{sub 3}), which were significantly enhanced when compared to the metal nanoparticles or GO alone. The electronic structure of the hybrids has been probed by scanning transmission X-ray microscopy (STXM). The distribution of metal elements was clearly imaged with identical electronic structure. Moreover, an interfacial interaction between metal and GO was observed with the peak intensity proportional to the catalytic performance in the hydrolysis of AB. The results provide new insight into the enhanced performance of the M-GO hybrids and may help for the design of advanced catalysts.

Dimensions of insight in schizophrenia: Exploratory factor analysis of items from multiple self- and interviewer-rated measures of insight.

Science.gov (United States)

Konsztowicz, Susanna; Schmitz, Norbert; Lepage, Martin

2018-03-10

Insight in schizophrenia is regarded as a multidimensional construct that comprises aspects such as awareness of the disorder and recognition of the need for treatment. The proposed number of underlying dimensions of insight is variable in the literature. In an effort to identify a range of existing dimensions of insight, we conducted a factor analysis on combined items from multiple measures of insight. We recruited 165 participants with enduring schizophrenia (treated for >3years). Exploratory factor analysis was conducted on itemized scores from two interviewer-rated measures of insight: the Schedule for the Assessment of Insight-Expanded and the abbreviated Scale to assess Unawareness of Mental Disorder; and two self-report measures: the Birchwood Insight Scale and the Beck Cognitive Insight Scale. A five-factor solution was selected as the best-fitting model, with the following dimensions of insight: 1) awareness of illness and the need for treatment; 2) awareness and attribution of symptoms and consequences; 3) self-certainty; 4) self-reflectiveness for objectivity and fallibility; and 5) self-reflectiveness for errors in reasoning and openness to feedback. Insight in schizophrenia is a multidimensional construct comprised of distinct clinical and cognitive domains of awareness. Multiple measures of insight, both clinician- and self-rated, are needed to capture all of the existing dimensions of insight. Future exploration of associations between the various dimensions and their potential determinants will facilitate the development of clinically useful models of insight and effective interventions to improve outcome. Copyright © 2018 Elsevier B.V. All rights reserved.

Insights into business student's book

CERN Document Server

Lannon, Michael; Trappe, Tonya

1993-01-01

With Challenging reading and listening texts from a range of authentic business sources, New Insights into Business will really engage your students. The thorough language and vocabulary syllabus together with the strong focus on business skills development gives students everything they need to function effectively in the workplace. New Insights into Business is a self-contained course and is also an ideal follow-on to First Insights into Business.

In Search of Insight.

Science.gov (United States)

Kaplan, Craig A.; Simon, Herbert A.

1990-01-01

Attaining the insight needed to solve the Mutilated Checkerboard problem, which requires discovery of an effective problem representation (EPR), is described. Performance on insight problems can be predicted from the availability of generators and constraints in the search for an EPR. Data for 23 undergraduates were analyzed. (TJH)

Photon science 2012. Highlights and annual report

International Nuclear Information System (INIS)

Appel, Karen; Gehrke, Rainer; Gutt, Christian; Incoccia-Hermes, Lucia; Laarmann, Tim; Morgenroth, Wolfgang; Roehlsberger, Ralf; Schulte-Schrepping, Horst; Vainio, Ulla; Zimmermann, Martin von

2012-12-01

The synchrotron-radiation research at DESY is reviewed. The following topics are dealt with: Research highlights, research platforms and outstations, light sources, new technologies and developments. (HSI)

Insights into the interaction between nucleoid-associated proteins H ha and H-NS by NMR and fluorescence anisotropy

International Nuclear Information System (INIS)

Cordeiro, T.N.; Garcia, J.; Pons, M.

2005-01-01

NMR and fluorescence anisotropy are both valuable tools for studying bio molecular interactions. NMR can provide structural insights at atomic resolution. Still, it can be wisely complemented by lower-resolution biophysical techniques, such as fluorescence anisotropy. In this article we report the combination of NMR and fluorescence anisotropy in establishing novel structure-function insights into the interaction between two bacterial nucleoid-associated proteins, H ha and H-NS. H ha (H-NS) complexes are known to play an important role in modulating the expression of some environmentally regulated genes that confer survival advantage in a particular growth condition. (author)

Insights into the interaction between nucleoid-associated proteins H ha and H-NS by NMR and fluorescence anisotropy

Energy Technology Data Exchange (ETDEWEB)

Cordeiro, T.N.; Garcia, J. [Institut de Recerca Biomedica-Parc Cientific de (Spain). Lab. of Biomolecular NMR; Pons, M. [Universitat de Barcelona (Spain). Dept. de Quimica Organica]. E-mail: mpons@ub.edu

2005-07-01

NMR and fluorescence anisotropy are both valuable tools for studying bio molecular interactions. NMR can provide structural insights at atomic resolution. Still, it can be wisely complemented by lower-resolution biophysical techniques, such as fluorescence anisotropy. In this article we report the combination of NMR and fluorescence anisotropy in establishing novel structure-function insights into the interaction between two bacterial nucleoid-associated proteins, H ha and H-NS. H ha (H-NS) complexes are known to play an important role in modulating the expression of some environmentally regulated genes that confer survival advantage in a particular growth condition. (author)

LHC Results Highlights (CLASHEP 2013)

CERN Document Server

Gonzalez, O.

2015-05-22

The good performance of the LHC provided enough data at 7 TeV and 8 TeV to allow the experiments to perform very competitive measurements and to expand the knowledge about the fundamental interaction far beyond that from previous colliders. This report summarizes the highlights of the results obtained with these data samples by the four large experiments, covering all the topics of the physics program and focusing on those exploiting the possibilities of the LHC.

Parental insightfulness: retrospect and prospect.

Science.gov (United States)

Koren-Karie, Nina; Oppenheim, David

2018-06-01

We open this introductory paper to the special issue with the theoretical and clinical roots of the insightfulness concept. Next, the Insightfulness Assessment (IA) is presented, followed by a review of key empirical findings supporting the IA. The central points in the papers in this special issue are reviewed next. These include the use of the IA with parents of children ranging in age from infancy to adolescence, its applicability outside the parent-child relationship (e.g. insightfulness toward a close friend), its use with high-risk mothers, and the usefulness of insightfulness both as a continuous and a categorical measure. The clinical applications of the IA are discussed, and we close with future directions for IA research.

Mesozoic and Cenozoic structural evolution of North Oman: New insights from high-quality 3D seismic from the Lekhwair area

Science.gov (United States)

Bazalgette, Loïc; Salem, Hisham

2018-06-01

This paper highlights the role of Triassic-Jurassic extension and late Cretaceous compression in the Mesozoic-Cenozoic (Alpine) structuring of North Oman. The syn/post-Mesozoic regional structural evolution is usually documented as a succession of two stages of deformation. The Alpine 1 phase, late Cretaceous in age, occurred in association with two ophiolite obduction stages (Semail and Masirah ophiolites). It was characterised by strike slip to extensional deformation in the North Oman foreland basin sub-surface. The Alpine 2 phase, Miocene in age, was related to the continental collision responsible for both the Zagros orogen and the uplift of the Oman Mountains. The Alpine 2 deformation was transpressional to compressional. Observation and interpretation of good quality 3D seismic in the Lekhwair High area enabled the distinction of two earlier phases. Early Mesozoic extension occurred concomitantly with the regional Triassic to Jurassic rifting, developing Jurassic-age normal faults. Late Cretaceous compression occurred prior to the main Alpine 1 phase and triggered the inversion of Jurassic-seated normal faults as well as the initiation of compressional folds in the Cretaceous overburden. These early phases have been ignored or overlooked as part of the North Oman history although they are at the origin of structures hosting major local and regional hydrocarbon accumulations.

Third-person Diagnostic Interview on the Cognitive Insight Level of Psychotic Patients with an Insight at the Denial Level.

Science.gov (United States)

Mehdizadeh, Mahsa; Rezaei, Omid

2016-01-01

According to the previous findings, the third-person technique improved the clinical insight of psychotic patients, therefore the present study aims to examine the effect of a third-person interview compared to a first-person interview on the level of cognitive insight of psychotic patients with an insight at the denial level. In this study, using interviews and questionnaires, a total number of 44 patients of Razi Psychiatric Educational and Treatment Center with an insight at the denial level being assessed using diagnostic interviews were divided randomly into two groups. Then, the two groups of patients' cognitive insights were evaluated using Beck Cognitive Insight Scale. The findings indicated that in psychotic patients with an insight at the denial level, the third-person technique of interview compared to the first-person had little effect on the improvement of overall cognitive insight and its components, including self-reflection and self-assurance; however, this effect was not strong enough to make a significant difference between the two groups of patients. According to the study findings, we can conclude that the third-person interview compared to the first-person interview has no effect on the improvement of the cognitive insight of psychotic patients with an insight at the denial level. This finding is consistent with the previous studies indicating that although the theory of mind has some correlations with the clinical insight of patients, it has no effect on their cognitive insight.

Crystallographic insight into the evolutionary origins of xyloglucan endotransglycosylases and endohydrolases.

Science.gov (United States)

McGregor, Nicholas; Yin, Victor; Tung, Ching-Chieh; Van Petegem, Filip; Brumer, Harry

2017-02-01

The xyloglucan endotransglycosylase/hydrolase (XTH) gene family encodes enzymes of central importance to plant cell wall remodeling. The evolutionary history of plant XTH gene products is incompletely understood vis-à-vis the larger body of bacterial endoglycanases in Glycoside Hydrolase Family 16 (GH16). To provide molecular insight into this issue, high-resolution X-ray crystal structures and detailed enzyme kinetics of an extant transitional plant endoglucanase (EG) were determined. Functionally intermediate between plant XTH gene products and bacterial licheninases of GH16, Vitis vinifera EG16 (VvEG16) effectively catalyzes the hydrolysis of the backbones of two dominant plant cell wall matrix glycans, xyloglucan (XyG) and β(1,3)/β(1,4)-mixed-linkage glucan (MLG). Crystallographic complexes with extended oligosaccharide substrates reveal the structural basis for the accommodation of both unbranched, mixed-linked (MLG) and highly decorated, linear (XyG) polysaccharide chains in a broad, extended active-site cleft. Structural comparison with representative bacterial licheninases, a xyloglucan endotranglycosylase (XET), and a xyloglucan endohydrolase (XEH) outline the functional ramifications of key sequence deletions and insertions across the phylogenetic landscape of GH16. Although the biological role(s) of EG16 orthologs remains to be fully resolved, the present biochemical and tertiary structural characterization provides key insight into plant cell wall enzyme evolution, which will continue to inform genomic analyses and functional studies across species. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Structural analysis and implicit 3D modelling of Jwaneng Mine: Insights into deformation of the Transvaal Supergroup in SE Botswana

Science.gov (United States)

Creus, P. K.; Basson, I. J.; Stoch, B.; Mogorosi, O.; Gabanakgosi, K.; Ramsden, F.; Gaegopolwe, P.

2018-01-01

Country rock at Jwaneng Diamond Mine provides a rare insight into the deformational history of the Transvaal Supergroup in southern Botswana. The ca. 235 Ma kimberlite diatremes intruded into late Archaean to Early Proterozoic, mixed, siliciclastic-carbonate sediments, that were subjected to at least three deformational events. The first deformational event (D1), caused by NW-SE directed compression, is responsible for NE-trending, open folds (F1) with associated diverging, fanning, axial planar cleavage. The second deformational event (D2) is probably progressive, involving a clockwise rotation of the principal stress to NE-SW trends. Early D2, which was N-S directed, involved left-lateral, oblique shearing along cleavage planes that developed around F1 folds, along with the development of antithetic structures. Progressive clockwise rotation of far-field forces saw the development of NW-trending folds (F2) and its associated, weak, axial planar cleavage. D3 is an extensional event in which normal faulting, along pre-existing cleavage planes, created a series of rhomboid-shaped, fault-bounded blocks. Normal faults, which bound these blocks, are the dominant structures at Jwaneng Mine. Combined with block rotation and NW-dipping bedding, a horst-like structure on the northwestern limb of a broad, gentle, NE-trending anticline is indicated. The early compressional and subsequent extensional events are consistent throughout the Jwaneng-Ramotswa-Lobatse-Thabazimbi area, suggesting that a large area records the same fault geometry and, consequently, deformational history. It is proposed that Jwaneng Mine is at or near the northernmost limit of the initial, northwards-directed compressional event.

Genomes and geography: genomic insights into the evolution and phylogeography of the genus Schistosoma

Directory of Open Access Journals (Sweden)

Ironside Joe E

2011-07-01

Full Text Available Abstract Blood flukes within the genus Schistosoma still remain a major cause of disease in the tropics and subtropics and the study of their evolution has been an area of major debate and research. With the advent of modern molecular and genomic approaches deeper insights have been attained not only into the divergence and speciation of these worms, but also into the historic movement of these parasites from Asia into Africa, via migration and dispersal of definitive and snail intermediate hosts. This movement was subsequently followed by a radiation of Schistosoma species giving rise to the S. mansoni and S. haematobium groups, as well as the S. indicum group that reinvaded Asia. Each of these major evolutionary events has been marked by distinct changes in genomic structure evident in differences in mitochondrial gene order and nuclear chromosomal architecture between the species associated with Asia and Africa. Data from DNA sequencing, comparative molecular genomics and karyotyping are indicative of major constitutional genomic events which would have become fixed in the ancestral populations of these worms. Here we examine how modern genomic techniques may give a more in depth understanding of the evolution of schistosomes and highlight the complexity of speciation and divergence in this group.

Further insights on the French WISC-IV factor structure through Bayesian structural equation modeling.

Science.gov (United States)

Golay, Philippe; Reverte, Isabelle; Rossier, Jérôme; Favez, Nicolas; Lecerf, Thierry

2013-06-01

The interpretation of the Wechsler Intelligence Scale for Children--Fourth Edition (WISC-IV) is based on a 4-factor model, which is only partially compatible with the mainstream Cattell-Horn-Carroll (CHC) model of intelligence measurement. The structure of cognitive batteries is frequently analyzed via exploratory factor analysis and/or confirmatory factor analysis. With classical confirmatory factor analysis, almost all cross-loadings between latent variables and measures are fixed to zero in order to allow the model to be identified. However, inappropriate zero cross-loadings can contribute to poor model fit, distorted factors, and biased factor correlations; most important, they do not necessarily faithfully reflect theory. To deal with these methodological and theoretical limitations, we used a new statistical approach, Bayesian structural equation modeling (BSEM), among a sample of 249 French-speaking Swiss children (8-12 years). With BSEM, zero-fixed cross-loadings between latent variables and measures are replaced by approximate zeros, based on informative, small-variance priors. Results indicated that a direct hierarchical CHC-based model with 5 factors plus a general intelligence factor better represented the structure of the WISC-IV than did the 4-factor structure and the higher order models. Because a direct hierarchical CHC model was more adequate, it was concluded that the general factor should be considered as a breadth rather than a superordinate factor. Because it was possible for us to estimate the influence of each of the latent variables on the 15 subtest scores, BSEM allowed improvement of the understanding of the structure of intelligence tests and the clinical interpretation of the subtest scores. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Cellulose synthases: new insights from crystallography and modeling.

Science.gov (United States)

Slabaugh, Erin; Davis, Jonathan K; Haigler, Candace H; Yingling, Yaroslava G; Zimmer, Jochen

2014-02-01

Detailed information about the structure and biochemical mechanisms of cellulose synthase (CelS) proteins remained elusive until a complex containing the catalytic subunit (BcsA) of CelS from Rhodobacter sphaeroides was crystalized. Additionally, a 3D structure of most of the cytosolic domain of a plant CelS (GhCESA1 from cotton, Gossypium hirsutum) was produced by computational modeling. This predicted structure contributes to our understanding of how plant CelS proteins may be similar and different as compared with BcsA. In this review, we highlight how these structures impact our understanding of the synthesis of cellulose and other extracellular polysaccharides. We show how the structures can be used to generate hypotheses for experiments testing mechanisms of glucan synthesis and translocation in plant CelS. Copyright © 2013 Elsevier Ltd. All rights reserved.

Structural and Functional Insights into Foamy Viral Integrase

Directory of Open Access Journals (Sweden)

Cha-Gyun Shin

2013-07-01

Full Text Available Successful integration of retroviral DNA into the host chromosome is an essential step for viral replication. The process is mediated by virally encoded integrase (IN and orchestrated by 3'-end processing and the strand transfer reaction. In vitro reaction conditions, such as substrate specificity, cofactor usage, and cellular binding partners for such reactions by the three distinct domains of prototype foamy viral integrase (PFV-IN have been described well in several reports. Recent studies on the three‑dimensional structure of the interacting complexes between PFV-IN and DNA, cofactors, binding partners, or inhibitors have explored the mechanistic details of such interactions and shown its utilization as an important target to develop anti-retroviral drugs. The presence of a potent, non-transferable nuclear localization signal in the PFV C-terminal domain extends its use as a model for investigating cellular trafficking of large molecular complexes through the nuclear pore complex and also to identify novel cellular targets for such trafficking. This review focuses on recent advancements in the structural analysis and in vitro functional aspects of PFV-IN.

Insight in psychosis: Metacognitive processes and treatment

OpenAIRE

de Vos, Annerieke

2016-01-01

Insight is impaired in 50- 80% of the patients with schizophrenia. Annerieke de Vos working at GGZ Drenthe and the University Medical Hospital Groningen, aimed to elucidate which processes underlie impaired insight and tried to improve insight in patients by targeting these processes. On September 21st she will defend her thesis entitled: "Insight in psychosis. Metacognitive processes and treatment.". Patients with impaired insight may fail to recognize that things in life are not going well ...

Structural insight of dopamine β-hydroxylase, a drug target for complex traits, and functional significance of exonic single nucleotide polymorphisms.

Directory of Open Access Journals (Sweden)

Abhijeet Kapoor

Full Text Available Human dopamine β-hydroxylase (DBH is an important therapeutic target for complex traits. Several single nucleotide polymorphisms (SNPs have also been identified in DBH with potential adverse physiological effect. However, difficulty in obtaining diffractable crystals and lack of a suitable template for modeling the protein has ensured that neither crystallographic three-dimensional structure nor computational model for the enzyme is available to aid rational drug design, prediction of functional significance of SNPs or analytical protein engineering.Adequate biochemical information regarding human DBH, structural coordinates for peptidylglycine alpha-hydroxylating monooxygenase and computational data from a partial model of rat DBH were used along with logical manual intervention in a novel way to build an in silico model of human DBH. The model provides structural insight into the active site, metal coordination, subunit interface, substrate recognition and inhibitor binding. It reveals that DOMON domain potentially promotes tetramerization, while substrate dopamine and a potential therapeutic inhibitor nepicastat are stabilized in the active site through multiple hydrogen bonding. Functional significance of several exonic SNPs could be described from a structural analysis of the model. The model confirms that SNP resulting in Ala318Ser or Leu317Pro mutation may not influence enzyme activity, while Gly482Arg might actually do so being in the proximity of the active site. Arg549Cys may cause abnormal oligomerization through non-native disulfide bond formation. Other SNPs like Glu181, Glu250, Lys239 and Asp290 could potentially inhibit tetramerization thus affecting function.The first three-dimensional model of full-length human DBH protein was obtained in a novel manner with a set of experimental data as guideline for consistency of in silico prediction. Preliminary physicochemical tests validated the model. The model confirms, rationalizes and

Structural insight of dopamine β-hydroxylase, a drug target for complex traits, and functional significance of exonic single nucleotide polymorphisms.

Science.gov (United States)

Kapoor, Abhijeet; Shandilya, Manish; Kundu, Suman

2011-01-01

Human dopamine β-hydroxylase (DBH) is an important therapeutic target for complex traits. Several single nucleotide polymorphisms (SNPs) have also been identified in DBH with potential adverse physiological effect. However, difficulty in obtaining diffractable crystals and lack of a suitable template for modeling the protein has ensured that neither crystallographic three-dimensional structure nor computational model for the enzyme is available to aid rational drug design, prediction of functional significance of SNPs or analytical protein engineering. Adequate biochemical information regarding human DBH, structural coordinates for peptidylglycine alpha-hydroxylating monooxygenase and computational data from a partial model of rat DBH were used along with logical manual intervention in a novel way to build an in silico model of human DBH. The model provides structural insight into the active site, metal coordination, subunit interface, substrate recognition and inhibitor binding. It reveals that DOMON domain potentially promotes tetramerization, while substrate dopamine and a potential therapeutic inhibitor nepicastat are stabilized in the active site through multiple hydrogen bonding. Functional significance of several exonic SNPs could be described from a structural analysis of the model. The model confirms that SNP resulting in Ala318Ser or Leu317Pro mutation may not influence enzyme activity, while Gly482Arg might actually do so being in the proximity of the active site. Arg549Cys may cause abnormal oligomerization through non-native disulfide bond formation. Other SNPs like Glu181, Glu250, Lys239 and Asp290 could potentially inhibit tetramerization thus affecting function. The first three-dimensional model of full-length human DBH protein was obtained in a novel manner with a set of experimental data as guideline for consistency of in silico prediction. Preliminary physicochemical tests validated the model. The model confirms, rationalizes and provides

The CONNECT project: Combining macro- and micro-structure.

Science.gov (United States)

Assaf, Yaniv; Alexander, Daniel C; Jones, Derek K; Bizzi, Albero; Behrens, Tim E J; Clark, Chris A; Cohen, Yoram; Dyrby, Tim B; Huppi, Petra S; Knoesche, Thomas R; Lebihan, Denis; Parker, Geoff J M; Poupon, Cyril; Anaby, Debbie; Anwander, Alfred; Bar, Leah; Barazany, Daniel; Blumenfeld-Katzir, Tamar; De-Santis, Silvia; Duclap, Delphine; Figini, Matteo; Fischi, Elda; Guevara, Pamela; Hubbard, Penny; Hofstetter, Shir; Jbabdi, Saad; Kunz, Nicolas; Lazeyras, Francois; Lebois, Alice; Liptrot, Matthew G; Lundell, Henrik; Mangin, Jean-François; Dominguez, David Moreno; Morozov, Darya; Schreiber, Jan; Seunarine, Kiran; Nava, Simone; Poupon, Cyril; Riffert, Till; Sasson, Efrat; Schmitt, Benoit; Shemesh, Noam; Sotiropoulos, Stam N; Tavor, Ido; Zhang, Hui Gary; Zhou, Feng-Lei

2013-10-15

In recent years, diffusion MRI has become an extremely important tool for studying the morphology of living brain tissue, as it provides unique insights into both its macrostructure and microstructure. Recent applications of diffusion MRI aimed to characterize the structural connectome using tractography to infer connectivity between brain regions. In parallel to the development of tractography, additional diffusion MRI based frameworks (CHARMED, AxCaliber, ActiveAx) were developed enabling the extraction of a multitude of micro-structural parameters (axon diameter distribution, mean axonal diameter and axonal density). This unique insight into both tissue microstructure and connectivity has enormous potential value in understanding the structure and organization of the brain as well as providing unique insights to abnormalities that underpin disease states. The CONNECT (Consortium Of Neuroimagers for the Non-invasive Exploration of brain Connectivity and Tracts) project aimed to combine tractography and micro-structural measures of the living human brain in order to obtain a better estimate of the connectome, while also striving to extend validation of these measurements. This paper summarizes the project and describes the perspective of using micro-structural measures to study the connectome. Copyright © 2013 Elsevier Inc. All rights reserved.

Adsorption studies of alcohol molecules on monolayer MoS{sub 2} nanosheet—A first-principles insights

Energy Technology Data Exchange (ETDEWEB)

Nagarajan, V.; Chandiramouli, R., E-mail: rcmoulii@gmail.com

2017-08-15

Highlights: • The adsorption of methanol, ethanol & 1-propanol on MoS{sub 2} nanosheet are studied. • The PDOS & band structure confirms adsorption of alcohol vapors on MoS{sub 2} nanosheet. • The adsorption of 1-propanol vapor on MoS{sub 2} nanosheet is more favorable. • The alcohol molecules adsorption on MoS{sub 2} nanosheet is explored in atomistic level. - Abstract: The electronic and adsorption properties of three different alcohol molecules namely methanol, ethanol and 1-propanol vapors on MoS{sub 2} nanosheet is investigated using DFT method. The structural stability of MoS{sub 2} nanosheet is ascertained with formation energy. The adsorption properties of alcohol molecules on MoS{sub 2} base material is discussed in terms of average energy gap variation, Mulliken charge transfer, energy band gap and adsorption energy. The prominent adsorption sites of methanol, ethanol and 1-propanol vapors on MoS{sub 2} nanosheet are studied in atomistic level. The projected density of states (PDOS) spectrum gives the clear insights on the electronic properties of MoS{sub 2} nanosheet. The PDOS and energy band structure confirmed the adsorption of alcohol vapors on MoS{sub 2} nanosheet. The variation in the band structure and PDOS is noticed upon adsorption of methanol, ethanol and 1-propanol molecules on MoS{sub 2} nanosheet. The PDOS spectrum also reveals the variation in peak maxima owing to transfer of electron between alcohol molecules and MoS{sub 2} base material. The adsorption of 1-propanol vapor on MoS{sub 2} nanosheet is observed to be more favorable than other alcohol molecules. The findings confirm that monolayer MoS{sub 2} nanosheet can be used to detect the presence of alcohol vapors in the environment.

New insights into insight: Neurophysiological correlates of the difference between the intrinsic "aha" and the extrinsic "oh yes" moment.

Science.gov (United States)

Rothmaler, Katrin; Nigbur, Roland; Ivanova, Galina

2017-01-27

Insight refers to a situation in which a problem solver immediately changes his understanding of a problem situation. This representational change can either be triggered by external stimuli, like a hint or the solution itself, or by internal solution attempts. In the present paper, the differences and similarities between these two phenomena, namely "extrinsic" and "intrinsic" insight, are examined. To this end, electroencephalogram (EEG) is recorded while subjects either recognize or generate solutions to German verbal compound remote associate problems (CRA). Based on previous studies, we compare the alpha power prior to insightful solution recognition with the alpha power prior to insightful solution generation. Results show that intrinsic insights are preceded by an increase in alpha power at right parietal electrodes, while extrinsic insights are preceded by a respective decrease. These results can be interpreted in two ways. In consistency with other studies, the increase in alpha power before intrinsic insights can be interpreted as an increased internal focus of attention. Accordingly, the decrease in alpha power before extrinsic insights may be associated with a more externally oriented focus of attention. Alternatively, the increase in alpha power prior to intrinsic insights can be interpreted as an active inhibition of solution-related information, while the alpha power decrease prior to extrinsic insights may reflect its activation. Regardless of the interpretation, the results provide strong evidence that extrinsic and intrinsic insight differ on the behavioral as well as the neurophysiological level. Copyright © 2016 Elsevier Ltd. All rights reserved.

Consumer engagement: An insight from smart grid projects in Europe

International Nuclear Information System (INIS)

Gangale, Flavia; Mengolini, Anna; Onyeji, Ijeoma

2013-01-01

This paper provides an insight into consumer engagement in smart grid projects in Europe. Projects analysed are those included in the catalogue annexed in the JRC Report “Smart Grid projects in Europe: lessons learned and current developments”. The analysis suggests an increase in the interest in consumer engagement projects at European level and a strong focus on the residential sector, and emphasises the key importance of public funding to support these projects. The study also reveals that projects involving consumers are characterised by the pursuit of two main objectives: gaining deeper knowledge of consumer behaviour (observing and understanding the consumer) and motivating and empowering consumers to become active energy customers (engaging the consumer). The paper reviews the main activities undertaken to obtain these objectives and highlights trends and developments in the field. Finally, the paper discusses obstacles to consumer engagement and the strategies adopted by the projects surveyed to tackle them, highlighting the need to build consumer trust and to design targeted campaigns taking into consideration different consumer segments. The conclusions are in line with findings and analyses presented in the literature and underscore the need for further research and action at European level. - Highlights: • Consumers' key role in the success of the future electricity system (smart grids). • Survey on consumer engagement experiences in European smart grid projects. • Focus is on observing and understanding the consumers and on engaging them. • Trust and confidence as central elements. • Need to take into consideration different consumer segments/motivational factors

Insight and satisfaction with life among adolescents with mental disorders: assessing associations with self-stigma and parental insight.

Science.gov (United States)

Gaziel, M; Hasson-Ohayon, I; Morag-Yaffe, M; Schapir, L; Zalsman, G; Shoval, G

2015-02-01

The purpose of the current study was to assess the associations of illness perception-related variables with satisfaction with life (SwL) among adolescents with mental disorders. Insight into mental disorder (SAI-E), Internalized stigma of mental illness (ISMI) and Multidimensional Students' Life Satisfaction Scale (MSLSS) were administrated to 30 adolescent patients. Adapted version for parents of the SAI-E was also administrated to 37 of their parents. Significant positive correlations were found between insight into the illness, self-stigma and parental insight. Insight and self-stigma were significantly negatively related to the total score of SwL and few of its dimensions while parental insight was significantly associated only with the SwL dimensions of school and self. Regression models revealed main negative effects of insight and self-stigma on SwL and no interaction effect. The possible independent contribution of insight and self-stigma to SwL should be addressed in interventions designed for family and adolescents coping with mental illness. Special attention should be given to the possible negative implications that insight possesses. In lack of support of the moderation role of self-stigma, reported in studies among adults with mental illness, future studies should trace other variables in order to further understand the insight paradox among adolescents. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Hyperactive antifreeze proteins from longhorn beetles: some structural insights.

Science.gov (United States)

Kristiansen, Erlend; Wilkens, Casper; Vincents, Bjarne; Friis, Dennis; Lorentzen, Anders Blomkild; Jenssen, Håvard; Løbner-Olesen, Anders; Ramløv, Hans

2012-11-01

This study reports on structural characteristics of hyperactive antifreeze proteins (AFPs) from two species of longhorn beetles. In Rhagium mordax, eight unique mRNAs coding for five different mature AFPs were identified from cold-hardy individuals. These AFPs are apparently homologues to a previously characterized AFP from the closely related species Rhagium inquisitor, and consist of six identifiable repeats of a putative ice binding motif TxTxTxT spaced irregularly apart by segments varying in length from 13 to 20 residues. Circular dichroism spectra show that the AFPs from both species have a high content of β-sheet and low levels of α-helix and random coil. Theoretical predictions of residue-specific secondary structure locate these β-sheets within the putative ice-binding motifs and the central parts of the segments separating them, consistent with an overall β-helical structure with the ice-binding motifs stacked in a β-sheet on one side of the coil. Molecular dynamics models based on these findings show that these AFPs would be energetically stable in a β-helical conformation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Stigma as a predictor of insight in schizophrenia.

Science.gov (United States)

Pruß, Linda; Wiedl, Karl Heinz; Waldorf, Manuel

2012-07-30

Insight in schizophrenia can be seen as a multifactorial phenomenon. Although multifactorial pathways have also been suggested for insight formation, motivational explanations have rarely been tested. The present study explores stigma as one possible determinant of a motivated lack of insight in integrated models of insight formation. It examines the contribution of socio-demographic and clinical variables, neurocognitive functions, symptoms, and stigma to the prediction of insight into illness. Patients diagnosed with schizophrenia spectrum disorders (N=111) participated in a comprehensive battery of instruments to measure insight dimensions, stigma, neurocognitive functions, symptoms, socio-demographic and clinical variables. Blockwise multiple regression analysis indicates significant association of variability in insight dimensions with gender (7%) and stigma (i. e., stereotype agreement: 5%). Our findings demonstrate an incremental validity of stigma, which indicates a motivational pathway of insight formation. This study enables better understanding of the multifactorial nature of insight, which should be considered in therapeutic interventions to improve insight. The roles of gender and neurocognitive functions in insight formation are also discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Course of insight in manic episode

Directory of Open Access Journals (Sweden)

A Kumar

2013-01-01

Full Text Available Background: Insight is an important factor associated with non compliance and poor outcome. Poor level of insight has been described as a characteristic in patients with acute bipolar disorder with more unawareness in social consequences with increasing severity in manic episode. Aim: Main aim of study was to see the baseline and longitudinal relationship between dimensions of insight with improvement in psychopathology. Setting and Design: Forty four patients diagnosed with mania, were selected from an inpatient setting at Institute of Mental Health and Hospital, Agra with mean age of 31.07(±9.00 years. They were assessed at base line and were followed up weekly or psychopathology and insight. Materials and Methods: The Young′s mania rating scale for psychopathology and insight was assessed on three dimensions of SUMD. Results: Twenty five patients eventually completed the study. There was a positive correlation with global insight and with psychopathology consistent in longitudinal follow-up (P<0.05, but not correlating for awareness for achieved effect of medication and social consequences. Linear regression showed a positive relationship at the first and second week of assessment of SUMD and YMRS scores (P=0.001; 0.019. Conclusion: Improvement in insight is graded in a manic episode as compared to psychopathology. There is slower improvement in awareness of social consequences of mental disorder. It means that improvement in psychopathology may not necessarily indicate remission and need further supervision to improve insight and hence monitoring.

Structural insight into the UNC-45–myosin complex

DEFF Research Database (Denmark)

Fratev, Filip; Jonsdottir, Svava Osk; Pajeva, Ilza

2013-01-01

The UNC-45 chaperone protein interacts with and affects the folding, stability, and the ATPase activity of myosins. It plays a critical role in the cardiomyopathy development and in the breast cancer tumor growth. Here we propose the first structural model of the UNC-45–myosin complex using various...... is mainly stabilized by electrostatic interactions. Remarkably, the contact surface area is similar to that of the myosinactin complex. A significant interspecies difference in the myosin binding epitope is observed. Our results reveal the structural basis of MYH7 exons 15–16 hypertrophic cardiomyopathy...... mutations and provide directions for drug targeting. © 2013 Wiley Periodicals, Inc....

Senescence in the wild: Insights from a long-term study on Seychelles warblers.

Science.gov (United States)

Hammers, Martijn; Kingma, Sjouke A; Bebbington, Kat; van de Crommenacker, Janske; Spurgin, Lewis G; Richardson, David S; Burke, Terry; Dugdale, Hannah L; Komdeur, Jan

2015-11-01

Senescence--the progressive age-dependent decline in performance--occurs in most organisms. There is considerable variation in the onset and rate of senescence between and within species. Yet the causes of this variation are still poorly understood, despite being central to understanding the evolution of senescence. Long-term longitudinal studies on wild animals are extremely well-suited to studying the impact of environmental and individual characteristics (and the interaction between the two) on senescence, and can help us to understand the mechanisms that shape the evolution of senescence. In this review, we summarize and discuss the insights gained from our comprehensive long-term individual-based study of the Seychelles warbler (Acrocephalus sechellensis). This species provides an excellent model system in which to investigate the evolution of senescence in the wild. We found that Seychelles warblers show senescent declines in survival and reproduction, and discuss how individual characteristics (body condition, body size) and environmental effects (low- versus high-quality environments) may affect the onset and rate of senescence. Further, we highlight the evidence for trade-offs between early-life investment and senescence. We describe how key cellular and physiological processes (oxidative stress and telomere shortening) underpinning senescence are affected by individual and environmental characteristics in the Seychelles warbler (e.g. food availability, reproductive investment, disease) and we discuss how such physiological variation may mediate the relationship between environmental characteristics and senescence. Based on our work using Seychelles warblers as a model system, we show how insights from long-term studies of wild animals may help unravel the causes of the remarkable variation in senescence observed in natural systems, and highlight areas for promising future research.

Atomic resolution structural insights into PdPt nanoparticle–carbon interactions for the design of highly active and stable electrocatalysts

International Nuclear Information System (INIS)

Slanac, Daniel A.; Li Lin; Mayoral, Alvaro; Yacaman, Miguel José; Manthiram, Arumugam; Stevenson, Keith J.; Johnston, Keith P.

2012-01-01

Graphical abstract: - Abstract: Interfacial interactions between sub-4 nm metal alloy nanoparticles and carbon supports, although not well understood at the atomic level, may be expected to have a profound influence on catalytic properties. Pd 3 Pt 2 alloy particles comprised of a disordered surface layer over a corrugated crystalline core are shown to exhibit strong interfacial interactions with a ∼20–50 nm spherical carbon support, as characterized by probe aberration corrected scanning transmission electron microscopy (pcSTEM). The disordered shells were formed from defects introduced by Pd during arrested growth synthesis of the alloy nanoparticles. The chemical and morphological changes in the catalyst, before and after cyclic stability testing (1000 cycles, 0.5–1.2 V), were probed with cyclic voltammetry (CV), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and pcSTEM. The strong metal–support interaction, along with the uniform alloy structure raised the mass activity by a factor of 1.8 versus pure Pt. The metal–support interactions also mitigated nanoparticle coalescence, dissolution, and ripening, resulting in only a 20% loss in mass activity (versus 60% for pure Pt on carbon) after the cyclic stability test. The design of alloy structure, guided by insight from atomic scale pcSTEM, for enhanced catalytic activity and stability, resulting from strong wetting with a deformable disordered shell, has the potential to be a general paradigm for improving catalytic performance.

Understanding Insight in the Context of Q

Science.gov (United States)

Coghlan, David

2012-01-01

In Revans' learning formula, L = P + Q, Q represents "questioning insight", by which Revans means that insight comes out of the process of questioning programmed knowledge (P) in the light of experience. We typically focus on the content of an insight rather than on the act of insight. Drawing primarily on the work of Bernard Lonergan this paper…

Ultra-structural time-course study in the C. elegans model for Duchenne muscular dystrophy highlights a crucial role for sarcomere-anchoring structures and sarcolemma integrity in the earliest steps of the muscle degeneration process.

Science.gov (United States)

Brouilly, Nicolas; Lecroisey, Claire; Martin, Edwige; Pierson, Laura; Mariol, Marie-Christine; Qadota, Hiroshi; Labouesse, Michel; Streichenberger, Nathalie; Mounier, Nicole; Gieseler, Kathrin

2015-11-15

Duchenne muscular dystrophy (DMD) is a genetic disease characterized by progressive muscle degeneration due to mutations in the dystrophin gene. In spite of great advances in the design of curative treatments, most patients currently receive palliative therapies with steroid molecules such as prednisone or deflazacort thought to act through their immunosuppressive properties. These molecules only slightly slow down the progression of the disease and lead to severe side effects. Fundamental research is still needed to reveal the mechanisms involved in the disease that could be exploited as therapeutic targets. By studying a Caenorhabditis elegans model for DMD, we show here that dystrophin-dependent muscle degeneration is likely to be cell autonomous and affects the muscle cells the most involved in locomotion. We demonstrate that muscle degeneration is dependent on exercise and force production. Exhaustive studies by electron microscopy allowed establishing for the first time the chronology of subcellular events occurring during the entire process of muscle degeneration. This chronology highlighted the crucial role for dystrophin in stabilizing sarcomeric anchoring structures and the sarcolemma. Our results suggest that the disruption of sarcomeric anchoring structures and sarcolemma integrity, observed at the onset of the muscle degeneration process, triggers subcellular consequences that lead to muscle cell death. An ultra-structural analysis of muscle biopsies from DMD patients suggested that the chronology of subcellular events established in C. elegans models the pathogenesis in human. Finally, we found that the loss of sarcolemma integrity was greatly reduced after prednisone treatment suggesting a role for this molecule in plasma membrane stabilization. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

An insight into structural and functional characteristics of 3-hydoxy 3-methyl glutarylCoA reductase from Ocimum species

Directory of Open Access Journals (Sweden)

Shilpi Bansal

2017-10-01

Full Text Available Secondary metabolites, the biological compounds secreted by plants as an aid to support their growth and development under stress conditions or as a part of their defense mechanism, now hold equal importance for mankind who employs it immensely for medication, flavorings, aroma, etc. Wide applicability of these compounds instigates one to understand the biosynthesis, structure and regulation of these bioactive molecules. Terpenoids form the largest group of secondary metabolites which comprise of a wide range of structurally and functionally distinct metabolites synthesized either via mevalonate pathway or non-mevalonate pathway. Targeting a key regulatory enzyme of this pathway, modulation of which would alter the carbon flux would be beneficial to enhance our knowledge about the above issue. For this the transcriptome (from SRA of different Ocimum species was mined out for important pathway genes using various bioinformatics approaches. Amongst them 3-hydoxy 3-methyl glutaryl CoA reductase (HMGR was selected which is the rate limiting enzyme in mevalonate pathway which controls the conversion of HMG-CoA to mevalonic acid. Isolation, cloning, protein expression, purification, etc. would be discussed in detail in the meeting. Full length protein was also characterized through bioinformatics tools to study its structure, properties, conserved domains, etc. Increase in secondary metabolite production by alteration of HMGR pool along with transcript modulation studies in planta revealed that HMGR gene governs the biosynthesis of secondary metabolites. Transcriptome mapping of different HMGR homologs which on comparison within member of same genus revealed its divergent nature which could account to its multifunctional role in different plants. Besides, providing a deep insight about the enzyme function combination of such molecular, transgenic and bioinformatics tools would help to develop strategies to engineer the HMGR mediated flux and also

Supplementary Material for: Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance

KAUST Repository

Phelan, Jody

2016-01-01

Abstract Background Combating the spread of drug resistant tuberculosis is a global health priority. Whole genome association studies are being applied to identify genetic determinants of resistance to anti-tuberculosis drugs. Protein structure and interaction modelling are used to understand the functional effects of putative mutations and provide insight into the molecular mechanisms leading to resistance. Methods To investigate the potential utility of these approaches, we analysed the genomes of 144 Mycobacterium tuberculosis clinical isolates from The Special Programme for Research and Training in Tropical Diseases (TDR) collection sourced from 20 countries in four continents. A genome-wide approach was applied to 127 isolates to identify polymorphisms associated with minimum inhibitory concentrations for first-line anti-tuberculosis drugs. In addition, the effect of identified candidate mutations on protein stability and interactions was assessed quantitatively with well-established computational methods. Results The analysis revealed that mutations in the genes rpoB (rifampicin), katG (isoniazid), inhA-promoter (isoniazid), rpsL (streptomycin) and embB (ethambutol) were responsible for the majority of resistance observed. A subset of the mutations identified in rpoB and katG were predicted to affect protein stability. Further, a strong direct correlation was observed between the minimum inhibitory concentration values and the distance of the mutated residues in the three-dimensional structures of rpoB and katG to their respective drugs binding sites. Conclusions Using the TDR resource, we demonstrate the usefulness of whole genome association and convergent evolution approaches to detect known and potentially novel mutations associated with drug resistance. Further, protein structural modelling could provide a means of predicting the impact of polymorphisms on drug efficacy in the absence of phenotypic data. These approaches could ultimately lead to novel

Structure and sensitivity analysis of individual-based predator–prey models

International Nuclear Information System (INIS)

Imron, Muhammad Ali; Gergs, Andre; Berger, Uta

2012-01-01

The expensive computational cost of sensitivity analyses has hampered the use of these techniques for analysing individual-based models in ecology. A relatively cheap computational cost, referred to as the Morris method, was chosen to assess the relative effects of all parameters on the model’s outputs and to gain insights into predator–prey systems. Structure and results of the sensitivity analysis of the Sumatran tiger model – the Panthera Population Persistence (PPP) and the Notonecta foraging model (NFM) – were compared. Both models are based on a general predation cycle and designed to understand the mechanisms behind the predator–prey interaction being considered. However, the models differ significantly in their complexity and the details of the processes involved. In the sensitivity analysis, parameters that directly contribute to the number of prey items killed were found to be most influential. These were the growth rate of prey and the hunting radius of tigers in the PPP model as well as attack rate parameters and encounter distance of backswimmers in the NFM model. Analysis of distances in both of the models revealed further similarities in the sensitivity of the two individual-based models. The findings highlight the applicability and importance of sensitivity analyses in general, and screening design methods in particular, during early development of ecological individual-based models. Comparison of model structures and sensitivity analyses provides a first step for the derivation of general rules in the design of predator–prey models for both practical conservation and conceptual understanding. - Highlights: ► Structure of predation processes is similar in tiger and backswimmer model. ► The two individual-based models (IBM) differ in space formulations. ► In both models foraging distance is among the sensitive parameters. ► Morris method is applicable for the sensitivity analysis even of complex IBMs.

Sediment bacterial community structures and their predicted functions implied the impacts from natural processes and anthropogenic activities in coastal area.

Science.gov (United States)

Su, Zhiguo; Dai, Tianjiao; Tang, Yushi; Tao, Yile; Huang, Bei; Mu, Qinglin; Wen, Donghui

2018-06-01

Coastal ecosystem structures and functions are changing under natural and anthropogenic influences. In this study, surface sediment samples were collected from disturbed zone (DZ), near estuary zone (NEZ), and far estuary zone (FEZ) of Hangzhou Bay, one of the most seriously polluted bays in China. The bacterial community structures and predicted functions varied significantly in different zones. Firmicutes were found most abundantly in DZ, highlighting the impacts of anthropogenic activities. Sediment total phosphorus was most influential on the bacterial community structures. Predicted by PICRUSt analysis, DZ significantly exceeded FEZ and NEZ in the subcategory of Xenobiotics Biodegradation and Metabolism; and DZ enriched all the nitrate reduction related genes, except nrfA gene. Seawater salinity and inorganic nitrogen, respectively as the representative natural and anthropogenic factor, performed exact-oppositely in nitrogen metabolism functions. The changes of bacterial community compositions and predicted functions provide a new insight into human-induced pollution impacts on coastal ecosystem. Copyright © 2018 Elsevier Ltd. All rights reserved.

Functional materials for information and energy technology: Insights by photoelectron spectroscopy

International Nuclear Information System (INIS)

Müller, Martina; Nemšák, Slavomír; Plucinski, Lukasz; Schneider, Claus M.

2016-01-01

Highlights: • Photoemission spectro/microscopy studies of functional material systems. • Hard X-ray photoemission spectroscopy from magnetic semiconductors and insulators. • Information depth studies in hard X-ray photoemission microscopy. • Soft X-ray standing wave ambient pressure photoemission spectroscopy from liquid films. - Abstract: The evolution of both information and energy technology is intimately connected to complex condensed matter systems, the properties of which are determined by electronic and chemical interactions and processes on a broad range of length and time scales. Dedicated photoelectron spectroscopy and spectromicroscopy experiments can provide important insights into fundamental phenomena and applied functionalities. We discuss some recent methodological developments with application to relevant questions in spintronics, and towards operando studies of resistive switching and electrochemical processes.

Local Fine Structural Insight into Mechanism of Electrochemical Passivation of Titanium.

Science.gov (United States)

Wang, Lu; Yu, Hongying; Wang, Ke; Xu, Haisong; Wang, Shaoyang; Sun, Dongbai

2016-07-20

Electrochemically formed passive film on titanium in 1.0 M H2SO4 solution and its thickness, composition, chemical state, and local fine structure are examined by Auger electron spectroscopy (AES), X-ray photoelectron spectroscopy (XPS), and X-ray absorption fine structure. AES analysis reveals that the thickness and composition of oxide film are proportional to the reciprocal of current density in potentiodynamic polarization. XPS depth profiles of the chemical states of titanium exhibit the coexistence of various valences cations in the surface. Quantitative X-ray absorption near edge structure analysis of the local electronic structure of the topmost surface (∼5.0 nm) shows that the ratio of [TiO2]/[Ti2O3] is consistent with that of passivation/dissolution of electrochemical activity. Theoretical calculation and analysis of extended X-ray absorption fine structure spectra at Ti K-edge indicate that both the structures of passivation and dissolution are distorted caused by the appearance of two different sites of Ti-O and Ti-Ti. And the bound water in the topmost surface plays a vital role in structural disorder confirmed by XPS. Overall, the increase of average Ti-O coordination causes the electrochemical passivation, and the dissolution is due to the decrease of average Ti-Ti coordination. The structural variations of passivation in coordination number and interatomic distance are in good agreement with the prediction of point defect model.

PSI scientific highlights 2011

International Nuclear Information System (INIS)

Piwnicki, P.

2012-04-01

This comprehensive report for the Swiss Federal Office of Energy (SFOE) presents the major highlights of the work done at the Paul Scherrer Institute, Switzerland, in 2011. According to the institute's director, work was concerned with the design and analysis of advanced materials with new functionalities, for application in fields as diverse as communications and energy technology, transportation, construction and medicine. Of particular topical interest are research projects on materials for application in the field of energy, for example for improving batteries for future electrically powered vehicles. Another example is in the field of catalysts. Environmentally harmful compounds, such as nitrogen oxide and sulphur dioxide produced in an engine, are transformed into nontoxic gases through catalytic conversion. Work progress on the SwissFEL installation is noted, including a breakthrough for SwissFEL main Linac C-band accelerating systems. Further topics in relation to the SwissFEL system are noted. Planning of the initial set of experimental stations at the SwissFEL is discussed and close collaboration with growing number of user communities is noted. Cross-Correlation Scattering, and a theoretical framework for this method is being developed and experimentally verified, using artificial nanostructures and synchrotron radiation. Highlights of further research work are discussed, including topics such as Synchrotron light, work done on neutrons and muons, particle physics, micro and nanotechnology as well as on biomolecular research and radiopharmacy. Large research facilities are discussed as is the PSI proton therapy installation. General energy topics are looked at, as are nuclear energy and safety aspects and environmental and energy systems analysis. Various further work includes factors causing glacier retreat and aerosols. User facilities are listed, including accelerators, the SLS light source, the SINQ neutron source, the UCN ultra-cold neutron source

The impact of cognitive insight, self-stigma, and medication compliance on the quality of life in patients with schizophrenia.

Science.gov (United States)

Lien, Yin-Ju; Chang, Hsin-An; Kao, Yu-Chen; Tzeng, Nian-Sheng; Lu, Chien-Wen; Loh, Ching-Hui

2018-02-01

Impaired quality of life (QoL) is a common and clinically relevant feature of schizophrenia. In the present study, we attempted to formulate a model of QoL in the chronic stage of schizophrenia by including key variables-namely cognitive insight, self-stigma, insight into treatment, and medication compliance-that were proposed as its significant predictors in previous studies. We employed structural equation modeling (SEM) to simultaneously test the associations between these variables. A total of 170 community-dwelling patients with schizophrenia participated in this study. Cognitive insight, self-stigma, insight into treatment, medication compliance, and QoL were assessed through self-reporting. Symptoms were rated by interviewers. The influences of cognitive insight, stigma, insight into treatment, and medication compliance on QoL were supported using SEM. Our findings indicated that cognitive insight had a significant, positive, and direct effect on both self-stigma and insight into treatment; in contrast, it had a negative and direct effect on medication compliance. Notably, no evidence indicated a direct effect of cognitive insight on QoL. Thus, individuals with high cognitive insight reported low QoL because of stigma, low medication compliance, and their increased insight into treatment. In contrast, cognitive insight might indirectly ameliorate QoL mediated by the effect of insight into treatment on medication compliance. The findings provide additional support of the links between cognitive and clinical insight, self-stigma, medication compliance, and QoL in those with schizophrenia and suggest the need for screening and intervention services appropriate for this high-risk population.

Computational analysis of perturbations in the post-fusion Dengue virus envelope protein highlights known epitopes and conserved residues in the Zika virus [version 2; referees: 3 approved

Directory of Open Access Journals (Sweden)

Sandeep Chakraborty

2016-09-01

Full Text Available The dramatic transformation of the Zika virus (ZIKV from a relatively unknown virus to a pathogen generating global-wide panic has exposed the dearth of detailed knowledge about this virus. Decades of research in the related Dengue virus (DENV, finally culminating in a vaccine registered for use in endemic regions (CYD-TDV in three countries, provides key insights in developing strategies for tackling ZIKV, which has caused global panic to microcephaly and Guillain-Barre Syndrome. Dengue virus (DENV, a member of the family Flaviviridae, the causal agent of the self-limiting Dengue fever and the potentially fatal hemorrhagic fever/dengue shock syndrome, has been a scourge in tropical countries for many centuries. The recently solved structure of mature ZIKV (PDB ID:5IRE has provided key insights into the structure of the envelope (E and membrane (M proteins, the primary target of neutralizing antibodies. The previously established MEPP methodology compares two conformations of the same protein and identifies residues with significant spatial and electrostatic perturbations. In the current work, MEPP analyzed the pre-and post-fusion DENV type 2 envelope (E protein, and identified several known epitopes (His317, Tyr299, Glu26, Arg188, etc. (MEPPitope. These residues are overwhelmingly conserved in ZIKV and all DENV serotypes, and also enumerates residue pairs that undergo significant polarity reversal. Characterization of α-helices in E-proteins show that α1 is not conserved in the sequence space of ZIKV and DENV. Furthermore, perturbation of α1 in the post-fusion DENV structure includes a known epitope Asp215, a residue absent in the pre-fusion α1. A cationic β-sheet in the GAG-binding domain that is stereochemically equivalent in ZIKV and all DENV serotypes is also highlighted due to a residue pair (Arg286-Arg288 that has a significant electrostatic polarity reversal upon fusion. Finally, two highly conserved residues (Thr32 and Thr40, with

Insights into Basal Signaling Regulation, Oligomerization, and Structural Organization of the Human G-Protein Coupled Receptor 83.

Directory of Open Access Journals (Sweden)

Anne Müller

Full Text Available The murine G-protein coupled receptor 83 (mGPR83 is expressed in the hypothalamus and was previously suggested to be involved in the regulation of metabolism. The neuropeptide PEN has been recently identified as a potent GPR83 ligand. Moreover, GPR83 constitutes functionally relevant hetero-oligomers with other G-protein coupled receptors (GPCR such as the ghrelin receptor (GHSR or GPR171. Previous deletion studies also revealed that the long N-terminal extracellular receptor domain (eNDo of mGPR83 may act as an intra-molecular ligand, which participates in the regulation of basal signaling activity, which is a key feature of GPCR function. Here, we investigated particular amino acids at the eNDo of human GPR83 (hGPR83 by side-directed mutagenesis to identify determinants of the internal ligand. These studies were accompanied by structure homology modeling to combine functional insights with structural information. The capacity for hetero-oligomer formation of hGPR83 with diverse family A GPCRs such as the melanocortin-4 receptor (MC4R was also investigated, with a specific emphasis on the impact of the eNDo on oligomerization and basal signaling properties. Finally, we demonstrate that hGPR83 exhibits an unusual basal signaling for different effectors, which also supports signaling promiscuity. hGPR83 interacts with a variety of hypothalamic GPCRs such as the MC4R or GHSR. These interactions are not dependent on the ectodomain and most likely occur at interfaces constituted in the transmembrane regions. Moreover, several amino acids at the transition between the eNDo and transmembrane helix 1 were identified, where mutations lead also to biased basal signaling modulation.

Cyclone Center: Insights on Historical Tropical Cyclones from Citizen Volunteers

Science.gov (United States)

Thorne, P.; Hennon, C. C.; Knapp, K. R.; Schreck, C. J., III; Stevens, S. E.; Kossin, J. P.; Rennie, J.; Hennon, P. A.; Kruk, M. C.

2015-12-01

The cyclonecenter.org project started in fall 2012 and has been collecting citizen scientist volunteer tropical cyclone intensity estimates ever since. The project is hosted by the Citizen Science Alliance (zooniverse) and the platform is supported by a range of scientists. We have over 30 years of satellite imagery of tropical cyclones but the analysis to date has been done on an ocean-basin by ocean-basin basis and worse still practices have changed over time. We therefore do not, presently, have a homogeneous record relevant for discerning climatic changes. Automated techniques can classify many of the images but have a propensity to be challenged during storm transitions. The problem is fundamentally one where many pairs of eyes are invaluable as there is no substitute for human eyes in discerning patterns. Each image is classified by ten unique users before it is retired. This provides a unique insight into the uncertainty inherent in classification. In the three years of the project much useful data has accrued. This presentation shall highlight some of the results and analyses to date and touch on insights as to what has worked and what perhaps has not worked so well. There are still many images left to complete so its far from too late to jump over to www.cyclonecenter.org and help out.

Hybrid discrete choice models: Gained insights versus increasing effort

Energy Technology Data Exchange (ETDEWEB)

Mariel, Petr, E-mail: petr.mariel@ehu.es [UPV/EHU, Economía Aplicada III, Avda. Lehendakari Aguire, 83, 48015 Bilbao (Spain); Meyerhoff, Jürgen [Institute for Landscape Architecture and Environmental Planning, Technical University of Berlin, D-10623 Berlin, Germany and The Kiel Institute for the World Economy, Duesternbrooker Weg 120, 24105 Kiel (Germany)

2016-10-15

Hybrid choice models expand the standard models in discrete choice modelling by incorporating psychological factors as latent variables. They could therefore provide further insights into choice processes and underlying taste heterogeneity but the costs of estimating these models often significantly increase. This paper aims at comparing the results from a hybrid choice model and a classical random parameter logit. Point of departure for this analysis is whether researchers and practitioners should add hybrid choice models to their suite of models routinely estimated. Our comparison reveals, in line with the few prior studies, that hybrid models gain in efficiency by the inclusion of additional information. The use of one of the two proposed approaches, however, depends on the objective of the analysis. If disentangling preference heterogeneity is most important, hybrid model seems to be preferable. If the focus is on predictive power, a standard random parameter logit model might be the better choice. Finally, we give recommendations for an adequate use of hybrid choice models based on known principles of elementary scientific inference. - Highlights: • The paper compares performance of a Hybrid Choice Model (HCM) and a classical Random Parameter Logit (RPL) model. • The HCM indeed provides insights regarding preference heterogeneity not gained from the RPL. • The RPL has similar predictive power as the HCM in our data. • The costs of estimating HCM seem to be justified when learning more on taste heterogeneity is a major study objective.

Hybrid discrete choice models: Gained insights versus increasing effort

International Nuclear Information System (INIS)

Mariel, Petr; Meyerhoff, Jürgen

2016-01-01

Hybrid choice models expand the standard models in discrete choice modelling by incorporating psychological factors as latent variables. They could therefore provide further insights into choice processes and underlying taste heterogeneity but the costs of estimating these models often significantly increase. This paper aims at comparing the results from a hybrid choice model and a classical random parameter logit. Point of departure for this analysis is whether researchers and practitioners should add hybrid choice models to their suite of models routinely estimated. Our comparison reveals, in line with the few prior studies, that hybrid models gain in efficiency by the inclusion of additional information. The use of one of the two proposed approaches, however, depends on the objective of the analysis. If disentangling preference heterogeneity is most important, hybrid model seems to be preferable. If the focus is on predictive power, a standard random parameter logit model might be the better choice. Finally, we give recommendations for an adequate use of hybrid choice models based on known principles of elementary scientific inference. - Highlights: • The paper compares performance of a Hybrid Choice Model (HCM) and a classical Random Parameter Logit (RPL) model. • The HCM indeed provides insights regarding preference heterogeneity not gained from the RPL. • The RPL has similar predictive power as the HCM in our data. • The costs of estimating HCM seem to be justified when learning more on taste heterogeneity is a major study objective.

The "Insight Paradox" in Schizophrenia: Magnitude, Moderators and Mediators of the Association Between Insight and Depression.

Science.gov (United States)

Belvederi Murri, Martino; Amore, Mario; Calcagno, Pietro; Respino, Matteo; Marozzi, Valentina; Masotti, Mattia; Bugliani, Michele; Innamorati, Marco; Pompili, Maurizio; Galderisi, Silvana; Maj, Mario

2016-09-01

The so-called "insight paradox" posits that among patients with schizophrenia higher levels of insight are associated with increased levels of depression. Although different studies examined this issue, only few took in account potential confounders or factors that could influence this association. In a sample of clinically stable patients with schizophrenia, insight and depression were evaluated using the Scale to assess Unawareness of Mental Disorder and the Calgary Depression Scale for Schizophrenia. Other rating scales were used to assess the severity of psychotic symptoms, extrapyramidal symptoms, hopelessness, internalized stigma, self-esteem, and service engagement. Regression models were used to estimate the magnitude of the association between insight and depression while accounting for the role of confounders. Putative psychological and sociodemographic factors that could act as mediators and moderators were examined using the PROCESS macro. By accounting for the role of confounding factors, the strength of the association between insight into symptoms and depression increased from 13% to 25% explained covariance. Patients with lower socioeconomic status (F = 8.5, P = .04), more severe illness (F = 4.8, P = .03) and lower levels of service engagement (F = 4.7, P = .03) displayed the strongest association between insight and depression. Lastly, hopelessness, internalized stigma and perceived discrimination acted as significant mediators. The relationship between insight and depression should be considered a well established phenomenon among patients with schizophrenia: it seems stronger than previously reported especially among patients with lower socioeconomic status, severe illness and poor engagement with services. These findings may have relevant implications for the promotion of insight among patients with schizophrenia. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved

The “Insight Paradox” in Schizophrenia: Magnitude, Moderators and Mediators of the Association Between Insight and Depression

Science.gov (United States)

Belvederi Murri, Martino; Amore, Mario; Calcagno, Pietro; Respino, Matteo; Marozzi, Valentina; Masotti, Mattia; Bugliani, Michele; Innamorati, Marco; Pompili, Maurizio; Galderisi, Silvana; Maj, Mario

2016-01-01

The so-called “insight paradox” posits that among patients with schizophrenia higher levels of insight are associated with increased levels of depression. Although different studies examined this issue, only few took in account potential confounders or factors that could influence this association. In a sample of clinically stable patients with schizophrenia, insight and depression were evaluated using the Scale to assess Unawareness of Mental Disorder and the Calgary Depression Scale for Schizophrenia. Other rating scales were used to assess the severity of psychotic symptoms, extrapyramidal symptoms, hopelessness, internalized stigma, self-esteem, and service engagement. Regression models were used to estimate the magnitude of the association between insight and depression while accounting for the role of confounders. Putative psychological and sociodemographic factors that could act as mediators and moderators were examined using the PROCESS macro. By accounting for the role of confounding factors, the strength of the association between insight into symptoms and depression increased from 13% to 25% explained covariance. Patients with lower socioeconomic status (F = 8.5, P = .04), more severe illness (F = 4.8, P = .03) and lower levels of service engagement (F = 4.7, P = .03) displayed the strongest association between insight and depression. Lastly, hopelessness, internalized stigma and perceived discrimination acted as significant mediators. The relationship between insight and depression should be considered a well established phenomenon among patients with schizophrenia: it seems stronger than previously reported especially among patients with lower socioeconomic status, severe illness and poor engagement with services. These findings may have relevant implications for the promotion of insight among patients with schizophrenia. PMID:27069064

Syndicate of renewable energies - Highlights 2015

International Nuclear Information System (INIS)

2016-01-01

This publication first proposes a presentation of the SER (Syndicat des Energies Renouvelables, Syndicate of Renewable Energies), a professional body: missions, scope of action, members. It outlines its commitment in the French policy for energy transition as a major actor of the sector of renewable energies. It addresses the legal and regulatory framework by indicating evolutions introduced by the French law for energy transition and for a green growth for the different renewable energies (hydroelectricity, wind energy, solar photovoltaic, geothermal, biofuels and bio-energies, biogas), by the new regimes of authorisations for onshore wind energy, methanization and hydroelectricity, and by the law for growth, activity and equality of economic opportunities. It proposes brief presentations of transverse actions (agreements, meetings, partnership in exhibitions, commitment in the COP21), and of actions regarding power grids, overseas territories, or the building sector. Some highlights related bio-energy sectors, geothermal energy, onshore wind energy, renewable marine energies and offshore wind energy, solar photovoltaic energy, hydroelectricity, or solar thermodynamic energy are mentioned. These highlights may concern legal, organisational, political or financial frameworks. Actions in the field of communication are indicated, and projects for 2016 are briefly indicated

Modeling sports highlights using a time-series clustering framework and model interpretation

Science.gov (United States)

Radhakrishnan, Regunathan; Otsuka, Isao; Xiong, Ziyou; Divakaran, Ajay

2005-01-01

In our past work on sports highlights extraction, we have shown the utility of detecting audience reaction using an audio classification framework. The audio classes in the framework were chosen based on intuition. In this paper, we present a systematic way of identifying the key audio classes for sports highlights extraction using a time series clustering framework. We treat the low-level audio features as a time series and model the highlight segments as "unusual" events in a background of an "usual" process. The set of audio classes to characterize the sports domain is then identified by analyzing the consistent patterns in each of the clusters output from the time series clustering framework. The distribution of features from the training data so obtained for each of the key audio classes, is parameterized by a Minimum Description Length Gaussian Mixture Model (MDL-GMM). We also interpret the meaning of each of the mixture components of the MDL-GMM for the key audio class (the "highlight" class) that is correlated with highlight moments. Our results show that the "highlight" class is a mixture of audience cheering and commentator's excited speech. Furthermore, we show that the precision-recall performance for highlights extraction based on this "highlight" class is better than that of our previous approach which uses only audience cheering as the key highlight class.

[Poor insight and psychosis].

Science.gov (United States)

Giotakos, O

2017-01-01

A variety of phenomena might be considered as reflecting impaired insight in psychosis, like failure to recognize signs, symptoms or disease, failure to derive appropriate cognitive representations, despite recognition of the disease, and misattribution of the source or cause of the disease. The unawareness of tardive dyskinesia symptoms in schizophrenic patients points that self-awareness deficits in schizophrenia may be domain specific. Poor insight is an independent phenomenological and a prevalent feature in psychotic disorders in general, and in schizophrenia in particular, but we don't know yet if delusions in schizophrenia are the result of an entirely normal attempt to account for abnormal perceptual experiences or a product of abnormal experience but of normal reasoning. The theoretical approaches regarding impaired insight include the disturbed perceptual input, the impaired linkage between thought and emotion and the breakdown of the process of self-monitoring and error checking. The inability to distinguish between internally and externally generated mental events has been described by the metarepresentation theory. This theory includes the awareness of ones' goals, which leads to disorders of willed action, the awareness of intention, which leads to movement disorders, and the awareness of intentions of others, which leads to paranoid delusions. The theory of metarepresentation implies mainly output mechanisms, like the frontal cortex, while the input mechanism implies posterior brain systems, including the parietal lobe. There are many similarities between the disturbances of awareness seen in schizophrenia and those seen as a result of known neurological impairment. Neuropsychological models of impaired insight typically attribute the disturbance to any of a variety of core deficits in the processing of information. In this respect, lack of insight is on conceptual par with alogia, apraxia or aphasia in reflecting disturbed cognitive processing. In

Atomistic insight into the catalytic mechanism of glycosyltransferases by combined quantum mechanics/molecular mechanics (QM/MM) methods.

Science.gov (United States)

Tvaroška, Igor

2015-02-11

Glycosyltransferases catalyze the formation of glycosidic bonds by assisting the transfer of a sugar residue from donors to specific acceptor molecules. Although structural and kinetic data have provided insight into mechanistic strategies employed by these enzymes, molecular modeling studies are essential for the understanding of glycosyltransferase catalyzed reactions at the atomistic level. For such modeling, combined quantum mechanics/molecular mechanics (QM/MM) methods have emerged as crucial. These methods allow the modeling of enzymatic reactions by using quantum mechanical methods for the calculation of the electronic structure of the active site models and treating the remaining enzyme environment by faster molecular mechanics methods. Herein, the application of QM/MM methods to glycosyltransferase catalyzed reactions is reviewed, and the insight from modeling of glycosyl transfer into the mechanisms and transition states structures of both inverting and retaining glycosyltransferases are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sequence-Dependent Self-Assembly and Structural Diversity of Islet Amyloid Polypeptide-Derived β-Sheet Fibrils

International Nuclear Information System (INIS)

Wang, Shih-Ting; Lin, Yiyang; Spencer, Ryan K.; Thomas, Michael R.; Nguyen, Andy I.

2017-01-01

Determining the structural origins of amyloid fibrillation is essential for understanding both the pathology of amyloidosis and the rational design of inhibitors to prevent or reverse amyloid formation. In this work, the decisive roles of peptide structures on amyloid self-assembly and morphological diversity were investigated by the design of eight amyloidogenic peptides derived from islet amyloid polypeptide. Among the segments, two distinct morphologies were highlighted in the form of twisted and planar (untwisted) ribbons with varied diameters, thicknesses, and lengths. In particular, transformation of amyloid fibrils from twisted ribbons into untwisted structures was triggered by substitution of the C-terminal serine with threonine, where the side chain methyl group was responsible for the distinct morphological change. This effect was confirmed following serine substitution with alanine and valine and was ascribed to the restriction of intersheet torsional strain through the increased hydrophobic interactions and hydrogen bonding. We also studied the variation of fibril morphology (i.e., association and helicity) and peptide aggregation propensity by increasing the hydrophobicity of the peptide side group, capping the N-terminus, and extending sequence length. Lastly, we anticipate that our insights into sequence-dependent fibrillation and morphological diversity will shed light on the structural interpretation of amyloidogenesis and development of structure-specific imaging agents and aggregation inhibitors.

The role of temporal structure in the investigation of sensory memory, auditory scene analysis, and speech perception: a healthy-aging perspective.

Science.gov (United States)

Rimmele, Johanna Maria; Sussman, Elyse; Poeppel, David

2015-02-01

Listening situations with multiple talkers or background noise are common in everyday communication and are particularly demanding for older adults. Here we review current research on auditory perception in aging individuals in order to gain insights into the challenges of listening under noisy conditions. Informationally rich temporal structure in auditory signals--over a range of time scales from milliseconds to seconds--renders temporal processing central to perception in the auditory domain. We discuss the role of temporal structure in auditory processing, in particular from a perspective relevant for hearing in background noise, and focusing on sensory memory, auditory scene analysis, and speech perception. Interestingly, these auditory processes, usually studied in an independent manner, show considerable overlap of processing time scales, even though each has its own 'privileged' temporal regimes. By integrating perspectives on temporal structure processing in these three areas of investigation, we aim to highlight similarities typically not recognized. Copyright © 2014 Elsevier B.V. All rights reserved.

Structural phase transition and opto-electronic properties of NaZnAs

Energy Technology Data Exchange (ETDEWEB)

Djied, A.; Seddik, T.; Merabiha, O. [Laboratoire de Physique Quantique et de Modélisation Mathématique, Université de Mascara, 29000 (Algeria); Murtaza, G. [Materials Modeling Lab, Department of Physics, Islamia College University, Peshawar (Pakistan); Khenata, R. [Laboratoire de Physique Quantique et de Modélisation Mathématique, Université de Mascara, 29000 (Algeria); Ahmed, R., E-mail: rashidahmed@utm.my [Department of Physics, Faculty of Science, Universiti Teknologi Malaysia, UTM Skudai, 81310 Johor (Malaysia); Bin-Omran, S. [Department of Physics and Astronomy, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Uğur, Ş. [Department of Physics, Faculty of Sciences, Gazi University, 06500 Teknikokullar, Ankara (Turkey); Bouhemadou, A. [Laboratory for Developing New Materials and their Characterization, Department of Physics, Faculty of Science, University Setif 1, 19000 Setif (Algeria)

2015-02-15

Highlights: • First competent characterizations of NaZnAs at the level of FP-LAPW+lo. • NaZnAs, a potential alternative candidate to III-V for photovoltaic applications. • NaZnAs, a cheaper and abundantly available direct band gap semiconductor. • Potential material for solar radiation absorber from infrared to ultraviolet. - Abstract: In this study, we predict the structural phase transitions as well as opto-electronic properties of the filled-tetrahedral (Nowotny-Juza) NaZnAs compound. Calculations employ the full potential (FP) linearized augmented plane wave (LAPW) plus local orbitals (lo) scheme. The exchange-correlation potential is treated within the generalized gradient approximation of Perdew-Burke and Ernzerhof (GGA-PBE). In addition, Tran and Blaha (TB) modified Becke-Johnson (mBJ) potential is also used to obtain more accurate optoelectronic properties. Geometry optimization is performed to obtain reliable total energies and other structural parameters for each NaZnAs phase. In our study, the sequence of the structural phase transition on compression is Cu{sub 2}Sb-type → β → α phase. NaZnAs is a direct (Γ-Γ) band gap semiconductor for all the structural phases. However, compared to PBE-GGA, the mBJ approximation reproduces better fundamental band gaps. Moreover, for insight into its potential for photovoltaic applications, different optical parameters are studied.

Structural phase transition and opto-electronic properties of NaZnAs

International Nuclear Information System (INIS)

Djied, A.; Seddik, T.; Merabiha, O.; Murtaza, G.; Khenata, R.; Ahmed, R.; Bin-Omran, S.; Uğur, Ş.; Bouhemadou, A.

2015-01-01

Highlights: • First competent characterizations of NaZnAs at the level of FP-LAPW+lo. • NaZnAs, a potential alternative candidate to III-V for photovoltaic applications. • NaZnAs, a cheaper and abundantly available direct band gap semiconductor. • Potential material for solar radiation absorber from infrared to ultraviolet. - Abstract: In this study, we predict the structural phase transitions as well as opto-electronic properties of the filled-tetrahedral (Nowotny-Juza) NaZnAs compound. Calculations employ the full potential (FP) linearized augmented plane wave (LAPW) plus local orbitals (lo) scheme. The exchange-correlation potential is treated within the generalized gradient approximation of Perdew-Burke and Ernzerhof (GGA-PBE). In addition, Tran and Blaha (TB) modified Becke-Johnson (mBJ) potential is also used to obtain more accurate optoelectronic properties. Geometry optimization is performed to obtain reliable total energies and other structural parameters for each NaZnAs phase. In our study, the sequence of the structural phase transition on compression is Cu 2 Sb-type → β → α phase. NaZnAs is a direct (Γ-Γ) band gap semiconductor for all the structural phases. However, compared to PBE-GGA, the mBJ approximation reproduces better fundamental band gaps. Moreover, for insight into its potential for photovoltaic applications, different optical parameters are studied

Reassessing the evolutionary history of ass-like equids: insights from patterns of genetic variation in contemporary extant populations.

Science.gov (United States)

Rosenbom, Sónia; Costa, Vânia; Chen, Shanyuan; Khalatbari, Leili; Yusefi, Gholam Hosein; Abdukadir, Ablimit; Yangzom, Chamba; Kebede, Fanuel; Teclai, Redae; Yohannes, Hagos; Hagos, Futsum; Moehlman, Patricia D; Beja-Pereira, Albano

2015-04-01

All extant equid species are grouped in a single genus - Equus. Among those, ass-like equids have remained particularly unstudied and their phylogenetic relations were poorly understood, most probably because they inhabit extreme environments in remote geographic areas. To gain further insights into the evolutionary history of ass-like equids, we have used a non-invasive sampling approach to collect representative fecal samples of extant African and Asiatic ass-like equid populations across their distribution range and mitochondrial DNA (mtDNA) sequencing analyses to examine intraspecific genetic diversity and population structure, and to reconstruct phylogenetic relations among wild ass species/subspecies. Sequence analyses of 410 base pairs of the fast evolving mtDNA control region identified the Asiatic wild ass population of Kalamaili (China) as the one displaying the highest diversity among all wild ass populations. Phylogenetic analyses of complete cytochrome b sequences revealed that African and Asiatic wild asses shared a common ancestor approximately 2.3Mya and that diversification in both groups occurred much latter, probably driven by climatic events during the Pleistocene. Inferred genetic relationships among Asiatic wild ass species do not support E. kiang monophyly, highlighting the need of more extensive studies in order to clarify the taxonomic status of species/subspecies belonging to this branch of the Equus phylogeny. These results highlight the importance of re-assessing the evolutionary history of ass-like equid species, and urge to extend studies at the population level to efficiently design conservation and management actions for these threatened species. Copyright © 2015 Elsevier Inc. All rights reserved.

B-GATA transcription factors - insights into their structure, regulation and role in plant development

Directory of Open Access Journals (Sweden)

Claus eSchwechheimer

2015-02-01

Full Text Available GATA transcription factors are evolutionarily conserved transcriptional regulators that recognize promoter elements with a G-A-T-A core sequence. In comparison to animal genomes, the GATA transcription factor family in plants is comparatively large with approximately 30 members. In spite of a long-standing interest of plant molecular biologists in GATA factors, only research conducted in the last years has led to reliable insights into their functions during plant development. Here, we review the current knowledge on B-GATAs, one of four GATA factor subfamilies from Arabidopsis thaliana. We show that B-GATAs can be subdivided based on structural features and their biological function into family members with a C-terminal LLM- (leucine-leucine-methionine domain or an N-terminal HAN- (HANABA TARANU domain. The paralogous GNC (GATA, NITRATE-INDUCIBLE, CARBON-METABOLISM INVOLVED and CGA1/GNL (CYTOKININ-INDUCED GATA1/GNC-LIKE are introduced as LLM-domain containing B-GATAs from Arabidopsis that control germination, greening, senescence and flowering time downstream from several growth regulatory signals including light and the hormones gibberellin, auxin, and cytokinin. Arabidopsis HAN and its monocot-specific paralogs from rice (NECK LEAF1, maize (TASSEL SHEATH1, and barley (THIRD OUTER GLUME are HAN-domain-containing B-GATAs with a predominant role in embryo development and floral development. We also review GATA23, a regulator of lateral root initiation from Arabidopsis, that is closely related to GNC and GNL but has a degenerate LLM-domain that is seemingly specific for the Brassicaceae family. The Brassicaceae-specific GATA23 together with the above-mentioned monocot-specific HAN-domain GATAs provide evidence that neofunctionalization of the B-GATAs was used during plant evolution to expand the functional repertoire of these transcription factors.

New Genetic Insights into Pearl Millet Diversity As Revealed by Characterization of Early- and Late-Flowering Landraces from Senegal

Directory of Open Access Journals (Sweden)

Oumar Diack

2017-05-01

Full Text Available Pearl millet (Pennisetum glaucum (L. R. Br. is a staple food and a drought-tolerant cereal well adapted to Sub-Saharan Africa agro-ecosystems. An important diversity of pearl millet landraces has been widely conserved by farmers and therefore could help copping with climate changes and contribute to future food security. Hence, characterizing its genetic diversity and population structure can contribute to better assist breeding programs for a sustainable agricultural productivity enhancement. Toward this goal, a comprehensive panel of 404 accessions were used that correspond to 12 improved varieties, 306 early flowering and 86 late-flowering cultivated landraces from Senegal. Twelve highly polymorphic SSR markers were used to study diversity and population structure. Two genes, PgMADS11 and PgPHYC, were genotyped to assess their association to flowering phenotypic difference in landraces. Results indicate a large diversity and untapped potential of Senegalese pearl millet germplasm as well as a genetic differentiation between early- and late-flowering landraces. Further, a fine-scale genetic difference of PgPHYC and PgMADS11 (SNP and indel, respectively and co-variation of their alleles with flowering time were found among landraces. These findings highlight new genetic insights of pearl millet useful to define heterotic populations for breeding, genomic association panel, or crosses for trait-specific mapping.

Band alignment studies of Al2O3/CuGaO2 and ZnO/CuGaO2 hetero-structures grown by pulsed laser deposition

International Nuclear Information System (INIS)

Ajimsha, R.S.; Das, Amit K.; Joshi, M.P.; Kukreja, L.M.

2014-01-01

Highlights: • Band offset studies at the interface of Al 2 O 3 /CuGaO 2 and ZnO/CuGaO 2 hetero-structures were performed using X-ray photoelectron spectroscopy. • Valance band offsets (VBO) of these hetero-structures were obtained from respective XPS peak positions and VB spectra using Kraut's equation. • Al 2 O 3 /CuGaO 2 interface exhibited a type I band alignment with valance band offset (VBO) of 4.05 eV whereas type II band alignment was observed in ZnO/CuGaO 2 hetero-structure with a VBO of 2.32 eV. • Schematic band alignment diagram for the interface of these hetero-structures has been constructed. • Band offset and alignment studies of these heterojunctions are important for gaining insight to the design of various optoelectronic devices based on such hetero-structures. - Abstract: We have studied the band offset and alignment of pulsed laser deposited Al 2 O 3 /CuGaO 2 and ZnO/CuGaO 2 hetero-structures using photoelectron spectroscopy. Al 2 O 3 /CuGaO 2 interface exhibited a type I band alignment with valance band offset (VBO) of 4.05 eV whereas type II band alignment was observed in ZnO/CuGaO 2 hetero-structure with a VBO of 2.32 eV. Schematic band alignment diagram for the interface of these hetero-structures has been constructed. Band offset and alignment studies of these heterojunctions are important for gaining insight to the design of various optoelectronic devices based on such hetero-structures

Structural and evolutionary relationships of "AT-less" type I polyketide synthase ketosynthases.

Science.gov (United States)

Lohman, Jeremy R; Ma, Ming; Osipiuk, Jerzy; Nocek, Boguslaw; Kim, Youngchang; Chang, Changsoo; Cuff, Marianne; Mack, Jamey; Bigelow, Lance; Li, Hui; Endres, Michael; Babnigg, Gyorgy; Joachimiak, Andrzej; Phillips, George N; Shen, Ben

2015-10-13

Acyltransferase (AT)-less type I polyketide synthases (PKSs) break the type I PKS paradigm. They lack the integrated AT domains within their modules and instead use a discrete AT that acts in trans, whereas a type I PKS module minimally contains AT, acyl carrier protein (ACP), and ketosynthase (KS) domains. Structures of canonical type I PKS KS-AT didomains reveal structured linkers that connect the two domains. AT-less type I PKS KSs have remnants of these linkers, which have been hypothesized to be AT docking domains. Natural products produced by AT-less type I PKSs are very complex because of an increased representation of unique modifying domains. AT-less type I PKS KSs possess substrate specificity and fall into phylogenetic clades that correlate with their substrates, whereas canonical type I PKS KSs are monophyletic. We have solved crystal structures of seven AT-less type I PKS KS domains that represent various sequence clusters, revealing insight into the large structural and subtle amino acid residue differences that lead to unique active site topologies and substrate specificities. One set of structures represents a larger group of KS domains from both canonical and AT-less type I PKSs that accept amino acid-containing substrates. One structure has a partial AT-domain, revealing the structural consequences of a type I PKS KS evolving into an AT-less type I PKS KS. These structures highlight the structural diversity within the AT-less type I PKS KS family, and most important, provide a unique opportunity to study the molecular evolution of substrate specificity within the type I PKSs.

Structural and evolutionary relationships of "AT-less" type I polyketide synthase ketosynthases

Energy Technology Data Exchange (ETDEWEB)

Lohman, Jeremy; Ma, Ming; Osipiuk, Jerzy; Nocek, Boguslaw; Kim, Youngchang; Chang, Changsoo; Cuff, Marianne E.; Mack, Jamey; Bigelow, Lance; Li, Hui; Endres, Michael; Babnigg, Gyorgy; Joachimiak, Andrzej; Phillips, George N.; Shen, B G

2015-10-13

Acyltransferase (AT)-less type I polyketide synthases (PKSs) break the type I PKS paradigm. They lack the integrated AT domains within their modules and instead use a discrete AT that acts in trans, whereas a type I PKS module minimally contains AT, acyl carrier protein (ACP), and ketosynthase (KS) domains. Structures of canonical type I PKS KS-AT didomains reveal structured linkers that connect the two domains. AT-less type I PKS KSs have remnants of these linkers, which have been hypothesized to be AT docking domains. Natural products produced by AT-less type I PKSs are very complex because of an increased representation of unique modifying domains. AT-less type I PKS KSs possess substrate specificity and fall into phylogenetic clades that correlate with their substrates, whereas canonical type I PKS KSs are monophyletic. We have solved crystal structures of seven AT-less type I PKS KS domains that represent various sequence clusters, revealing insight into the large structural and subtle amino acid residue differences that lead to unique active site topologies and substrate specificities. One set of structures represents a larger group of KS domains from both canonical and AT-less type I PKSs that accept amino acid-containing substrates. One structure has a partial AT-domain, revealing the structural consequences of a type I PKS KS evolving into an AT-less type I PKS KS. These structures highlight the structural diversity within the AT-less type I PKS KS family, and most important, provide a unique opportunity to study the molecular evolution of substrate specificity within the type I PKSs.

OpenGL Insights

CERN Document Server

Cozzi, Patrick

2012-01-01

Get Real-World Insight from Experienced Professionals in the OpenGL Community With OpenGL, OpenGL ES, and WebGL, real-time rendering is becoming available everywhere, from AAA games to mobile phones to web pages. Assembling contributions from experienced developers, vendors, researchers, and educators, OpenGL Insights presents real-world techniques for intermediate and advanced OpenGL, OpenGL ES, and WebGL developers. Go Beyond the Basics The book thoroughly covers a range of topics, including OpenGL 4.2 and recent extensions. It explains how to optimize for mobile devices, explores the design

Structure and evolution of a European Parliament via a network and correlation analysis

Science.gov (United States)

Puccio, Elena; Pajala, Antti; Piilo, Jyrki; Tumminello, Michele

2016-11-01

We present a study of the network of relationships among elected members of the Finnish parliament, based on a quantitative analysis of initiative co-signatures, and its evolution over 16 years. To understand the structure of the parliament, we constructed a statistically validated network of members, based on the similarity between the patterns of initiatives they signed. We looked for communities within the network and characterized them in terms of members' attributes, such as electoral district and party. To gain insight on the nested structure of communities, we constructed a hierarchical tree of members from the correlation matrix. Afterwards, we studied parliament dynamics yearly, with a focus on correlations within and between parties, by also distinguishing between government and opposition. Finally, we investigated the role played by specific individuals, at a local level. In particular, whether they act as proponents who gather consensus, or as signers. Our results provide a quantitative background to current theories in political science. From a methodological point of view, our network approach has proven able to highlight both local and global features of a complex social system.

Surface/structure functionalization of copper-based catalysts by metal-support and/or metal–metal interactions

Energy Technology Data Exchange (ETDEWEB)

Konsolakis, Michalis, E-mail: mkonsol@science.tuc.gr [School of Production Engineering and Management, Technical University of Crete, GR-73100 Chania, Crete (Greece); Ioakeimidis, Zisis [Department of Mechanical Engineering, University of Western Macedonia, Bakola and Sialvera, GR-50100 Kozani (Greece)

2014-11-30

Highlights: • The surface chemistry of Cu-based catalysts is adjusted by metal-support or metal–metal interactions. • Three series of catalysts, i.e., Cu/REOs, Cu/Ce{sub 1−x}Sm{sub x}O{sub δ} and Cu–Co/CeO{sub 2} were prepared. • The local structure of Cu sites is remarkably affected by support or active phase modification. • Useful insights toward the fundamental understanding of Cu-catalyzed reactions are provided. - Abstract: Cu-based catalysts have recently attracted great attention both in catalysis and electro-catalysis fields due to their excellent catalytic performance and low cost. Given that their performance is determined, to a great extent, by Cu sites local environment, considerable efforts have been devoted on the strategic modifications of the electronic and structural properties of Cu sites. In this regard, the feasibility of tuning the local structure of Cu entities by means of metal-support or metal–metal interactions is investigated. More specifically, the physicochemical properties of Cu entities are modified by employing: (i) different oxides (CeO{sub 2}, La{sub 2}O{sub 3}, Sm{sub 2}O{sub 3}), or (ii) ceria-based mixed oxides (Ce{sub 1−x}Sm{sub x}O{sub δ}) as supporting carriers, and (iii) a second metal (Cobalt) adjacent to Cu (bimetallic Cu–Co/CeO{sub 2}). A characterization study, involving BET, XRD, TPR, and XPS, reveal that significant modifications on structural, redox and electronic properties of Cu sites can be induced by adopting either different oxide carriers or bimetallic complexes. Fundamental insights into the tuning of Cu local environment by metal-support or metal–metal interactions are provided, paving the way for real-life industrial applications.

Insight to structural subsite recognition in plant thiol protease-inhibitor complexes : Understanding the basis of differential inhibition and the role of water

Directory of Open Access Journals (Sweden)

Mukhopadhayay Bishnu P

2001-09-01

Full Text Available Abstract Background This work represents an extensive MD simulation / water-dynamics studies on a series of complexes of inhibitors (leupeptin, E-64, E-64-C, ZPACK and plant cysteine proteases (actinidin, caricain, chymopapain, calotropin DI of papain family to understand the various interactions, water binding mode, factors influencing it and the structural basis of differential inhibition. Results The tertiary structure of the enzyme-inhibitor complexes were built by visual interactive modeling and energy minimization followed by dynamic simulation of 120 ps in water environment. DASA study with and without the inhibitor revealed the potential subsite residues involved in inhibition. Though the interaction involving main chain atoms are similar, critical inspection of the complexes reveal significant differences in the side chain interactions in S2-P2 and S3-P3 pairs due to sequence differences in the equivalent positions of respective subsites leading to differential inhibition. Conclusion The key finding of the study is a conserved site of a water molecule near oxyanion hole of the enzyme active site, which is found in all the modeled complexes and in most crystal structures of papain family either native or complexed. Conserved water molecules at the ligand binding sites of these homologous proteins suggest the structural importance of the water, which changes the conventional definition of chemical geometry of inhibitor binding domain, its shape and complimentarity. The water mediated recognition of inhibitor to enzyme subsites (Pn...H2O....Sn of leupeptin acetyl oxygen to caricain, chymopapain and calotropinDI is an additional information and offer valuable insight to potent inhibitor design.

New insight on bismuth cuprates with incommensurate modulated structures

Czech Academy of Sciences Publication Activity Database

Mironov, A. V.; Petříček, Václav; Khasanova, N. R.; Antipov, E. V.

2016-01-01

Roč. 72, č. 3 (2016), s. 395-403 ISSN 2052-5206 Institutional support: RVO:68378271 Keywords : modulated structure * high Tc superconductor * superspace approach Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.032, year: 2016

Controlled self-assembly of PbS nanoparticles into macrostar-like hierarchical structures

International Nuclear Information System (INIS)

Li, Guowei; Li, Changsheng; Tang, Hua; Cao, Kesheng; Chen, Juan

2011-01-01

Graphical abstract: The aggregation and rotation of nanoparticles to adopt parallel orientations in three dimensions was indirectly illustrated by TEM and HRTEM images. Highlights: → Macrostar-like PbS hierarchical structures was successfully synthesized by a simple hydrothermal method and mesostars were assembled from the PbS nanocube building blocks with edge lengths of about 100 nm. → Ostwald-ripening-assisted oriented attachment is believed to play a key role in the growth behavior of novel 3D structures. → Optical properties indicating few defects on the surface of the PbS structure and exhibit large blue-shifts compared to bulk PbS. -- Abstract: The synthesis of macrostar-like PbS hierarchical structures by a simple hydrothermal method at 180 o C for 24 h is proven successful with the assistance of a new surfactant called tetrabutylammonium bromide (TBAB). The as-obtained product is characterized by means of X-ray powder diffraction, field emission scanning electron microscopy, energy dispersive spectrometry, high resolution transmission electron microscopy, and selected area electron diffraction. The presence of TBAB and NaF plays an important role in the formation of PbS macrostructures. Ostwald-ripening-assisted oriented attachment is believed to play a key role in the growth behavior of novel 3D structures. As such, a possible self-assembly mechanism is proposed to explain the formation of the said structures. The present study aims to introduce new insights into understanding the formation process of such unique hierarchical superstructures.

Journey of DNA Evidence in Legal Arena: An Insight on Its Legal Perspective Worldwide and Highlight on Admissibility in India

Directory of Open Access Journals (Sweden)

Ramakant Gupta

2016-01-01

Full Text Available DNA profiling is one of the powerful breakthroughs in forensics. This specialized technique has made the identification of an individual possible even by a tiny shred of tissue or drop of blood thus, has strongly revolutionized various criminal investigations. Rape, paternity, and murder cases are the type of criminal cases commonly solved by the use of this technique. It has been recently introduced to forensic odontology and is also used frequently. Although this is a powerful and reliable scientific technique but its forensic use is a major contribution to the debate on law reform. The application of DNA profiling in the criminal justice system, i.e., the admissibility of DNA evidence in court of law is an important issue which is being faced by the courts and forensic experts worldwide today. Thus, a proper legal outlook is required while dealing with this kind of scientific evidence. Therefore, this review intends to make forensic experts/odontologists aware about the admissibility of DNA evidence in court, with a highlight on the laws related to the admissibility of evidence worldwide, having a special focus on the laws related to admissibility of evidence in Indian judicial system. For this review, the literature was overviewed from articles on DNA evidence and admissibility retrieved by searches on electronic databases such as Google, PubMed, and EMBASE from 1975 through July 2015.

Probabilistic safety assessment applications and insights

International Nuclear Information System (INIS)

Hitchler, M.J.; Burns, N.L.; Liparulo, N.J.; Mink, F.J.

1987-01-01

The insights gained through a comparison of seven PRA studies (Italian PUN, Sizewell B, Ringhals 2, Millstone 3, Zion 1 and 2, Oconee 3, and Seabrook) included insights regarding the adequacy of the PRA technology utilized in the studies and the potential areas for improvement and insights regarding the adequacy of plant designs and how PRA has been utilized to enhance the design and operation of nuclear power plants. (orig.)

The Value of Change: Surprises and Insights in Stellar Evolution

Science.gov (United States)

Bildsten, Lars

2018-01-01

Astronomers with large-format cameras regularly scan the sky many times per night to detect what's changing, and telescopes in space such as Kepler and, soon, TESS obtain very accurate brightness measurements of nearly a million stars over time periods of years. These capabilities, in conjunction with theoretical and computational efforts, have yielded surprises and remarkable new insights into the internal properties of stars and how they end their lives. I will show how asteroseismology reveals the properties of the deep interiors of red giants, and highlight how astrophysical transients may be revealing unusual thermonuclear outcomes from exploding white dwarfs and the births of highly magnetic neutron stars. All the while, stellar science has been accelerated by the availability of open source tools, such as Modules for Experiments in Stellar Astrophysics (MESA), and the nearly immediate availability of observational results.

Insights into the Mechanism of Deubiquitination by JAMM Deubiquitinases from Cocrystal Structures of the Enzyme with the Substrate and Product

Science.gov (United States)

2015-01-01

AMSH, a conserved zinc metallo deubiquitinase, controls downregulation and degradation of cell-surface receptors mediated by the endosomal sorting complexes required for transport (ESCRT) machinery. It displays high specificity toward the Lys63-linked polyubiquitin chain, which is used as a signal for ESCRT-mediated endosomal–lysosomal sorting of receptors. Herein, we report the crystal structures of the catalytic domain of AMSH orthologue Sst2 from fission yeast, its ubiquitin (product)-bound form, and its Lys63-linked diubiquitin (substrate)-bound form at 1.45, 1.7, and 2.3 Å, respectively. The structures reveal that the P-side product fragment maintains nearly all the contacts with the enzyme as seen with the P portion (distal ubiquitin) of the Lys63-linked diubiquitin substrate, with additional coordination of the Gly76 carboxylate group of the product with the active-site Zn2+. One of the product-bound structures described herein is the result of an attempt to cocrystallize the diubiquitin substrate bound to an active site mutant presumed to render the enzyme inactive, instead yielding a cocrystal structure of the enzyme bound to the P-side ubiquitin fragment of the substrate (distal ubiquitin). This fragment was generated in situ from the residual activity of the mutant enzyme. In this structure, the catalytic water is seen placed between the active-site Zn2+ and the carboxylate group of Gly76 of ubiquitin, providing what appears to be a snapshot of the active site when the product is about to depart. Comparison of this structure with that of the substrate-bound form suggests the importance of dynamics of a flexible flap near the active site in catalysis. The crystal structure of the Thr319Ile mutant of the catalytic domain of Sst2 provides insight into structural basis of microcephaly capillary malformation syndrome. Isothermal titration calorimetry yields a dissociation constant (KD) of 10.2 ± 0.6 μM for the binding of ubiquitin to the enzyme, a value

When gender matters: new insights into the relationships between social systems and the genetic structure of human populations.

Science.gov (United States)

Destro Bisol, Giovanni; Capocasa, Marco; Anagnostou, Paolo

2012-10-01

Due to its important effects on the ecological dynamics and the genetic structure of species, biologists have long been interested in gender-biased dispersal, a condition where one gender is more prone to move from the natal site. More recently, this topic has attracted a great attention from human evolutionary geneticists. Considering the close relations between residential rules and social structure, gender-biased dispersal is, in fact, regarded as an important case study concerning the effects of socio-cultural factors on human genetic variation. It all started with the seminal paper by Mark Seielstad, Erich Minch and Luigi Luca Cavalli Sforza from Stanford University (Seielstad et al. 1998). They observed a larger differentiation for Y-chromosome than mitochondrial DNA between extant human populations, purportedly a consequence of the prevalence of long-term patrilocality in human societies. Subsequent studies, however, have highlighted the need to consider geographically close and culturally homogeneous groups, disentangle signals due to different peopling events and obtain unbiased estimates of genetic diversity. In this issue of Molecular Ecology, not only do Marks et al. (2012) adopt an experimental design which addresses these concerns, but they also take a further and important step forward by integrating the genetic analysis of two distant populations, the Basotho and Spanish, with data regarding migration rates and matrimonial distances. Using both empirical evidence and simulations, the authors show that female-biased migration due to patrilocality might shape the genetic structure of human populations only at short ranges and under substantial differences in migration rates between genders. Providing a quantitative framework for future studies of the effects of residential rules on the human genome, this study paves the way for further developments in the field. On a wider perspective, Marks et al.'s work demonstrates the power of approaches which

Structural Insights Into The Bacterial Carbon-Phosphorus Lyase Machinery

DEFF Research Database (Denmark)

Brodersen, Ditlev Egeskov

the proteins encoded in the phn operon act in concert to catabolise phosphonate remain unknown. We have determined the crystal structure of a 240 kDa Escherichia coli carbon-phosphorus lyase core complex at 1.7 Å and show that it comprises a highly intertwined network of subunits with several unexpected......Phosphonate compounds act as a nutrient source for some microorganisms when phosphate is limiting but require a specialised enzymatic machinery due to the presence of the highly stable carbon-phosphorus bond. Despite the fundamental importance to microbial metabolism, the details of how...... structural features. The complex contains at least two different active sites and suggest a revision of current models of carbon-phosphorus bond cleavage. Using electron microscopy, we map the binding site of an additional protein subunit, which may use ATP for driving conformational changes during...

Readiness for self-directed change in professional behaviours: factorial validation of the Self-Reflection and Insight Scale.

Science.gov (United States)

Roberts, Chris; Stark, Patsy

2008-11-01

Self-reflection, the practice of inspecting and evaluating one's own thoughts, feelings and behaviour, and insight, the ability to understand one's own thoughts, feelings and behaviour, are central to the self-regulation of behaviours. The Self-Reflection and Insight Scale (SRIS) measures three factors in the self-regulation cycle: need for reflection; engagement in reflection, and insight. We used structural equation modelling to undertake a confirmatory factor analysis of the SRIS. We re-specified our model to analyse all of the data to explain relationships between the SRIS, medical student characteristics, and responses to issues of teaching and learning in professionalism. The factorial validity of a modified SRIS showed all items loading significantly on their expected factors, with a good fit to the data. Each subscale had good internal reliability (> 0.8). There was a strong relationship between the need for reflection and engagement in reflection (r = 0.77). Insight was related to need for reflection (0.22) and age (0.21), but not to the process of engaging in reflection (0.06). Validation of the SRIS provides researchers with a new instrument with which to measure and investigate the processes of self-reflection and insight in the context of students' self-regulation of their professionalism. Insight is related to the motive or need for reflection, but the process of reflection does not lead to insight. Attending to feelings is an important and integral aspect of self-reflection and insight. Effective strategies are needed to develop students' insight as they reflect on their professionalism.

Insight in schizophrenia: involvement of self-reflection networks?

Science.gov (United States)

van der Meer, Lisette; de Vos, Annerieke E; Stiekema, Annemarie P M; Pijnenborg, Gerdina H M; van Tol, Marie-José; Nolen, Willem A; David, Anthony S; Aleman, André

2013-11-01

Impaired insight is a common feature in psychosis and an important predictor of variables such as functional outcome, prognosis, and treatment adherence. A cognitive process that may underlie insight in psychosis is self-reflection, or the conscious evaluation of one's traits and characteristics. The current study aims to investigate the neural correlates of self-reflective processing and its relationship with insight in schizophrenia. Forty-seven schizophrenia patients and 21 healthy controls performed a self-reflection task in a functional magnetic resonance imaging (fMRI) scanner. The tasks comprised a self-reflection, close other-reflection, and a semantic (baseline) condition. Insight scores were obtained with the Schedule of Assessment of Insight Expanded. In addition, cognitive insight scores were obtained (Beck Cognitive Insight Scale [BCIS]). Schizophrenia patients demonstrated less activation in the posterior cingulate cortex in the self- and other-reflection conditions and less activation in the precuneus in the other-reflection condition compared with healthy controls. Better insight was associated with greater response in the inferior frontal gyrus, anterior insula, and inferior parietal lobule during self-reflection. In addition, better cognitive insight was associated with higher activation in ventromedial prefrontal cortex during self-reflection. In the current study, evidence for a relationship between self-reflection and insight in patients with schizophrenia was found in brain areas related to self-reflection, self/other distinction and source attribution. The findings support the rationale for a treatment that is currently under evaluation, which attempts to increase insight by enhancing self-reflection.

Structure and tectonic evolution of the southwestern Trinidad dome, Escambray complex, Central Cuba: Insights into deformation in an accretionary wedge

Science.gov (United States)

Despaigne-Díaz, Ana Ibis; García Casco, Antonio; Cáceres Govea, Dámaso; Wilde, Simon A.; Millán Trujillo, Guillermo

2017-10-01

The Trinidad dome, Escambray complex, Cuba, forms part of an accretionary wedge built during intra-oceanic subduction in the Caribbean from the Late Cretaceous to Cenozoic. The structure reflects syn-subduction exhumation during thickening of the wedge, followed by extension. Field mapping, metamorphic and structural analysis constrain the tectonic evolution into five stages. Three ductile deformation events (D1, D2 and D3) are related to metamorphism in a compressional setting and formation of several nappes. D1 subduction fabrics are only preserved as relict S1 foliation and rootless isoclinal folds strongly overprinted by the main S2 foliation. The S2 foliation is parallel to sheared serpentinised lenses that define tectonic contacts, suggesting thrust stacks and underthrusting at mantle depths. Thrusting caused an inverted metamorphic structure with higher-grade on top of lower-grade nappes. Exhumation started during D2 when the units were incorporated into the growing accretionary wedge along NNE-directed thrust faults and was accompanied by substantial decompression and cooling. Folding and thrusting continued during D3 and marks the transition from ductile to brittle-ductile conditions at shallower crustal levels. The D4-5 events are related to extension and contributed to the final exhumation (likely as a core complex). D4 is associated with a regional spaced S4 cleavage, late open folds, and numerous extension veins, whereas D5 is recorded by normal and strike-slip faults affecting all nappes. The P-t path shows rapid exhumation during D2 and slower rates during D3 when the units were progressively incorporated into the accretionary prism. The domal shape formed in response to tectonic denudation assisted by normal faulting and erosion at the surface during the final stages of structural development. These results support tectonic models of SW subduction of the Proto-Caribbean crust under the Caribbean plate during the latest Cretaceous and provide

Structural-relaxation phenomena in As–S glasses as probed by combined PAL/DBAR technique

Energy Technology Data Exchange (ETDEWEB)

Shpotyuk, O., E-mail: shpotyuk@novas.lviv.ua [Institute of Materials of Scientific Research Company “Carat”, 202 Stryjska Str., Lviv, 79031 (Ukraine); Institute of Physics of Jan Dlugosz University, 13/15 al. Armii Krajowej, Czestochowa, 42200 (Poland); Ingram, A. [Faculty of Physics of Opole Technical University, 75 Ozimska Str., Opole, 45370 (Poland); Szatanik, R. [Institute of Physics of Opole University, 48 Oleska Str., Opole, 45052 (Poland); Shpotyuk, M. [Institute of Materials of Scientific Research Company “Carat”, 202 Stryjska Str., Lviv, 79031 (Ukraine); Lviv Polytechnic National University, 12 Bandery Str., Lviv, 79013 (Ukraine); Golovchak, R. [Physics and Astronomy Department, Austin Peay State University, 601 College Str., Clarksville, TN, 37044 (United States)

2015-04-01

Experimental techniques exploring phenomena of positron–electron interaction, namely the positron annihilation lifetime spectroscopy and Doppler broadening of annihilation radiation, are shown to be very informative tools to study radiation- and thermally-induced phenomena in chalcogenide glasses of binary As–S system. Time-dependent processes of free-volume voids agglomeration (expansion), fragmentation (refining) and disappearing (contraction) are identified as main stages of physical aging in S-rich glasses, while a competitive channel of coordination topological defects formation associated with void charging becomes significant in a vicinity of near-stoichiometric glass compositions under γ-irradiation. The data of combined positron lifetime and Doppler broadening of annihilation radiation measurements are correlated with radiation-induced shift of fundamental optical absorption edge of the studied glasses. The meaningful model for γ-induced and relaxation-driven evolution in free-volume void structure of As–S glasses giving a unified insight on their structural-chemical nature is proposed. - Highlights: • Combined optical, PAL and DBAR probes to study structural relaxation in As–S glasses. • Void agglomeration, fragmentation and disappearing are main stages of physical aging. • Radiation-induced coordination defects are important in near-stoichiometric As–S. • Proposed model describes free-volume evolution in the void structure of As–S glasses.

Structural-relaxation phenomena in As–S glasses as probed by combined PAL/DBAR technique

International Nuclear Information System (INIS)

Shpotyuk, O.; Ingram, A.; Szatanik, R.; Shpotyuk, M.; Golovchak, R.

2015-01-01

Experimental techniques exploring phenomena of positron–electron interaction, namely the positron annihilation lifetime spectroscopy and Doppler broadening of annihilation radiation, are shown to be very informative tools to study radiation- and thermally-induced phenomena in chalcogenide glasses of binary As–S system. Time-dependent processes of free-volume voids agglomeration (expansion), fragmentation (refining) and disappearing (contraction) are identified as main stages of physical aging in S-rich glasses, while a competitive channel of coordination topological defects formation associated with void charging becomes significant in a vicinity of near-stoichiometric glass compositions under γ-irradiation. The data of combined positron lifetime and Doppler broadening of annihilation radiation measurements are correlated with radiation-induced shift of fundamental optical absorption edge of the studied glasses. The meaningful model for γ-induced and relaxation-driven evolution in free-volume void structure of As–S glasses giving a unified insight on their structural-chemical nature is proposed. - Highlights: • Combined optical, PAL and DBAR probes to study structural relaxation in As–S glasses. • Void agglomeration, fragmentation and disappearing are main stages of physical aging. • Radiation-induced coordination defects are important in near-stoichiometric As–S. • Proposed model describes free-volume evolution in the void structure of As–S glasses

O conceito do insight em pacientes com transtorno obsessivo-compulsivo The concept of insight in patients with obsessive-compulsive disorder

Directory of Open Access Journals (Sweden)

Júlia M. Fontenelle

2010-03-01

Full Text Available OBJETIVO: Atualizar os clínicos sobre a existência de um possível subtipo do transtorno obsessivo-compulsivo caracterizado por pouco insight. MÉTODO: Revisão opinativa baseada em estudos indexados na base de dados PubMed e PsychINFO, identificados por meio dos unitermos "obsessive-compulsive disorder" e "insight" ou "ego-dystonic" e publicados entre 1966 e outubro de 2009. Os resultados foram examinados de acordo com a estratégia utilizada para abordar o insight, i.e. categórica vs. dimensional. RESULTADOS: Análise dos estudos nos permitiu identificar pontos que colocam em dúvida a existência de um subtipo do transtorno obsessivo-compulsivo bem delimitado caracterizado por pouco insight. Estes pontos incluem 1 prevalência extremamente variável do transtorno obsessivo-compulsivo com insight reduzido encontrada em estudos categóricos, 2 homogeneidade dos achados fenotípicos (i.e. maior gravidade associados a baixo insight em estudos categóricos e dimensionais e 3 ausência de estudos que investigam "zonas de raridade" entre as formas de transtorno obsessivo-compulsivo com pouco e bom insight. CONCLUSÃO: Embora uma abordagem categórica do insight no transtorno obsessivo-compulsivo seja importante em ambientes clínicos, uma vez que neles existem demandas prementes para tomada de decisões, a abordagem dimensional do insight parece refletir de forma mais fidedigna o fenômeno apresentado pelos pacientes em tela.OBJECTIVE: To update clinicians regarding the existence of a putative subtype of obsessive-compulsive disorder based on poor insight. METHOD: Opinionative review based on studies indexed in the PubMed and PsychINFO databases, identified by means of the keywords "obsessive-compulsive disorder" AND "insight" OR "ego-syntonic", and published between 1966 and October 2009. The results were analyzed according to the approach adopted, i.e. a categorical or dimensional view of insight in obsessive-compulsive disorder. RESULTS: The

Insights into the Mechanisms of Chloroplast Division

Directory of Open Access Journals (Sweden)

Yamato Yoshida

2018-03-01

Full Text Available The endosymbiosis of a free-living cyanobacterium into an ancestral eukaryote led to the evolution of the chloroplast (plastid more than one billion years ago. Given their independent origins, plastid proliferation is restricted to the binary fission of pre-existing plastids within a cell. In the last 25 years, the structure of the supramolecular machinery regulating plastid division has been discovered, and some of its component proteins identified. More recently, isolated plastid-division machineries have been examined to elucidate their structural and mechanistic details. Furthermore, complex studies have revealed how the plastid-division machinery morphologically transforms during plastid division, and which of its component proteins play a critical role in generating the contractile force. Identifying the three-dimensional structures and putative functional domains of the component proteins has given us hints about the mechanisms driving the machinery. Surprisingly, the mechanisms driving plastid division resemble those of mitochondrial division, indicating that these division machineries likely developed from the same evolutionary origin, providing a key insight into how endosymbiotic organelles were established. These findings have opened new avenues of research into organelle proliferation mechanisms and the evolution of organelles.

Insight in psychosis : Metacognitive processes and treatment

NARCIS (Netherlands)

de Vos, Annerieke

2016-01-01

Insight is impaired in 50- 80% of the patients with schizophrenia. Annerieke de Vos working at GGZ Drenthe and the University Medical Hospital Groningen, aimed to elucidate which processes underlie impaired insight and tried to improve insight in patients by targeting these processes. On September

Large-scale brain network associated with creative insight: combined voxel-based morphometry and resting-state functional connectivity analyses.

Science.gov (United States)

Ogawa, Takeshi; Aihara, Takatsugu; Shimokawa, Takeaki; Yamashita, Okito

2018-04-24

Creative insight occurs with an "Aha!" experience when solving a difficult problem. Here, we investigated large-scale networks associated with insight problem solving. We recruited 232 healthy participants aged 21-69 years old. Participants completed a magnetic resonance imaging study (MRI; structural imaging and a 10 min resting-state functional MRI) and an insight test battery (ITB) consisting of written questionnaires (matchstick arithmetic task, remote associates test, and insight problem solving task). To identify the resting-state functional connectivity (RSFC) associated with individual creative insight, we conducted an exploratory voxel-based morphometry (VBM)-constrained RSFC analysis. We identified positive correlations between ITB score and grey matter volume (GMV) in the right insula and middle cingulate cortex/precuneus, and a negative correlation between ITB score and GMV in the left cerebellum crus 1 and right supplementary motor area. We applied seed-based RSFC analysis to whole brain voxels using the seeds obtained from the VBM and identified insight-positive/negative connections, i.e. a positive/negative correlation between the ITB score and individual RSFCs between two brain regions. Insight-specific connections included motor-related regions whereas creative-common connections included a default mode network. Our results indicate that creative insight requires a coupling of multiple networks, such as the default mode, semantic and cerebral-cerebellum networks.