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Sample records for adopt multiple conformations

  1. Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition.

    PubMed

    Liu, Zhu; Gong, Zhou; Jiang, Wen-Xue; Yang, Ju; Zhu, Wen-Kai; Guo, Da-Chuan; Zhang, Wei-Ping; Liu, Mai-Li; Tang, Chun

    2015-01-01

    A polyubiquitin comprises multiple covalently linked ubiquitins and recognizes myriad targets. Free or bound to ligands, polyubiquitins are found in different arrangements of ubiquitin subunits. To understand the structural basis for polyubiquitin quaternary plasticity and to explore the target recognition mechanism, we characterize the conformational space of Lys63-linked diubiquitin (K63-Ub2). Refining against inter-subunit paramagnetic NMR data, we show that free K63-Ub2 exists as a dynamic ensemble comprising multiple closed and open quaternary states. The quaternary dynamics enables K63-Ub2 to be specifically recognized in a variety of signaling pathways. When binding to a target protein, one of the preexisting quaternary states is selected and stabilized. A point mutation that shifts the equilibrium between the different states modulates the binding affinities towards K63-Ub2 ligands. This conformational selection mechanism at the quaternary level may be used by polyubiquitins of different lengths and linkages for target recognition. PMID:26090905

  2. c-Abl Tyrosine Kinase Adopts Multiple Active Conformational States in Solution.

    PubMed

    Badger, John; Grover, Prerna; Shi, Haibin; Panjarian, Shoghag B; Engen, John R; Smithgall, Thomas E; Makowski, Lee

    2016-06-14

    Protein tyrosine kinases of the Abl family have diverse roles in normal cellular regulation and drive several forms of leukemia as oncogenic fusion proteins. In the crystal structure of the inactive c-Abl kinase core, the SH2 and SH3 domains dock onto the back of the kinase domain, resulting in a compact, assembled state. This inactive conformation is stabilized by the interaction of the myristoylated N-cap with a pocket in the C-lobe of the kinase domain. Mutations that perturb these intramolecular interactions result in kinase activation. Here, we present X-ray scattering solution structures of multidomain c-Abl kinase core proteins modeling diverse active states. Surprisingly, the relative positions of the regulatory N-cap, SH3, and SH2 domains in an active myristic acid binding pocket mutant (A356N) were virtually identical to those of the assembled wild-type kinase core, indicating that Abl kinase activation does not require dramatic reorganization of the downregulated core structure. In contrast, the positions of the SH2 and SH3 domains in a clinically relevant imatinib-resistant gatekeeper mutant (T315I) appear to be reconfigured relative to their positions in the wild-type protein. Our results demonstrate that c-Abl kinase activation can occur either with (T315I) or without (A356N) global allosteric changes in the core, revealing the potential for previously unrecognized signaling diversity. PMID:27166638

  3. c-Abl Tyrosine Kinase Adopts Multiple Active Conformational States in Solution

    PubMed Central

    2016-01-01

    Protein tyrosine kinases of the Abl family have diverse roles in normal cellular regulation and drive several forms of leukemia as oncogenic fusion proteins. In the crystal structure of the inactive c-Abl kinase core, the SH2 and SH3 domains dock onto the back of the kinase domain, resulting in a compact, assembled state. This inactive conformation is stabilized by the interaction of the myristoylated N-cap with a pocket in the C-lobe of the kinase domain. Mutations that perturb these intramolecular interactions result in kinase activation. Here, we present X-ray scattering solution structures of multidomain c-Abl kinase core proteins modeling diverse active states. Surprisingly, the relative positions of the regulatory N-cap, SH3, and SH2 domains in an active myristic acid binding pocket mutant (A356N) were virtually identical to those of the assembled wild-type kinase core, indicating that Abl kinase activation does not require dramatic reorganization of the downregulated core structure. In contrast, the positions of the SH2 and SH3 domains in a clinically relevant imatinib-resistant gatekeeper mutant (T315I) appear to be reconfigured relative to their positions in the wild-type protein. Our results demonstrate that c-Abl kinase activation can occur either with (T315I) or without (A356N) global allosteric changes in the core, revealing the potential for previously unrecognized signaling diversity. PMID:27166638

  4. Cortactin Adopts a Globular Conformation and Bundles Actin into Sheets

    SciTech Connect

    Cowieson, Nathan P.; King, Gordon; Cookson, David; Ross, Ian; Huber, Thomas; Hume, David A.; Kobe, Bostjan; Martin, Jennifer L.

    2008-08-21

    Cortactin is a filamentous actin-binding protein that plays a pivotal role in translating environmental signals into coordinated rearrangement of the cytoskeleton. The dynamic reorganization of actin in the cytoskeleton drives processes including changes in cell morphology, cell migration, and phagocytosis. In general, structural proteins of the cytoskeleton bind in the N-terminal region of cortactin and regulatory proteins in the C-terminal region. Previous structural studies have reported an extended conformation for cortactin. It is therefore unclear how cortactin facilitates cross-talk between structural proteins and their regulators. In the study presented here, circular dichroism, chemical cross-linking, and small angle x-ray scattering are used to demonstrate that cortactin adopts a globular conformation, thereby bringing distant parts of the molecule into close proximity. In addition, the actin bundling activity of cortactin is characterized, showing that fully polymerized actin filaments are bundled into sheet-like structures. We present a low resolution structure that suggests how the various domains of cortactin interact to coordinate its array of binding partners at sites of actin branching.

  5. Multiple conformations are a conserved and regulatory feature of the RB1 5′ UTR

    PubMed Central

    Kutchko, Katrina M.; Sanders, Wes; Ziehr, Ben; Phillips, Gabriela; Solem, Amanda; Halvorsen, Matthew; Weeks, Kevin M.; Moorman, Nathaniel

    2015-01-01

    Folding to a well-defined conformation is essential for the function of structured ribonucleic acids (RNAs) like the ribosome and tRNA. Structured elements in the untranslated regions (UTRs) of specific messenger RNAs (mRNAs) are known to control expression. The importance of unstructured regions adopting multiple conformations, however, is still poorly understood. High-resolution SHAPE-directed Boltzmann suboptimal sampling of the Homo sapiens Retinoblastoma 1 (RB1) 5′ UTR yields three distinct conformations compatible with the experimental data. Private single nucleotide variants (SNVs) identified in two patients with retinoblastoma each collapse the structural ensemble to a single but distinct well-defined conformation. The RB1 5′ UTRs from Bos taurus (cow) and Trichechus manatus latirostris (manatee) are divergent in sequence from H. sapiens (human) yet maintain structural compatibility with high-probability base pairs. SHAPE chemical probing of the cow and manatee RB1 5′ UTRs reveals that they also adopt multiple conformations. Luciferase reporter assays reveal that 5′ UTR mutations alter RB1 expression. In a traditional model of disease, causative SNVs disrupt a key structural element in the RNA. For the subset of patients with heritable retinoblastoma-associated SNVs in the RB1 5′ UTR, the absence of multiple structures is likely causative of the cancer. Our data therefore suggest that selective pressure will favor multiple conformations in eukaryotic UTRs to regulate expression. PMID:25999316

  6. Multiple conformations are a conserved and regulatory feature of the RB1 5' UTR.

    PubMed

    Kutchko, Katrina M; Sanders, Wes; Ziehr, Ben; Phillips, Gabriela; Solem, Amanda; Halvorsen, Matthew; Weeks, Kevin M; Moorman, Nathaniel; Laederach, Alain

    2015-07-01

    Folding to a well-defined conformation is essential for the function of structured ribonucleic acids (RNAs) like the ribosome and tRNA. Structured elements in the untranslated regions (UTRs) of specific messenger RNAs (mRNAs) are known to control expression. The importance of unstructured regions adopting multiple conformations, however, is still poorly understood. High-resolution SHAPE-directed Boltzmann suboptimal sampling of the Homo sapiens Retinoblastoma 1 (RB1) 5' UTR yields three distinct conformations compatible with the experimental data. Private single nucleotide variants (SNVs) identified in two patients with retinoblastoma each collapse the structural ensemble to a single but distinct well-defined conformation. The RB1 5' UTRs from Bos taurus (cow) and Trichechus manatus latirostris (manatee) are divergent in sequence from H. sapiens (human) yet maintain structural compatibility with high-probability base pairs. SHAPE chemical probing of the cow and manatee RB1 5' UTRs reveals that they also adopt multiple conformations. Luciferase reporter assays reveal that 5' UTR mutations alter RB1 expression. In a traditional model of disease, causative SNVs disrupt a key structural element in the RNA. For the subset of patients with heritable retinoblastoma-associated SNVs in the RB1 5' UTR, the absence of multiple structures is likely causative of the cancer. Our data therefore suggest that selective pressure will favor multiple conformations in eukaryotic UTRs to regulate expression. PMID:25999316

  7. Mycobacterium tuberculosis acyl carrier protein synthase adopts two different pH-dependent structural conformations

    SciTech Connect

    Gokulan, Kuppan; Aggarwal, Anup; Shipman, Lance; Besra, Gurdyal S.; Sacchettini, James C.

    2011-07-01

    Bacterial acyl carrier protein synthase plays an essential role in the synthesis of fatty acids, nonribosomal peptides and polyketides. In Mycobacterium tuberculosis, AcpS or group I phosphopentatheine transferase exhibits two different structural conformations depending upon the pH. The crystal structures of acyl carrier protein synthase (AcpS) from Mycobacterium tuberculosis (Mtb) and Corynebacterium ammoniagenes determined at pH 5.3 and pH 6.5, respectively, are reported. Comparison of the Mtb apo-AcpS structure with the recently reported structure of the Mtb AcpS–ADP complex revealed that AcpS adopts two different conformations: the orthorhombic and trigonal space-group structures show structural differences in the α2 helix and in the conformation of the α3–α4 connecting loop, which is in a closed conformation. The apo-AcpS structure shows electron density for the entire model and was obtained at lower pH values (4.4–6.0). In contrast, at a higher pH value (6.5) AcpS undergoes significant conformational changes, resulting in disordered regions that show no electron density in the AcpS model. The solved structures also reveal that C. ammoniagenes AcpS undergoes structural rearrangement in two regions, similar to the recently reported Mtb AcpS–ADP complex structure. In vitro reconstitution experiments show that AcpS has a higher post-translational modification activity between pH 4.4 and 6.0 than at pH values above 6.5, where the activity drops owing to the change in conformation. The results show that apo-AcpS and AcpS–ADP adopt different conformations depending upon the pH conditions of the crystallization solution.

  8. Mycobacterium tuberculosis acyl carrier protein synthase adopts two different pH-dependent structural conformations

    SciTech Connect

    Gokulan, Kuppan; Aggarwal, Anup; Shipman, Lance; Besra, Gurdyal S.; Sacchettini, James C.

    2011-09-20

    The crystal structures of acyl carrier protein synthase (AcpS) from Mycobacterium tuberculosis (Mtb) and Corynebacterium ammoniagenes determined at pH 5.3 and pH 6.5, respectively, are reported. Comparison of the Mtb apo-AcpS structure with the recently reported structure of the Mtb AcpS-ADP complex revealed that AcpS adopts two different conformations: the orthorhombic and trigonal space-group structures show structural differences in the {alpha}2 helix and in the conformation of the {alpha}3-{alpha}4 connecting loop, which is in a closed conformation. The apo-AcpS structure shows electron density for the entire model and was obtained at lower pH values (4.4-6.0). In contrast, at a higher pH value (6.5) AcpS undergoes significant conformational changes, resulting in disordered regions that show no electron density in the AcpS model. The solved structures also reveal that C. ammoniagenes AcpS undergoes structural rearrangement in two regions, similar to the recently reported Mtb AcpS-ADP complex structure. In vitro reconstitution experiments show that AcpS has a higher post-translational modification activity between pH 4.4 and 6.0 than at pH values above 6.5, where the activity drops owing to the change in conformation. The results show that apo-AcpS and AcpS-ADP adopt different conformations depending upon the pH conditions of the crystallization solution.

  9. Mapping early conformational changes in alphaIIb and beta3 during biogenesis reveals a potential mechanism for alphaIIbbeta3 adopting its bent conformation.

    PubMed

    Mitchell, W Beau; Li, Jihong; Murcia, Marta; Valentin, Nathalie; Newman, Peter J; Coller, Barry S

    2007-05-01

    Current evidence supports a model in which the low-affinity state of the platelet integrin alphaIIbbeta3 results from alphaIIbbeta3 adopting a bent conformation. To assess alphaIIbbeta3 biogenesis and how alphaIIbbeta3 initially adopts the bent conformation, we mapped the conformational states occupied by alphaIIb and beta3 during biogenesis using conformation-specific monoclonal antibodies (mAbs). We found that alphaIIbbeta3 complex formation was not limited by the availability of either free pro-alphaIIb or free beta3, suggesting that other molecules, perhaps chaperones, control complex formation. Five beta3-specific, ligand-induced binding site (LIBS) mAbs reacted with much or all free beta3 but not with beta3 when in complex with mature alphaIIb, suggesting that beta3 adopts its mature conformation only after complex formation. Conversely, 2 alphaIIb-specific LIBS mAbs directed against the alphaIIb Calf-2 region adjacent to the membrane reacted with only minor fractions of free pro-alphaIIb, raising the possibility that pro-alphaIIb adopts a bent conformation early in biogenesis. Our data suggest a working model in which pro-alphaIIb adopts a bent conformation soon after synthesis, and then beta3 assumes its bent conformation by virtue of its interaction with the bent pro-alphaIIb.

  10. Calmodulin Adopts an Extended Conformation when Interacting with L-Selectin in Membranes

    PubMed Central

    Deng, Wei; Putkey, John A.; Li, Renhao

    2013-01-01

    Calmodulin, an intracellular calcium-binding protein, is thought to regulate ectodomain shedding of many membrane proteins, but the underlying molecular mechanism has remained unclear. Basing on a solution structure of calcium-loaded calmodulin in complex with a L-selectin fragment that contains a portion of its transmembrane domain, Gifford et al. (University of Calgary) recently suggested that calmodulin regulates L-selectin shedding by binding directly to a portion of the L-selectin transmembrane domain in a compact conformation. Using fluorescently labeled calmodulin, we show however that calmodulin adopts a distinctly different and much more extended conformation when it binds to the CLS peptide (i.e. the entire transmembrane and cytoplasmic domains of L-selectin) reconstituted in the phosphatidylcholine liposome with micromolar dissociation constant and in a calcium-independent manner. Calmodulin adopts a similarly extended conformation in a ternary complex with the N-terminal FERM domain of moesin and CLS reconstituted in the phospholipid liposome that mimics the native membrane environment. These results indicate that calmodulin does not bind directly to the transmembrane domain of L-selectin. Understanding the association of calmodulin with L-selectin helps to shed light on the mechanisms underlying regulation of ectodomain shedding. PMID:23658780

  11. Adoption

    MedlinePlus

    ... the birth nor adoptive parents know the others' identities. Other adoptions are handled more openly. Open adoptions, ... desire to seek out more information about the identity of the birth family. Most of us (whether ...

  12. Beyond spectral tuning: human cone visual pigments adopt different transient conformations for chromophore regeneration.

    PubMed

    Srinivasan, Sundaramoorthy; Cordomí, Arnau; Ramon, Eva; Garriga, Pere

    2016-03-01

    Human red and green visual pigments are seven transmembrane receptors of cone photoreceptor cells of the retina that mediate color vision. These pigments share a very high degree of homology and have been assumed to feature analogous structural and functional properties. We report on a different regeneration mechanism among red and green cone opsins with retinal analogs using UV-Vis/fluorescence spectroscopic analyses, molecular modeling and site-directed mutagenesis. We find that photoactivated green cone opsin adopts a transient conformation which regenerates via an unprotonated Schiff base linkage with its natural chromophore, whereas red cone opsin forms a typical protonated Schiff base. The chromophore regeneration kinetics is consistent with a secondary retinal uptake by the cone pigments. Overall, our findings reveal, for the first time, structural differences in the photoactivated conformation between red and green cone pigments that may be linked to their molecular evolution, and support the proposal of secondary retinal binding to visual pigments, in addition to binding to the canonical primary site, which may serve as a regulatory mechanism of dark adaptation in the phototransduction process. PMID:26387074

  13. Beyond spectral tuning: human cone visual pigments adopt different transient conformations for chromophore regeneration.

    PubMed

    Srinivasan, Sundaramoorthy; Cordomí, Arnau; Ramon, Eva; Garriga, Pere

    2016-03-01

    Human red and green visual pigments are seven transmembrane receptors of cone photoreceptor cells of the retina that mediate color vision. These pigments share a very high degree of homology and have been assumed to feature analogous structural and functional properties. We report on a different regeneration mechanism among red and green cone opsins with retinal analogs using UV-Vis/fluorescence spectroscopic analyses, molecular modeling and site-directed mutagenesis. We find that photoactivated green cone opsin adopts a transient conformation which regenerates via an unprotonated Schiff base linkage with its natural chromophore, whereas red cone opsin forms a typical protonated Schiff base. The chromophore regeneration kinetics is consistent with a secondary retinal uptake by the cone pigments. Overall, our findings reveal, for the first time, structural differences in the photoactivated conformation between red and green cone pigments that may be linked to their molecular evolution, and support the proposal of secondary retinal binding to visual pigments, in addition to binding to the canonical primary site, which may serve as a regulatory mechanism of dark adaptation in the phototransduction process.

  14. The longin SNARE VAMP7/TI-VAMP adopts a closed conformation.

    PubMed

    Vivona, Sandro; Liu, Corey W; Strop, Pavel; Rossi, Valeria; Filippini, Francesco; Brunger, Axel T

    2010-06-01

    SNARE protein complexes are key mediators of exocytosis by juxtaposing opposing membranes, leading to membrane fusion. SNAREs generally consist of one or two core domains that can form a four-helix bundle with other SNARE core domains. Some SNAREs, such as syntaxin target-SNAREs and longin vesicular-SNAREs, have independent, folded N-terminal domains that can interact with their respective SNARE core domains and thereby affect the kinetics of SNARE complex formation. This autoinhibition mechanism is believed to regulate the role of the longin VAMP7/TI-VAMP in neuronal morphogenesis. Here we use nuclear magnetic resonance spectroscopy to study the longin-SNARE core domain interaction for VAMP7. Using complete backbone resonance assignments, chemical shift perturbations analysis, and hydrogen/deuterium exchange experiments, we conclusively show that VAMP7 adopts a preferentially closed conformation in solution. Taken together, the closed conformation of longins is conserved, in contrast to the syntaxin family of SNAREs for which mixtures of open and closed states have been observed. This may indicate different regulatory mechanisms for SNARE complexes containing syntaxins and longins, respectively.

  15. The Longin SNARE VAMP7/TI-VAMP Adopts a Closed Conformation*

    PubMed Central

    Vivona, Sandro; Liu, Corey W.; Strop, Pavel; Rossi, Valeria; Filippini, Francesco; Brunger, Axel T.

    2010-01-01

    SNARE protein complexes are key mediators of exocytosis by juxtaposing opposing membranes, leading to membrane fusion. SNAREs generally consist of one or two core domains that can form a four-helix bundle with other SNARE core domains. Some SNAREs, such as syntaxin target-SNAREs and longin vesicular-SNAREs, have independent, folded N-terminal domains that can interact with their respective SNARE core domains and thereby affect the kinetics of SNARE complex formation. This autoinhibition mechanism is believed to regulate the role of the longin VAMP7/TI-VAMP in neuronal morphogenesis. Here we use nuclear magnetic resonance spectroscopy to study the longin-SNARE core domain interaction for VAMP7. Using complete backbone resonance assignments, chemical shift perturbations analysis, and hydrogen/deuterium exchange experiments, we conclusively show that VAMP7 adopts a preferentially closed conformation in solution. Taken together, the closed conformation of longins is conserved, in contrast to the syntaxin family of SNAREs for which mixtures of open and closed states have been observed. This may indicate different regulatory mechanisms for SNARE complexes containing syntaxins and longins, respectively. PMID:20378544

  16. CLEMAPS: multiple alignment of protein structures based on conformational letters.

    PubMed

    Liu, Xin; Zhao, Ya-Pu; Zheng, Wei-Mou

    2008-05-01

    CLEMAPS is a tool for multiple alignment of protein structures. It distinguishes itself from other existing algorithms for multiple structure alignment by the use of conformational letters, which are discretized states of 3D segmental structural states. A letter corresponds to a cluster of combinations of three angles formed by C(alpha) pseudobonds of four contiguous residues. A substitution matrix called CLESUM is available to measure the similarity between any two such letters. The input 3D structures are first converted to sequences of conformational letters. Each string of a fixed length is then taken as the center seed to search other sequences for neighbors of the seed, which are strings similar to the seed. A seed and its neighbors form a center-star, which corresponds to a fragment set of local structural similarity shared by many proteins. The detection of center-stars using CLESUM is extremely efficient. Local similarity is a necessary, but insufficient, condition for structural alignment. Once center-stars are found, the spatial consistency between any two stars are examined to find consistent star duads using atomic coordinates. Consistent duads are later joined to create a core for multiple alignment, which is further polished to produce the final alignment. The utility of CLEMAPS is tested on various protein structure ensembles.

  17. Systematic Exploitation of Multiple Receptor Conformations for Virtual Ligand Screening

    PubMed Central

    Bottegoni, Giovanni; Rocchia, Walter; Rueda, Manuel; Abagyan, Ruben; Cavalli, Andrea

    2011-01-01

    The role of virtual ligand screening in modern drug discovery is to mine large chemical collections and to prioritize for experimental testing a comparatively small and diverse set of compounds with expected activity against a target. Several studies have pointed out that the performance of virtual ligand screening can be improved by taking into account receptor flexibility. Here, we systematically assess how multiple crystallographic receptor conformations, a powerful way of discretely representing protein plasticity, can be exploited in screening protocols to separate binders from non-binders. Our analyses encompass 36 targets of pharmaceutical relevance and are based on actual molecules with reported activity against those targets. The results suggest that an ensemble receptor-based protocol displays a stronger discriminating power between active and inactive molecules as compared to its standard single rigid receptor counterpart. Moreover, such a protocol can be engineered not only to enrich a higher number of active compounds, but also to enhance their chemical diversity. Finally, some clear indications can be gathered on how to select a subset of receptor conformations that is most likely to provide the best performance in a real life scenario. PMID:21625529

  18. Premutation huntingtin allele adopts a non-B conformation and contains a hot spot for DNA damage

    SciTech Connect

    Jarem, Daniel A.; Delaney, Sarah

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer First structural and thermodynamic analysis of premutation allele of HD. Black-Right-Pointing-Pointer Premutation allele of HD adopts a stem-loop non-B conformation. Black-Right-Pointing-Pointer Healthy and premutation length stem-loops are hyper-susceptible to oxidative damage. Black-Right-Pointing-Pointer Stability of stem-loop structures increases linearly with repeat length. Black-Right-Pointing-Pointer Thermodynamic stability, not the ability to adopt non-B conformation, distinguishes DNA prone to expansion from stable DNA. -- Abstract: The expansion of a CAG trinucleotide repeat (TNR) sequence has been linked to several neurological disorders, for example, Huntington's disease (HD). In HD, healthy individuals have 5-35 CAG repeats. Those with 36-39 repeats have the premutation allele, which is known to be prone to expansion. In the disease state, greater than 40 repeats are present. Interestingly, the formation of non-B DNA conformations by the TNR sequence is proposed to contribute to the expansion. Here we provide the first structural and thermodynamic analysis of a premutation length TNR sequence. Using chemical probes of nucleobase accessibility, we found that similar to (CAG){sub 10}, the premutation length sequence (CAG){sub 36} forms a stem-loop hairpin and contains a hot spot for DNA damage. Additionally, calorimetric analysis of a series of (CAG){sub n} sequences, that includes repeat tracts in both the healthy and premutation ranges, reveal that thermodynamic stability increases linearly with the number of repeats. Based on these data, we propose that while non-B conformations can be formed by TNR tracts found in both the healthy and premutation allele, only sequences containing at least 36 repeats have sufficient thermodynamic stability to contribute to expansion.

  19. The hexameric helicase DnaB adopts a nonplanar conformation during translocation.

    PubMed

    Itsathitphaisarn, Ornchuma; Wing, Richard A; Eliason, William K; Wang, Jimin; Steitz, Thomas A

    2012-10-12

    DNA polymerases can only synthesize nascent DNA from single-stranded DNA (ssDNA) templates. In bacteria, the unwinding of parental duplex DNA is carried out by the replicative DNA helicase (DnaB) that couples NTP hydrolysis to 5' to 3' translocation. The crystal structure of the DnaB hexamer in complex with GDP-AlF(4) and ssDNA reported here reveals that DnaB adopts a closed spiral staircase quaternary structure around an A-form ssDNA with each C-terminal domain coordinating two nucleotides of ssDNA. The structure not only provides structural insights into the translocation mechanism of superfamily IV helicases but also suggests that members of this superfamily employ a translocation mechanism that is distinct from other helicase superfamilies. We propose a hand-over-hand mechanism in which sequential hydrolysis of NTP causes a sequential 5' to 3' movement of the subunits along the helical axis of the staircase, resulting in the unwinding of two nucleotides per subunit. PMID:23022319

  20. Exhaustive Metropolis Monte Carlo sampling and analysis of polyalanine conformations adopted under the influence of hydrogen bonds.

    PubMed

    Podtelezhnikov, Alexei A; Wild, David L

    2005-10-01

    We propose a novel Metropolis Monte Carlo procedure for protein modeling and analyze the influence of hydrogen bonding on the distribution of polyalanine conformations. We use an atomistic model of the polyalanine chain with rigid and planar polypeptide bonds, and elastic alpha carbon valence geometry. We adopt a simplified energy function in which only hard-sphere repulsion and hydrogen bonding interactions between the atoms are considered. Our Metropolis Monte Carlo procedure utilizes local crankshaft moves and is combined with parallel tempering to exhaustively sample the conformations of 16-mer polyalanine. We confirm that Flory's isolated-pair hypothesis (the steric independence between the dihedral angles of individual amino acids) does not hold true in long polypeptide chains. In addition to 3(10)- and alpha-helices, we identify a kink stabilized by 2 hydrogen bonds with a shared acceptor as a common structural motif. Varying the strength of hydrogen bonds, we induce the helix-coil transition in the model polypeptide chain. We compare the propensities for various hydrogen bonding patterns and determine the degree of cooperativity of hydrogen bond formation in terms of the Hill coefficient. The observed helix-coil transition is also quantified according to Zimm-Bragg theory. PMID:16049911

  1. The stringent factor RelA adopts an open conformation on the ribosome to stimulate ppGpp synthesis.

    PubMed

    Arenz, Stefan; Abdelshahid, Maha; Sohmen, Daniel; Payoe, Roshani; Starosta, Agata L; Berninghausen, Otto; Hauryliuk, Vasili; Beckmann, Roland; Wilson, Daniel N

    2016-07-27

    Under stress conditions, such as nutrient starvation, deacylated tRNAs bound within the ribosomal A-site are recognized by the stringent factor RelA, which converts ATP and GTP/GDP to (p)ppGpp. The signaling molecules (p)ppGpp globally rewire the cellular transcriptional program and general metabolism, leading to stress adaptation. Despite the additional importance of the stringent response for regulation of bacterial virulence, antibiotic resistance and persistence, structural insight into how the ribosome and deacylated-tRNA stimulate RelA-mediated (p)ppGpp has been lacking. Here, we present a cryo-EM structure of RelA in complex with the Escherichia coli 70S ribosome with an average resolution of 3.7 Å and local resolution of 4 to >10 Å for RelA. The structure reveals that RelA adopts a unique 'open' conformation, where the C-terminal domain (CTD) is intertwined around an A/T-like tRNA within the intersubunit cavity of the ribosome and the N-terminal domain (NTD) extends into the solvent. We propose that the open conformation of RelA on the ribosome relieves the autoinhibitory effect of the CTD on the NTD, thus leading to stimulation of (p)ppGpp synthesis by RelA.

  2. Locally accessible conformations of proteins: multiple molecular dynamics simulations of crambin.

    PubMed Central

    Caves, L. S.; Evanseck, J. D.; Karplus, M.

    1998-01-01

    Multiple molecular dynamics (MD) simulations of crambin with different initial atomic velocities are used to sample conformations in the vicinity of the native structure. Individual trajectories of length up to 5 ns sample only a fraction of the conformational distribution generated by ten independent 120 ps trajectories at 300 K. The backbone atom conformational space distribution is analyzed using principal components analysis (PCA). Four different major conformational regions are found. In general, a trajectory samples only one region and few transitions between the regions are observed. Consequently, the averages of structural and dynamic properties over the ten trajectories differ significantly from those obtained from individual trajectories. The nature of the conformational sampling has important consequences for the utilization of MD simulations for a wide range of problems, such as comparisons with X-ray or NMR data. The overall average structure is significantly closer to the X-ray structure than any of the individual trajectory average structures. The high frequency (less than 10 ps) atomic fluctuations from the ten trajectories tend to be similar, but the lower frequency (100 ps) motions are different. To improve conformational sampling in molecular dynamics simulations of proteins, as in nucleic acids, multiple trajectories with different initial conditions should be used rather than a single long trajectory. PMID:9541397

  3. A novel approach to the study of conformality in the SU(3) theory with multiple flavors

    SciTech Connect

    Brower, R.; Hasenfratz, A.; Rebbi, C. Weinberg, E.; Witzel, O.

    2015-03-15

    We investigate the transition between spontaneous chiral symmetry breaking and conformal behavior in the SU(3) theory with multiple fermion flavors. We propose a new strategy for studying this transition. Instead of changing the number of flavors, we lift the mass of a subset of the fermions, keeping the rest of the fermions near the massless chiral limit in order to probe the transition.

  4. Mapping the conformational transition in Src activation by cumulating the information from multiple molecular dynamics trajectories

    PubMed Central

    Yang, Sichun; Banavali, Nilesh K.; Roux, Benoît

    2009-01-01

    The Src-family kinases are allosteric enzymes that play a key role in the regulation of cell growth and proliferation. In response to cellular signals, they undergo large conformational changes to switch between distinct inactive and active states. A computational strategy for characterizing the conformational transition pathway is presented to bridge the inactive and active states of the catalytic domain of Hck. The information from a large number (78) of independent all-atom molecular dynamics trajectories with explicit solvent is combined together to assemble a connectivity map of the conformational transition. Two intermediate states along the activation pathways are identified, and their structural features are characterized. A coarse free-energy landscape is built in terms of the collective motions corresponding to the opening of the activation loop (A-loop) and the rotation of the αC helix. This landscape shows that the protein can adopt a multitude of conformations in which the A-loop is partially open, while the αC helix remains in the orientation characteristic of the inactive conformation. The complete transition leading to the active conformation requires a concerted movement involving further opening of the A-loop, the relative alignment of N-lobe and C-lobe, and the rotation of the αC helix needed to recruit the residues necessary for catalysis in the active site. The analysis leads to a dynamic view of the full-length kinase activation, whereby transitions of the catalytic domain to intermediate configurations with a partially open A-loop are permitted, even while the SH2-SH3 clamp remains fully engaged. These transitions would render Y416 available for the transphosphorylation event that ultimately locks down the active state. The results provide a broad framework for picturing the conformational transitions leading to kinase activation. PMID:19225111

  5. Hydrocarbons depending on the chain length and head group adopt different conformations within a water-soluble nanocapsule: 1H NMR and molecular dynamics studies.

    PubMed

    Choudhury, Rajib; Barman, Arghya; Prabhakar, Rajeev; Ramamurthy, V

    2013-01-10

    In this study we have examined the conformational preference of phenyl-substituted hydrocarbons (alkanes, alkenes, and alkynes) of different chain lengths included within a confined space provided by a molecular capsule made of two host cavitands known by the trivial name "octa acid" (OA). One- and two-dimensional (1)H NMR experiments and molecular dynamics (MD) simulations were employed to probe the location and conformation of hydrocarbons within the OA capsule. In general, small hydrocarbons adopted a linear conformation while longer ones preferred a folded conformation. In addition, the extent of folding and the location of the end groups (methyl and phenyl) were dependent on the group (H(2)C-CH(2), HC═CH, and C≡C) adjacent to the phenyl group. In addition, the rotational mobility of the hydrocarbons within the capsule varied; for example, while phenylated alkanes tumbled freely, phenylated alkenes and alkynes resisted such a motion at room temperature. Combined NMR and MD simulation studies have confirmed that molecules could adopt conformations within confined spaces different from that in solution, opening opportunities to modulate chemical behavior of guest molecules.

  6. Transmission of multiple resistant Salmonella Concord from internationally adopted children to their adoptive families and social environment: proposition of guidelines.

    PubMed

    Vanhoof, R; Gillis, P; Stévart, O; Boland, C; Vandenberg, O; Fux, F; Collard, J-M; Bertrand, S

    2012-04-01

    Since 2004, an increasing number of multidrug-resistant Salmonella serovar Concord infections have been isolated in Belgium among children adopted from Ethiopia. The patients or their family were interviewed and the isolates were subtyped. Between 2004 and 2009, a total of 39 Salmonella Concord infections were isolated from patients. Thirty-four isolates presented a multidrug resistance including resistance to extended-spectrum cephalosporins. Thirty-six cases involved children and 30 of these were adopted from Ethiopia. One case was due to contact with an adopted child and for the other 5 cases no direct epidemiological link with Ethiopia could be found, although four isolates displayed the same patterns observed on the adoptees' isolates, strongly suggesting a phylogenetic relationship with the Ethiopian isolates. Our study confirmed the emergence in Europe of S. Concord isolates resistant to third-generation cephalosporin among Ethiopian adoptees. We have demonstrated that transmission (intra- and extra familial) can happen even if the frequency seems to be low. The presence and the transmission of such a multidrug-resistant Salmonella infection constitute a major concern, since such strains could jeopardize classical antibiotic therapy in patients at risk. This study provides useful information for parents adopting children and for their family practitioner.

  7. Exploring experimental sources of multiple protein conformations in structure-based drug design.

    PubMed

    Damm, Kelly L; Carlson, Heather A

    2007-07-01

    Receptor flexibility must be incorporated into structure-based drug design in order to portray a more accurate representation of a protein in solution. Our approach is to generate pharmacophore models based on multiple conformations of a protein and is very similar to solvent mapping of hot spots. Previously, we had success using computer-generated conformations of apo human immunodeficiency virus-1 protease (HIV-1p). Here, we examine the use of an NMR ensemble versus a collection of crystal structures, and we compare back to our previous study based on computer-generated conformations. To our knowledge, this is the first direct comparison of an NMR ensemble and a collection of crystal structures to incorporate protein flexibility in structure-based drug design. To provide an accurate comparison between the experimental sources, we used bound structures for our multiple protein structure (MPS) pharmacophore models. The models from an NMR ensemble and a collection of crystal structures were both able to discriminate known HIV-1p inhibitors from decoy molecules and displayed superior performance over models created from single conformations of the protein. Although the active-site conformations were already predefined by bound ligands, the use of MPS allows us to overcome the cross-docking problem and generate a model that does not simply reproduce the chemical characteristics of a specific ligand class. We show that there is more structural variation between 28 structures in an NMR ensemble than 90 crystal structures bound to a variety of ligands. MPS models from both sources performed well, but the model determined using the NMR ensemble appeared to be the most general yet accurate representation of the active site. This work encourages the use of NMR models in structure-based design.

  8. Motions on the Millisecond Timescale and Multiple Conformations of HIV-1 Capsid Protein: Implications for Structural Polymorphism of CA Assemblies

    PubMed Central

    Byeon, In-Ja L.; Hou, Guangjin; Han, Yun; Suiter, Christopher L.; Ahn, Jinwoo; Jung, Jinwon; Byeon, Chang-Hyeock; Gronenborn, Angela M.; Polenova, Tatyana

    2012-01-01

    The capsid protein (CA) of human immunodeficiency virus 1 (HIV-1) assembles into a cone-like structure that encloses the viral RNA genome. Interestingly, significant heterogeneity in shape and organization of capsids can be observed in mature HIV-1 virions. In vitro, CA also exhibits structural polymorphism and can assemble into various morphologies, such as cones, tubes and spheres. Many intermolecular contacts that are critical for CA assembly are formed by its C-terminal domain (CTD), a dimerization domain, which was found to adopt different orientations in several X-ray and NMR structures of the the CTD dimer and full-length CA proteins. Tyr145 (Y145), residue two in our CTD construct used for NMR structure determination, but not present in the crystallographic constructs, was found to be crucial for infectivity and engaged in numerous interactions at the CTD dimer interface. Here we investigate the origin of CA structural plasticity using solid-state and solution NMR spectroscopy. In the solid-state, the hinge region connecting the NTD and CTD is flexible on the millisecond timescale, as evidenced by the backbone motions of Y145 in CA conical assemblies and in two CTD constructs (137–231 and 142–231), allowing the protein to access multiple conformations essential for pleimorphic capsid assemblies. In solution, the CTD dimer exists as two major conformers, whose relative populations differ for the different CTD constructs. In the longer CTD (144–231) construct that contains the hinge region between the NTD and CTD, the populations of the two conformers are likely determined by the protonation state of the E175 side chain that is located at the dimer interface and within hydrogen bonding distance of the W184 side chain on the other monomer. At pH 6.5, the major conformer exhibits the same dimer interface as full-length CA. In the short CTD (150–231) construct, no pH-dependent conformational shift is observed. These findings suggest that the presence of

  9. Nano-Positioning System for Structural Analysis of Functional Homomeric Proteins in Multiple Conformations

    PubMed Central

    Hyde, H. Clark; Sandtner, Walter; Vargas, Ernesto; Dagcan, Alper; Robertson, Janice L.; Roux, Benoit; Correa, Ana M.; Bezanilla, Francisco

    2012-01-01

    SUMMARY Proteins may undergo multiple conformational changes required for their function. One strategy used to estimate target site positions in unknown structural conformations involves single-pair resonance energy transfer (RET) distance measurements. However, interpretation of inter-residue distances is difficult when applied to three-dimensional structural rearrangements, especially in homomeric systems. We developed a novel method using inverse trilateration/triangulation to map target sites within a homomeric protein in all defined states with simultaneous functional recordings. The procedure accounts for probe diffusion to accurately determine the three-dimensional position and confidence region of lanthanide LRET donors attached to a target site (one/subunit), relative to a single fluorescent acceptor placed in a static site. As a first application, the method is used to determine the position of a functional voltage-gated potassium channel’s voltage sensor. Our results verify the crystal structure relaxed conformation and report on the resting and active conformations for which crystal structures are not available. PMID:23063010

  10. Small-molecule G-quadruplex interactions: Systematic exploration of conformational space using multiple molecular dynamics.

    PubMed

    Husby, Jarmila; Todd, Alan K; Platts, James A; Neidle, Stephen

    2013-12-01

    G-quadruplexes are higher-order four-stranded structures formed from repetitive guanine-containing tracts in nucleic acids. They comprise a core of stacked guanine-quartets linked by loops of length and sequence that vary with the context in which the quadruplex sequence occurs. Such sequences can be found in a number of genomic environments; at the telomeric ends of eukaryotic chromosomes, in promoter regions, in untranslated sequences and in open reading frames. Quadruplex formation can inhibit telomere maintenance, transcription and translation, especially when enhanced by quadruplex-binding small molecules, and quadruplex targeting is currently of considerable interest. The available experimental structural data shows that quadruplexes can have high conformational flexibility, especially in loop regions, which has hampered attempts to use high-throughput docking to find quadruplex-binding small-molecules with new scaffolds or to optimize existing ones with structure-based design methods. An approach to overcome the challenge of quadruplex conformational flexibility is presented here, which uses a combined multiple molecular dynamics and sampling approach. Two test small molecules have been used, RHPS4 and pyridostatin, which themselves have contrasting degrees of conformational flexibility.

  11. A critical base pair in k-turns determines the conformational class adopted, and correlates with biological function

    PubMed Central

    Huang, Lin; Wang, Jia; Lilley, David M. J.

    2016-01-01

    k-turns are commonly-occurring motifs that introduce sharp kinks into duplex RNA, thereby facilitating tertiary contacts. Both the folding and conformation of k-turns are determined by their local sequence. k-turns fall into two conformational classes, called N3 and N1, that differ in the pattern of hydrogen bonding in the core. We show here that this is determined by the basepair adjacent to the critical G•A pairs. We determined crystal structures of a series of Kt-7 variants in which this 3b,3n position has been systematically varied, showing that this leads to a switch in the conformation. We have previously shown that the 3b,3n position also determines the folding characteristics of the k-turn, i.e. whether or not the k-turn can fold in the presence of metal ions alone. We have analyzed the distribution of 3b,3n sequences from four classes of k-turns from ribosomes, riboswitches and U4 snRNA, finding a strong conservation of properties for a given k-turn type. We thus demonstrate a strong association between biological function, 3b,3n sequence and k-turn folding and conformation. This has strong predictive power, and can be applied to the modeling of large RNA architectures. PMID:27016741

  12. A critical base pair in k-turns determines the conformational class adopted, and correlates with biological function.

    PubMed

    Huang, Lin; Wang, Jia; Lilley, David M J

    2016-06-20

    k-turns are commonly-occurring motifs that introduce sharp kinks into duplex RNA, thereby facilitating tertiary contacts. Both the folding and conformation of k-turns are determined by their local sequence. k-turns fall into two conformational classes, called N3 and N1, that differ in the pattern of hydrogen bonding in the core. We show here that this is determined by the basepair adjacent to the critical G•A pairs. We determined crystal structures of a series of Kt-7 variants in which this 3b,3n position has been systematically varied, showing that this leads to a switch in the conformation. We have previously shown that the 3b,3n position also determines the folding characteristics of the k-turn, i.e. whether or not the k-turn can fold in the presence of metal ions alone. We have analyzed the distribution of 3b,3n sequences from four classes of k-turns from ribosomes, riboswitches and U4 snRNA, finding a strong conservation of properties for a given k-turn type. We thus demonstrate a strong association between biological function, 3b,3n sequence and k-turn folding and conformation. This has strong predictive power, and can be applied to the modeling of large RNA architectures. PMID:27016741

  13. The isoforms generated by alternative translation initiation adopt similar conformation in the selectivity filter in TREK-2.

    PubMed

    Zhuo, Ren-Gong; Peng, Peng; Liu, Xiao-Yan; Zhang, Shu-Zhuo; Xu, Jiang-Ping; Zheng, Jian-Quan; Wei, Xiao-Li; Ma, Xiao-Yun

    2015-12-01

    TREK-2 (TWIK-related K(+) channel-2), a member of two-pore domain potassium (K2P) channel family, tunes cellular excitability via conducting leak or background currents. In TREK-2, the isoforms generated by alternative translation initiation (ATI) mechanism exhibit large divergence in unitary conductance, but similar in selectivity to K(+). Up to now, the structural basis for this similarity in ion selectivity is unknown. Here, we report that externally applied Ba(2+) inhibits the currents of TREK-2 in a concentration- and time-dependent manner. The blocking effect is blunted by elevated extracellular K(+) or mutation of S4 K(+) binding site, which suggests that the inhibitory mechanism of Ba(2+) is due to its competitive docking properties within the selectivity filter (SF). Next, we demonstrate that all the ATI isoforms exhibit analogous behaviors upon the application of Ba(2+) and alteration of extracellular pH (pHo), which acts on the outer position of the SF. These results strongly support the notion that all the ATI isoforms of TREK-2 possess resembled SF conformation in S4 site and the position defined by pHo, which implicates that neither the role of N-terminus (Nt) nor the unitary conductance is associated with SF conformation. Our findings might help to understand the detail gating mechanism of TREK-2 and K2P channels. PMID:26271386

  14. Supramolecular Assemblies of Ferrocene-Hinged Naphthalenediimides: Multiple Conformational Changes in Film States.

    PubMed

    Takai, Atsuro; Kajitani, Takashi; Fukushima, Takanori; Kishikawa, Keiki; Yasuda, Takeshi; Takeuchi, Masayuki

    2016-09-01

    We design a new naphthalenediimide (NDI) π-system, NDI-Fc-NDI, having a ferrocene linker as a hinge unit and long alkyl chains as supramolecular assembling units. The NDI units are "directionally flexible" in concert with the pivoting motion of the ferrocene unit with a small rotational barrier. The NDI units rotate around the ferrocene unit faster than the NMR time scale in solution at room temperature. UV-vis absorption, synchrotron X-ray diffraction, and atomic force microscope studies reveal that NDI-Fc-NDI forms a fibrous supramolecular assembly in solution (methylcyclohexane and highly concentrated chloroform) and film states, wherein the NDI units are in the slipped-stack conformation. The NDI-Fc-NDI supramolecular assembly in the film state exhibits multiple phase transitions associated with conformational changes at different temperatures, which are confirmed by differential scanning calorimetry, polarized optical microscopy, and temperature-dependent X-ray diffraction. Such thermal transitions of NDI-Fc-NDI films also induce changes in the optical and electronic properties as revealed by UV-vis absorption and photoelectron yield spectroscopies, respectively. The thermal behaviors of NDI-Fc-NDI, realized by the unique molecular design, are considerably different from the reference compounds such as an NDI dimer connected with a flexible 1,4-butylene linker. These results provide us with a plausible strategy to propagate the molecular dynamics of the π-system into macroscopic properties in film states; the key factors are (i) the supramolecular alignment of molecular switching units and (ii) the directional motion of the switching units perpendicular to the supramolecular axis. PMID:27564327

  15. Adoption of Innovative E-Learning Support for Teaching: A Multiple Case Study at the University of Waikato

    ERIC Educational Resources Information Center

    Johnson, E. Marcia; Cowie, Bronwen; De Lange, Willem; Falloon, Garry; Hight, Craig; Khoo, Elaine

    2011-01-01

    In response to recent social, economic, and pedagogical challenges to tertiary-level teaching and learning, universities are increasingly investigating and adopting e-learning as a way to engage and motivate students. This paper reports on the first year of a two-year (2009-2010) qualitative multiple case study research project in New Zealand.…

  16. A chimera grid scheme. [multiple overset body-conforming mesh system for finite difference adaptation to complex aircraft configurations

    NASA Technical Reports Server (NTRS)

    Steger, J. L.; Dougherty, F. C.; Benek, J. A.

    1983-01-01

    A mesh system composed of multiple overset body-conforming grids is described for adapting finite-difference procedures to complex aircraft configurations. In this so-called 'chimera mesh,' a major grid is generated about a main component of the configuration and overset minor grids are used to resolve all other features. Methods for connecting overset multiple grids and modifications of flow-simulation algorithms are discussed. Computational tests in two dimensions indicate that the use of multiple overset grids can simplify the task of grid generation without an adverse effect on flow-field algorithms and computer code complexity.

  17. Adopting and implementing nutrition guidelines in recreational facilities: Public and private sector roles. A multiple case study

    PubMed Central

    2012-01-01

    Background Recreational facilities are an important community resource for health promotion because they provide access to affordable physical activities. However, despite their health mandate, many have unhealthy food environments that may paradoxically increase the risk of childhood obesity. The Alberta Nutrition Guidelines for Children and Youth (ANGCY) are government-initiated, voluntary guidelines intended to facilitate children’s access to healthy food and beverage choices in schools, childcare and recreational facilities, however few recreational facilities are using them. Methods We used mixed methods within an exploratory multiple case study to examine factors that influenced adoption and implementation of the ANGCY and the nature of the food environment within three cases: an adopter, a semi-adopter and a non-adopter of the ANGCY. Diffusion of Innovations theory provided the theoretical platform for the study. Qualitative data were generated through interviews, observations, and document reviews, and were analysed using directed content analysis. Set theoretic logic was used to identify factors that differentiated adopters from the non-adopter. Quantitative sales data were also collected, and the quality of the food environment was scored using four complementary tools. Results The keys to adoption and implementation of nutrition guidelines in recreational facilities related to the managers’ nutrition-related knowledge, beliefs and perceptions, as these shaped his decisions and actions. The manager, however, could not accomplish adoption and implementation alone. Intersectoral linkages with schools and formal, health promoting partnerships with industry were also important for adoption and implementation to occur. The food environment in facilities that had adopted the ANGCY did not appear to be superior to the food environment in facilities that had not adopted the ANGCY. Conclusions ANGCY uptake may continue to falter under the current voluntary

  18. Infrared multiple photon dissociation spectroscopy of cationized methionine: effects of alkali-metal cation size on gas-phase conformation.

    PubMed

    Carl, Damon R; Cooper, Theresa E; Oomens, Jos; Steill, Jeff D; Armentrout, P B

    2010-04-14

    The gas-phase structures of alkali-metal cation complexes of the amino acid methionine (Met) as well as protonated methionine are investigated using infrared multiple photon dissociation (IRMPD) spectroscopy utilizing light generated by a free electron laser. Spectra of Li(+)(Met) and Na(+)(Met) are similar and relatively simple, whereas the spectra of K(+)(Met), Rb(+)(Met), and Cs(+)(Met) include distinctive new bands. Measured IRMPD spectra are compared to spectra calculated at the B3LYP/6-311+G(d,p) level of theory to identify the conformations present in the experimental studies. For Li(+) and Na(+) complexes, the only conformation present is a charge-solvated, tridentate structure that binds the metal cation to the amine and carbonyl groups of the amino acid backbone and the sulfur atom of the side chain, [N,CO,S]. In addition to the [N,CO,S] conformer, bands corresponding to alkali-metal cation binding to a bidentate zwitterionic structure, [CO(2)(-)], are clearly present for the K(+), Rb(+), and Cs(+) complexes. Theoretical calculations of the lowest energy conformations of Rb(+) and Cs(+) complexes suggest that the experimental spectra could also include contributions from two additional charge-solvated structures, tridentate [COOH,S] and bidentate [COOH]. For H(+)(Met), the IRMPD action spectrum is reproduced by multiple low-energy [N,CO,S] conformers, in which the protonated amine group hydrogen bonds to the carbonyl oxygen atom and the sulfur atom of the amino acid side chain. These [N,CO,S] conformers only differ in their side-chain orientations.

  19. Insights into mechanism of glucokinase activation: observation of multiple distinct protein conformations.

    PubMed

    Liu, Shenping; Ammirati, Mark J; Song, Xi; Knafels, John D; Zhang, Jeff; Greasley, Samantha E; Pfefferkorn, Jeffrey A; Qiu, Xiayang

    2012-04-20

    Human glucokinase (GK) is a principal regulating sensor of plasma glucose levels. Mutations that inactivate GK are linked to diabetes, and mutations that activate it are associated with hypoglycemia. Unique kinetic properties equip GK for its regulatory role: although it has weak basal affinity for glucose, positive cooperativity in its binding of glucose causes a rapid increase in catalytic activity when plasma glucose concentrations rise above euglycemic levels. In clinical trials, small molecule GK activators (GKAs) have been efficacious in lowering plasma glucose and enhancing glucose-stimulated insulin secretion, but they carry a risk of overly activating GK and causing hypoglycemia. The theoretical models proposed to date attribute the positive cooperativity of GK to the existence of distinct protein conformations that interconvert slowly and exhibit different affinities for glucose. Here we report the respective crystal structures of the catalytic complex of GK and of a GK-glucose complex in a wide open conformation. To assess conformations of GK in solution, we also carried out small angle x-ray scattering experiments. The results showed that glucose dose-dependently converts GK from an apo conformation to an active open conformation. Compared with wild type GK, activating mutants required notably lower concentrations of glucose to be converted to the active open conformation. GKAs decreased the level of glucose required for GK activation, and different compounds demonstrated distinct activation profiles. These results lead us to propose a modified mnemonic model to explain cooperativity in GK. Our findings may offer new approaches for designing GKAs with reduced hypoglycemic risk.

  20. 2D-3D MIGRATION AND CONFORMATIONAL MULTIPLICATION OF CHEMICALS IN LARGE CHEMICAL INVENTORIES

    EPA Science Inventory

    Chemical interactions are three-dimensional (3D) in nature and require modeling chemicals as 3D entities. In turn, using 3D models of chemicals leads to the realization that a single 2D structure can have hundreds of different conformations, and the electronic properties of these...

  1. A “Mechanistic” Explanation of the Multiple Helical Forms Adopted by Bacterial Flagellar Filaments

    PubMed Central

    Calladine, C.R.; Luisi, B.F.; Pratap, J.V.

    2013-01-01

    The corkscrew-like flagellar filaments emerging from the surface of bacteria such as Salmonella typhimurium propel the cells toward nutrient and away from repellents. This kind of motility depends upon the ability of the flagellar filaments to adopt a range of distinct helical forms. A filament is typically constructed from ~ 30,000 identical flagellin molecules, which self-assemble into a tubular structure containing 11 near-longitudinal protofilaments. A “mechanical” model, in which the flagellin building block has the capacity to switch between two principal interfacial states, predicts that the filament can assemble into a “canonical” family of 12 distinct helical forms, each having unique curvature and twist: these include two “extreme” straight forms having left- and right-handed twists, respectively, and 10 intermediate helical forms. Measured shapes of the filaments correspond well with predictions of the model. This report is concerned with two unanswered questions. First, what properties of the flagellin determine which of the 12 discrete forms is preferred? Second, how does the interfacial “switch” work, at a molecular level? Our proposed solution of these problems is based mainly on a detailed examination of differences between the available electron cryo-microscopy structures of the straight L and R filaments, respectively. PMID:23274110

  2. Correlative multiple porosimetries for reservoir sandstones with adoption of a new reference-sample-guided computed-tomographic method

    NASA Astrophysics Data System (ADS)

    Jin, Jae Hwa; Kim, Junho; Lee, Jeong-Yil; Oh, Young Min

    2016-07-01

    One of the main interests in petroleum geology and reservoir engineering is to quantify the porosity of reservoir beds as accurately as possible. A variety of direct measurements, including methods of mercury intrusion, helium injection and petrographic image analysis, have been developed; however, their application frequently yields equivocal results because these methods are different in theoretical bases, means of measurement, and causes of measurement errors. Here, we present a set of porosities measured in Berea Sandstone samples by the multiple methods, in particular with adoption of a new method using computed tomography and reference samples. The multiple porosimetric data show a marked correlativeness among different methods, suggesting that these methods are compatible with each other. The new method of reference-sample-guided computed tomography is more effective than the previous methods when the accompanied merits such as experimental conveniences are taken into account.

  3. Correlative multiple porosimetries for reservoir sandstones with adoption of a new reference-sample-guided computed-tomographic method.

    PubMed

    Jin, Jae Hwa; Kim, Junho; Lee, Jeong-Yil; Oh, Young Min

    2016-07-22

    One of the main interests in petroleum geology and reservoir engineering is to quantify the porosity of reservoir beds as accurately as possible. A variety of direct measurements, including methods of mercury intrusion, helium injection and petrographic image analysis, have been developed; however, their application frequently yields equivocal results because these methods are different in theoretical bases, means of measurement, and causes of measurement errors. Here, we present a set of porosities measured in Berea Sandstone samples by the multiple methods, in particular with adoption of a new method using computed tomography and reference samples. The multiple porosimetric data show a marked correlativeness among different methods, suggesting that these methods are compatible with each other. The new method of reference-sample-guided computed tomography is more effective than the previous methods when the accompanied merits such as experimental conveniences are taken into account.

  4. Correlative multiple porosimetries for reservoir sandstones with adoption of a new reference-sample-guided computed-tomographic method

    PubMed Central

    Jin, Jae Hwa; Kim, Junho; Lee, Jeong-Yil; Oh, Young Min

    2016-01-01

    One of the main interests in petroleum geology and reservoir engineering is to quantify the porosity of reservoir beds as accurately as possible. A variety of direct measurements, including methods of mercury intrusion, helium injection and petrographic image analysis, have been developed; however, their application frequently yields equivocal results because these methods are different in theoretical bases, means of measurement, and causes of measurement errors. Here, we present a set of porosities measured in Berea Sandstone samples by the multiple methods, in particular with adoption of a new method using computed tomography and reference samples. The multiple porosimetric data show a marked correlativeness among different methods, suggesting that these methods are compatible with each other. The new method of reference-sample-guided computed tomography is more effective than the previous methods when the accompanied merits such as experimental conveniences are taken into account. PMID:27445105

  5. Correlative multiple porosimetries for reservoir sandstones with adoption of a new reference-sample-guided computed-tomographic method.

    PubMed

    Jin, Jae Hwa; Kim, Junho; Lee, Jeong-Yil; Oh, Young Min

    2016-01-01

    One of the main interests in petroleum geology and reservoir engineering is to quantify the porosity of reservoir beds as accurately as possible. A variety of direct measurements, including methods of mercury intrusion, helium injection and petrographic image analysis, have been developed; however, their application frequently yields equivocal results because these methods are different in theoretical bases, means of measurement, and causes of measurement errors. Here, we present a set of porosities measured in Berea Sandstone samples by the multiple methods, in particular with adoption of a new method using computed tomography and reference samples. The multiple porosimetric data show a marked correlativeness among different methods, suggesting that these methods are compatible with each other. The new method of reference-sample-guided computed tomography is more effective than the previous methods when the accompanied merits such as experimental conveniences are taken into account. PMID:27445105

  6. Discordances Between Serology and Culture for Strongyloides in an Ethiopian Adopted Child With Multiple Parasitic Infections

    PubMed Central

    Soriano-Arandes, Antoni; Sulleiro, Elena; Zarzuela, Francesc; Ruiz, Edurne; Clavería, Isabel; Espasa, Mateu

    2016-01-01

    Abstract Rationale: infectious diseases screening of international adoptees is complex because of the concurrence of different pathogens in a child at same time. We describe an international adopted child born at Ethiopia infected by 5 different pathogens (Hymenolepis nana, Giardia intestinalis, Entamoeba histolytica, Strongyloides stercoralis, and Trichuris trichiura), 2 of them S. stercoralis and E. histolytica with a capacity to develop severe clinical complications if not detected promptly with appropriate diagnosis tests. Concerns of the patient: according to the screening protocol a stool sample is always processed for culture addressed to find out protozoan and helminthic pathogens but not specifically for S. stercoralis. Only, when eosinophilia is detected 3 serial stool samples are collected to rule out intestinal parasitic infection including S. stercoralis. Interventions: in our case, S. stercoralis would not have been detected if we had followed the protocol because eosinophilia was absent and its specific serology was negative. Fortunately, the initial inclusion of the feces charcoal culture for S. stercoralis allowed us to detect this infection. Outcomes: discordances between direct methods such as culture and indirect as serology or antigen test forces us to be very cautious before ruling out S. stercoralis or E. histolytica infection, respectively. Also, if a child from tropical areas has persistent symptoms (such as diarrhea or fever) that have not been treated we have to rule out other infections that have not been detected yet. Main lessons: The introduction of different sequencing tests and the insistence to find out pathogens such as S. stercoralis or E. histolytica was determinant to be able to cure this symptomatic child and to prevent potential severe clinical forms in case of immunosuppression. PMID:26962825

  7. Multiple stable conformations account for reversible concentration-dependent oligomerization and autoinhibition of a metamorphic metallopeptidase.

    PubMed

    López-Pelegrín, Mar; Cerdà-Costa, Núria; Cintas-Pedrola, Anna; Herranz-Trillo, Fátima; Bernadó, Pau; Peinado, Juan R; Arolas, Joan L; Gomis-Rüth, F Xavier

    2014-09-26

    Molecular plasticity controls enzymatic activity: the native fold of a protein in a given environment is normally unique and at a global free-energy minimum. Some proteins, however, spontaneously undergo substantial fold switching to reversibly transit between defined conformers, the "metamorphic" proteins. Here, we present a minimal metamorphic, selective, and specific caseinolytic metallopeptidase, selecase, which reversibly transits between several different states of defined three-dimensional structure, which are associated with loss of enzymatic activity due to autoinhibition. The latter is triggered by sequestering the competent conformation in incompetent but structured dimers, tetramers, and octamers. This system, which is compatible with a discrete multifunnel energy landscape, affords a switch that provides a reversible mechanism of control of catalytic activity unique in nature.

  8. Multiple Conformations of Phosphodiesterase-5: Implications for Enzyme Function and Drug Developement

    SciTech Connect

    Wang,H.; Liu, Y.; Huai, Q.; Cai, J.; Zoraghi, R.; Francis, S.; Corbin, J.; Robinson, H.; Xin, Z.; et al.

    2006-01-01

    Phosphodiesterase-5 (PDE5) is the target for sildenafil, vardenafil, and tadalafil, which are drugs for treatment of erectile dysfunction and pulmonary hypertension. We report here the crystal structures of a fully active catalytic domain of unliganded PDE5A1 and its complexes with sildenafil or icarisid II. These structures together with the PDE5A1-isobutyl-1-methylxanthine complex show that the H-loop (residues 660-683) at the active site of PDE5A1 has four different conformations and migrates 7 to 35 Angstroms upon inhibitor binding. In addition, the conformation of sildenafil reported herein differs significantly from those in the previous structures of chimerically hybridized or almost inactive PDE5. Mutagenesis and kinetic analyses confirm that the H-loop is particularly important for substrate recognition and that invariant Gly659 which immediately precedes the H-loop is critical for optimal substrate affinity and catalytic activity.

  9. Sodium phenylacetate inhibits adoptive transfer of experimental allergic encephalomyelitis in SJL/J mice at multiple steps.

    PubMed

    Dasgupta, Subhajit; Zhou, You; Jana, Malabendu; Banik, Naren L; Pahan, Kalipada

    2003-04-01

    Experimental allergic encephalomyelitis (EAE) is the animal model for multiple sclerosis. The present study underlines the importance of sodium phenylacetate (NaPA), a drug approved for urea cycle disorders, in inhibiting the disease process of adoptively transferred EAE in female SJL/J mice at multiple steps. Myelin basic protein (MBP)-primed T cells alone induced the expression of NO synthase (iNOS) and the activation of NF-kappaB in mouse microglial cells through cell-cell contact. However, pretreatment of MBP-primed T cells with NaPA markedly inhibited its ability to induce microglial expression of iNOS and activation of NF-kappaB. Consistently, adoptive transfer of MBP-primed T cells, but not that of NaPA-pretreated MBP-primed T cells, induced the clinical symptoms of EAE in female SJL/J mice. Furthermore, MBP-primed T cells isolated from NaPA-treated donor mice were also less efficient than MBP-primed T cells isolated from normal donor mice in inducing iNOS in microglial cells and transferring EAE to recipient mice. Interestingly, clinical symptoms of EAE were much less in mice receiving NaPA through drinking water than those without NaPA. Similar to NaPA, sodium phenylbutyrate, a chemically synthesized precursor of NaPA, also inhibited the disease process of EAE. Histological and immunocytochemical analysis showed that NaPA inhibited EAE-induced spinal cord mononuclear cell invasion and normalized iNOS, nitrotyrosine, and p65 (the RelA subunit of NF-kappaB) expression within the spinal cord. Taken together, our results raise the possibility that NaPA or sodium phenylbutyrate taken through drinking water or milk may reduce the observed neuroinflammation and disease process in multiple sclerosis patients. PMID:12646656

  10. tBid Undergoes Multiple Conformational Changes at the Membrane Required for Bax Activation*

    PubMed Central

    Shamas-Din, Aisha; Bindner, Scott; Zhu, Weijia; Zaltsman, Yehudit; Campbell, Clinton; Gross, Atan; Leber, Brian; Andrews, David W.; Fradin, Cécile

    2013-01-01

    Bid is a Bcl-2 family protein that promotes apoptosis by activating Bax and eliciting mitochondrial outer membrane permeabilization (MOMP). Full-length Bid is cleaved in response to apoptotic stimuli into two fragments, p7 and tBid (p15), that are held together by strong hydrophobic interactions until the complex binds to membranes. The detailed mechanism(s) of fragment separation including tBid binding to membranes and release of the p7 fragment to the cytoplasm remain unclear. Using liposomes or isolated mitochondria with fluorescently labeled proteins at physiological concentrations as in vitro models, we report that the two components of the complex quickly separate upon interaction with a membrane. Once tBid binds to the membrane, it undergoes slow structural rearrangements that result in an equilibrium between two major tBid conformations on the membrane. The conformational change of tBid is a prerequisite for interaction with Bax and is, therefore, a novel step that can be modulated to promote or inhibit MOMP. Using automated high-throughput image analysis in cells, we show that down-regulation of Mtch2 causes a significant delay between tBid and Bax relocalization in cells. We propose that by promoting insertion of tBid via a conformational change at the mitochondrial outer membrane, Mtch2 accelerates tBid-mediated Bax activation and MOMP. Thus the interaction of Mtch2 and tBid is a potential target for therapeutic control of Bid initiated cell death. PMID:23744079

  11. Representation of target-bound drugs by computed conformers: implications for conformational libraries

    PubMed Central

    Günther, Stefan; Senger, Christian; Michalsky, Elke; Goede, Andrean; Preissner, Robert

    2006-01-01

    Background The increasing number of known protein structures provides valuable information about pharmaceutical targets. Drug binding sites are identifiable and suitable lead compounds can be proposed. The flexibility of ligands is a critical point for the selection of potential drugs. Since computed 3D structures of millions of compounds are available, the knowledge of their binding conformations would be a great benefit for the development of efficient screening methods. Results Integration of two public databases allowed superposition of conformers for 193 approved drugs with 5507 crystallised target-bound counterparts. The generation of 9600 drug conformers using an atomic force field was carried out to obtain an optimal coverage of the conformational space. Bioactive conformations are best described by a conformational ensemble: half of all drugs exhibit multiple active states, distributed over the entire range of the reachable energy and conformational space. A number of up to 100 conformers per drug enabled us to reproduce the bound states within a similarity threshold of 1.0 Å in 70% of all cases. This fraction rises to about 90% for smaller or average sized drugs. Conclusion Single drugs adopt multiple bioactive conformations if they interact with different target proteins. Due to the structural diversity of binding sites they adopt conformations that are distributed over a broad conformational space and wide energy range. Since the majority of drugs is well represented by a predefined low number of conformers (up to 100) this procedure is a valuable method to compare compounds by three-dimensional features or for fast similarity searches starting with pharmacophores. The underlying 9600 generated drug conformers are downloadable from the Super Drug Web site [1]. All superpositions are visualised at the same source. Additional conformers (110,000) of 2400 classified WHO-drugs are also available. PMID:16764718

  12. Conformal load-bearing antenna structures (CLAS): initiative for multiple military and commercial applications

    NASA Astrophysics Data System (ADS)

    Lockyer, Allen J.; Alt, Kevin H.; Kudva, Jayanth N.; Kinslow, Robert W.; Goetz, Allan C.

    1997-06-01

    The Structures Division of the Air Force's Wright Laboratory is sponsoring the development and demonstration of a new high pay-off technology termed CLAS--Conformal Load Bearing Antenna Structures. Northrop Grumman Corporation and TRW/ASD are developing the technology under the `Smart-Skin Structure Technology Demonstration (S3D)' program, contract, No. F33615-93-C-3200. The program goal is to design, develop, fabricate, and test a CLAS component and lay the foundation for future work where potential benefits from structurally integrated antennas may be realized. Key issues will focus but are not limited to the design, structures, and manufacturing aspects of antenna embedment into load bearing aircraft structures. Results from Phase 1 of the program have been previously reported, where initial pay-offs in reducing overall airframe acquisition and support cost, weight, signature, and drag were quantitatively and qualitatively identified. A full-sized CLAS component, featuring a broadband multi-arm spiral embedded in sandwich stiffened structure, will be fabricated and tested for static strength, durability, and damage tolerance. Basic electrical performance, (e.g., radiation patterns, gain, and impedance) will also be verified; however, extensive electrical validation will be the subject of further work. Key aspects of the work and progress to date are detailed below. Also covered are future projections of CLAS technology expansion beyond tactical aircraft into other military products highlighting ships, army vehicles, and `spin-off' commercial applications to civil aircraft and the automotive industry.

  13. Multiple disulfide bridges modulate conformational stability and flexibility in hyperthermophilic archaeal purine nucleoside phosphorylase.

    PubMed

    Bagarolo, Maria Libera; Porcelli, Marina; Martino, Elisa; Feller, Georges; Cacciapuoti, Giovanna

    2015-10-01

    5'-Deoxy-5'-methylthioadenosine phosphorylase from Sulfolobus solfataricus is a hexameric hyperthermophilic protein containing in each subunit two pairs of disulfide bridges, a CXC motif, and one free cysteine. The contribution of each disulfide bridge to the protein conformational stability and flexibility has been assessed by comparing the thermal unfolding and the limited proteolysis of the wild-type enzyme and its variants obtained by site-directed mutagenesis of the seven cysteine residues. All variants catalyzed efficiently MTA cleavage with specific activity similar to the wild-type enzyme. The elimination of all cysteine residues caused a substantial decrease of ΔHcal (850 kcal/mol) and Tmax (39°C) with respect to the wild-type indicating that all cysteine pairs and especially the CXC motif significantly contribute to the enzyme thermal stability. Disulfide bond Cys200-Cys262 and the CXC motif weakly affected protein flexibility while the elimination of the disulfide bond Cys138-Cys205 lead to an increased protease susceptibility. Experimental evidence from limited proteolysis, differential scanning calorimetry, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing and nonreducing conditions also allowed to propose a stabilizing role for the free Cys164.

  14. Conformal operators in QCD

    SciTech Connect

    Makeenko, Y.M.

    1981-03-01

    Utilizing the properties of the representations of the conformal group, we obtain new expressions for the conformal operators composed of spinor or scalar fields of arbitrary dimension in terms of Jacobi polynomials. These expressions generalize the known formulas in terms of Gegenbauer polynomials. Using the conformal Ward identities, we prove the multiplicative renormalizability of conformal operators in the leading logarithmic approximation.

  15. B-cell Maturation Antigen is a Promising Target for Adoptive T-cell Therapy of Multiple Myeloma

    PubMed Central

    Carpenter, Robert O.; Evbuomwan, Moses O.; Pittaluga, Stefania; Rose, Jeremy J.; Raffeld, Mark; Yang, Shicheng; Gress, Ronald E.; Hakim, Frances T.; Kochenderfer, James N.

    2013-01-01

    Purpose Multiple myeloma (MM) is a usually incurable malignancy of plasma cells. New therapies are urgently needed for MM. Adoptive transfer of chimeric antigen receptor (CAR)-expressing T cells is a promising new therapy for hematologic malignancies, but an ideal target antigen for CAR-expressing T cell therapies of MM has not been identified. B-cell maturation antigen (BCMA) is a protein that has been reported to be selectively expressed by B-lineage cells including MM cells. Our goal was to determine if BCMA is a suitable target for CAR-expressing T cells. Experimental Design We conducted an assessment of BCMA expression in normal human tissues and MM cells by flow cytometry, quantitative PCR, and immunohistochemistry. We designed and tested novel anti-BCMA CARs. Results BCMA had a restricted RNA expression pattern. Except for expression on plasma cells, BCMA protein was not detected in normal human tissues. BCMA was not detected on primary human CD34+ hematopoietic cells. We detected uniform BCMA cell-surface expression on primary MM cells from 5 of 5 patients. We designed the first anti-BCMA CARs to be reported, and we transduced T cells with lentiviral vectors encoding these CARs. The CARs gave T cells the ability to specifically recognize BCMA. The anti-BCMA-CAR-transduced T cells exhibited BCMA-specific functions including cytokine production, proliferation, cytotoxicity, and in vivo tumor eradication. Importantly, anti-BCMA-CAR-transduced T cells recognized and killed primary MM cells. Conclusions BCMA is a suitable target for CAR-expressing T cells, and adoptive transfer of anti-BCMA-CAR-expressing T cells is a promising new strategy for treating MM. PMID:23344265

  16. Cocrystal Structures of Glycyl-tRNA Synthetase in Complex with tRNA Suggest Multiple Conformational States in Glycylation*

    PubMed Central

    Qin, Xiangjing; Hao, Zhitai; Tian, Qingnan; Zhang, Zhemin; Zhou, Chun; Xie, Wei

    2014-01-01

    Aminoacyl-tRNA synthetases are an ancient enzyme family that specifically charges tRNA molecules with cognate amino acids for protein synthesis. Glycyl-tRNA synthetase (GlyRS) is one of the most intriguing aminoacyl-tRNA synthetases due to its divergent quaternary structure and abnormal charging properties. In the past decade, mutations of human GlyRS (hGlyRS) were also found to be associated with Charcot-Marie-Tooth disease. However, the mechanisms of traditional and alternative functions of hGlyRS are poorly understood due to a lack of studies at the molecular basis. In this study we report crystal structures of wild type and mutant hGlyRS in complex with tRNA and with small substrates and describe the molecular details of enzymatic recognition of the key tRNA identity elements in the acceptor stem and the anticodon loop. The cocrystal structures suggest that insertions 1 and 3 work together with the active site in a cooperative manner to facilitate efficient substrate binding. Both the enzyme and tRNA molecules undergo significant conformational changes during glycylation. A working model of multiple conformations for hGlyRS catalysis is proposed based on the crystallographic and biochemical studies. This study provides insights into the catalytic pathway of hGlyRS and may also contribute to our understanding of Charcot-Marie-Tooth disease. PMID:24898252

  17. Cocrystal structures of glycyl-tRNA synthetase in complex with tRNA suggest multiple conformational states in glycylation.

    PubMed

    Qin, Xiangjing; Hao, Zhitai; Tian, Qingnan; Zhang, Zhemin; Zhou, Chun; Xie, Wei

    2014-07-18

    Aminoacyl-tRNA synthetases are an ancient enzyme family that specifically charges tRNA molecules with cognate amino acids for protein synthesis. Glycyl-tRNA synthetase (GlyRS) is one of the most intriguing aminoacyl-tRNA synthetases due to its divergent quaternary structure and abnormal charging properties. In the past decade, mutations of human GlyRS (hGlyRS) were also found to be associated with Charcot-Marie-Tooth disease. However, the mechanisms of traditional and alternative functions of hGlyRS are poorly understood due to a lack of studies at the molecular basis. In this study we report crystal structures of wild type and mutant hGlyRS in complex with tRNA and with small substrates and describe the molecular details of enzymatic recognition of the key tRNA identity elements in the acceptor stem and the anticodon loop. The cocrystal structures suggest that insertions 1 and 3 work together with the active site in a cooperative manner to facilitate efficient substrate binding. Both the enzyme and tRNA molecules undergo significant conformational changes during glycylation. A working model of multiple conformations for hGlyRS catalysis is proposed based on the crystallographic and biochemical studies. This study provides insights into the catalytic pathway of hGlyRS and may also contribute to our understanding of Charcot-Marie-Tooth disease.

  18. Improved Atomistic Monte Carlo Simulations Demonstrate that Poly-L-Proline Adopts Heterogeneous Ensembles of Conformations of Semi-Rigid Segments Interrupted by Kinks

    PubMed Central

    Radhakrishnan, Aditya; Vitalis, Andreas; Mao, Albert H.; Steffen, Adam T.; Pappu, Rohit V.

    2012-01-01

    Poly-L-proline (PLP) polymers are useful mimics of biologically relevant proline-rich sequences. Biophysical and computational studies of PLP polymers in aqueous solutions are challenging because of the diversity of length scales and the slow time scales for conformational conversions. We describe an atomistic simulation approach that combines an improved ABSINTH implicit solvation model, with conformational sampling based on standard and novel Metropolis Monte Carlo moves. Refinements to forcefield parameters were guided by published experimental data for proline-rich systems. We assessed the validity of our simulation results through quantitative comparisons to experimental data that were not used in refining the forcefield parameters. Our analysis shows that PLP polymers form heterogeneous ensembles of conformations characterized by semi-rigid, rod-like segments interrupted by kinks, which result from a combination of internal cis peptide bonds, flexible backbone ψ-angles, and the coupling between ring puckering and backbone degrees of freedom. PMID:22329658

  19. Multiple GPCR conformations and signalling pathways: implications for antagonist affinity estimates

    PubMed Central

    Baker, Jillian G.; Hill, Stephen J.

    2007-01-01

    Antagonist affinity measurements have traditionally been considered important in characterizing the cell-surface receptors present in a particular cell or tissue. A central assumption has been that antagonist affinity is constant for a given receptor–antagonist interaction, regardless of the agonist used to stimulate that receptor or the downstream response that is measured. As a consequence, changes in antagonist affinity values have been taken as initial evidence for the presence of novel receptor subtypes. Emerging evidence suggests, however, that receptors can possess multiple binding sites and the same receptor can show different antagonist affinity measurements under distinct experimental conditions. Here, we discuss several mechanisms by which antagonists have different affinities for the same receptor as a consequence of allosterism, coupling to different G proteins, multiple (but non-interacting) receptor sites, and signal-pathway-dependent pharmacology (where the pharmacology observed varies depending on the signalling pathway measured). PMID:17629959

  20. Multiple conformational states of the hammerhead ribozyme, broad time range of relaxation and topology of dynamics

    PubMed Central

    Menger, Marcus; Eckstein, Fritz; Porschke, Dietmar

    2000-01-01

    The dynamics of a hammerhead ribozyme was analyzed by measurements of fluorescence-detected temperature jump relaxation. The ribozyme was substituted at different positions by 2-aminopurine (2-AP) as fluorescence indicator; these substitutions do not inhibit catalysis. The general shape of relaxation curves reported from different positions of the ribozyme is very similar: a fast decrease of fluorescence, mainly due to physical quenching, is followed by a slower increase of fluorescence due to conformational relaxation. In most cases at least three relaxation time constants in the time range from a few microseconds to ~200 ms are required for fitting. Although the relaxation at different positions of the ribozyme is similar in general, suggesting a global type of ribozyme dynamics, a close examination reveals differences, indicating an individual local response. For example, 2-AP in a tetraloop reports mainly the local loop dynamics known from isolated loops, whereas 2-AP located at the core, e.g. at the cleavage site or its vicinity, also reports relatively large amplitudes of slower components of the ribozyme dynamics. A variant with an A→G substitution in domain II, resulting in an inactive form, leads to the appearance of a particularly slow relaxation process (τ ≈200 ms). Addition of Mg2+ ions induces a reduction of amplitudes and in most cases a general increase of time constants. Differences between the hammerhead variants are clearly demonstrated by subtraction of relaxation curves recorded under corresponding conditions. The changes induced in the relaxation response by Mg2+ are very similar to those induced by Ca2+. The relaxation data do not provide any evidence for formation of Mg2+-inner sphere complexes in hammerhead ribozymes, because a Mg2+-specific relaxation effect was not visible. However, a Mg2+-specific effect was found for a dodeca-riboadenylate substituted with 2-AP, showing that the fluorescence of 2-AP is able to indicate inner sphere

  1. The yeast prion [SWI+] abolishes multicellular growth by triggering conformational changes of multiple regulators required for flocculin gene expression

    PubMed Central

    Du, Zhiqiang; Zhang, Ying; Li, Liming

    2016-01-01

    Summary While transcription factors are prevalent among yeast prion proteins, the role of prion-mediated transcriptional regulation remains elusive. We show here that the yeast prion [SWI+] abolishes flocculin (FLO) gene expression and results in a complete loss of multicellularity. Further investigation demonstrates that besides Swi1, multiple other proteins essential for FLO expression, including Mss11, Sap30, and Msn1 also undergo conformational changes, and become inactivated in [SWI+] cells. Moreover, the asparagine-rich region of Mss11 can exist as prion-like aggregates specifically in [SWI+] cells, which are SDS-resistant, heritable, and curable, but become metastable after separation from [SWI+]. Our findings thus reveal a prion-mediated mechanism through which multiple regulators in a biological pathway can be inactivated. In combination with the partial loss-of-function phenotypes of [SWI+] cells on non-glucose sugar utilization, our data therefore demonstrate that a prion can influence differently on distinct traits through multi-level regulations, providing insights into the biological roles of prions. PMID:26711350

  2. Megaripples, multiple cap carbonates, and apparently conformable sections: observations that normalize some interpretations of Snowball Earth stratigraphy while complicating others

    NASA Astrophysics Data System (ADS)

    Raub, T.; Lamb, M. P.; Fischer, W. W.; Myrow, P.; Perron, T.; Kunzmann, M.; Liu, C.; Prave, A. R.

    2012-12-01

    Neoproterozoic Snowball Earth is intellectually alluring in part because its remarkable sedimentary and geochemical record challenges uniformitarian description and demands multiple working hypotheses. Apparently exceptional features in that record may represent the end-products of truly nonuniformitarian processes acting on a fundamentally different Earth than the modern world: an Earth which is oxygen-poor, lacking terrestrial macrobiota, and of uncertain (or arguably bizarre) geomagnetic and geodynamic character. But many features in this remarkable rock record might be explained by perfectly ordinary processes acting on anomalous materials, or in systems bounded by conditions that are rare, but not mysterious, on modern Earth. I will present emerging examples of both interpretive modes. Exceptional bedforms known as cap carbonate megaripples can be explained under normal wave climates by aggradation of unusually large carbonate grains anomalously widespread in a shallow shelfal setting. Bedform topography may be inherited or else migrate laterally through discrete, episodic depositional events if cementation is fast. Trace metal isotopes excurse most prominently at the very base of conformable cap carbonate sections, and in the terminal stages of deglaciation, at times when the seawater saturation state is most dynamic. In the end, basic field geology without genetic presumption, and the interpretive context it lends specific geochemical analyses, remains most likely to successfully evaluate the likelihoods of both existing and new Snowball Earth scenarios. The most fundamental unanswered question remains one of stratigraphic architecture: what is the climatic phase, the timing, and the duration for both diamictite and cap carbonate deposition? End-member solutions remain viable: diamictite and cap carbonate may both be of prolonged duration and globally diachronous, with diamictite representing syn-glacial and interstadial cycles and cap carbonate spanning

  3. Multiple conformations of 5-HT2A and 5-HT 2C receptors in rat brain: an autoradiographic study with [125I](±)DOI.

    PubMed

    López-Giménez, Juan F; Vilaró, M Teresa; Palacios, José M; Mengod, Guadalupe

    2013-10-01

    Earlier autoradiographic studies with the 5-HT2 receptor agonist [(125)I](±)DOI in human brain showed unexpected biphasic competition curves for various 5-HT2A antagonists. We have performed similar studies in rat brain regions with selective 5-HT2A (M100907) and 5-HT2C (SB242084) antagonists together with ketanserin and mesulergine. The effect of GTP analogues on antagonist competition was also studied. Increasing concentrations of Gpp(NH)p or GTPγS resulted in a maximal inhibition of [(125)I](±)DOI-specific binding of approximately 50 %. M100907 competed biphasically in all regions. In the presence of 100 μM Gpp(NH)p, M100907 still displaced biphasically the remaining [(125)I](±)DOI binding. Ketanserin showed biphasic curves in some regions and monophasic curves in others. In the latter, Gpp(NH)p evidenced an additional high-affinity site. SB242084 competed biphasically in brainstem nuclei and monophasically in the other regions. In most areas, SB242084 affinities were not notably altered by Gpp(NH)p. Mesulergine competed monophasically in all regions without alteration by Gpp(NH)p. These results conform with the extended ternary complex model of receptor action: receptor exists as an equilibrium of multiple conformations, i.e. ground (R), partly activated (R*) and activated G-protein-coupled (R*G) conformation/s. Thus, [(125)I](±)DOI would label multiple conformations of both 5-HT2A and 5-HT2C receptors in rat brain, and M100907 and ketanserin would recognise these conformations with different affinities.

  4. Conformable seal

    DOEpatents

    Neef, W.S.; Lambert, D.R.

    1982-08-10

    Sealing apparatus and method, comprising first and second surfaces or membranes, at least one of which surfaces is deformable, placed in proximity to one another. Urging means cause these surfaces to contact one another in a manner such that the deformable surface deforms to conform to the geometry of the other surface, thereby creating a seal. The seal is capable of undergoing multiple cycles of sealing and unsealing.

  5. PB1-F2 influenza A virus protein adopts a beta-sheet conformation and forms amyloid fibers in membrane environments.

    PubMed

    Chevalier, Christophe; Al Bazzal, Ali; Vidic, Jasmina; Février, Vincent; Bourdieu, Christiane; Bouguyon, Edwige; Le Goffic, Ronan; Vautherot, Jean-François; Bernard, Julie; Moudjou, Mohammed; Noinville, Sylvie; Chich, Jean-François; Da Costa, Bruno; Rezaei, Human; Delmas, Bernard

    2010-04-23

    The influenza A virus PB1-F2 protein, encoded by an alternative reading frame in the PB1 polymerase gene, displays a high sequence polymorphism and is reported to contribute to viral pathogenesis in a sequence-specific manner. To gain insights into the functions of PB1-F2, the molecular structure of several PB1-F2 variants produced in Escherichia coli was investigated in different environments. Circular dichroism spectroscopy shows that all variants have a random coil secondary structure in aqueous solution. When incubated in trifluoroethanol polar solvent, all PB1-F2 variants adopt an alpha-helix-rich structure, whereas incubated in acetonitrile, a solvent of medium polarity mimicking the membrane environment, they display beta-sheet secondary structures. Incubated with asolectin liposomes and SDS micelles, PB1-F2 variants also acquire a beta-sheet structure. Dynamic light scattering revealed that the presence of beta-sheets is correlated with an oligomerization/aggregation of PB1-F2. Electron microscopy showed that PB1-F2 forms amorphous aggregates in acetonitrile. In contrast, at low concentrations of SDS, PB1-F2 variants exhibited various abilities to form fibers that were evidenced as amyloid fibers in a thioflavin T assay. Using a recombinant virus and its PB1-F2 knock-out mutant, we show that PB1-F2 also forms amyloid structures in infected cells. Functional membrane permeabilization assays revealed that the PB1-F2 variants can perforate membranes at nanomolar concentrations but with activities found to be sequence-dependent and not obviously correlated with their differential ability to form amyloid fibers. All of these observations suggest that PB1-F2 could be involved in physiological processes through different pathways, permeabilization of cellular membranes, and amyloid fiber formation.

  6. PB1-F2 Influenza A Virus Protein Adopts a β-Sheet Conformation and Forms Amyloid Fibers in Membrane Environments

    PubMed Central

    Chevalier, Christophe; Al Bazzal, Ali; Vidic, Jasmina; Février, Vincent; Bourdieu, Christiane; Bouguyon, Edwige; Le Goffic, Ronan; Vautherot, Jean-François; Bernard, Julie; Moudjou, Mohammed; Noinville, Sylvie; Chich, Jean-François; Da Costa, Bruno; Rezaei, Human; Delmas, Bernard

    2010-01-01

    The influenza A virus PB1-F2 protein, encoded by an alternative reading frame in the PB1 polymerase gene, displays a high sequence polymorphism and is reported to contribute to viral pathogenesis in a sequence-specific manner. To gain insights into the functions of PB1-F2, the molecular structure of several PB1-F2 variants produced in Escherichia coli was investigated in different environments. Circular dichroism spectroscopy shows that all variants have a random coil secondary structure in aqueous solution. When incubated in trifluoroethanol polar solvent, all PB1-F2 variants adopt an α-helix-rich structure, whereas incubated in acetonitrile, a solvent of medium polarity mimicking the membrane environment, they display β-sheet secondary structures. Incubated with asolectin liposomes and SDS micelles, PB1-F2 variants also acquire a β-sheet structure. Dynamic light scattering revealed that the presence of β-sheets is correlated with an oligomerization/aggregation of PB1-F2. Electron microscopy showed that PB1-F2 forms amorphous aggregates in acetonitrile. In contrast, at low concentrations of SDS, PB1-F2 variants exhibited various abilities to form fibers that were evidenced as amyloid fibers in a thioflavin T assay. Using a recombinant virus and its PB1-F2 knock-out mutant, we show that PB1-F2 also forms amyloid structures in infected cells. Functional membrane permeabilization assays revealed that the PB1-F2 variants can perforate membranes at nanomolar concentrations but with activities found to be sequence-dependent and not obviously correlated with their differential ability to form amyloid fibers. All of these observations suggest that PB1-F2 could be involved in physiological processes through different pathways, permeabilization of cellular membranes, and amyloid fiber formation. PMID:20172856

  7. Multiple conformational states of a new hematopoietic cytokine (megakaryocyte growth and development factor): pH- and urea-induced denaturation.

    PubMed

    Hamburger, J B; Chen, E; Narhi, L O; Wu, G M; Brems, D N

    1998-09-01

    The effect of pH and urea on the conformation of recombinant human megakaryocyte growth and development factor (rHuMGDF) was determined by circular dichroism, intrinsic fluorescence spectroscopy, and equilibrium ultracentrifugation. The conformation of rHuMGDF was dependent on pH and urea concentration. Multiple folding forms were evidenced by multiple pH-induced transitions and urea-induced equilibrium transitions that deviated from a simple two-state process. In neutral to alkaline pH, rHuMGDF exists as a monomer, but an acid-induced conformational state self-associates to form a soluble aggregate. A folding intermediate(s) was observed with a more stable secondary structure than tertiary structure and was dependent on the pH of the urea-induced denaturation. The differences in the stabilities of the folding states were most distinct in the pH range of 4.5 to 6.5. The presence of intermediates in the folding pathway of rHuMGDF are similar to findings of previous studies of related growth factors that share a common three-dimensional structure.

  8. Multiple gas-phase conformations of proline-containing peptides: is it always cis/trans isomerization?

    PubMed

    Lietz, Christopher B; Chen, Zhengwei; Yun Son, Chang; Pang, Xueqin; Cui, Qiang; Li, Lingjun

    2016-08-01

    Ion mobility-mass spectrometry (IM-MS) is often employed to look at the secondary, tertiary, and quaternary structures of naked peptides and proteins in the gas-phase. Recently, it has offered a unique glimpse into proline-containing peptides and their cis/trans Xxx-Pro isomers. An experimental "signature" has been identified wherein a proline-containing peptide has its Pro residues substituted with another amino acid and the presence or absence of conformations in the IM-MS spectra is observed. Despite the high probability that one could attribute these conformations to cis/trans isomers, it is also possible that cis/trans isomers are not the cause of the additional conformations in proline-containing peptides. However, the experimental evidence of such a system has not been demonstrated or reported. Herein, we present the IM-MS analysis of Neuropeptide Y's wild-type (WT) signal sequence and Leu7Pro (L7P) mutant. Although comparison of arrival times and collision cross-sections of [M + 4H](4+) ions yields the cis/trans "signature", molecular dynamics indicates that a cis-Pro7 is not very stable and that trans-Pro7 conformations of the same cross-section arise with equal frequency. We believe that this work further underscores the importance of theoretical calculations in IM-MS structural assignments. PMID:27434776

  9. Identification of multiple conformers of the ionic liquid [emim][tf2n] in the gas phase using IR/UV action spectroscopy.

    PubMed

    Booth, Ryan S; Annesley, Christopher J; Young, Justin W; Vogelhuber, Kristen M; Boatz, Jerry A; Stearns, Jaime A

    2016-06-22

    In this study we investigate the effect of deuteration and molecular beam temperature on the hydrogen bond in the ionic liquid [emim][tf2n]. Using IR/UV double resonance spectroscopy, we probe the microscopic structure of the [emim][tf2n] ion pair and its mono-deuterated, [emim-d1][tf2n], analog. Comparisons of the infrared absorption frequencies between these two species show that there are multiple conformers of the ion pair present in the gas phase and trapped through the molecular beam cooling process. Furthermore, each conformer has a characteristic red shift in the frequency of its C2-H group that reveals the variation in strength of a hydrogen bond between the cation and anion. PMID:27298098

  10. Multiple receptor conformation docking, dock pose clustering and 3D QSAR studies on human poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors.

    PubMed

    Fatima, Sabiha; Jatavath, Mohan Babu; Bathini, Raju; Sivan, Sree Kanth; Manga, Vijjulatha

    2014-10-01

    Poly(ADP-ribose) polymerase-1 (PARP-1) functions as a DNA damage sensor and signaling molecule. It plays a vital role in the repair of DNA strand breaks induced by radiation and chemotherapeutic drugs; inhibitors of this enzyme have the potential to improve cancer chemotherapy or radiotherapy. Three-dimensional quantitative structure activity relationship (3D QSAR) models were developed using comparative molecular field analysis, comparative molecular similarity indices analysis and docking studies. A set of 88 molecules were docked into the active site of six X-ray crystal structures of poly(ADP-ribose)polymerase-1 (PARP-1), by a procedure called multiple receptor conformation docking (MRCD), in order to improve the 3D QSAR models through the analysis of binding conformations. The docked poses were clustered to obtain the best receptor binding conformation. These dock poses from clustering were used for 3D QSAR analysis. Based on MRCD and QSAR information, some key features have been identified that explain the observed variance in the activity. Two receptor-based QSAR models were generated; these models showed good internal and external statistical reliability that is evident from the [Formula: see text], [Formula: see text] and [Formula: see text]. The identified key features enabled us to design new PARP-1 inhibitors. PMID:25046176

  11. Multiple receptor conformation docking, dock pose clustering and 3D QSAR studies on human poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors.

    PubMed

    Fatima, Sabiha; Jatavath, Mohan Babu; Bathini, Raju; Sivan, Sree Kanth; Manga, Vijjulatha

    2014-10-01

    Poly(ADP-ribose) polymerase-1 (PARP-1) functions as a DNA damage sensor and signaling molecule. It plays a vital role in the repair of DNA strand breaks induced by radiation and chemotherapeutic drugs; inhibitors of this enzyme have the potential to improve cancer chemotherapy or radiotherapy. Three-dimensional quantitative structure activity relationship (3D QSAR) models were developed using comparative molecular field analysis, comparative molecular similarity indices analysis and docking studies. A set of 88 molecules were docked into the active site of six X-ray crystal structures of poly(ADP-ribose)polymerase-1 (PARP-1), by a procedure called multiple receptor conformation docking (MRCD), in order to improve the 3D QSAR models through the analysis of binding conformations. The docked poses were clustered to obtain the best receptor binding conformation. These dock poses from clustering were used for 3D QSAR analysis. Based on MRCD and QSAR information, some key features have been identified that explain the observed variance in the activity. Two receptor-based QSAR models were generated; these models showed good internal and external statistical reliability that is evident from the [Formula: see text], [Formula: see text] and [Formula: see text]. The identified key features enabled us to design new PARP-1 inhibitors.

  12. Multiple receptor conformation docking and dock pose clustering as tool for CoMFA and CoMSIA analysis - a case study on HIV-1 protease inhibitors.

    PubMed

    Sivan, Sree Kanth; Manga, Vijjulatha

    2012-02-01

    Multiple receptors conformation docking (MRCD) and clustering of dock poses allows seamless incorporation of receptor binding conformation of the molecules on wide range of ligands with varied structural scaffold. The accuracy of the approach was tested on a set of 120 cyclic urea molecules having HIV-1 protease inhibitory activity using 12 high resolution X-ray crystal structures and one NMR resolved conformation of HIV-1 protease extracted from protein data bank. A cross validation was performed on 25 non-cyclic urea HIV-1 protease inhibitor having varied structures. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models were generated using 60 molecules in the training set by applying leave one out cross validation method, r (loo) (2) values of 0.598 and 0.674 for CoMFA and CoMSIA respectively and non-cross validated regression coefficient r(2) values of 0.983 and 0.985 were obtained for CoMFA and CoMSIA respectively. The predictive ability of these models was determined using a test set of 60 cyclic urea molecules that gave predictive correlation (r (pred) (2) ) of 0.684 and 0.64 respectively for CoMFA and CoMSIA indicating good internal predictive ability. Based on this information 25 non-cyclic urea molecules were taken as a test set to check the external predictive ability of these models. This gave remarkable out come with r (pred) (2) of 0.61 and 0.53 for CoMFA and CoMSIA respectively. The results invariably show that this method is useful for performing 3D QSAR analysis on molecules having different structural motifs.

  13. Multiple N-methylation of MT-II backbone amide bonds leads to melanocortin receptor subtype hMC1R selectivity; pharmacological and conformational studies

    PubMed Central

    Doedens, Lucas; Opperer, Florian; Cai, Minying; Beck, Johannes G.; Dedek, Matt; Palmer, Erin; Hruby, Victor J.; Kessler, Horst

    2010-01-01

    Multiple N-methylation is a novel technology to improve bioavailability of peptides and increase receptor subtype selectivity. This technique has been applied here to the superpotent but non-selective cyclic peptide MT-II. A library of all possible 31 backbone N-methylated derivatives has been synthesized and tested for binding and activation at melanocortin receptor subtypes 1, 3, 4 and 5. It turned out that selectivity is improved with every introduced N-methyl group, resulting in several N-methylated selective and potent agonists for the hMC1R. The most potent of these derivatives is N-methylated on four out of five amide bonds in the cyclic structure. Its solution structure indicates a strongly preferred backbone conformation which resembles other a-MSH analogs but possesses much less flexibility and in addition distinct differences in the spatial arrangement of individual amino acid side chains. PMID:20496895

  14. Increased plasma-immune cytokines throughout the high-dose melphalan-induced lymphodepletion in patients with multiple myeloma: a window for adoptive immunotherapy.

    PubMed

    Condomines, Maud; Veyrune, Jean-Luc; Larroque, Marion; Quittet, Philippe; Latry, Pascal; Lugagne, Cécile; Hertogh, Catherine; Kanouni, Tarik; Rossi, Jean-François; Klein, Bernard

    2010-01-15

    High-dose melphalan (HDM) followed by autologous stem cell transplantation (ASCT) is a standard treatment for patients with multiple myeloma. However, lymphocyte reconstitution is impaired after HDM. Recent work has suggested that the lymphopenia period occurring after various immunosuppressive or chemotherapy treatments may provide an interesting opportunity for adoptive antitumor immunotherapy. The objective of this study was to determine an immunotherapy window after HDM and ASCT, evaluating T cell lymphopenia, and measuring circulating immune cytokine concentrations in patients with multiple myeloma. The counts of T cell subpopulations reached a nadir at day 8 post-ASCT (day 10 post-HDM) and recovered by day 30. IL-6, IL-7, and IL-15 plasma levels increased on a median day 8 post-ASCT, respectively, 35-fold, 8-fold, and 10-fold compared with pre-HDM levels (p < or = 0.05). The increases in IL-7 and IL-15 levels were inversely correlated to the absolute lymphocyte count, unlike monocyte or myeloid counts. Furthermore, we have shown that CD3 T cells present in the ASC graft are activated, die rapidly when they are cultured without cytokine in vitro, and that addition of IL-7 or IL-15 could induce their survival and proliferation. In conclusion, the early lymphodepletion period, occurring 4-11 d post-HDM and ASCT, is associated with an increase of circulating immune cytokines and could be an optimal window to enhance the survival and proliferation of polyclonal T cells present in the ASC autograft and also of specific antimyeloma T cells previously expanded in vitro.

  15. Low-dose thalidomide and donor lymphocyte infusion as adoptive immunotherapy after allogeneic stem cell transplantation in patients with multiple myeloma.

    PubMed

    Kröger, Nicolaus; Shimoni, Avichai; Zagrivnaja, Maria; Ayuk, Francis; Lioznov, Michael; Schieder, Heike; Renges, Helmut; Fehse, Boris; Zabelina, Tatjana; Nagler, Arnon; Zander, Axel R

    2004-11-15

    To improve the antimyeloma effect of donor lymphocyte infusion (DLI) after allogeneic stem cell transplantation in multiple myeloma, we investigated in a phase 1/2 study the effect of low-dose thalidomide (100 mg) followed by DLI in 18 patients with progressive disease or residual disease and prior ineffective DLI after allografting. The overall response rate was 67%, including 22% complete remission. Major toxicity of thalidomide was weakness grade I/II (68%) and peripheral neuropathy grade I/II (28%). Only 2 patients experienced mild grade I acute graft versus host disease (aGvHD) of the skin, while no grades II to IV aGvHD was seen. De novo limited chronic GvHD (cGvHD) was seen in 2 patients (11%). The 2-year estimated overall and progression-free survival were 100% and 84%, respectively. Adoptive immunotherapy with low-dose thalidomide and DLI induces a strong antimyeloma effect with low incidence of graft versus host disease.

  16. A 23Na Multiple-Quantum-Filtered NMR Study of the Effect of the Cytoskeleton Conformation on the Anisotropic Motion of Sodium Ions in Red Blood Cells

    NASA Astrophysics Data System (ADS)

    Knubovets, Tatyana; Shinar, Hadassah; Eliav, Uzi; Navon, Gil

    1996-01-01

    Recently, it has been shown that23Na double-quantum-filtered NMR spectroscopy can be used to detect anisotropic motion of bound sodium ions in biological systems. The technique is based on the formation of the second-rank tensor when the quadrupolar interaction is not averaged to zero. Using this method, anisotropic motion of bound sodium in human and dog red blood cells was detected, and the effect was shown to depend on the integrity of the membrane cytoskeleton. In the present study, multiple-quantum-filtered techniques were applied in combination with a quadrupolar echo to measure the transverse-relaxation times,T2fandT2s. Line fitting was performed to obtain the values of the residual quadrupolar interaction, which was measured for sodium in a variety of mammalian erythrocytes of different size, shape, rheological properties, and sodium concentrations. Human unsealed white ghosts were used to study sodium bound at the anisotropic sites on the inner side of the RBC membrane. Modulations of the conformation of the cytoskeleton by the variation of either the ionic strength or pH of the suspending medium caused drastic changes in both the residual quadrupolar interaction andT2fdue to changes in the fraction of bound sodium ions as well as changes in the structure of the binding sites. By combining the two spectroscopic parameters, structural change can be followed. The changes in the structure of the sodium anisotropic binding sites deduced by this method were found to correlate with known conformational changes of the membrane cytoskeleton. Variations of the medium pH affected both the fraction of bound sodium ions and the structure of the anisotropic binding sites. Sodium and potassium were shown to bind to the anisotropic binding sites with the same affinity.

  17. 40 CFR 51.854 - Conformity analysis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 2 2010-07-01 2010-07-01 false Conformity analysis. 51.854 Section 51... FOR PREPARATION, ADOPTION, AND SUBMITTAL OF IMPLEMENTATION PLANS Determining Conformity of General Federal Actions to State or Federal Implementation Plans § 51.854 Conformity analysis. Link to...

  18. Quantitative analysis of conformational exchange contributions to 1H-15N multiple-quantum relaxation using field-dependent measurements. Time scale and structural characterization of exchange in a calmodulin C-terminal domain mutant.

    PubMed

    Lundström, Patrik; Akke, Mikael

    2004-01-28

    Multiple-quantum spin relaxation is a sensitive probe for correlated conformational exchange dynamics on microsecond to millisecond time scales in biomolecules. We measured differential 1H-15N multiple-quantum relaxation rates for the backbone amide groups of the E140Q mutant of the C-terminal domain of calmodulin at three static magnetic field strengths. The differential multiple-quantum relaxation rates range between -88.7 and 92.7 s(-1), and the mean and standard deviation are 7.0 +/- 24 s(-1), at a static magnetic field strength of 14.1 T. Together with values of the 1H and 15N chemical shift anisotropies (CSA) determined separately, the field-dependent data enable separation of the different contributions from dipolar-dipolar, CSA-CSA, and conformational exchange cross-correlated relaxation mechanisms to the differential multiple-quantum relaxation rates. The procedure yields precise quantitative information on the dominant conformational exchange contributions observed in this protein. The field-dependent differences between double- and zero-quantum relaxation rates directly benchmark the rates of conformational exchange, showing that these are fast on the chemical shift time scale for the large majority of residues in the protein. Further analysis of the differential 1H-15N multiple-quantum relaxation rates using previously determined exchange rate constants and populations, obtained from 15N off-resonance rotating-frame relaxation data, enables extraction of the product of the chemical shift differences between the resonance frequencies of the 1H and 15N spins in the exchanging conformations, deltasigma(H)deltasigma(N). Thus, information on the 1H chemical shift differences is obtained, while circumventing complications associated with direct measurements of conformational exchange effects on 1H single-quantum coherences in nondeuterated proteins. The method significantly increases the information content available for structural interpretation of the

  19. Targeting Multiple Conformations Leads to Small Molecule Inhibitors of the uPAR·uPA Protein-Protein Interaction that Block Cancer Cell Invasion

    PubMed Central

    Khanna, May; Wang, Fang; Jo, Inha; Knabe, W. Eric; Wilson, Sarah M.; Li, Liwei; Bum-Erdene, Khuchtumur; Li, Jing; Sledge, George; Khanna, Rajesh; Meroueh, Samy O.

    2011-01-01

    Interaction of the urokinase receptor (uPAR) with its binding partners including the urokinase-type plasminogen activator (uPA) at the cell surface triggers a series of proteolytic and signaling events that promote invasion and metastasis. Here, we report the discovery of a small molecule (IPR-456) and its derivatives that inhibit the tight uPAR·uPA protein-protein interaction. IPR-456 was discovered by virtual screening against multiple conformations of uPAR sampled from explicit-solvent molecular dynamics simulations. Biochemical characterization reveal that the compound binds to uPAR with sub-micromolar affinity (Kd = 310 nM) and inhibits the tight protein-protein interaction with an IC50 of 10 μM. Free energy calculations based on explicit-solvent molecular dynamics simulations suggested the importance of a carboxylate moiety on IPR-456, which was confirmed by the activity of several derivatives including IPR-803. Immunofluorescence imaging showed that IPR-456 inhibited uPA binding to uPAR of breast MDA-MB-231 tumor cells with an IC50 of 8 μM. The compounds blocked MDA-MB-231 cell invasion, but IPR-456 showed little effect on MDA-MB-231 migration, and no effect on adhesion, suggesting that uPAR mediates these processes through its other binding partners. PMID:21875078

  20. Improving docking results via reranking of ensembles of ligand poses in multiple X-ray protein conformations with MM-GBSA.

    PubMed

    Greenidge, P A; Kramer, C; Mozziconacci, J-C; Sherman, W

    2014-10-27

    There is a tendency in the literature to be critical of scoring functions when docking programs perform poorly. The assumption is that existing scoring functions need to be enhanced or new ones developed in order to improve the performance of docking programs for tasks such as pose prediction and virtual screening. However, failures can result from either sampling or scoring (or a combination of the two), although less emphasis tends to be given to the former. In this work, we use the programs GOLD and Glide on a high-quality data set to explore whether failures in pose prediction and binding affinity estimation can be attributable more to sampling or scoring. We show that identification of the correct pose (docking power) can be improved by incorporating ligand strain into the scoring function or rescoring an ensemble of diverse docking poses with MM-GBSA in a postprocessing step. We explore the use of nondefault docking settings and find that enhancing ligand sampling also improves docking power, again suggesting that sampling is more limiting than scoring for the docking programs investigated in this work. In cross-docking calculations (docking a ligand to a noncognate receptor structure) we observe a significant reduction in the accuracy of pose ranking, as expected and has been reported by others; however, we demonstrate that these alternate poses may in fact be more complementary between the ligand and the rigid receptor conformation, emphasizing that treating the receptor rigidly is an artificial constraint on the docking problem. We simulate protein flexibility by the use of multiple crystallographic conformations of a protein and demonstrate that docking results can be improved with this level of protein sampling. This work indicates the need for better sampling in docking programs, especially for the receptor. This study also highlights the variable descriptive value of RMSD as the sole arbiter of pose replication quality. It is shown that ligand poses

  1. 76 FR 77182 - Approval and Promulgation of Air Quality Implementation Plans; Virginia; General Conformity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-12

    ... Conformity Requirements for Federal Agencies Applicable to Federal Actions AGENCY: Environmental Protection... adopted by Virginia for the purpose of incorporating Federal general conformity requirements revisions... approving Virginia's general conformity SIP revision and if that provision may be severed from the...

  2. Strengthening Adoption Practice, Listening to Adoptive Families

    ERIC Educational Resources Information Center

    Atkinson, Anne; Gonet, Patricia

    2007-01-01

    In-depth interviews with 500 adoptive families who received postadoption services through Virginia's Adoptive Family Preservation (AFP) program paint a richly detailed picture of the challenges adoptive families face and what they need to sustain adoption for many years after finalization. Findings document the need for support in a variety of…

  3. Medical Issues in Adoption

    MedlinePlus

    ... to Know About Zika & Pregnancy Medical Issues in Adoption KidsHealth > For Parents > Medical Issues in Adoption Print ... or emotional abuse of the child continue Agency Adoptions If you adopt through an agency, you might ...

  4. Biomedical Ph.D. Students Enrolled in Two Elite Universities in the United Kingdom and the United States Report Adopting Multiple Learning Relationships

    PubMed Central

    Kemp, Matthew W.; Lazarus, Benjamin M.; Perron, Gabriel G.; Hanage, William P.; Chapman, Elaine

    2014-01-01

    Objective The ability to form multiple learning relationships is a key element of the doctoral learning environment in the biomedical sciences. Of these relationships, that between student and supervisor has long been viewed as key. There are, however, limited data to describe the student perspective on what makes this relationship valuable. In the present study, we discuss the findings of semi-structured interviews with biomedical Ph.D. students from the United Kingdom and the United States to: i) determine if the learning relationships identified in an Australian biomedical Ph.D. cohort are also important in a larger international student cohort; and ii) improve our understanding of student perceptions of value in their supervisory relationships. Study Design 32 students from two research intensive universities, one in the United Kingdom (n = 17), and one in the United States (n = 15) were recruited to participate in a semi-structured interview. Verbatim transcripts were transcribed, validated and analysed using a Miles and Huberman method for thematic analysis. Results Students reported that relationships with other Ph.D. students, post-doctoral scientists and supervisors were all essential to their learning. Effective supervisory relationships were perceived as the primary source of high-level project guidance, intellectual support and confidence. Relationships with fellow students were viewed as essential for the provision of empathetic emotional support. Technical learning was facilitated, almost exclusively, by relationships with postdoctoral staff. Conclusions These data make two important contributions to the scholarship of doctoral education in the biomedical sciences. Firstly, they provide further evidence for the importance of multiple learning relationships in the biomedical doctorate. Secondly, they clarify the form of a ‘valued’ supervisory relationship from a student perspective. We conclude that biomedical doctoral programs should be

  5. Conformational stability of apoflavodoxin.

    PubMed Central

    Genzor, C. G.; Beldarraín, A.; Gómez-Moreno, C.; López-Lacomba, J. L.; Cortijo, M.; Sancho, J.

    1996-01-01

    Flavodoxins are alpha/beta proteins that mediate electron transfer reactions. The conformational stability of apoflavodoxin from Anaboena PCC 7119 has been studied by calorimetry and urea denaturation as a function of pH and ionic strength. At pH > 12, the protein is unfolded. Between pH 11 and pH 6, the apoprotein is folded properly as judged from near-ultraviolet (UV) circular dichroism (CD) and high-field 1H NMR spectra. In this pH interval, apoflavodoxin is a monomer and its unfolding by urea or temperature follows a simple two-state mechanism. The specific heat capacity of unfolding for this native conformation is unusually low. Near its isoelectric point (3.9), the protein is highly insoluble. At lower pH values (pH 3.5-2.0), apoflavodoxin adopts a conformation with the properties of a molten globule. Although apoflavodoxin at pH 2 unfolds cooperatively with urea in a reversible fashion and the fluorescence and far-UV CD unfolding curves coincide, the transition midpoint depends on the concentration of protein, ruling out a simple two-state process at acidic pH. Apoflavodoxin constitutes a promising system for the analysis of the stability and folding of alpha/beta proteins and for the study of the interaction between apoflavoproteins and their corresponding redox cofactors. PMID:8819170

  6. Conformational Landscape of Nicotinoids: Solving the "conformational - Rity" of Anabasine

    NASA Astrophysics Data System (ADS)

    Lesarri, Alberto; Cocinero, Emilio J.; Evangelisti, Luca; Suenram, Richard D.; Caminati, Walther; Grabow, Jens-Uwe

    2010-06-01

    The conformational landscape of the alkaloid anabasine (neonicotine) has been investigated using rotational spectroscopy and ab initio calculations. The results allow a detailed comparison of the structural properties of the prototype piperidinic and pyrrolidinic nicotinoids (anabasine vs. nicotine). Anabasine adopts two most stable conformations in isolation conditions, for which we determined accurate rotational and nuclear quadrupole coupling parameters. The preferred conformations are characterized by an equatorial pyridine moiety and additional N-H equatorial stereochemistry at the piperidine ring (Eq-Eq). The two rings of anabasine are close to a bisecting arrangement, with the observed conformations differing in a ca. 180° rotation of the pyridine subunit, denoted either Syn or Anti. The preference of anabasine for the Eq-Eq-Syn conformation has been established by relative intensity measurements (Syn/Anti˜5(2)). The conformational preferences of free anabasine are directed by a N\\cdot\\cdot\\cdotH-C weak hydrogen bond interaction between the nitrogen lone pair at piperidine and the closest hydrogen bond in pyridine, with N\\cdot\\cdot\\cdotN distances ranging from 4.750 Å (Syn) to 4.233 Å (Anti). R. J. Lavrich, R. D. Suenram, D. F. Plusquellic and S. Davis, 58^th OSU Int. Symp. on Mol. Spectrosc., Columbus, OH, 2003, Comm. RH13.

  7. Synthesis and conformation of fluorinated β-peptidic compounds.

    PubMed

    Peddie, Victoria; Butcher, Raymond J; Robinson, Ward T; Wilce, Matthew C J; Traore, Daouda A K; Abell, Andrew D

    2012-05-21

    Experimental and theoretical data indicate that, for α-fluoroamides, the F-C-C(O)-N(H) moiety adopts an antiperiplanar conformation. In addition, a gauche conformation is favoured between the vicinal C-F and C-N(CO) bonds in N-β-fluoroethylamides. This study details the synthesis of a series of fluorinated β-peptides (1-8) designed to use these stereoelectronic effects to control the conformation of β-peptide bonds. X-ray crystal structures of these compounds revealed the expected conformations: with fluorine β to a nitrogen adopting a gauche conformation, and fluorine α to a C=O group adopting an antiperiplanar conformation. Thus, the strategic placement of fluorine can control the conformation of a β-peptide bond, with the possibility of directing the secondary structures of β-peptides.

  8. Adopted Children and Discipline

    MedlinePlus

    ... a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care Communication & Discipline Types of Families Media ... Your Community Healthy Children > Family Life > Family Dynamics > Adoption & Foster Care > Adopted Children & Discipline Family Life Listen ...

  9. Adoption & Foster Care

    MedlinePlus

    ... Children > Family Life > Family Dynamics > Adoption & Foster Care Adoption & Foster Care Article Body ​Each year, many children join families through adoption and foster care. These families may face unique ...

  10. Populations of the Minor α-Conformation in AcGXGNH2 and the α-Helical Nucleation Propensities

    NASA Astrophysics Data System (ADS)

    Zhou, Yanjun; He, Liu; Zhang, Wenwen; Hu, Jingjing; Shi, Zhengshuang

    2016-06-01

    Intrinsic backbone conformational preferences of different amino acids are important for understanding the local structure of unfolded protein chains. Recent evidence suggests α-structure is relatively minor among three major backbone conformations for unfolded proteins. The α-helices are the dominant structures in many proteins. For these proteins, how could the α-structures occur from the least in unfolded to the most in folded states? Populations of the minor α-conformation in model peptides provide vital information. Reliable determination of populations of the α-conformers in these peptides that exist in multiple equilibriums of different conformations remains a challenge. Combined analyses on data from AcGXPNH2 and AcGXGNH2 peptides allow us to derive the populations of PII, β and α in AcGXGNH2. Our results show that on average residue X in AcGXGNH2 adopt PII, β, and α 44.7%, 44.5% and 10.8% of time, respectively. The contents of α-conformations for different amino acids define an α-helix nucleation propensity scale. With derived PII, β and α-contents, we can construct a free energy-conformation diagram on each AcGXGNH2 in aqueous solution for the three major backbone conformations. Our results would have broad implications on early-stage events of protein folding.

  11. Populations of the Minor α-Conformation in AcGXGNH2 and the α-Helical Nucleation Propensities

    PubMed Central

    Zhou, Yanjun; He, Liu; Zhang, Wenwen; Hu, Jingjing; Shi, Zhengshuang

    2016-01-01

    Intrinsic backbone conformational preferences of different amino acids are important for understanding the local structure of unfolded protein chains. Recent evidence suggests α-structure is relatively minor among three major backbone conformations for unfolded proteins. The α-helices are the dominant structures in many proteins. For these proteins, how could the α-structures occur from the least in unfolded to the most in folded states? Populations of the minor α-conformation in model peptides provide vital information. Reliable determination of populations of the α-conformers in these peptides that exist in multiple equilibriums of different conformations remains a challenge. Combined analyses on data from AcGXPNH2 and AcGXGNH2 peptides allow us to derive the populations of PII, β and α in AcGXGNH2. Our results show that on average residue X in AcGXGNH2 adopt PII, β, and α 44.7%, 44.5% and 10.8% of time, respectively. The contents of α-conformations for different amino acids define an α-helix nucleation propensity scale. With derived PII, β and α-contents, we can construct a free energy-conformation diagram on each AcGXGNH2 in aqueous solution for the three major backbone conformations. Our results would have broad implications on early-stage events of protein folding. PMID:27256621

  12. Flexible ligand docking using conformational ensembles.

    PubMed Central

    Lorber, D. M.; Shoichet, B. K.

    1998-01-01

    Molecular docking algorithms suggest possible structures for molecular complexes. They are used to model biological function and to discover potential ligands. A present challenge for docking algorithms is the treatment of molecular flexibility. Here, the rigid body program, DOCK, is modified to allow it to rapidly fit multiple conformations of ligands. Conformations of a given molecule are pre-calculated in the same frame of reference, so that each conformer shares a common rigid fragment with all other conformations. The ligand conformers are then docked together, as an ensemble, into a receptor binding site. This takes advantage of the redundancy present in differing conformers of the same molecule. The algorithm was tested using three organic ligand protein systems and two protein-protein systems. Both the bound and unbound conformations of the receptors were used. The ligand ensemble method found conformations that resembled those determined in X-ray crystal structures (RMS values typically less than 1.5 A). To test the method's usefulness for inhibitor discovery, multi-compound and multi-conformer databases were screened for compounds known to bind to dihydrofolate reductase and compounds known to bind to thymidylate synthase. In both cases, known inhibitors and substrates were identified in conformations resembling those observed experimentally. The ligand ensemble method was 100-fold faster than docking a single conformation at a time and was able to screen a database of over 34 million conformations from 117,000 molecules in one to four CPU days on a workstation. PMID:9568900

  13. The counterreceptor binding site of human CD2 exhibits an extended surface patch with multiple conformations fluctuating with millisecond to microsecond motions.

    PubMed Central

    Wyss, D. F.; Dayie, K. T.; Wagner, G.

    1997-01-01

    We have used 15N NMR relaxation experiments to probe, for the glycosylated human CD2 adhesion domain, the overall molecular motion, as well as very fast nanosecond-picosecond (ns-ps) and slow millisecond-microsecond (ms-microsecond) internal motions. Using a novel analysis method that considers all residues, we obtained a correlation time for the overall motion of 9.5 +/- 0.3 ns. Surprisingly, we found a large contiguous patch of residues in the counterreceptor (CD58) binding site of human CD2 exhibiting slow conformational exchange motions (ms-microsecond). On the other hand, almost none of the residues of the CD58 binding side display fast (ns-ps) internal motions of amplitudes larger than what is seen for well-ordered regions of the structure. Residues close to the N-glycosylation site, and the first N-acetylglucosamine of the high mannose glycan are as rigid as the protein core. Residues conserved in the immunoglobulin superfamily V-set domain are generally very rigid. PMID:9070436

  14. (19)F NMR reveals multiple conformations at the dimer interface of the nonstructural protein 1 effector domain from influenza A virus.

    PubMed

    Aramini, James M; Hamilton, Keith; Ma, Li-Chung; Swapna, G V T; Leonard, Paul G; Ladbury, John E; Krug, Robert M; Montelione, Gaetano T

    2014-04-01

    Nonstructural protein 1 of influenza A virus (NS1A) is a conserved virulence factor comprised of an N-terminal double-stranded RNA (dsRNA)-binding domain and a multifunctional C-terminal effector domain (ED), each of which can independently form symmetric homodimers. Here we apply (19)F NMR to NS1A from influenza A/Udorn/307/1972 virus (H3N2) labeled with 5-fluorotryptophan, and we demonstrate that the (19)F signal of Trp187 is a sensitive, direct monitor of the ED helix:helix dimer interface. (19)F relaxation dispersion data reveal the presence of conformational dynamics within this functionally important protein:protein interface, whose rate is more than three orders of magnitude faster than the kinetics of ED dimerization. (19)F NMR also affords direct spectroscopic evidence that Trp187, which mediates intermolecular ED:ED interactions required for cooperative dsRNA binding, is solvent exposed in full-length NS1A at concentrations below aggregation. These results have important implications for the diverse roles of this NS1A epitope during influenza virus infection.

  15. The Family of Adoption.

    ERIC Educational Resources Information Center

    Pavao, Joyce Maguire

    This book aims to provide a broad framework within which to think about adoption as a whole system, so that everyone involved will learn to feel some empathy for the other members of the adoption process. The book, written by a family and adoption therapist who was adopted as an infant, describes predictable developmental stages and challenges for…

  16. Taking Adoption Seriously.

    ERIC Educational Resources Information Center

    Pierce, William

    1990-01-01

    Argues that adoption should be included in strategies to help children, teen parents, and other women with difficult pregnancies because adolescents are not equipped to raise children. Discusses the need for longitudinal research on adoption, adoption education in secondary schools, and studying mass media impact on adoption. (FMW)

  17. Conformational implications of asparagine-linked glycosylation.

    PubMed Central

    Imperiali, B; Rickert, K W

    1995-01-01

    The effects of cotranslational protein modification on the process of protein folding are poorly understood. Time-resolved fluorescence energy transfer has been used to assess the impact of glycosylation on the conformational dynamics of flexible oligopeptides. The peptide sequences examined are selected from glycoproteins of known three-dimensional structure. The energy transfer modulation associated with N-linked glycosylation is consistent with the glycopeptides sampling different conformational profiles in water. Results show that glycosylation causes the modified peptides to adopt a different ensemble of conformations, and for some peptides this change may lead to conformations that are more compact and better approximate the conformation of these peptides in the final folded protein. This result further implies that cotranslational glycosylation can trigger the timely formation of structural nucleation elements and thus assist in the complex process of protein folding. PMID:7816856

  18. Questions about Adoption

    MedlinePlus

    ... Español Text Size Email Print Share Questions About Adoption Page Content Article Body What's the best way to handle my child's questions about her adoption? Many parents want to know when is the ...

  19. What's Happening in Adoption?

    ERIC Educational Resources Information Center

    Gallagher, Ursula M.

    1975-01-01

    Reviews current issues in adoption: termination of parental rights, rights of unwed fathers, subsidized adoption, the recent influx of Vietnamese children, black market babies, agency accountability in placing children, the right of the adoptee to know his biological parents. (ED)

  20. Measures for Predictors of Innovation Adoption

    PubMed Central

    Chor, Ka Ho Brian; Wisdom, Jennifer P.; Olin, Su-Chin Serene; Hoagwood, Kimberly E.; Horwitz, Sarah M.

    2014-01-01

    Building on a narrative synthesis of adoption theories by Wisdom et al. (2013), this review identifies 118 measures associated with the 27 adoption predictors in the synthesis. The distribution of measures is uneven across the predictors and predictors vary in modifiability. Multiple dimensions and definitions of predictors further complicate measurement efforts. For state policymakers and researchers, more effective and integrated measurement can advance the adoption of complex innovations such as evidence-based practices. PMID:24740175

  1. Adoption: The Bigger Boxes.

    ERIC Educational Resources Information Center

    Smyer, Michael A.

    1999-01-01

    Identifies two theoretical frameworks for adoption research: stress and coping literature and life-span developmental psychology. Recognizes that placing adoption within these larger study areas encourages differentiated, conditional questions such as when does adoption have which types of impacts for which types of individuals. (DLH)

  2. Structuring and sampling complex conformation space: Weighted ensemble dynamics simulations.

    PubMed

    Gong, Linchen; Zhou, Xin

    2009-08-01

    Based on multiple simulation trajectories, which started from dispersively selected initial conformations, the weighted ensemble dynamics method is designed to robustly and systematically explore the hierarchical structure of complex conformational space through the spectral analysis of the variance-covariance matrix of trajectory-mapped vectors. The nondegenerate ground state of the matrix directly predicts the ergodicity of simulation data. The ground state could be adopted as statistical weights of trajectories to correctly reconstruct the equilibrium properties, even though each trajectory only explores part of the conformational space. Otherwise, the degree of degeneracy simply gives the number of metastable states of the system under the time scale of individual trajectory. Manipulation on the eigenvectors leads to the classification of trajectories into nontransition ones within the states and transition ones between them. The transition states may also be predicted without a priori knowledge of the system. We demonstrate the application of the general method both to the system with a one-dimensional glassy potential and with the one of alanine dipeptide in explicit solvent.

  3. Structuring and sampling complex conformation space: Weighted ensemble dynamics simulations

    NASA Astrophysics Data System (ADS)

    Gong, Linchen; Zhou, Xin

    2009-08-01

    Based on multiple simulation trajectories, which started from dispersively selected initial conformations, the weighted ensemble dynamics method is designed to robustly and systematically explore the hierarchical structure of complex conformational space through the spectral analysis of the variance-covariance matrix of trajectory-mapped vectors. The nondegenerate ground state of the matrix directly predicts the ergodicity of simulation data. The ground state could be adopted as statistical weights of trajectories to correctly reconstruct the equilibrium properties, even though each trajectory only explores part of the conformational space. Otherwise, the degree of degeneracy simply gives the number of metastable states of the system under the time scale of individual trajectory. Manipulation on the eigenvectors leads to the classification of trajectories into nontransition ones within the states and transition ones between them. The transition states may also be predicted without a priori knowledge of the system. We demonstrate the application of the general method both to the system with a one-dimensional glassy potential and with the one of alanine dipeptide in explicit solvent.

  4. The Transracial Adoption Paradox

    PubMed Central

    Lee, Richard M.

    2008-01-01

    The number of transracial adoptions in the United States, particularly international adoptions, is increasing annually. Counseling psychology as a profession, however, is a relatively silent voice in the research on and practice of transracial adoption. This article presents an overview of the history and research on transracial adoption to inform counseling psychologists of the set of racial and ethnic challenges and opportunities that transracial adoptive families face in everyday living. Particular attention is given to emergent theory and research on the cultural socialization process within these families. PMID:18458794

  5. Cell adhesion promoting peptide GVKGDKGNPGWPGAP from the collagen type IV triple helix: Cis/trans proline-induced multiple sup 1 H NMR conformations and evidence for a KG/PG multiple turn repeat motif in the all-trans proline state

    SciTech Connect

    Mayo, K.H.; Parra-Diaz, D. ); McCarthy, J.B.; Chelberg, M. )

    1991-08-20

    Peptide GVKGDKGNPGWPGAPY (called peptide IV-H1), derived from the protein sequence of human collagen type IV, triple-helix domain residues 1263-1277, represents an RGD-independent, cell-specific, adhesion, spreading, and motility promoting domain in type IV collagen. In this study, peptide IV-H1 has been investigated by {sup 1}H NMR (500 MHz) spectroscopy. Cis-trans proline isomerization at each of the three proline residues gives rise to a number of slowly exchanging (500-MHz NMR time scale) conformation states. The presence of more than two sets of resonances for residues sequentially proximal to a proline, e.g., A14-cis-P15 K3, indicates long range conformation interactions and the presence of preferred structure in this short linear peptide. Many resonances belonging to these multiple species have been assigned by using mono-proline-substituted analogues. Conformational (isomer) state-specific 2D {sup 1}H NMR assignments for the combination of cis and trans proline states have been made via analysis of COSY-type, HOHAHA, and NOESY spectra. The NMR data indicate significant {beta}-turn populations centered at K3-G4, K5-G6, P9-G10, and P12-G13, and a C-terminal {gamma}-turn within the A14-P15-Y16 sequence. These NMR data are supported by circular dichroic studies which indicate the presence of 52% {beta}-turn, 10% helix, and 38% random coil structural populations. Since equally spaced KG and PG residues are found on both sides of peptide IV-H1 in the native collagen type IV sequence, this multiple turn repeat motif may continue through a longer segment of the protein.

  6. The Effect of Family Communication Patterns on Adopted Adolescent Adjustment

    PubMed Central

    Rueter, Martha A.

    2008-01-01

    Adoption and family communication both affect adolescent adjustment. We proposed that adoption status and family communication interact such that adopted adolescents in families with certain communication patterns are at greater risk for adjustment problems. We tested this hypothesis using a community-based sample of 384 adoptive and 208 nonadoptive families. Adolescents in these families were, on average, 16 years of age. The results supported our hypothesis. Adopted adolescents were at significantly greater risk for adjustment problems compared to nonadopted adolescents in families that emphasized conformity orientation without conversation orientation and in families that emphasized neither conformity nor conversation orientation. Adolescents in families emphasizing conversation orientation were at lower risk for adjustment problems, regardless of adoption status. PMID:19649145

  7. Conformational readout of RNA by small ligands

    PubMed Central

    Kligun, Efrat; Mandel-Gutfreund, Yael

    2013-01-01

    RNA molecules have highly versatile structures that can fold into myriad conformations, providing many potential pockets for binding small molecules. The increasing number of available RNA structures, in complex with proteins, small ligands and in free form, enables the design of new therapeutically useful RNA-binding ligands. Here we studied RNA ligand complexes from 10 RNA groups extracted from the protein data bank (PDB), including adaptive and non-adaptive complexes. We analyzed the chemical, physical, structural and conformational properties of binding pockets around the ligand. Comparing the properties of ligand-binding pockets to the properties of computed pockets extracted from all available RNA structures and RNA-protein interfaces, revealed that ligand-binding pockets, mainly the adaptive pockets, are characterized by unique properties, specifically enriched in rare conformations of the nucleobase and the sugar pucker. Further, we demonstrate that nucleotides possessing the rare conformations are preferentially involved in direct interactions with the ligand. Overall, based on our comprehensive analysis of RNA-ligand complexes, we suggest that the unique conformations adopted by RNA nucleotides play an important role in RNA recognition by small ligands. We term the recognition of a binding site by a ligand via the unique RNA conformations “RNA conformational readout.” We propose that “conformational readout” is a general way by which RNA binding pockets are recognized and selected from an ensemble of different RNA states. PMID:23618839

  8. Evolutionary Conserved Positions Define Protein Conformational Diversity.

    PubMed

    Saldaño, Tadeo E; Monzon, Alexander M; Parisi, Gustavo; Fernandez-Alberti, Sebastian

    2016-03-01

    Conformational diversity of the native state plays a central role in modulating protein function. The selection paradigm sustains that different ligands shift the conformational equilibrium through their binding to highest-affinity conformers. Intramolecular vibrational dynamics associated to each conformation should guarantee conformational transitions, which due to its importance, could possibly be associated with evolutionary conserved traits. Normal mode analysis, based on a coarse-grained model of the protein, can provide the required information to explore these features. Herein, we present a novel procedure to identify key positions sustaining the conformational diversity associated to ligand binding. The method is applied to an adequate refined dataset of 188 paired protein structures in their bound and unbound forms. Firstly, normal modes most involved in the conformational change are selected according to their corresponding overlap with structural distortions introduced by ligand binding. The subspace defined by these modes is used to analyze the effect of simulated point mutations on preserving the conformational diversity of the protein. We find a negative correlation between the effects of mutations on these normal mode subspaces associated to ligand-binding and position-specific evolutionary conservations obtained from multiple sequence-structure alignments. Positions whose mutations are found to alter the most these subspaces are defined as key positions, that is, dynamically important residues that mediate the ligand-binding conformational change. These positions are shown to be evolutionary conserved, mostly buried aliphatic residues localized in regular structural regions of the protein like β-sheets and α-helix. PMID:27008419

  9. Evolutionary Conserved Positions Define Protein Conformational Diversity

    PubMed Central

    Saldaño, Tadeo E.; Monzon, Alexander M.; Parisi, Gustavo; Fernandez-Alberti, Sebastian

    2016-01-01

    Conformational diversity of the native state plays a central role in modulating protein function. The selection paradigm sustains that different ligands shift the conformational equilibrium through their binding to highest-affinity conformers. Intramolecular vibrational dynamics associated to each conformation should guarantee conformational transitions, which due to its importance, could possibly be associated with evolutionary conserved traits. Normal mode analysis, based on a coarse-grained model of the protein, can provide the required information to explore these features. Herein, we present a novel procedure to identify key positions sustaining the conformational diversity associated to ligand binding. The method is applied to an adequate refined dataset of 188 paired protein structures in their bound and unbound forms. Firstly, normal modes most involved in the conformational change are selected according to their corresponding overlap with structural distortions introduced by ligand binding. The subspace defined by these modes is used to analyze the effect of simulated point mutations on preserving the conformational diversity of the protein. We find a negative correlation between the effects of mutations on these normal mode subspaces associated to ligand-binding and position-specific evolutionary conservations obtained from multiple sequence-structure alignments. Positions whose mutations are found to alter the most these subspaces are defined as key positions, that is, dynamically important residues that mediate the ligand-binding conformational change. These positions are shown to be evolutionary conserved, mostly buried aliphatic residues localized in regular structural regions of the protein like β-sheets and α-helix. PMID:27008419

  10. The claim from adoption.

    PubMed

    Petersen, Thomas Sobirk

    2002-08-01

    In this article several justifications of what I call 'the claim from adoption' are examined. The claim from adoption is that, instead of expending resources on bringing new children into the world using reproductive technology and then caring for these children, we ought to devote these resources to the adoption and care of existing destitute children. Arguments trading on the idea that resources should be directed to adoption instead of assisted reproduction because already existing people can benefit from such a use of resources whereas we cannot benefit individuals by bringing them into existence are rejected. It is then argued that a utilitarian argument proposed by Christian Munthe that supports the claim from adoption in some situations should be rejected because the support it offers does not extend to certain situations in which it seems morally obvious that resources should be expended on adoption rather than assisted reproduction. A version of the Priority View improves upon Munthe's utilitarianism by supporting the claim from adoption in the cases in which Munthe's argument failed. Some allegedly counterintuitive implications of the Priority View are then discussed, and it is concluded that the Priority View is more plausible than utilitarianism. In a concluding section on policy issues it is argued that, even though the claim from adoption can be justified in a variety of situations, it does not follow that, in these situations, governments should direct resources away from assisted reproduction and towards adoption.

  11. Toward Focusing Conformational Ensembles on Bioactive Conformations: A Molecular Mechanics/Quantum Mechanics Study.

    PubMed

    Avgy-David, Hannah H; Senderowitz, Hanoch

    2015-10-26

    The identification of bound conformations, namely, conformations adopted by ligands when binding their target is critical for target-based and ligand-based drug design. Bound conformations could be obtained computationally from unbound conformational ensembles generated by conformational search tools. However, these tools also generate many nonrelevant conformations thus requiring a focusing mechanism. To identify such a mechanism, this work focuses on a comparison of energies and structural properties of bound and unbound conformations for a set of FDA approved drugs whose complexes are available in the PDB. Unbound conformational ensembles were initially obtained with three force fields. These were merged, clustered, and reminimized using the same force fields and four QM methods. Bound conformations of all ligands were represented by their crystal structures or by approximations to these structures. Energy differences were calculated between global minima of the unbound state or the Boltzmann averaged energies of the unbound ensemble and the approximated bound conformations. Ligand conformations which resemble the X-ray conformation (RMSD < 1.0 Å) were obtained in 91%-97% and 96%-98% of the cases using the ensembles generated by the individual force fields and the reminimized ensembles, respectively, yet only in 52%-56% (original ensembles) and 47%-65% (reminimized ensembles) as global energy minima. The energy window within which the different methods identified the bound conformation (approximated by its closest local energy minimum) was found to be at 4-6 kcal/mol with respect to the global minimum and marginally lower with respect to a Boltzmann averaged energy of the unbound ensemble. Better approximations to the bound conformation obtained with a constrained minimization using the crystallographic B-factors or with a newly developed Knee Point Detection (KPD) method gave lower values (2-5 kcal/mol). Overall, QM methods gave lower energy differences than

  12. Single Parent Adoption.

    ERIC Educational Resources Information Center

    Administration for Children, Youth, and Families (DHHS), Washington, DC.

    Presenting two views of the single-parent family, this pamphlet includes an article by two researchers (William Feigelman and Arnold R. Silverman) and a short statement by a single adoptive parent (Amanda Richards). The first paper summarizes earlier research on single-parent adoptions and discusses the results of a nationwide survey of 713…

  13. Associations between Family Communication Patterns, Sibling Closeness, and Adoptive Status

    PubMed Central

    Samek, Diana R.; Rueter, Martha A.

    2011-01-01

    Previous research has demonstrated the protective effect of family and sibling closeness on child adjustment, but fewer studies have investigated how closeness is promoted within families. Guided by Family Communication Patterns Theory, we tested the association between family communication and sibling emotional and behavioral closeness, and whether adoptive status moderated this relationship. Participating families included 616 adoptive and non-adoptive families with two adolescent children. Hypotheses were tested using structural equation modeling. Sibling closeness was highest in families that emphasized both conversation and conformity and lowest in families that emphasized only conversation or neither conversation nor conformity. Emotional and behavioral closeness were differentially associated with adoption status, sibling age, and sibling gender. Few moderating effects of adoption status were found. Post hoc analyses showed moderating effects of sibling gender composition. PMID:21984844

  14. Caspase Allostery and Conformational Selection.

    PubMed

    Clark, A Clay

    2016-06-01

    The role of caspase proteases in regulated processes such as apoptosis and inflammation has been studied for more than two decades, and the activation cascades are known in detail. Apoptotic caspases also are utilized in critical developmental processes, although it is not known how cells maintain the exquisite control over caspase activity in order to retain subthreshold levels required for a particular adaptive response while preventing entry into apoptosis. In addition to active site-directed inhibitors, caspase activity is modulated by post-translational modifications or metal binding to allosteric sites on the enzyme, which stabilize inactive states in the conformational ensemble. This review provides a comprehensive global view of the complex conformational landscape of caspases and mechanisms used to select states in the ensemble. The caspase structural database provides considerable detail on the active and inactive conformations in the ensemble, which provide the cell multiple opportunities to fine tune caspase activity. In contrast, the current database on caspase modifications is largely incomplete and thus provides only a low-resolution picture of global allosteric communications and their effects on the conformational landscape. In recent years, allosteric control has been utilized in the design of small drug compounds or other allosteric effectors to modulate caspase activity.

  15. The Colorado Adoption Project.

    PubMed

    Plomin, R; DeFries, J C

    1983-04-01

    This report provides an overview of the Colorado Adoption Project (CAP), a longitudinal, prospective, multivariate adoption study of behavioral development. Examples of the types of analyses that can be conducted using this design are presented. The examples are based on general cognitive-ability data for adoptive, biological, and control parents; assessments of their home environment; and Bayley Mental Development Index scores for 152 adopted children and 120 matched control children tested at both 1 and 2 years of age. The illustrative analyses include matched control children tested at both 1 and 2 years of age. The illustrative analyses include examination of genetic and environmental sources of variance, identification of environmental influence devoid of genetic bias, assessment of genotype-environment interaction and correlation, and analyses of the etiology of change and continuity in development.

  16. Adoption and Sibling Rivalry

    MedlinePlus

    ... child in your family should understand her own origins, and those of her brothers and sisters. But ... children can seem exaggerated because of their different origins. For instance, i f your adoptive child does ...

  17. Parenting Your Adopted Teenager

    MedlinePlus

    ... https: / / www. childwelfare. gov/ pubs/ f- openadopt/ .) The Internet and the explosion of social media sites (e. ... 4 Howard, J. (2012). Untangling the web: The Internet’s transformative impact on adoption . New York, NY: Evan ...

  18. Travelers' Health: International Adoption

    MedlinePlus

    ... preadoption living standards, varying disease epidemiology in the countries of origin, the presence of previously unidentified medical problems, and ... know the disease risks in the adopted child’s country of origin and the medical and social histories of the ...

  19. Conformational studies of nucleic acids

    SciTech Connect

    Pearlman, D.A.

    1984-11-01

    Techniques are developed for thorough examinations of the conformational energetics of nucleic acids and their constituents. The first one is a method for modeling the furanose sugar ring in nucleic acids. This method allows the coordinates corresponding to any sugar conformation to be generated rapidly and unambiguously from just the phase angle of pseudorotation. Taking advantage of this simplification, we carry out the first calculations to completely explore the conformational spaces available to the eight commonly occurring nucleosides using experimentally consistent furanose geometries and an appropriate classical potential energy force field. Results are in excellent agreement with experiment. We also develop empirically fit multiple correlation functions between the torsion angles of nucleic acids. This reduces the number of conformations which need to be considered in a thorough energetic survey for a nucleic acid. Such surveys are then carried out for two single-stranded nucleic acid tetramers: d(ApApApA) and ApApApA. We create energy contour maps for each of the 21 possible torsion angle pairs in a nucleotide repeating unit. The maps are quite consistent with the experimental distribution of oligonucleotide data and provide rationalizations for several experimentally observed angle-angle correlations. Complete energy minimization is carried out on all local minima found in the surveys. Both the maps and minimizations indicate DNA and RNA to be highly polymorphic. Conformational changes in DNA upon damage by uv radiation are also studied using energy minimization techniques. Finally, we derive a set of partial charges for a nucleotide (2'-deoxycytidine 5'-monophosphate monohydrate) from high resolution x-ray data.

  20. 78 FR 67952 - Approval and Promulgation of Implementation Plans; Mississippi; Transportation Conformity SIP...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-13

    ... adopts a memorandum of agreement (MOA) establishing transportation conformity criteria and procedures... approve MDEQ's May 31, 2013 SIP submission, to adopt a MOA establishing transportation conformity criteria...) with plans developed under section 175A of the Act, for transportation related criteria...

  1. 45 CFR 233.110 - Foster care maintenance and adoption assistance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 2 2013-10-01 2012-10-01 true Foster care maintenance and adoption assistance... maintenance and adoption assistance. (a) State plan requirements. A State plan under title IV-A of the Social... Security Act, and operates a foster care maintenance and adoption assistance program in conformity...

  2. 45 CFR 233.110 - Foster care maintenance and adoption assistance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 2 2012-10-01 2012-10-01 false Foster care maintenance and adoption assistance... maintenance and adoption assistance. (a) State plan requirements. A State plan under title IV-A of the Social... Security Act, and operates a foster care maintenance and adoption assistance program in conformity...

  3. 45 CFR 233.110 - Foster care maintenance and adoption assistance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 2 2014-10-01 2012-10-01 true Foster care maintenance and adoption assistance... maintenance and adoption assistance. (a) State plan requirements. A State plan under title IV-A of the Social... Security Act, and operates a foster care maintenance and adoption assistance program in conformity...

  4. 45 CFR 233.110 - Foster care maintenance and adoption assistance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 2 2011-10-01 2011-10-01 false Foster care maintenance and adoption assistance... maintenance and adoption assistance. (a) State plan requirements. A State plan under title IV-A of the Social... Security Act, and operates a foster care maintenance and adoption assistance program in conformity...

  5. 45 CFR 233.110 - Foster care maintenance and adoption assistance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 2 2010-10-01 2010-10-01 false Foster care maintenance and adoption assistance... maintenance and adoption assistance. (a) State plan requirements. A State plan under title IV-A of the Social... Security Act, and operates a foster care maintenance and adoption assistance program in conformity...

  6. Conformations of Low-Molecular-Weight Lignin Polymers in Water.

    PubMed

    Petridis, Loukas; Smith, Jeremy C

    2016-02-01

    Low-molecular-weight lignin binds to cellulose during the thermochemical pretreatment of biomass for biofuel production, which prevents the efficient hydrolysis of the cellulose to sugars. The binding properties of lignin are influenced strongly by the conformations it adopts. Here, we use molecular dynamics simulations in aqueous solution to investigate the dependence of the shape of lignin polymers on chain length and temperature. Lignin is found to adopt collapsed conformations in water at 300 and 500 K. However, at 300 K, a discontinuous transition is found in the shape of the polymer as a function of the chain length. Below a critical degree of polymerization, Nc =15, the polymer adopts less spherical conformations than above Nc. The transition disappears at high temperatures (500 K) at which only spherical shapes are adopted. An implication relevant to cellulosic biofuel production is that lignin will self-aggregate even at high pretreatment temperatures.

  7. Conformations of low-molecular-weight lignin polymers in water

    DOE PAGES

    Petridis, Loukas; Smith, Jeremy C.

    2016-01-13

    Low-molecular-weight lignin binds to cellulose during the thermochemical pretreatment of biomass for biofuel production, which prevents the efficient hydrolysis of the cellulose to sugars. The binding properties of lignin are influenced strongly by the conformations it adopts. Here, we use molecular dynamics simulations in aqueous solution to investigate the dependence of the shape of lignin polymers on chain length and temperature. Lignin is found to adopt collapsed conformations in water at 300 and 500 K. However, at 300 K, a discontinuous transition is found in the shape of the polymer as a function of the chain length. Below a criticalmore » degree of polymerization, Nc=15, the polymer adopts less spherical conformations than above Nc. The transition disappears at high temperatures (500 K) at which only spherical shapes are adopted. As a result, an implication relevant to cellulosic biofuel production is that lignin will self-aggregate even at high pretreatment temperatures.« less

  8. Adolescents' Feelings about Openness in Adoption: Implications for Adoption Agencies

    ERIC Educational Resources Information Center

    Berge, Jerica M.; Mendenhall, Tai J.; Wrobel, Gretchen M.; Grotevant, Harold D.; McRoy, Ruth G.

    2006-01-01

    Adoption research commonly uses parents' reports of satisfaction when examining openness in adoption arrangements. This qualitative study aimed to fill a gap in the adoption research by using adolescents' voices to gain a better understanding of their adoption experiences. Adopted adolescents (n = 152) were interviewed concerning their…

  9. Solid-state NMR investigation of effect of fluorination and methylation on prednisolone conformation.

    PubMed

    Carillo, Kathleen D; Arco, Susan; Wang, Cheng-Chung; Tzou, Der-Lii M

    2015-12-01

    Prednisolone (Prd) is a polymorphous synthetic corticosteroid that has three crystalline forms mediated by different solvents. In this study, we have demonstrated that solid-state {(1)H}(13)C cross-polarization/magic angle spinning (CP/MAS) NMR spectroscopy is able to resolve the effects of methylation and fluorination on the conformation of the steroidal rings in Prd. Two compounds were chosen for the study, 6-α-methylprednisolone (Prd-6M) and 6-α-fluoroprednisolone (Prd-6F). The (13)C signals of Prd-6F showed primarily doublet patterns, with splittings of 40-380 Hz, indicating multiple ring conformations, whereas the (13)C signals of Prd and Prd-6M exhibited a singlet pattern, indicating a unique conformation. Using evidence from chemical shift deviation and anisotropy analysis, we have demonstrated by solid-state NMR that Prd-6F adopts two different steroidal ring conformations that are different from that of Prd-6M, and less similar to that of unsubstituted Prd.

  10. CONSENSUS AND CONFORMITY.

    ERIC Educational Resources Information Center

    ALLEN, VERNON L.; LEVINE, JOHN M.

    IN THIS STUDY, PROFESSOR ALLEN EMPLOYS TWO METHODS OF BREAKING GROUP CONSENSUS, AND HE MEASURES THE EFFECTS ON THE RESPONSES OF COLLEGE SUBJECTS TO BOTH OBJECTIVE AND SUBJECTIVE STIMULI. THE RESULTS SUGGEST THE NEED FOR MODIFICATION OF EXISTING THEORIES OF CONFORMITY BEHAVIOR. IN ADDITION, THESE RESULTS EMPHASIZE THE DIFFERENCES IN CONFORMITY OF…

  11. Conformational Electroresistance and Hysteresis in Nanoclusters

    SciTech Connect

    Li, Xiangguo; Zhang, Xiaoguang; Cheng, Hai-Ping

    2014-07-02

    Among many mechanisms proposed for electroresistance, ones involving structural changes are the least understood because of challenges of controllability and repeatability. Yet structural changes can cause dramatic changes in electronic properties, leading to multiple ways in which conduction paths can be opened and closed, not limited to filament movement or variation in molecular conductance. Here we show at least another way: conformational dependence of the Coulomb charging energy of a nanocluster, where charging induced conformational distortion changes the blockade voltage, which in turn leads to a giant electroresistance. This intricate interplay between charging and conformation change is demonstrated in a nanocluster Zn3O4 by combining a first-principles calculation with a temperature dependent transport model. The predicted hysteretic Coulomb blockade staircase in the current-voltage curve adds another dimension to the rich phenomenon of tunneling electroresistance. The new mechanism also provides a better controlled and repeatable platform to study conformational electroresistance.

  12. Conformational Electroresistance and Hysteresis in Nanoclusters

    DOE PAGES

    Li, Xiangguo; Zhang, Xiaoguang; Cheng, Hai-Ping

    2014-07-02

    Among many mechanisms proposed for electroresistance, ones involving structural changes are the least understood because of challenges of controllability and repeatability. Yet structural changes can cause dramatic changes in electronic properties, leading to multiple ways in which conduction paths can be opened and closed, not limited to filament movement or variation in molecular conductance. Here we show at least another way: conformational dependence of the Coulomb charging energy of a nanocluster, where charging induced conformational distortion changes the blockade voltage, which in turn leads to a giant electroresistance. This intricate interplay between charging and conformation change is demonstrated in amore » nanocluster Zn3O4 by combining a first-principles calculation with a temperature dependent transport model. The predicted hysteretic Coulomb blockade staircase in the current-voltage curve adds another dimension to the rich phenomenon of tunneling electroresistance. The new mechanism also provides a better controlled and repeatable platform to study conformational electroresistance.« less

  13. The Colorado Adoption Project.

    PubMed

    Rhea, Sally-Ann; Bricker, Josh B; Wadsworth, Sally J; Corley, Robin P

    2013-02-01

    This paper describes the Colorado Adoption Project (CAP), an ongoing genetically informative longitudinal study of behavioral development. We describe the features of the adoption design used in CAP, and discuss how this type of design uses data from both parent-offspring and related- versus unrelated-sibling comparisons to estimate the importance of genetic and shared environmental influences for resemblance among family members. The paper provides an overview of CAP's history, how subjects were ascertained, recruited, and retained, and the domains of assessment that have been explored since the CAP's initiation in 1975. Findings from some representative papers that make use of data from CAP participants illustrate the study's multifaceted nature as a parent-offspring and sibling behavioral genetic study, a study that parallels a complimentary twin study, a longitudinal study of development, a source of subjects for molecular genetic investigation, and a study of the outcomes of the adoption process itself. As subjects assessed first at age 1 approach age 40, we hope the CAP will establish itself as the first prospective adoption study of lifespan development.

  14. The Colorado Adoption Project

    PubMed Central

    Rhea, Sally-Ann; Bricker, Josh B.; Wadsworth, Sally J.; Corley, Robin P.

    2013-01-01

    This paper describes the Colorado Adoption Project (CAP), an ongoing genetically-informative longitudinal study of behavioral development. We describe the features of the adoption design used in CAP, and discuss how this type of design uses data from both parent-offspring and related- versus unrelated- sibling comparisons to estimate the importance of genetic and shared environmental influences for resemblance among family members. The paper provides an overview of CAP’s history, how subjects were ascertained, recruited, and retained, and the domains of assessment that have been explored since the CAP’s initiation in 1975. Findings from some representative papers that make use of data from CAP participants illustrate the study’s multifaceted nature as a parent-offspring and sibling behavioral genetic study, a study that parallels a complimentary twin study, a longitudinal study of development, a source of subjects for molecular genetic investigation, and a study of the outcomes of the adoption process itself. As subjects assessed first at age 1 approach age 40, we hope the CAP will establish itself as the first prospective adoption study of lifespan development. PMID:23158098

  15. CERTS customer adoption model

    SciTech Connect

    Rubio, F. Javier; Siddiqui, Afzal S.; Marnay, Chris; Hamachi,Kristina S.

    2000-03-01

    This effort represents a contribution to the wider distributed energy resources (DER) research of the Consortium for Electric Reliability Technology Solutions (CERTS, http://certs.lbl.gov) that is intended to attack and, hopefully, resolve the technical barriers to DER adoption, particularly those that are unlikely to be of high priority to individual equipment vendors. The longer term goal of the Berkeley Lab effort is to guide the wider technical research towards the key technical problems by forecasting some likely patterns of DER adoption. In sharp contrast to traditional electricity utility planning, this work takes a customer-centric approach and focuses on DER adoption decision making at, what we currently think of as, the customer level. This study reports on Berkeley Lab's second year effort (completed in Federal fiscal year 2000, FY00) of a project aimed to anticipate patterns of customer adoption of distributed energy resources (DER). Marnay, et al., 2000 describes the earlier FY99 Berkeley Lab work. The results presented herein are not intended to represent definitive economic analyses of possible DER projects by any means. The paucity of data available and the importance of excluded factors, such as environmental implications, are simply too important to make such an analysis possible at this time. Rather, the work presented represents a demonstration of the current model and an indicator of the potential to conduct more relevant studies in the future.

  16. Toddler Adoption: The Weaver's Craft.

    ERIC Educational Resources Information Center

    Hopkins-Best, Mary

    Based on concern about the lack of information on adopting toddlers, this book examines the special needs of adopted toddlers and their adoptive parents. Chapter 1, "Why Write a Book on Toddler Adoption?" details the lack of information on the difficulties of adopted toddlers in forming attachments and parents' child rearing difficulties. Chapter…

  17. Pioneers of Asynchronous Online Education at Religion-Based Institutions of Higher Education: A Multiple Case Study Exploring the Process of Adoption of Online Education at Three Private Catholic Colleges

    ERIC Educational Resources Information Center

    Hansen, Alan

    2008-01-01

    This qualitative study examined the process of adopting online education at three private colleges. All three institutions participating in the study were private Catholic colleges that offered their first online courses in the late 1990s. The research question posed for this study was: Within the participating institutions, how did online…

  18. Enhancing Moral Conformity and Enhancing Moral Worth.

    PubMed

    Douglas, Thomas

    2014-01-01

    It is plausible that we have moral reasons to become better at conforming to our moral reasons. However, it is not always clear what means to greater moral conformity we should adopt. John Harris has recently argued that we have reason to adopt traditional, deliberative means in preference to means that alter our affective or conative states directly-that is, without engaging our deliberative faculties. One of Harris' concerns about direct means is that they would produce only a superficial kind of moral improvement. Though they might increase our moral conformity, there is some deeper kind of moral improvement that they would fail to produce, or would produce to a lesser degree than more traditional means. I consider whether this concern might be justified by appeal to the concept of moral worth. I assess three attempts to show that, even where they were equally effective at increasing one's moral conformity, direct interventions would be less conducive to moral worth than typical deliberative alternatives. Each of these attempts is inspired by Kant's views on moral worth. Each, I argue, fails.

  19. Comprehensive objective maps of macromolecular conformations by quantitative SAXS analysis

    PubMed Central

    Hura, Greg L.; Budworth, Helen; Dyer, Kevin N.; Rambo, Robert P.; Hammel, Michal

    2013-01-01

    Comprehensive perspectives of macromolecular conformations are required to connect structure to biology. Here we present a small angle X-ray scattering (SAXS) Structural Similarity Map (SSM) and Volatility of Ratio (VR) metric providing comprehensive, quantitative and objective (superposition-independent) perspectives on solution state conformations. We validate VR and SSM utility on human MutSβ, a key ABC ATPase and chemotherapeutic target, by revealing MutSβ DNA sculpting and identifying multiple conformational states for biological activity. PMID:23624664

  20. The Biological Bases of Conformity

    PubMed Central

    Morgan, T. J. H.; Laland, K. N.

    2012-01-01

    Humans are characterized by an extreme dependence on culturally transmitted information and recent formal theory predicts that natural selection should favor adaptive learning strategies that facilitate effective copying and decision making. One strategy that has attracted particular attention is conformist transmission, defined as the disproportionately likely adoption of the most common variant. Conformity has historically been emphasized as significant in the social psychology literature, and recently there have also been reports of conformist behavior in non-human animals. However, mathematical analyses differ in how important and widespread they expect conformity to be, and relevant experimental work is scarce, and generates findings that are both mutually contradictory and inconsistent with the predictions of the models. We review the relevant literature considering the causation, function, history, and ontogeny of conformity, and describe a computer-based experiment on human subjects that we carried out in order to resolve ambiguities. We found that only when many demonstrators were available and subjects were uncertain was subject behavior conformist. A further analysis found that the underlying response to social information alone was generally conformist. Thus, our data are consistent with a conformist use of social information, but as subjects’ behavior is the result of both social and asocial influences, the resultant behavior may not be conformist. We end by relating these findings to an embryonic cognitive neuroscience literature that has recently begun to explore the neural bases of social learning. Here conformist transmission may be a particularly useful case study, not only because there are well-defined and tractable opportunities to characterize the biological underpinnings of this form of social learning, but also because early findings imply that humans may possess specific cognitive adaptations for effective social learning. PMID:22712006

  1. Open Adoption: Adoptive Parents' Reactions Two Decades Later

    ERIC Educational Resources Information Center

    Siegel, Deborah H.

    2013-01-01

    Unlike in the past, most adoption agencies today offer birth parents and adoptive parents the opportunity to share identifying information and have contact with each other. To understand the impacts of different open adoption arrangements, a qualitative descriptive study using a snowball sample of 44 adoptive parents throughout New England began…

  2. Hospitious Adoption: How Hospitality Empowers Children and Transforms Adoption

    ERIC Educational Resources Information Center

    Gritter, James L.

    2009-01-01

    Building on previous books by the author, "Hospitious Adoption: How Hospitality Empowers Children and Transforms Adoption" examines the next step after open adoption. Gritter takes the approach that practicing goodwill, respect, and courage within the realm of adoption makes the process move smoother and enriches children's lives. Following a…

  3. Assemblies of Conformal Tanks

    NASA Technical Reports Server (NTRS)

    DeLay, Tom

    2009-01-01

    Assemblies of tanks having shapes that conform to each other and/or conform to other proximate objects have been investigated for use in storing fuels and oxidizers in small available spaces in upper stages of spacecraft. Such assemblies might also prove useful in aircraft, automobiles, boats, and other terrestrial vehicles in which space available for tanks is limited. The basic concept of using conformal tanks to maximize the utilization of limited space is not new in itself: for example, conformal tanks are used in some automobiles to store windshield -washer liquid and coolant that overflows from radiators. The novelty of the present development lies in the concept of an assembly of smaller conformal tanks, as distinguished from a single larger conformal tank. In an assembly of smaller tanks, it would be possible to store different liquids in different tanks. Even if the same liquid were stored in all the tanks, the assembly would offer an advantage by reducing the mechanical disturbance caused by sloshing of fuel in a single larger tank: indeed, the requirement to reduce sloshing is critical in some applications. The figure shows a prototype assembly of conformal tanks. Each tank was fabricated by (1) copper plating a wax tank mandrel to form a liner and (2) wrapping and curing layers of graphite/epoxy composite to form a shell supporting the liner. In this case, the conformal tank surfaces are flat ones where they come in contact with the adjacent tanks. A band of fibers around the outside binds the tanks together tightly in the assembly, which has a quasi-toroidal shape. For proper functioning, it would be necessary to maintain equal pressure in all the tanks.

  4. Adoption Research: Trends, Topics, Outcomes

    ERIC Educational Resources Information Center

    Palacios, Jesus; Brodzinsky, David

    2010-01-01

    The current article provides a review of adoption research since its inception as a field of study. Three historical trends in adoption research are identified: the first focusing on risk in adoption and identifying adoptee-nonadoptee differences in adjustment; the second examining the capacity of adopted children to recover from early adversity;…

  5. Ethnic and adoption attitudes among Guatemalan University students.

    PubMed

    Gibbons, Judith L; González-Oliva, Ana Gabriela; Mylonas, Kostas

    2015-01-01

    Intercountry adoptions from Guatemala were highly controversial, because of the large numbers of children being adopted to the USA, along with evidence of corruption and child theft. Since the implementation of the Hague Convention on Intercountry Adoption in 2008, Guatemala's central authority for adoption has prioritized domestic placements for children over intercountry adoption. A possible attitudinal barrier to domestic adoption in Guatemala-negative attitudes and prejudice against Indigenous people-was investigated through questionnaires measuring attitudes toward adoption and attitudes toward and social distance from the two major ethnic groups (Ladino and Indigenous). Guatemalan university students (N = 177, 61 % men) were recruited from basic required courses at a private university. Results showed that attitudes toward adoption in general were more favorable than toward interethnic adoption, with the most negative attitudes toward adoption of Ladino children by Indigenous parents. Multiple regression and analysis of covariance models revealed that female gender, experience with adoption and more positive attitudes about Indigenous persons were associated with more positive attitudes toward adoption. The findings imply that negative attitudes toward Indigenous persons are associated with negative attitudes toward adoption, and serve as barriers to promoting domestic adoption in Guatemala. PMID:26702374

  6. Ethnic and adoption attitudes among Guatemalan University students.

    PubMed

    Gibbons, Judith L; González-Oliva, Ana Gabriela; Mylonas, Kostas

    2015-01-01

    Intercountry adoptions from Guatemala were highly controversial, because of the large numbers of children being adopted to the USA, along with evidence of corruption and child theft. Since the implementation of the Hague Convention on Intercountry Adoption in 2008, Guatemala's central authority for adoption has prioritized domestic placements for children over intercountry adoption. A possible attitudinal barrier to domestic adoption in Guatemala-negative attitudes and prejudice against Indigenous people-was investigated through questionnaires measuring attitudes toward adoption and attitudes toward and social distance from the two major ethnic groups (Ladino and Indigenous). Guatemalan university students (N = 177, 61 % men) were recruited from basic required courses at a private university. Results showed that attitudes toward adoption in general were more favorable than toward interethnic adoption, with the most negative attitudes toward adoption of Ladino children by Indigenous parents. Multiple regression and analysis of covariance models revealed that female gender, experience with adoption and more positive attitudes about Indigenous persons were associated with more positive attitudes toward adoption. The findings imply that negative attitudes toward Indigenous persons are associated with negative attitudes toward adoption, and serve as barriers to promoting domestic adoption in Guatemala.

  7. An SIS model for cultural trait transmission with conformity bias.

    PubMed

    Walters, Caroline E; Kendal, Jeremy R

    2013-12-01

    Epidemiological models have been applied to human health-related behaviors that are affected by social interaction. Typically these models have not considered conformity bias, that is, the exaggerated propensity to adopt commonly observed behaviors or opinions, or content biases, where the content of the learned trait affects the probability of adoption. Here we consider an interaction of these two effects, presenting an SIS-type model for the spread and persistence of a behavior which is transmitted via social learning. Uptake is controlled by a nonlinear dependence on the proportion of individuals demonstrating the behavior in a population. Three equilibrium solutions are found, their linear stability is analyzed and the results are compared with a model for unbiased social learning. Our analysis focuses on the effects of the strength of conformity bias and the effects of content biases which alter a conformity threshold frequency of the behavior, above which there is an exaggerated propensity for adoption. The strength of the conformity bias is found to qualitatively alter the predictions regarding whether the trait becomes endemic within the population and the proportion of individuals who display the trait when it is endemic. As the conformity strength increases, the number of feasible equilibrium solutions increases from two to three, leading to a situation where the stable equilibrium attained is dependent upon the initial state. Varying the conformity threshold frequency directionally alters the behavior invasion threshold. Finally we discuss the possible application of this model to binge drinking behavior.

  8. Superoxide dismutase 1 encoding mutations linked to ALS adopts a spectrum of misfolded states

    PubMed Central

    2011-01-01

    view that mutant SOD1 can adopt multiple misfolded conformations with the potential that different structural variants mediate different aspects of fALS. PMID:22094223

  9. Designing Molecular Dynamics Simulations to Shift Populations of the Conformational States of Calmodulin

    PubMed Central

    Aykut, Ayse Ozlem; Atilgan, Ali Rana; Atilgan, Canan

    2013-01-01

    We elucidate the mechanisms that lead to population shifts in the conformational states of calcium-loaded calmodulin (Ca2+-CaM). We design extensive molecular dynamics simulations to classify the effects that are responsible for adopting occupied conformations available in the ensemble of NMR structures. Electrostatic interactions amongst the different regions of the protein and with its vicinal water are herein mediated by lowering the ionic strength or the pH. Amino acid E31, which is one of the few charged residues whose ionization state is highly sensitive to pH differences in the physiological range, proves to be distinctive in its control of population shifts. E31A mutation at low ionic strength results in a distinct change from an extended to a compact Ca2+-CaM conformation within tens of nanoseconds, that otherwise occur on the time scales of microseconds. The kinked linker found in this particular compact form is observed in many of the target-bound forms of Ca2+-CaM, increasing the binding affinity. This mutation is unique in controlling C-lobe dynamics by affecting the fluctuations between the EF-hand motif helices. We also monitor the effect of the ionic strength on the conformational multiplicity of Ca2+-CaM. By lowering the ionic strength, the tendency of nonspecific anions in water to accumulate near the protein surface increases, especially in the vicinity of the linker. The change in the distribution of ions in the vicinal layer of water allows N- and C- lobes to span a wide variety of relative orientations that are otherwise not observed at physiological ionic strength. E31 protonation restores the conformations associated with physiological environmental conditions even at low ionic strength. PMID:24339763

  10. Becoming Lesbian Adoptive Parents: An Exploratory Study of Lesbian Adoptive, Lesbian Birth, and Heterosexual Adoptive Parents.

    ERIC Educational Resources Information Center

    Shelley-Sireci, Lynn M.; Ciano-Boyce, Claudia

    2002-01-01

    Surveyed lesbian adoptive parents, heterosexual adoptive parents, and lesbian parents who had used assisted fertilization, regarding the adoption process. Found that the process was similar for both heterosexual and lesbian parents, but lesbian adoptive parents perceived more discrimination and were more inclined to omit information during the…

  11. Special topics in international adoption.

    PubMed

    Jenista, Jerri Ann

    2005-10-01

    As international adoption has become more "mainstream," the issues recently addressed in domestic adoption have become more important in adoptions involving children originating in other countries. Certain groups of prospective adoptive parents, such as gay or lesbian couples, single parents, and parents with disabilities, have begun to apply to adopt in ever increasing numbers. Children who may have been considered unadoptable in the past are now routinely being offered to prospective adoptive parents. The numbers and ages of the children placed and the spacing between adoptions have come under scrutiny. The rates of adoption dissolutions and disruptions are being examined carefully by the receiving and sending countries. There is a pressing need for research into numerous social aspects of adoption.

  12. Charged conformal Killing spinors

    SciTech Connect

    Lischewski, Andree

    2015-01-15

    We study the twistor equation on pseudo-Riemannian Spin{sup c}-manifolds whose solutions we call charged conformal Killing spinors (CCKSs). We derive several integrability conditions for the existence of CCKS and study their relations to spinor bilinears. A construction principle for Lorentzian manifolds admitting CCKS with nontrivial charge starting from CR-geometry is presented. We obtain a partial classification result in the Lorentzian case under the additional assumption that the associated Dirac current is normal conformal and complete the classification of manifolds admitting CCKS in all dimensions and signatures ≤5 which has recently been initiated in the study of supersymmetric field theories on curved space.

  13. 13C-13C and 15N-13C correlation spectroscopy of membrane-associated and uniformly labeled human immunodeficiency virus and influenza fusion peptides: Amino acid-type assignments and evidence for multiple conformations

    NASA Astrophysics Data System (ADS)

    Bodner, Michele L.; Gabrys, Charles M.; Struppe, Jochem O.; Weliky, David P.

    2008-02-01

    Many viruses which cause disease including human immunodeficiency virus (HIV) and influenza are "enveloped" by a membrane and infection of a host cell begins with joining or "fusion" of the viral and target cell membranes. Fusion is catalyzed by viral proteins in the viral membrane. For HIV and for the influenza virus, these fusion proteins contain an ˜20-residue apolar "fusion peptide" that binds to target cell membranes and plays a critical role in fusion. For this study, the HIV fusion peptide (HFP) and influenza virus fusion peptide (IFP) were chemically synthesized with uniform C13, N15 labeling over large contiguous regions of amino acids. Two-dimensional C13-C13 and N15-C13 spectra were obtained for the membrane-bound fusion peptides and an amino acid-type C13 assignment was obtained for the labeled residues in HFP and IFP. The membrane used for the HFP sample had a lipid headgroup and cholesterol composition comparable to that of host cells of the virus, and the C13 chemical shifts were more consistent with β strand conformation than with helical conformation. The membrane used for the IFP sample did not contain cholesterol, and the chemical shifts of the dominant peaks were more consistent with helical conformation than with β strand conformation. There were additional peaks in the IFP spectrum whose shifts were not consistent with helical conformation. An unambiguous C13 and N15 assignment was obtained in an HFP sample with more selective labeling, and two shifts were identified for the Leu-9 CO, Gly-10 N, and Gly-10 Cα nuclei. These sets of two shifts may indicate two β strand registries such as parallel and antiparallel. Although most spectra were obtained on a 9.4T instrument, one C13-C13 correlation spectrum was obtained on a 16.4T instrument and was better resolved than the comparable 9.4T spectrum. More selective labeling and higher field may, therefore, be approaches to obtaining unambiguous assignments for membrane-associated fusion peptides.

  14. Essential role of conformational selection in ligand binding

    PubMed Central

    Vogt, Austin D.; Pozzi, Nicola; Chen, Zhiwei; Di Cera, Enrico

    2013-01-01

    Two competing and mutually exclusive mechanisms of ligand recognition – conformational selection and induced fit - have dominated our interpretation of ligand binding in biological macromolecules for almost six decades. Conformational selection posits the pre-existence of multiple conformations of the macromolecule from which the ligand selects the optimal one. Induced fit, on the other hand, postulates the existence of conformational rearrangements of the original conformation into an optimal one that is induced by binding of the ligand. In the former case, conformational transitions precede the binding event; in the latter, conformational changes follow the binding step. Kineticists have used a facile criterion to distinguish between the two mechanisms based on the dependence of the rate of relaxation to equilibrium, kobs, on the ligand concentration, [L]. A value of kobs decreasing hyperbolically with [L] is seen as diagnostic of conformational selection, while a value of kobs increasing hyperbolically with [L] is considered diagnostic of induced fit. However, this simple conclusion is only valid in the rather unrealistic assumption of conformational transitions being much slower than binding and dissociation events. In general, induced fit only produces values of kobs that increase with [L] but conformational selection is more versatile and is associated with values of kobs that increase, decrease with or are independent of [L]. The richer repertoire of kinetic properties of conformational selection applies to kinetic mechanisms with single or multiple saturable relaxations and explains the behavior of nearly all experimental systems reported in the literature thus far. Conformational selection is always sufficient and often necessary to account for the relaxation kinetics of ligand binding to a biological macromolecule and is therefore an essential component of any binding mechanism. On the other hand, induced fit is never necessary and only sufficient in a

  15. Parents' Feelings towards Their Adoptive and Non-Adoptive Children

    ERIC Educational Resources Information Center

    Glover, Marshaun B.; Mullineaux, Paula Y.; Deater-Deckard, Kirby; Petrill, Stephen A.

    2010-01-01

    In the current study, we examined parent gender differences in feelings (negativity and positivity) and perceptions of child behavioural and emotional problems in adoptive and biological parent-child dyads. In a sample of 85 families, we used a novel within-family adoption design in which one child was adopted and one child was a biological child…

  16. Open adoption: adoptive parents' reactions two decades later.

    PubMed

    Siegel, Deborah H

    2013-01-01

    Unlike in the past, most adoption agencies today offer birth parents and adoptive parents the opportunity to share identifying information and have contact with each other. To understand the impacts of different open adoption arrangements, a qualitative descriptive study using a snowball sample of 44 adoptive parents throughout New England began in 1988. Every seven years these parents who adopted infants in open adoptions have participated in tape-recorded interviews to explore their evolving reactions to their open adoption experiences. This article reports the results of in-depth interviews with these parents now that their children have reached young adulthood. This longitudinal research illuminates how open adoptions change over the course of childhood and adolescence, parents' feelings about open adoption, challenges that emerge in their relationships with their children's birth families, how those challenges are managed and viewed, and parents' advice for others living with open adoption and for clinical social work practice and policy. Findings reveal that regardless of the type of openness, these adoptive parents generally feel positive about knowing the birth parents and having contact with them, are comfortable with open adoption, and see it serving the child's best interests.

  17. Who Is Adopted? Measuring Adoption Status Using National Survey Data.

    ERIC Educational Resources Information Center

    Miller, Brent C.; Bayley, Bruce K.; Christensen, Mathew; Fan, Xitao; Coyl, Diana; Grotevant, Harold D.; van Dulmen, Manfred; Dunbar, Nora

    2001-01-01

    Draws on data from the National Longitudinal Survey of Adolescent Health to illustrate the complexities of using large-scale surveys to measure adoption status. Discusses conceptual and methodological issues in measuring adoption status. Presents decision rules for determining adoption status across three sources of data: school self-administered…

  18. Conformations of flanking bases in HIV-1 RNA DIS kissing complexes studied by molecular dynamics.

    PubMed

    Réblová, Kamila; Fadrná, Eva; Sarzynska, Joanna; Kulinski, Tadeusz; Kulhánek, Petr; Ennifar, Eric; Koca, Jaroslav; Sponer, Jirí

    2007-12-01

    Explicit solvent molecular dynamics simulations (in total almost 800 ns including locally enhanced sampling runs) were applied with different ion conditions and with two force fields (AMBER and CHARMM) to characterize typical geometries adopted by the flanking bases in the RNA kissing-loop complexes. We focus on flanking base positions in multiple x-ray and NMR structures of HIV-1 DIS kissing complexes and kissing complex from the large ribosomal subunit of Haloarcula marismortui. An initial x-ray open conformation of bulged-out bases in HIV-1 DIS complexes, affected by crystal packing, tends to convert to a closed conformation formed by consecutive stretch of four stacked purine bases. This is in agreement with those recent crystals where the packing is essentially avoided. We also observed variants of the closed conformation with three stacked bases, while nonnegligible populations of stacked geometries with bulged-in bases were detected, too. The simulation results reconcile differences in positions of the flanking bases observed in x-ray and NMR studies. Our results suggest that bulged-out geometries are somewhat more preferred, which is in accord with recent experiments showing that they may mediate tertiary contacts in biomolecular assemblies or allow binding of aminoglycoside antibiotics.

  19. Arcjet Testing of Advanced Conformal Ablative TPS

    NASA Technical Reports Server (NTRS)

    Gasch, Matthew; Beck, Robin; Agrawal, Parul

    2014-01-01

    A conformable TPS over a rigid aeroshell has the potential to solve a number of challenges faced by traditional rigid TPS materials (such as tiled Phenolic Impregnated Carbon Ablator (PICA) system on MSL. The compliant (high strain to failure) nature of the conformable ablative materials will allow integration of the TPS with the underlying aeroshell structure much easier and enable monolithic-like configuration and larger segments (or parts) to be used. In May of 2013 the CA250 project executed an arcjet test series in the Ames IHF facility to evaluate a phenolic-based conformal system (named Conformal-PICA) over a range of test conditions from 40-400Wcm2. The test series consisted of four runs in the 13-inch diameter nozzle. Test models were based on SPRITE configuration (a 55-deg sphere cone), as it was able to provide a combination of required heat flux, pressure and shear within a single entry. The preliminary in-depth TC data acquired during that test series allowed a mid-fidelity thermal response model for conformal-PICA to be created while testing of seam models began to address TPS attachment and joining of multiple segments for future fabrication of large-scale aeroshells. Discussed in this paper are the results.

  20. Resonance energy-transfer studies of the conformational change on the adsorption of oligonucleotides to a silica interface.

    PubMed

    Scholes, Colin A; Millar, David P; Gee, Michelle L; Smith, Trevor A

    2011-05-19

    Time-resolved evanescent wave-induced fluorescence studies have been carried out on a series of fluorescently labeled oligonucleotide sequences adsorbed to a silica surface from solution. The fluorescence decay profiles of a fluorescent energy donor group undergoing resonance energy transfer to a nonemissive energy-acceptor molecule have been analyzed in terms of a distribution of donor-acceptor distances to reveal the conformational changes that occur in these oligonucleotides upon adsorption. Evanescent wave-induced time-resolved Förster resonance energy-transfer (EW-TRFRET) measurements indicate that at a high electrolyte concentration, there is localized separation of the oligonucleotide strands, and the helical structure adopts an "unraveled" conformation as a result of adsorption. This is attributed to the flexibility within the oligonucleotide at high electrolyte concentration allowing multiple segments of the oligonucleotide to have direct surface interaction. In contrast, the EW-TRFRET measurements at a lower electrolyte concentration reveal that the oligonucleotide retains its helical conformation in a localized extended state. This behavior implies that the rigidity of the oligonucleotide at this electrolyte concentration restricts direct interaction with the silica to a few segments, which correspondingly introduces kinks in the double helix conformation and results in significant oligonucleotide segmental extension into solution.

  1. Extended conformal field theories

    NASA Astrophysics Data System (ADS)

    Taormina, Anne

    1990-08-01

    Some extended conformal field theories are briefly reviewed. They illustrate how non minimal models of the Virasoro algebra (c≥1) can become minimal with respect to a larger algebra. The accent is put on N-extended superconformal algebras, which are relevant in superstring compactification.

  2. The Texas Adoption Project: adopted children and their intellectual resemblance to biological and adoptive parents.

    PubMed

    Horn, J M

    1983-04-01

    Intelligence test scores were obtained from parents and children in 300 adoptive families and compared with similar measures available for the biological mothers of the same adopted children. Results supported the hypothesis that genetic variability is an important influence in the development of individual differences for intelligence. The most salient finding was that adopted children resemble their biological mothers more than they resemble the adoptive parents who reared them from birth. A small subset of the oldest adopted children did not resemble their biological mothers. The suggestion that the influence of genes declines with age is treated with caution since other adoption studies report a trend in the opposite direction.

  3. Conformational changes in biopolymers

    NASA Astrophysics Data System (ADS)

    Ivanov, Vassili

    2005-12-01

    Biopolymer conformational changes are involved in many biological processes. This thesis summarizes some theoretical and experimental approaches which I have taken at UCLA to explore conformational changes in biopolymers. The reversible thermal denaturation of the DNA double helix is, perhaps, the simplest example of biopolymer conformational change. I have developed a statistical mechanics model of DNA melting with reduced degrees of freedom, which allows base stacking interaction to be taken into account and treat base pairing and stacking separately. Unlike previous models, this model describes both the unpairing and unstacking parts of the experimental melting curves and explains the observed temperature dependence of the effective thermodynamic parameters used in models of the nearest neighbor type. I developed a basic kinetic model for irreversible thermal denaturation of F-actin, which incorporates depolymerization of F-actin from the ends and breaking of F-actin fiber in the middle. The model explains the cooperativity of F-actin thermal denaturation observed by D. Pavlov et al. in differential calorimetry measurements. CG-rich DNA sequences form left-handed Z-DNA at high ionic strength or upon binding of polyvalent ions and some proteins. I studied experimentally the B-to-Z transition of the (CG)6 dodecamer. Improvement of the locally linearized model used to interpret the data gives evidence for an intermediate state in the B-to-Z transition of DNA, contrary to previous research on this subject. In the past 15 years it has become possible to study the conformational changes of biomolecules using single-molecule techniques. In collaboration with other lab members I performed a single-molecule experiment, where we monitored the displacement of a micrometer-size bead tethered to a surface by a DNA probe undergoing the conformational change. This technique allows probing of conformational changes with subnanometer accuracy. We applied the method to detect

  4. Quantifying polypeptide conformational space: sensitivity to conformation and ensemble definition.

    PubMed

    Sullivan, David C; Lim, Carmay

    2006-08-24

    Quantifying the density of conformations over phase space (the conformational distribution) is needed to model important macromolecular processes such as protein folding. In this work, we quantify the conformational distribution for a simple polypeptide (N-mer polyalanine) using the cumulative distribution function (CDF), which gives the probability that two randomly selected conformations are separated by less than a "conformational" distance and whose inverse gives conformation counts as a function of conformational radius. An important finding is that the conformation counts obtained by the CDF inverse depend critically on the assignment of a conformation's distance span and the ensemble (e.g., unfolded state model): varying ensemble and conformation definition (1 --> 2 A) varies the CDF-based conformation counts for Ala(50) from 10(11) to 10(69). In particular, relatively short molecular dynamics (MD) relaxation of Ala(50)'s random-walk ensemble reduces the number of conformers from 10(55) to 10(14) (using a 1 A root-mean-square-deviation radius conformation definition) pointing to potential disconnections in comparing the results from simplified models of unfolded proteins with those from all-atom MD simulations. Explicit waters are found to roughen the landscape considerably. Under some common conformation definitions, the results herein provide (i) an upper limit to the number of accessible conformations that compose unfolded states of proteins, (ii) the optimal clustering radius/conformation radius for counting conformations for a given energy and solvent model, (iii) a means of comparing various studies, and (iv) an assessment of the applicability of random search in protein folding.

  5. Adoptive cellular therapy.

    PubMed

    Grupp, Stephan A; June, Carl H

    2011-01-01

    Cell-based therapies with various lymphocytes and antigen-presenting cells are promising approaches for cancer immunotherapy. The transfusion of T lymphocytes, also called adoptive cell therapy (ACT), is an effective treatment for viral infections, has induced regression of cancer in early stage clinical trials, and may be a particularly important and efficacious modality in the period following hematopoietic stem cell transplantation (HSCT). Immune reconstitution post-SCT is often slow and incomplete, which in turn leads to an increased risk of infection and may impact relapse risk in patients with malignant disease. Immunization post-HSCT is frequently unsuccessful, due to the prolonged lymphopenia, especially of CD4 T cells, seen following transplant. ACT has the potential to enhance antitumor and overall immunity, and augment vaccine efficacy in the post-transplant setting. The ability to genetically engineer lymphocyte subsets has the further potential to improve the natural immune response, correct impaired immunity, and redirect T cells to an antitumor effector response. This chapter focuses on various applications of ACT for cancer immunotherapy, and we discuss some of the latest progress and hurdles in translating these technologies to the clinic.

  6. Adoption Resource Directory: Region X.

    ERIC Educational Resources Information Center

    1983

    State, regional, and national adoption resources are described in this directory for residents of Region X states (Alaska, Idaho, Oregon, and Washington). Emphasizing the adoption of children with special needs, the directory gives organizational contacts for parents in various stages of the adoption process and mentions resources for social…

  7. Recruiting Mexican American Adoptive Parents.

    ERIC Educational Resources Information Center

    Bausch, Robert S.; Serpe, Richard T.

    1999-01-01

    Interviews were conducted with 591 Mexican Americans to determine adoption interest and create recruiting practices for prospective parents. Approximately one-third of sample reported an interest in adoption, but many perceived both structural and cultural obstacles to adoption. Based on findings, recommendations for increasing recruitment of…

  8. The Nature and Determinants of Intranet Discontinuance after Mandatory Adoption

    ERIC Educational Resources Information Center

    Cho, Inho

    2008-01-01

    This research examines post-adoption behavior (discontinuance versus continuance) with the context of Intranet use. Multiple theories are used as theoretical frameworks to extend information communication technology research to the case of post-adoption behavior. Three research questions and six sets of hypotheses are formulated to distinguish…

  9. Relating conformation to function in integrin α5β1.

    PubMed

    Su, Yang; Xia, Wei; Li, Jing; Walz, Thomas; Humphries, Martin J; Vestweber, Dietmar; Cabañas, Carlos; Lu, Chafen; Springer, Timothy A

    2016-07-01

    Whether β1 integrin ectodomains visit conformational states similarly to β2 and β3 integrins has not been characterized. Furthermore, despite a wealth of activating and inhibitory antibodies to β1 integrins, the conformational states that these antibodies stabilize, and the relation of these conformations to function, remain incompletely characterized. Using negative-stain electron microscopy, we show that the integrin α5β1 ectodomain adopts extended-closed and extended-open conformations as well as a bent conformation. Antibodies SNAKA51, 8E3, N29, and 9EG7 bind to different domains in the α5 or β1 legs, activate, and stabilize extended ectodomain conformations. Antibodies 12G10 and HUTS-4 bind to the β1 βI domain and hybrid domains, respectively, activate, and stabilize the open headpiece conformation. Antibody TS2/16 binds a similar epitope as 12G10, activates, and appears to stabilize an open βI domain conformation without requiring extension or hybrid domain swing-out. mAb13 and SG/19 bind to the βI domain and βI-hybrid domain interface, respectively, inhibit, and stabilize the closed conformation of the headpiece. The effects of the antibodies on cell adhesion to fibronectin substrates suggest that the extended-open conformation of α5β1 is adhesive and that the extended-closed and bent-closed conformations are nonadhesive. The functional effects and binding sites of antibodies and fibronectin were consistent with their ability in binding to α5β1 on cell surfaces to cross-enhance or inhibit one another by competitive or noncompetitive (allosteric) mechanisms.

  10. Intellectual resemblance among adoptive adoptive and biological relatives: the Texas adoption project.

    PubMed

    Horn, J M; Loehlin, J C; Willerman, L

    1979-05-01

    Intellectual and personality measures were available from unwed mothers who gave their children up for adoption at birth. The same or similar measures have been obtained from 300 sets of adoptive parents and all of their adopted and natural children in the Texas Adoption Project. The sample characteristics are discussed in detail, and the basic findings for IQ are presented. Initial analyses of the data on IQ suggest moderate heritabilities. Emphasis is placed on the preliminary nature of these findings.

  11. Technology Adoption: an Interaction Perspective

    NASA Astrophysics Data System (ADS)

    Sitorus, Hotna M.; Govindaraju, Rajesri; Wiratmadja, I. I.; Sudirman, Iman

    2016-02-01

    The success of a new technology depends on how well it is accepted by its intended users. Many technologies face the problem of low adoption rate, despite the benefits. An understanding of what makes people accept or reject a new technology can help speed up the adoption rate. This paper presents a framework for technology adoption based on an interactive perspective, resulting from a literature study on technology adoption. In studying technology adoption, it is necessary to consider the interactions among elements involved in the system, for these interactions may generate new characteristics or new relationships. The interactions among elements in a system adoption have not received sufficient consideration in previous studies of technology adoption. Based on the proposed interaction perspective, technology adoption is elaborated by examining interactions among the individual (i.e. the user or prospective user), the technology, the task and the environment. The framework is formulated by adopting several theories, including Perceived Characteristics of Innovating, Diffusion of Innovation Theory, Technology Acceptance Model, Task-Technology Fit and usability theory. The proposed framework is illustrated in the context of mobile banking adoption. It is aimed to offer a better understanding of determinants of technology adoption in various contexts, including technology in manufacturing systems.

  12. Adoption: medical and legal aspects.

    PubMed

    Bhalla, C K

    1978-06-01

    The problem of abandoned children is of great magnitude in India. Placement of these children in a family environment is essential for their physical, mental, and emotional development. Adoption must be approached from the child welfare perspective. The pediatrician can play an important role in the adoption process. The pediatrician should perform a thorough medical examination of infants to be adopted, both to ensure the child's welfare and to give adoptive parents an assessment of the child's health. Information should be collected on the medical history of the child's biologic parents to aid in the evaluation process. Adoptive parents should also undergo medical and pyschological examinations. Pediatricians can additionally work with social welfare departments in establishing criteria for matching children with adoptive parents. Adoptions in India are currently governed by provisions or the 1956 Hindu Adoptions and Maintenance Act. Since this legislation excludes groups such as Muslims, Christians, and Parsis from its purview, there has been a demand for national legislation providing a uniform adoption law for all the communities in India. The Union Government introduced such a comprehensive bill in 1972, the Adoption of Children Bill; however, no action was ever taken. It is urged that this legislation be reactivated, and that the restriction on the removal of children for adoption outside India be lifted. PMID:721273

  13. Sealing apparatus utilizing a conformable member

    DOEpatents

    Neef, William S.; Lambert, Donald R.

    1988-01-01

    Sealing apparatus and method, comprising first and second surfaces or membranes, at least one of which surfaces is deformable, placed in proximity to one another. Urging means cause these surfaces to contact one another in a manner such that the deformable surface "deforms" to conform to the geometry of the other surface, thereby creating a seal. The seal is capable of undergoing multiple cycles of sealing and unsealing.

  14. Intercountry versus Transracial Adoption: Analysis of Adoptive Parents' Motivations and Preferences in Adoption

    ERIC Educational Resources Information Center

    Zhang, Yuanting; Lee, Gary R.

    2011-01-01

    The United States is one of the major baby-receiving countries in the world. Relatively little research has focused on why there is such a high demand for intercountry adoption. Using in-depth qualitative interviews with adoptive parents, the authors explored the reasons why Americans prefer to adopt foreign-born children instead of adopting…

  15. Movement of elongation factor G between compact and extended conformations.

    PubMed

    Salsi, Enea; Farah, Elie; Netter, Zoe; Dann, Jillian; Ermolenko, Dmitri N

    2015-01-30

    Previous structural studies suggested that ribosomal translocation is accompanied by large interdomain rearrangements of elongation factor G (EF-G). Here, we follow the movement of domain IV of EF-G relative to domain II of EF-G using ensemble and single-molecule Förster resonance energy transfer. Our results indicate that ribosome-free EF-G predominantly adopts a compact conformation that can also, albeit infrequently, transition into a more extended conformation in which domain IV moves away from domain II. By contrast, ribosome-bound EF-G predominantly adopts an extended conformation regardless of whether it is interacting with pretranslocation ribosomes or with posttranslocation ribosomes. Our data suggest that ribosome-bound EF-G may also occasionally sample at least one more compact conformation. GTP hydrolysis catalyzed by EF-G does not affect the relative stability of the observed conformations in ribosome-free and ribosome-bound EF-G. Our data support a model suggesting that, upon binding to a pretranslocation ribosome, EF-G moves from a compact to a more extended conformation. This transition is not coupled to but likely precedes both GTP hydrolysis and mRNA/tRNA translocation.

  16. Movement of Elongation Factor G between Compact and Extended Conformations

    PubMed Central

    Salsi, Enea; Farah, Elie; Netter, Zoe; Dann, Jillian; Ermolenko, Dmitri N.

    2014-01-01

    Previous structural studies suggested that ribosomal translocation is accompanied by large interdomain rearrangements of elongation factor G (EF-G). Here, we follow the movement of domain IV of EF-G relative to domain II of EF-G using ensemble and single-molecule Förster resonance energy transfer (smFRET). Our results indicate that ribosome-free EF-G predominantly adopts a compact conformation that can also, albeit infrequently, transition into a more extended conformation in which domain IV moves away from domain II. By contrast, ribosome-bound EF-G predominantly adopts an extended conformation regardless of whether it is interacting with pre- or posttranslocation ribosomes. Our data suggest that ribosome-bound EF-G may also occasionally sample at least one more compact conformation. GTP hydrolysis catalyzed by EF-G does not affect the relative stability of the observed conformations in ribosome-free and ribosome-bound EF-G. Our data support a model suggesting that, upon binding to a pretranslocation ribosome, EF-G moves from a compact to a more extended conformation. This transition is not coupled to, but likely precedes both GTP hydrolysis and mRNA/tRNA translocation. PMID:25463439

  17. An indirect latent informational conformity social influence choice model: Formulation and case study

    DOE PAGES

    Maness, Michael; Cirillo, Cinzia

    2016-11-01

    The current state-of-the-art in social influence models of travel behavior is conformity models with direct benefit social influence effects. Indirect effects have seen limited development, but this paper presents a latent class discrete choice model of an indirect informational conformity hypothesis. Moreover, class membership depends on the proportion of group members who adopt a behavior. Membership into the more informed class causes changes in the preferences of those individuals thus making adoption more attractive. Equilibrium properties are derived for this model showing the possibility of multiple equilibria but under different conditions than the direct-benefit formulations. Social influence elasticity is derivedmore » for both models types. The informational conformity model can represent non-linear elasticity behavior unlike the direct-benefit formulation. Additionally, a two-stage control function is developed to obtain consistent parameter estimates in the presence of an endogenous class membership model covariate that is correlated with choice model unobservables. A case study to study social influence in bicycle ownership in the United States is presented. Our results showed that more informed households had a greater chance of owning a bike due to preference changes with less sensitivity to smaller home footprints and limited incomes. The behavioral hypothesis of positive preference change due to information transfer was confirmed. Observed ownership share closely matched predicted local-level equilibrium in some metropolitan areas but was unable to achieve expected prediction rate within confidence intervals. Finally, the elasticity of social influence was found to range locally from about 0.5% to 1.0%.« less

  18. Conformational flexibility of aspartame.

    PubMed

    Toniolo, Claudio; Temussi, Pierandrea

    2016-05-01

    L-Aspartyl-L-phenylalanine methyl ester, better known as aspartame, is not only one of the most used artificial sweeteners, but also a very interesting molecule with respect to the correlation between molecular structure and taste. The extreme conformational flexibility of this dipeptide posed a huge difficulty when researchers tried to use it as a lead compound to design new sweeteners. In particular, it was difficult to take advantage of its molecular model as a mold to infer the shape of the, then unknown, active site of the sweet taste receptor. Here, we follow the story of the 3D structural aspects of aspartame from early conformational studies to recent docking into homology models of the receptor. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 376-384, 2016. PMID:27038223

  19. Conformal complementarity maps

    NASA Astrophysics Data System (ADS)

    Barbón, José L. F.; Rabinovici, Eliezer

    2013-12-01

    We study quantum cosmological models for certain classes of bang/crunch singularities, using the duality between expanding bubbles in AdS with a FRW interior cosmology and perturbed CFTs on de Sitter space-time. It is pointed out that horizon complementarity in the AdS bulk geometries is realized as a conformal transformation in the dual deformed CFT. The quantum version of this map is described in full detail in a toy model involving conformal quantum mechanics. In this system the complementarity map acts as an exact duality between eternal and apocalyptic Hamiltonian evolutions. We calculate the commutation relation between the Hamiltonians corresponding to the different frames. It vanishes only on scale invariant states.

  20. Multiscale conformal pattern transfer.

    PubMed

    Lodewijks, Kristof; Miljkovic, Vladimir; Massiot, Inès; Mekonnen, Addis; Verre, Ruggero; Olsson, Eva; Dmitriev, Alexandre

    2016-01-01

    We demonstrate a method for seamless transfer from a parent flat substrate of basically any lithographic top-down or bottom-up pattern onto essentially any kind of surface. The nano- or microscale patterns, spanning macroscopic surface areas, can be transferred with high conformity onto a large variety of surfaces when such patterns are produced on a thin carbon film, grown on top of a sacrificial layer. The latter allows lifting the patterns from the flat parent substrate onto a water-air interface to be picked up by the host surface of choice. We illustrate the power of this technique by functionalizing broad range of materials including glass, plastics, metals, rough semiconductors and polymers, highlighting the potential applications in in situ colorimetry of the chemistry of materials, anti-counterfeit technologies, biomolecular and biomedical studies, light-matter interactions at the nanoscale, conformal photovoltaics and flexible electronics. PMID:27329824

  1. Multiscale conformal pattern transfer

    PubMed Central

    Lodewijks, Kristof; Miljkovic, Vladimir; Massiot, Inès; Mekonnen, Addis; Verre, Ruggero; Olsson, Eva; Dmitriev, Alexandre

    2016-01-01

    We demonstrate a method for seamless transfer from a parent flat substrate of basically any lithographic top-down or bottom-up pattern onto essentially any kind of surface. The nano- or microscale patterns, spanning macroscopic surface areas, can be transferred with high conformity onto a large variety of surfaces when such patterns are produced on a thin carbon film, grown on top of a sacrificial layer. The latter allows lifting the patterns from the flat parent substrate onto a water-air interface to be picked up by the host surface of choice. We illustrate the power of this technique by functionalizing broad range of materials including glass, plastics, metals, rough semiconductors and polymers, highlighting the potential applications in in situ colorimetry of the chemistry of materials, anti-counterfeit technologies, biomolecular and biomedical studies, light-matter interactions at the nanoscale, conformal photovoltaics and flexible electronics. PMID:27329824

  2. Multiscale conformal pattern transfer

    NASA Astrophysics Data System (ADS)

    Lodewijks, Kristof; Miljkovic, Vladimir; Massiot, Inès; Mekonnen, Addis; Verre, Ruggero; Olsson, Eva; Dmitriev, Alexandre

    2016-06-01

    We demonstrate a method for seamless transfer from a parent flat substrate of basically any lithographic top-down or bottom-up pattern onto essentially any kind of surface. The nano- or microscale patterns, spanning macroscopic surface areas, can be transferred with high conformity onto a large variety of surfaces when such patterns are produced on a thin carbon film, grown on top of a sacrificial layer. The latter allows lifting the patterns from the flat parent substrate onto a water-air interface to be picked up by the host surface of choice. We illustrate the power of this technique by functionalizing broad range of materials including glass, plastics, metals, rough semiconductors and polymers, highlighting the potential applications in in situ colorimetry of the chemistry of materials, anti-counterfeit technologies, biomolecular and biomedical studies, light-matter interactions at the nanoscale, conformal photovoltaics and flexible electronics.

  3. Conformational flexibility of aspartame.

    PubMed

    Toniolo, Claudio; Temussi, Pierandrea

    2016-05-01

    L-Aspartyl-L-phenylalanine methyl ester, better known as aspartame, is not only one of the most used artificial sweeteners, but also a very interesting molecule with respect to the correlation between molecular structure and taste. The extreme conformational flexibility of this dipeptide posed a huge difficulty when researchers tried to use it as a lead compound to design new sweeteners. In particular, it was difficult to take advantage of its molecular model as a mold to infer the shape of the, then unknown, active site of the sweet taste receptor. Here, we follow the story of the 3D structural aspects of aspartame from early conformational studies to recent docking into homology models of the receptor. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 376-384, 2016.

  4. Conformal scalar field wormholes

    NASA Technical Reports Server (NTRS)

    Halliwell, Jonathan J.; Laflamme, Raymond

    1989-01-01

    The Euclidian Einstein equations with a cosmological constant and a conformally coupled scalar field are solved, taking the metric to be of the Robertson-Walker type. In the case Lambda = 0, solutions are found which represent a wormhole connecting two asymptotically flat Euclidian regions. In the case Lambda greater than 0, the solutions represent tunneling from a small Tolman-like universe to a large Robertson-Walker universe.

  5. The conformal bootstrap

    NASA Astrophysics Data System (ADS)

    Poland, David; Simmons-Duffin, David

    2016-06-01

    The conformal bootstrap was proposed in the 1970s as a strategy for calculating the properties of second-order phase transitions. After spectacular success elucidating two-dimensional systems, little progress was made on systems in higher dimensions until a recent renaissance beginning in 2008. We report on some of the main results and ideas from this renaissance, focusing on new determinations of critical exponents and correlation functions in the three-dimensional Ising and O(N) models.

  6. Conformations of organophosphine oxides

    SciTech Connect

    De Silva, Nuwan; Zahariev, Federico; Hay, Benjamin P.; Gordon, Mark S.; Windus, Theresa L.

    2015-07-17

    The conformations of a series of organophosphine oxides, OP(CH3)2R, where R = methyl, ethyl, isopropyl, tert-butyl, vinyl, and phenyl, are predicted using the MP2/cc-pVTZ level of theory. Comparison of potential energy surfaces for rotation about P–C bonds with crystal structure data reveals a strong correlation between predicted location and energetics of minima and histograms of dihedral angle distributions observed in the solid state. In addition, the most stable conformers are those that minimize the extent of steric repulsion between adjacent rotor substituents, and the torsional barriers tend to increase with the steric bulk of the rotating alkyl group. MM3 force field parameters were adjusted to fit the MP2 results, providing a fast and accurate model for predicting organophosphine oxides shapes—an essential part of understanding the chemistry of these compounds. As a result, the predictive power of the modified MM3 model was tested against MP2/cc-pVTZ conformations for triethylphosphine oxide, OP(CH2CH3)3, and triphenylphosphine oxide, OP(Ph)3.

  7. Conformations of organophosphine oxides

    DOE PAGES

    De Silva, Nuwan; Zahariev, Federico; Hay, Benjamin P.; Gordon, Mark S.; Windus, Theresa L.

    2015-07-17

    The conformations of a series of organophosphine oxides, OP(CH3)2R, where R = methyl, ethyl, isopropyl, tert-butyl, vinyl, and phenyl, are predicted using the MP2/cc-pVTZ level of theory. Comparison of potential energy surfaces for rotation about P–C bonds with crystal structure data reveals a strong correlation between predicted location and energetics of minima and histograms of dihedral angle distributions observed in the solid state. In addition, the most stable conformers are those that minimize the extent of steric repulsion between adjacent rotor substituents, and the torsional barriers tend to increase with the steric bulk of the rotating alkyl group. MM3 forcemore » field parameters were adjusted to fit the MP2 results, providing a fast and accurate model for predicting organophosphine oxides shapes—an essential part of understanding the chemistry of these compounds. As a result, the predictive power of the modified MM3 model was tested against MP2/cc-pVTZ conformations for triethylphosphine oxide, OP(CH2CH3)3, and triphenylphosphine oxide, OP(Ph)3.« less

  8. Protein Conformational Populations and Functionally Relevant Sub-states

    SciTech Connect

    Agarwal, Pratul K; Burger, Virginia; Savol, Andrej; Ramanathan, Arvind; Chennubhotla, Chakra

    2013-01-01

    Functioning proteins do not remain fixed in a unique structure, but instead they sample a range of conformations facilitated by motions within the protein. Even in the native state, a protein exists as a collection of interconverting conformations driven by thermodynamic fluctuations. Motions on the fast time scale allow a protein to sample conformations in the nearby area of its conformational landscape, while motions on slower time scales give it access to conformations in distal areas of the landscape. Emerging evidence indicates that protein landscapes contain conformational substates with dynamic and structural features that support the designated function of the protein. Nuclear magnetic resonance (NMR) experiments provide information about conformational ensembles of proteins. X-ray crystallography allows researchers to identify the most populated states along the landscape, and computational simulations give atom-level information about the conformational substates of different proteins. This ability to characterize and obtain quantitative information about the conformational substates and the populations of proteins within them is allowing researchers to better understand the relationship between protein structure and dynamics and the mechanisms of protein function. In this Account, we discuss recent developments and challenges in the characterization of functionally relevant conformational populations and substates of proteins. In some enzymes, the sampling of functionally relevant conformational substates is connected to promoting the overall mechanism of catalysis. For example, the conformational landscape of the enzyme dihydrofolate reductase has multiple substates, which facilitate the binding and the release of the cofactor and substrate and catalyze the hydride transfer. For the enzyme cyclophilin A, computational simulations reveal that the long time scale conformational fluctuations enable the enzyme to access conformational substates that allow

  9. Dynamics and Conformational Energetics of a Peptide Hormone: Vasopressin

    NASA Astrophysics Data System (ADS)

    Hagler, A. T.; Osguthorpe, D. J.; Dauber-Osguthorpe, P.; Hempel, J. C.

    1985-03-01

    A theoretical methodology for use in conjunction with experiment was applied to the neurohypophyseal hormone lysine vasopressin for elucidation of its accessible molecular conformations and associated flexibility, conformational transitions, and dynamics. Molecular dynamics and energy minimization techniques make possible a description of the conformational properties of a peptide in terms of the precise positions of atoms, their fluctuations in time, and the interatomic forces acting on them. Analysis of the dynamic trajectory of lysine vasopressin shows the ability of a flexible peptide hormone to undergo spontaneous conformational transitions. The excursions of an individual phenylalanine residue exemplify the dynamic flexibility and multiple conformational states available to small peptide hormones and their component residues, even within constraints imposed by a cyclic hexapeptide ring.

  10. Structure of an intermediate conformer of the spindle checkpoint protein Mad2.

    PubMed

    Hara, Mayuko; Özkan, Engin; Sun, Hongbin; Yu, Hongtao; Luo, Xuelian

    2015-09-01

    The spindle checkpoint senses unattached kinetochores during prometaphase and inhibits the anaphase-promoting complex or cyclosome (APC/C), thus ensuring accurate chromosome segregation. The checkpoint protein mitotic arrest deficient 2 (Mad2) is an unusual protein with multiple folded states. Mad2 adopts the closed conformation (C-Mad2) in a Mad1-Mad2 core complex. In mitosis, kinetochore-bound Mad1-C-Mad2 recruits latent, open Mad2 (O-Mad2) from the cytosol and converts it to an intermediate conformer (I-Mad2), which can then bind and inhibit the APC/C activator cell division cycle 20 (Cdc20) as C-Mad2. Here, we report the crystal structure and NMR analysis of I-Mad2 bound to C-Mad2. Although I-Mad2 retains the O-Mad2 fold in crystal and in solution, its core structural elements undergo discernible rigid-body movements and more closely resemble C-Mad2. Residues exhibiting methyl chemical shift changes in I-Mad2 form a contiguous, interior network that connects its C-Mad2-binding site to the conformationally malleable C-terminal region. Mutations of residues at the I-Mad2-C-Mad2 interface hinder I-Mad2 formation and impede the structural transition of Mad2. Our study provides insight into the conformational activation of Mad2 and establishes the basis of allosteric communication between two distal sites in Mad2. PMID:26305957

  11. Adoption and Assisted Reproduction. Adoption and Ethics, Volume 4.

    ERIC Educational Resources Information Center

    Freundlich, Madelyn

    The controversies in adoption have extended across a spectrum of policy and practice issues, and although the issues have become clear, resolution has not been achieved nor has consensus developed regarding a framework on which to improve the quality of adoption policy and practice. This book is the fourth in a series to use an ethics-based…

  12. The Market Forces in Adoption. Adoption and Ethics, Volume 2.

    ERIC Educational Resources Information Center

    Freundlich, Madelyn

    The controversies in adoption have extended across a spectrum of policy and practice issues, and although the issues have become clear, resolution has not been achieved nor has consensus developed regarding a framework on which to improve the quality of adoption policy and practice. This book is the second in a series to use an ethics-based…

  13. Homosexuality and adoption in Brazil.

    PubMed

    Uziel, A P

    2001-11-01

    Western societies are undergoing legal and policy changes in relation to laws governing the family, marital status, sexual orientation and the welfare of children, including in Brazil where, in the 1990s, the rights of homosexuals were incorporated into ongoing debates about what constitutes a family. This paper discusses the issue of adoption of children by homosexual men in Brazil, using information from court records from 1995-2000 in Rio de Janeiro, and from interviews with two judges, five psychologists and four social workers who evaluate those wishing to adopt. It uses the case records of one man's application to adopt, in which homosexuality became a central issue. Both the construction of masculinity in relation to parenting and concepts of the family were the parameters upon which the decision to allow him to adopt or not depended. Because the legislation does not specify what the sexual orientation of would-be adoptive parents should be, it is possible for single persons to adopt if they show they can be good parents. As more single people, alone or in couples, seek to adopt, it is important to clarify the criteria for judicial decisions on adoption applications. A dialogue is therefore needed on the meaning of family and whether and how it relates to sexual orientation. It is only on this basis that the courts can take a clear decision as to whether being homosexual is a relevant issue in regard to applications to adopt or not.

  14. Conformational manifold of alpha-aminoisobutyric acid (Aib) containing alanine-based tripeptides in aqueous solution explored by vibrational spectroscopy, electronic circular dichroism spectroscopy, and molecular dynamics simulations.

    PubMed

    Schweitzer-Stenner, Reinhard; Gonzales, Widalys; Bourne, Gregory T; Feng, Jianwen A; Marshall, Garland R

    2007-10-31

    Replacement of the alpha-proton of an alanine residue to generate alpha-aminoisobutyric acid (Aib) in alanine-based oligopeptides favors the formation of a 3(10) helix when the length of the oligopeptide is about four to six residues. This research was aimed at experimentally identifying the structural impact of an individual Aib residue in an alanine context of short peptides in water and Aib's influence on the conformation of nearest-neighbor residues. The amide I band profile of the IR, isotropic and anisotropic Raman, and vibrational circular dichroism (VCD) spectra of Ac-Ala-Ala-Aib-OMe, Ac-Ala-Aib-Ala-OMe, and Ac-Aib-Ala-Ala-OMe were measured and analyzed in terms of different structural models by utilizing an algorithm that exploits the excitonic coupling between amide I' modes. The conformational search was guided by the respective 1H NMR and electronic circular dichroism spectra of the respective peptides, which were also recorded. From these analyses, all peptides adopted multiple conformations. Aib predominantly sampled the right-handed and left-handed 3(10)-helix region and to a minor extent the bridge region between the polyproline (PPII) and the helical regions of the Ramachandran plot. Generally, alanine showed the anticipated PPII propensity, but its conformational equilibrium was shifted towards helical conformations in Ac-Aib-Ala-Ala-OMe, indicating that Aib can induce helical conformations of neighboring residues positioned towards the C-terminal direction of the peptide. An energy landscape exploration by molecular dynamics simulations corroborated the results of the spectroscopic studies. They also revealed the dynamics and pathways of potential conformational transitions of the corresponding Aib residues.

  15. Steric interactions determine side-chain conformations in protein cores.

    PubMed

    Caballero, D; Virrueta, A; O'Hern, C S; Regan, L

    2016-09-01

    We investigate the role of steric interactions in defining side-chain conformations in protein cores. Previously, we explored the strengths and limitations of hard-sphere dipeptide models in defining sterically allowed side-chain conformations and recapitulating key features of the side-chain dihedral angle distributions observed in high-resolution protein structures. Here, we show that modeling residues in the context of a particular protein environment, with both intra- and inter-residue steric interactions, is sufficient to specify which of the allowed side-chain conformations is adopted. This model predicts 97% of the side-chain conformations of Leu, Ile, Val, Phe, Tyr, Trp and Thr core residues to within 20°. Although the hard-sphere dipeptide model predicts the observed side-chain dihedral angle distributions for both Thr and Ser, the model including the protein environment predicts side-chain conformations to within 20° for only 60% of core Ser residues. Thus, this approach can identify the amino acids for which hard-sphere interactions alone are sufficient and those for which additional interactions are necessary to accurately predict side-chain conformations in protein cores. We also show that our approach can predict alternate side-chain conformations of core residues, which are supported by the observed electron density.

  16. The dynamic conformational landscape of γ-secretase

    PubMed Central

    Elad, Nadav; De Strooper, Bart; Lismont, Sam; Hagen, Wim; Veugelen, Sarah; Arimon, Muriel; Horré, Katrien; Berezovska, Oksana; Sachse, Carsten; Chávez-Gutiérrez, Lucía

    2015-01-01

    ABSTRACT The structure and function of the γ-secretase proteases are of great interest because of their crucial roles in cellular and disease processes. We established a novel purification protocol for the γ-secretase complex that involves a conformation- and complex-specific nanobody, yielding highly pure and active enzyme. Using single particle electron microscopy, we analyzed the γ-secretase structure and its conformational variability. Under steady-state conditions, the complex adopts three major conformations, which differ in overall compactness and relative position of the nicastrin ectodomain. Occupancy of the active or substrate-binding sites by inhibitors differentially stabilizes subpopulations of particles with compact conformations, whereas a mutation linked to familial Alzheimer disease results in enrichment of extended-conformation complexes with increased flexibility. Our study presents the γ-secretase complex as a dynamic population of interconverting conformations, involving rearrangements at the nanometer scale and a high level of structural interdependence between subunits. The fact that protease inhibition or clinical mutations, which affect amyloid β (Aβ) generation, enrich for particular subpopulations of conformers indicates the functional relevance of the observed dynamic changes, which are likely to be instrumental for highly allosteric behavior of the enzyme. PMID:25501811

  17. Conformation and hydration of aspartame.

    PubMed

    Kang, Y K

    1991-07-01

    Conformational free energy calculations using an empirical potential (ECEPP/2) and the hydration shell model were carried out on the neutral, acidic, zwitterionic, and basic forms of aspartame in the hydrated state. The results indicate that as the molecule becomes more charged, the number of low energy conformations becomes smaller and the molecule becomes less flexible. The calculated free energies of hydration of charged aspartames show that hydration has a significant effect on the conformation in solution. Only two feasible conformations were found for the zwitterionic form, and these are consistent with the conformations deduced from NMR and X-ray diffraction experiments. The calculated free energy difference between these two conformations was 1.25 kcal/mol. The less favored of the two solvated conformations can be expected to be stabilized by hydrophobic interaction of the phenyl groups in the crystal.

  18. Conformal superalgebras via tractor calculus

    NASA Astrophysics Data System (ADS)

    Lischewski, Andree

    2015-01-01

    We use the manifestly conformally invariant description of a Lorentzian conformal structure in terms of a parabolic Cartan geometry in order to introduce a superalgebra structure on the space of twistor spinors and normal conformal vector fields formulated in purely algebraic terms on parallel sections in tractor bundles. Via a fixed metric in the conformal class, one reproduces a conformal superalgebra structure that has been considered in the literature before. The tractor approach, however, makes clear that the failure of this object to be a Lie superalgebra in certain cases is due to purely algebraic identities on the spinor module and to special properties of the conformal holonomy representation. Moreover, it naturally generalizes to higher signatures. This yields new formulas for constructing new twistor spinors and higher order normal conformal Killing forms out of existing ones, generalizing the well-known spinorial Lie derivative. Moreover, we derive restrictions on the possible dimension of the space of twistor spinors in any metric signature.

  19. Computing the conformational entropy for RNA folds

    NASA Astrophysics Data System (ADS)

    Liu, Liang; Chen, Shi-Jie

    2010-06-01

    We develop a polymer physics-based method to compute the conformational entropy for RNA tertiary folds, namely, conformations consisting of multiple helices connected through (cross-linked) loops. The theory is based on a virtual bond conformational model for the nucleotide chain. A key issue in the calculation of the entropy is how to treat the excluded volume interactions. The weak excluded volume interference between the different loops leads to the decomposition of the whole structure into a number of three-body building blocks, each consisting of a loop and two helices connected to the two ends of the loop. The simple construct of the three-body system allows an accurate computation for the conformational entropy for each building block. The assembly of the building blocks gives the entropy of the whole structure. This approach enables treatment of molten globule-like folds (partially unfolded tertiary structures) for RNAs. Extensive tests against experiments and exact computer enumerations indicate that the method can give accurate results for the entropy. The method developed here provides a solid first step toward a systematic development of a theory for the entropy and free energy landscape for complex tertiary folds for RNAs and proteins.

  20. NMR Studies of Dynamic Biomolecular Conformational Ensembles

    PubMed Central

    Torchia, Dennis A.

    2015-01-01

    Multidimensional heteronuclear NMR approaches can provide nearly complete sequential signal assignments of isotopically enriched biomolecules. The availability of assignments together with measurements of spin relaxation rates, residual spin interactions, J-couplings and chemical shifts provides information at atomic resolution about internal dynamics on timescales ranging from ps to ms, both in solution and in the solid state. However, due to the complexity of biomolecules, it is not possible to extract a unique atomic-resolution description of biomolecular motions even from extensive NMR data when many conformations are sampled on multiple timescales. For this reason, powerful computational approaches are increasingly applied to large NMR data sets to elucidate conformational ensembles sampled by biomolecules. In the past decade, considerable attention has been directed at an important class of biomolecules that function by binding to a wide variety of target molecules. Questions of current interest are: “Does the free biomolecule sample a conformational ensemble that encompasses the conformations found when it binds to various targets; and if so, on what time scale is the ensemble sampled?” This article reviews recent efforts to answer these questions, with a focus on comparing ensembles obtained for the same biomolecules by different investigators. A detailed comparison of results obtained is provided for three biomolecules: ubiquitin, calmodulin and the HIV-1 trans-activation response RNA. PMID:25669739

  1. Leaf growth is conformal

    NASA Astrophysics Data System (ADS)

    Alim, Karen; Armon, Shahaf; Shraiman, Boris I.; Boudaoud, Arezki

    2016-10-01

    Growth pattern dynamics lie at the heart of morphogenesis. Here, we investigate the growth of plant leaves. We compute the conformal transformation that maps the contour of a leaf at a given stage onto the contour of the same leaf at a later stage. Based on the mapping we predict the local displacement field in the leaf blade and find it to agree with the experimentally measured displacement field to 92%. This approach is applicable to any two-dimensional system with locally isotropic growth, enabling the deduction of the whole growth field just from observation of the tissue contour.

  2. Leaf growth is conformal.

    PubMed

    Alim, Karen; Armon, Shahaf; Shraiman, Boris I; Boudaoud, Arezki

    2016-01-01

    Growth pattern dynamics lie at the heart of morphogenesis. Here, we investigate the growth of plant leaves. We compute the conformal transformation that maps the contour of a leaf at a given stage onto the contour of the same leaf at a later stage. Based on the mapping we predict the local displacement field in the leaf blade and find it to agree with the experimentally measured displacement field to 92%. This approach is applicable to any two-dimensional system with locally isotropic growth, enabling the deduction of the whole growth field just from observation of the tissue contour. PMID:27597439

  3. Conformational Recognition of an Intrinsically Disordered Protein

    PubMed Central

    Krieger, James M.; Fusco, Giuliana; Lewitzky, Marc; Simister, Philip C.; Marchant, Jan; Camilloni, Carlo; Feller, Stephan M.; De Simone, Alfonso

    2014-01-01

    There is a growing interest in understanding the properties of intrinsically disordered proteins (IDPs); however, the characterization of these states remains an open challenge. IDPs appear to have functional roles that diverge from those of folded proteins and revolve around their ability to act as hubs for protein-protein interactions. To gain a better understanding of the modes of binding of IDPs, we combined statistical mechanics, calorimetry, and NMR spectroscopy to investigate the recognition and binding of a fragment from the disordered protein Gab2 by the growth factor receptor-bound protein 2 (Grb2), a key interaction for normal cell signaling and cancer development. Structural ensemble refinement by NMR chemical shifts, thermodynamics measurements, and analysis of point mutations indicated that the population of preexisting bound conformations in the free-state ensemble of Gab2 is an essential determinant for recognition and binding by Grb2. A key role was found for transient polyproline II (PPII) structures and extended conformations. Our findings are likely to have very general implications for the biological behavior of IDPs in light of the evidence that a large fraction of these proteins possess a specific propensity to form PPII and to adopt conformations that are more extended than the typical random-coil states. PMID:24739176

  4. Pyranose sulfamates: conformation and hydrogen bonding

    NASA Astrophysics Data System (ADS)

    Kubicki, Maciej; Codding, Penelope W.; Litster, Stephen A.; Szkaradziñska, Maria B.; Bassyouni, Hanan A. R.

    1999-01-01

    The crystal structure of a new anticonvulsant drug, topiramate — 2,3:4,5-bis- O-(1-methylethylidene)- β-D-fructopyranose sulfamate ( 1), together with those of three similar but biologically almost inactive sugar sulfamates: 4,5- O-cyclohexylidene-2,3- O-(1-methyl-ethylidene)- β-D-fructopyranose sulfamate ( 2), 2,3:- O-(1-methylethylidene)- β-D-fructo-pyranose sulfamate ( 3), and 1,2:3,4-bis- O-(1-methylethylidene)- α-D-galactopyranose sulfamate ( 4), have been determined by X-rays. The pyranose rings adopt distorted twist-boat 2S O conformations as a result of flattening of the chair conformation, observed in free pyranoses, by the fused five-membered ring(s). In 3 an unfavourable gauche-trans conformation about C1-C2 bond is observed. The active compound, topiramate ( 1), shows, in comparison with the other three compounds, a different disposition of nitrogen and oxygen atoms from the sulfamate group with respect to the O1-S1 bond. As a result, the nitrogen atom in 1 is ca. 1 Å farther from the O6 pyranose ring oxygen atom than in the other three compounds. This difference describes the mutual disposition of the hydrophilic and hydrophobic parts of the molecule, and can be related to the difference in biological activity. In all compounds, hydrogen bonds connect molecules into three-dimensional networks; simple chains and more complicated rings are found and described using the graph set notation.

  5. OSI Conformance Testing for Bibliographic Applications.

    ERIC Educational Resources Information Center

    Arbez, Gilbert; Swain, Leigh

    1990-01-01

    Describes the development of Open Systems Interconnection (OSI) conformance testing sites, conformance testing tools, and conformance testing services. Discusses related topics such as interoperability testing, arbitration testing, and international harmonization of conformance testing. A glossary is included. (24 references) (SD)

  6. Stories of Aboriginal Transracial Adoption

    ERIC Educational Resources Information Center

    Nuttgens, Simon

    2013-01-01

    Despite the significant number of transracial Aboriginal adoptions that have taken place in Canada, little research is available that addresses the psychological and psychosocial ramifications for the children involved. The scant literature that does exist raises concerns about the psychological impact of this type of adoption. The present…

  7. The Temporal Context of Adoption.

    ERIC Educational Resources Information Center

    Pontius, Steven K.

    This paper analyzes the amount of time required by farmers in four villages on the western edge of the central plain of Thailand to adopt four agricultural innovations--fertilizer, herbicide, insecticide, and fungicide. The general objective is to help researchers interested in the relationship of the adoption of new ideas to economic development…

  8. Adopting Children with Attachment Problems.

    ERIC Educational Resources Information Center

    Hughes, Daniel A.

    1999-01-01

    Notes that attachment behavior in infants is a facet of normal child development, and that children with attachment problems require special attention during and after the adoption process. Presents actions needed to increase the probability that such children can be successfully adopted, detailed attachment patterns, and parenting strategies and…

  9. Faculty Adoption of Educational Technology

    ERIC Educational Resources Information Center

    Moser, Franziska Zellweger

    2007-01-01

    Although faculty support has been identified as a critical factor in the success of educational-technology programs, many people involved in such efforts underestimate the complexities of integrating technology into teaching. In this article, the author proposes an adoption cycle to help tackle the complex issue of technology adoption for…

  10. Characteristics of adopted juvenile delinquents.

    PubMed

    Kim, W J; Zrull, J P; Davenport, C W; Weaver, M

    1992-05-01

    There have been many reports describing the uniqueness of adopted children and adolescents' delinquent behaviors in terms of both their delinquent characteristics and courts' treatment of them. A total of 43 adopted juveniles, 32 extrafamilial (1.0%) and 11 intrafamilial (0.3%) adoptions were initially identified out of 3,280 juvenile delinquents. The adopted subjects were then compared with the demographically matched and offense matched nonadopted subjects. The family variables, such as marital and employment status of parents, were significantly different. However, there were only a few discernible trends, and in general there were no significant differences between the adopted and nonadopted juveniles in terms of their offense characteristics and dispositions. PMID:1592787

  11. Reversible ratchet effects for vortices in conformal pinning arrays

    NASA Astrophysics Data System (ADS)

    Reichhardt, C.; Ray, D.; Reichhardt, C. J. Olson

    2015-05-01

    A conformal transformation of a uniform triangular pinning array produces a structure called a conformal crystal which preserves the sixfold ordering of the original lattice but contains a gradient in the pinning density. Here we use numerical simulations to show that vortices in type-II superconductors driven with an ac drive over gradient pinning arrays produce the most pronounced ratchet effect over a wide range of parameters for a conformal array, while square gradient or random gradient arrays with equivalent pinning densities give reduced ratchet effects. In the conformal array, the larger spacing of the pinning sites in the direction transverse to the ac drive permits easy funneling of interstitial vortices for one driving direction, producing the enhanced ratchet effect. In the square array, the transverse spacing between pinning sites is uniform, giving no asymmetry in the funneling of the vortices as the driving direction switches, while in the random array, there are numerous easy-flow channels present for either direction of drive. We find multiple ratchet reversals in the conformal arrays as a function of vortex density and ac amplitude, and correlate the features with a reversal in the vortex ordering, which is greater for motion in the ratchet direction. The enhanced conformal pinning ratchet effect can also be realized for colloidal particles moving over a conformal array, indicating the general usefulness of conformal structures for controlling the motion of particles.

  12. Reversible ratchet effects for vortices in conformal pinning arrays

    DOE PAGES

    Reichhardt, Charles; Ray, Dipanjan; Reichhardt, Cynthia Jane Olson

    2015-05-04

    A conformal transformation of a uniform triangular pinning array produces a structure called a conformal crystal which preserves the sixfold ordering of the original lattice but contains a gradient in the pinning density. Here we use numerical simulations to show that vortices in type-II superconductors driven with an ac drive over gradient pinning arrays produce the most pronounced ratchet effect over a wide range of parameters for a conformal array, while square gradient or random gradient arrays with equivalent pinning densities give reduced ratchet effects. In the conformal array, the larger spacing of the pinning sites in the direction transversemore » to the ac drive permits easy funneling of interstitial vortices for one driving direction, producing the enhanced ratchet effect. In the square array, the transverse spacing between pinning sites is uniform, giving no asymmetry in the funneling of the vortices as the driving direction switches, while in the random array, there are numerous easy-flow channels present for either direction of drive. We find multiple ratchet reversals in the conformal arrays as a function of vortex density and ac amplitude, and correlate the features with a reversal in the vortex ordering, which is greater for motion in the ratchet direction. In conclusion, the enhanced conformal pinning ratchet effect can also be realized for colloidal particles moving over a conformal array, indicating the general usefulness of conformal structures for controlling the motion of particles.« less

  13. Reversible ratchet effects for vortices in conformal pinning arrays

    SciTech Connect

    Reichhardt, Charles; Ray, Dipanjan; Reichhardt, Cynthia Jane Olson

    2015-05-04

    A conformal transformation of a uniform triangular pinning array produces a structure called a conformal crystal which preserves the sixfold ordering of the original lattice but contains a gradient in the pinning density. Here we use numerical simulations to show that vortices in type-II superconductors driven with an ac drive over gradient pinning arrays produce the most pronounced ratchet effect over a wide range of parameters for a conformal array, while square gradient or random gradient arrays with equivalent pinning densities give reduced ratchet effects. In the conformal array, the larger spacing of the pinning sites in the direction transverse to the ac drive permits easy funneling of interstitial vortices for one driving direction, producing the enhanced ratchet effect. In the square array, the transverse spacing between pinning sites is uniform, giving no asymmetry in the funneling of the vortices as the driving direction switches, while in the random array, there are numerous easy-flow channels present for either direction of drive. We find multiple ratchet reversals in the conformal arrays as a function of vortex density and ac amplitude, and correlate the features with a reversal in the vortex ordering, which is greater for motion in the ratchet direction. In conclusion, the enhanced conformal pinning ratchet effect can also be realized for colloidal particles moving over a conformal array, indicating the general usefulness of conformal structures for controlling the motion of particles.

  14. Targeting Inactive Enzyme Conformation

    PubMed Central

    Liu, Sijiu; Zeng, Li-Fan; Wu, Li; Yu, Xiao; Xue, Ting; Gunawan, Andrea M.; Ya-Qiu, Long; Zhang, Zhong-Yin

    2009-01-01

    There has been considerable interest in protein tyrosine phosphatase 1B (PTP1B) as a therapeutic target for diabetes, obesity, as well as cancer. Identifying inhibitory compounds with good bioavailability is a major challenge of drug discovery programs targeted toward PTPs. Most current PTP active site-directed pharmacophores are negatively charged pTyr mimetics which cannot readily enter the cell. This lack of cell permeability limits the utility of such compounds in signaling studies and further therapeutic development. We identify aryl diketoacids as novel pTyr surrogates and show that neutral amide-linked aryl diketoacid dimers also exhibit excellent PTP inhibitory activity. Kinetic studies establish that these aryl diketoacid derivatives act as noncompetitive inhibitors of PTP1B. Crystal structures of ligand-bound PTP1B reveal that both the aryl diketoacid and its dimeric derivative bind PTP1B at the active site, albeit with distinct modes of interaction, in the catalytically inactive, WPD loop open conformation. Furthermore, dimeric aryl diketoacids are cell permeable and enhance insulin signaling in hepatoma cells, suggesting that targeting the inactive conformation may provide a unique opportunity for creating active site-directed PTP1B inhibitors with improved pharmacological properties. PMID:19012396

  15. Conformally symmetric traversable wormholes

    SciTech Connect

    Boehmer, Christian G.; Harko, Tiberiu; Lobo, Francisco S. N.

    2007-10-15

    Exact solutions of traversable wormholes are found under the assumption of spherical symmetry and the existence of a nonstatic conformal symmetry, which presents a more systematic approach in searching for exact wormhole solutions. In this work, a wide variety of solutions are deduced by considering choices for the form function, a specific linear equation of state relating the energy density and the pressure anisotropy, and various phantom wormhole geometries are explored. A large class of solutions impose that the spatial distribution of the exotic matter is restricted to the throat neighborhood, with a cutoff of the stress-energy tensor at a finite junction interface, although asymptotically flat exact solutions are also found. Using the 'volume integral quantifier', it is found that the conformally symmetric phantom wormhole geometries may, in principle, be constructed by infinitesimally small amounts of averaged null energy condition violating matter. Considering the tidal acceleration traversability conditions for the phantom wormhole geometry, specific wormhole dimensions and the traversal velocity are also deduced.

  16. Eikonalization of conformal blocks

    SciTech Connect

    Fitzpatrick, A. Liam; Kaplan, Jared; Walters, Matthew T.; Wang, Junpu

    2015-09-03

    Classical field configurations such as the Coulomb potential and Schwarzschild solution are built from the t-channel exchange of many light degrees of freedom. We study the CFT analog of this phenomenon, which we term the 'eikonalization' of conformal blocks. We show that when an operator T appears in the OPE Ο(x)Ο(0), then the large spin Fock space states [TT···T] also appear in this OPE with a computable coefficient. The sum over the exchange of these Fock space states in an correlator build the classical 'T field' in the dual AdS description. In some limits the sum of all Fock space exchanges can be represented as the exponential of a single T exchange in the 4-pt correlator of O. Our results should be useful for systematizing 1/ℓ perturbation theory in general CFTs and simplifying the computation of large spin OPE coefficients. As examples we obtain the leading log ℓ dependence of Fock space conformal block coefficients, and we directly compute the OPE coefficients of the simplest ‘triple-trace’ operators.

  17. Eikonalization of conformal blocks

    DOE PAGES

    Fitzpatrick, A. Liam; Kaplan, Jared; Walters, Matthew T.; Wang, Junpu

    2015-09-03

    Classical field configurations such as the Coulomb potential and Schwarzschild solution are built from the t-channel exchange of many light degrees of freedom. We study the CFT analog of this phenomenon, which we term the 'eikonalization' of conformal blocks. We show that when an operator T appears in the OPE Ο(x)Ο(0), then the large spin Fock space states [TT···T]ℓ also appear in this OPE with a computable coefficient. The sum over the exchange of these Fock space states in an correlator build the classical 'T field' in the dual AdS description. In some limits the sum of all Fock spacemore » exchanges can be represented as the exponential of a single T exchange in the 4-pt correlator of O. Our results should be useful for systematizing 1/ℓ perturbation theory in general CFTs and simplifying the computation of large spin OPE coefficients. As examples we obtain the leading log ℓ dependence of Fock space conformal block coefficients, and we directly compute the OPE coefficients of the simplest ‘triple-trace’ operators.« less

  18. Conformational Flexibility in the Transmembrane Protein TSPO.

    PubMed

    Jaremko, Łukasz; Jaremko, Mariusz; Giller, Karin; Becker, Stefan; Zweckstetter, Markus

    2015-11-01

    The translocator protein (TSPO) is an integral membrane protein that interacts with a wide variety of endogenous ligands, such as cholesterol and porphyrins, and is also the target for several small molecules with substantial in vivo efficacy. When complexed with the TSPO-specific radioligand (R)-PK11195, TSPO folds into a rigid five-helix bundle. However, little is known about the structure and dynamics of TSPO in the absence of high-affinity ligands. By means of NMR spectroscopy, we show that TSPO exchanges between multiple conformations in the absence of (R)-PK11195. Extensive motions on time scales from pico- to microseconds occur all along the primary sequence of the protein, leading to a loss of stable tertiary interactions and local unfolding of the helical structure in the vicinity of the ligand-binding site. The flexible nature of TSPO highlights the importance of conformational plasticity in integral membrane proteins.

  19. Recent Advances in Conformal Gravity

    NASA Astrophysics Data System (ADS)

    O'Brien, James; Chaykov, Spasen

    2016-03-01

    In recent years, significant advances have been made in alternative gravitational theories. Although MOND remains the leading candidate among the alternative models, Conformal Gravity has been studied by Mannheim and O'Brien to solve the rotation curve problem without the need for dark matter. Recently, Mannheim, O'Brien and Chaykov have begun solving other gravitational questions in Conformal Gravity. In this presentation, we highlight the new work of Conformal Gravity's application to random motions of clusters (the original Zwicky problem), gravitational bending of light, gravitational lensing and a very recent survey of dwarf galaxy rotation curves. We will show in each case that Conformal Gravity can provide an accurate explanation and prediction of the data without the need for dark matter. Coupled with the fact that Conformal Gravity is a fully re-normalizable metric theory of gravity, these results help to push Conformal Gravity onto a competitive stage against other alternative models.

  20. Fermion-scalar conformal blocks

    DOE PAGES

    Iliesiu, Luca; Kos, Filip; Poland, David; Pufu, Silviu S.; Simmons-Duffin, David; Yacoby, Ran

    2016-04-13

    In this study, we compute the conformal blocks associated with scalar-scalar-fermionfermion 4-point functions in 3D CFTs. Together with the known scalar conformal blocks, our result completes the task of determining the so-called ‘seed blocks’ in three dimensions. In addition, conformal blocks associated with 4-point functions of operators with arbitrary spins can now be determined from these seed blocks by using known differential operators.

  1. Killing and conformal Killing tensors

    NASA Astrophysics Data System (ADS)

    Heil, Konstantin; Moroianu, Andrei; Semmelmann, Uwe

    2016-08-01

    We introduce an appropriate formalism in order to study conformal Killing (symmetric) tensors on Riemannian manifolds. We reprove in a simple way some known results in the field and obtain several new results, like the classification of conformal Killing 2-tensors on Riemannian products of compact manifolds, Weitzenböck formulas leading to non-existence results, and construct various examples of manifolds with conformal Killing tensors.

  2. Reflections on conformal spectra

    NASA Astrophysics Data System (ADS)

    Kim, Hyungrok; Kravchuk, Petr; Ooguri, Hirosi

    2016-04-01

    We use modular invariance and crossing symmetry of conformal field theory to reveal approximate reflection symmetries in the spectral decompositions of the partition function in two dimensions in the limit of large central charge and of the four-point function in any dimension in the limit of large scaling dimensions Δ0 of external operators. We use these symmetries to motivate universal upper bounds on the spectrum and the operator product expansion coefficients, which we then derive by independent techniques. Some of the bounds for four-point functions are valid for finite Δ0 as well as for large Δ0. We discuss a similar symmetry in a large spacetime dimension limit. Finally, we comment on the analogue of the Cardy formula and sparse light spectrum condition for the four-point function.

  3. Capturing Chromosome Conformation

    NASA Astrophysics Data System (ADS)

    Dekker, Job; Rippe, Karsten; Dekker, Martijn; Kleckner, Nancy

    2002-02-01

    We describe an approach to detect the frequency of interaction between any two genomic loci. Generation of a matrix of interaction frequencies between sites on the same or different chromosomes reveals their relative spatial disposition and provides information about the physical properties of the chromatin fiber. This methodology can be applied to the spatial organization of entire genomes in organisms from bacteria to human. Using the yeast Saccharomyces cerevisiae, we could confirm known qualitative features of chromosome organization within the nucleus and dynamic changes in that organization during meiosis. We also analyzed yeast chromosome III at the G1 stage of the cell cycle. We found that chromatin is highly flexible throughout. Furthermore, functionally distinct AT- and GC-rich domains were found to exhibit different conformations, and a population-average 3D model of chromosome III could be determined. Chromosome III emerges as a contorted ring.

  4. Using Multiple Technologies to Teach Nursing Students about Adoption

    ERIC Educational Resources Information Center

    Harrison, Sharonlyn; Henneman, Kris; Herrera, Maida Y.; Hockman, Elaine; Brooks, Evelyn; Darland, Nancy; Kulik, Noel; Sandy-Hanson, Anika E.

    2013-01-01

    Technology is becoming increasingly more important in the enhancement of educating university students. Very little research has been done regarding how the combination of educational technologies affects test scores, compared to the use of one technology alone. This research article examines whether the post-scores of nursing students increased…

  5. Counseling Issues in Adoptions by Stepparents.

    ERIC Educational Resources Information Center

    Wolf, Patricia A.; Mast, Emily

    1987-01-01

    Although the number of nonrelative adoptions is decreasing, stepparent adoptions are not. These adoptions are viewed as nonproblematic family business separate from the general adoption picture. This article examines demographic data in Lancaster County, Pennsylvania, from 55 stepparent adoptions concerning stepparent adopters, birth parents, and…

  6. Replacement between conformity and counter-conformity in consumption decisions.

    PubMed

    Chou, Ting-Jui; Chang, En-Chung; Dai, Qi; Wong, Veronica

    2013-02-01

    This study assessed, in a Chinese context, how self-esteem interacts with perceived similarity and uniqueness to yield cognitive dissonance, and whether the dissonance leads to self-reported conformity or counter-conformity behavior. Participants were 408 respondents from 4 major Chinese cities (M age = 33.0 yr., SD = 4.3; 48% men). Self-perceptions of uniqueness, similarity, cognitive dissonance, self-esteem and need to behave in conformity or counter-conformity were measured. A theoretical model was assessed in four situations, relating the ratings of self-esteem and perceived similarity/uniqueness to the way other people at a wedding were dressed, and the resultant cognitive dissonance and conformity/ counter-conformity behavior. Regardless of high or low self-esteem, all participants reported cognitive dissonance when they were told that they were dressed extremely similarly to or extremely differently from the other people attending the wedding. However, the conforming/counter-conforming strategies used by participants to resolve the cognitive dissonance differed. When encountering dissonance induced by the perceived extreme uniqueness of dress, participants with low self-esteem tended to say they would dress next time so as to conform with the way others were dressed, while those with high self-esteem indicated they would continue their counter-conformity in attire. When encountering dissonance induced by the perceived extreme similarity to others, both those with high and low self-esteem tended to say they would dress in an unorthodox manner to surprise other people in the future. PMID:23654033

  7. Replacement between conformity and counter-conformity in consumption decisions.

    PubMed

    Chou, Ting-Jui; Chang, En-Chung; Dai, Qi; Wong, Veronica

    2013-02-01

    This study assessed, in a Chinese context, how self-esteem interacts with perceived similarity and uniqueness to yield cognitive dissonance, and whether the dissonance leads to self-reported conformity or counter-conformity behavior. Participants were 408 respondents from 4 major Chinese cities (M age = 33.0 yr., SD = 4.3; 48% men). Self-perceptions of uniqueness, similarity, cognitive dissonance, self-esteem and need to behave in conformity or counter-conformity were measured. A theoretical model was assessed in four situations, relating the ratings of self-esteem and perceived similarity/uniqueness to the way other people at a wedding were dressed, and the resultant cognitive dissonance and conformity/ counter-conformity behavior. Regardless of high or low self-esteem, all participants reported cognitive dissonance when they were told that they were dressed extremely similarly to or extremely differently from the other people attending the wedding. However, the conforming/counter-conforming strategies used by participants to resolve the cognitive dissonance differed. When encountering dissonance induced by the perceived extreme uniqueness of dress, participants with low self-esteem tended to say they would dress next time so as to conform with the way others were dressed, while those with high self-esteem indicated they would continue their counter-conformity in attire. When encountering dissonance induced by the perceived extreme similarity to others, both those with high and low self-esteem tended to say they would dress in an unorthodox manner to surprise other people in the future.

  8. Conformations and structural transitions in polydeoxynucleotides.

    PubMed

    Pilet, J; Blicharski, J; Brahms, J

    1975-05-01

    Polydeoxynucleotides of different base sequence, the alternating poly[d(A-T)]-poly[d(A-T)], crab satellite DNA, on the one hand, and double-stranded homopolymer complexes poly[d(A)]-poly[d(T)], poly[d(I)]-poly[d(C)], on the other, display significant differences in their conformation and conformational transitions. Infrared linear dichroism investigations indicate that the alternating poly[d(A-T)]-poly[d(A-T)], enzymatically synthesized, adopts a lower humidity a well-expressed A* form in which stability is relatively small,i.e., restricted to limited relative humidity. This A form is characterized by the orientation of the bisector of the phosphate OPO group at 34 degrees with respect to the helical axis, which is slightly lower than that of DNA. In contrast, for the homopolynucleotide double-stranded complex poly(dA)-poly(dT) and also for poly(dI)-poly(dC), the B yields A conformational change is not observed. Instead poly(dA)-poly(dT) exists at lower humidity in a stable modified B form. Thus the present results indicate that homo(dA)-homo(dT) double-stranded sequences prevent the B yields A structural transition. All AT-containing polydeoxynucleotides and crab satellite DNA adopt a high humidity a modified B form characterized by the orientation of the bisector of the phosphate group OPO at 64 degrees with respect to the helical axis which is significantly lower than 68-74 degrees observed in DNAs. The base pairing geometry in poly(dA)-poly(dT), poly[d(A-T)]-poly[d(A-T)], and also in poly(dI)-poly(dC) is apparently a Watson and Crick type. Thus the observed differences in conformation are not due to different base pairing scheme. It is suggested that in DNAs of high AT content the presence of homo(dT)-homo(dA) sequences and the relatively low stability of the A form of d(A-T) alternating sequences may inhibit the change to the A form. A possible role of these sequences in DNA recognition by protein is suggested.

  9. Stochastic ensembles, conformationally adaptive teamwork, and enzymatic detoxification.

    PubMed

    Atkins, William M; Qian, Hong

    2011-05-17

    It has been appreciated for a long time that enzymes exist as conformational ensembles throughout multiple stages of the reactions they catalyze, but there is renewed interest in the functional implications. The energy landscape that results from conformationlly diverse poteins is a complex surface with an energetic topography in multiple dimensions, even at the transition state(s) leading to product formation, and this represents a new paradigm. At the same time there has been renewed interest in conformational ensembles, a new paradigm concerning enzyme function has emerged, wherein catalytic promiscuity has clear biological advantages in some cases. "Useful", or biologically functional, promiscuity or the related behavior of "multifunctionality" can be found in the immune system, enzymatic detoxification, signal transduction, and the evolution of new function from an existing pool of folded protein scaffolds. Experimental evidence supports the widely held assumption that conformational heterogeneity promotes functional promiscuity. The common link between these coevolving paradigms is the inherent structural plasticity and conformational dynamics of proteins that, on one hand, lead to complex but evolutionarily selected energy landscapes and, on the other hand, promote functional promiscuity. Here we consider a logical extension of the overlap between these two nascent paradigms: functionally promiscuous and multifunctional enzymes such as detoxification enzymes are expected to have an ensemble landscape with more states accessible on multiple time scales than substrate specific enzymes. Two attributes of detoxification enzymes become important in the context of conformational ensembles: these enzymes metabolize multiple substrates, often in substrate mixtures, and they can form multiple products from a single substrate. These properties, combined with complex conformational landscapes, lead to the possibility of interesting time-dependent, or emergent

  10. Conformal gravity and time

    NASA Astrophysics Data System (ADS)

    Hazboun, Jeffrey Shafiq

    2014-10-01

    Cartan geometry provides a rich formalism from which to look at various geometrically motivated extensions to general relativity. In this manuscript, we start by motivating reasons to extend the theory of general relativity. We then introduce the reader to our technique, called the quotient manifold method, for extending the geometry of spacetime. We will specifically look at the class of theories formed from the various quotients of the conformal group. Starting with the conformal symmetries of Euclidean space, we construct a manifold where time manifests as a part of the geometry. Though there is no matter present in the geome- try studied here, geometric terms analogous to dark energy and dark matter appear when we write down the Einstein tensor. Specifically, the quotient of the conformal group of Euclidean four-space by its Weyl subgroup results in a geometry possessing many of the properties of relativistic phase space, including both a natural symplectic form and nondegenerate Killing metric. We show the general solution possesses orthogonal Lagrangian submanifolds, with the induced metric and the spin connection on the submanifolds necessarily Lorentzian, despite the Euclidean starting point. By examining the structure equations of the biconformal space in an orthonormal frame adapted to its phase space properties, we also find two new tensor fields exist in this geometry, not present in Riemannian geometry. The first is a combination of the Weyl vector with the scale factor on the metric, and determines the time-like directions on the submanifolds. The second comes from the components of the spin connection, symmetric with respect to the new metric. Though this field comes from the spin connection, it transforms ho- mogeneously. Finally, we show in the absence of Cartan curvature or sources, the configuration space has geometric terms equivalent to a perfect fluid and a cosmological constant. We complete the analysis of this homogeneous space by

  11. Conformal Transformations and Space Travel.

    PubMed

    Gupta, S N

    1961-10-27

    Conformal transformations are applied to the motion of a space ship experiencing a constant acceleration. The role of proper time is interpreted in terms of atomic periods, and the relationship between the conformal transformations and the general theory of relativity is clarified.

  12. Counselor Identity: Conformity or Distinction?

    ERIC Educational Resources Information Center

    McLaughlin, Jerry E.; Boettcher, Kathryn

    2009-01-01

    The authors explore 3 debates in other disciplines similar to counseling's identity debate in order to learn about common themes and outcomes. Conformity, distinction, and cohesion emerged as common themes. They conclude that counselors should retain their distinctive, humanistic approach rather than conforming to the dominant, medical approach.

  13. [Conformal radiotherapy: principles and classification].

    PubMed

    Rosenwald, J C; Gaboriaud, G; Pontvert, D

    1999-01-01

    'Conformal radiotherapy' is the name fixed by usage and given to a new form of radiotherapy resulting from the technological improvements observed during, the last ten years. While this terminology is now widely used, no precise definition can be found in the literature. Conformal radiotherapy refers to an approach in which the dose distribution is more closely 'conformed' or adapted to the actual shape of the target volume. However, the achievement of a consensus on a more specific definition is hampered by various difficulties, namely in characterizing the degree of 'conformality'. We have therefore suggested a classification scheme be established on the basis of the tools and the procedures actually used for all steps of the process, i.e., from prescription to treatment completion. Our classification consists of four levels: schematically, at level 0, there is no conformation (rectangular fields); at level 1, a simple conformation takes place, on the basis of conventional 2D imaging; at level 2, a 3D reconstruction of the structures is used for a more accurate conformation; and level 3 includes research and advanced dynamic techniques. We have used our personal experience, contacts with colleagues and data from the literature to analyze all the steps of the planning process, and to define the tools and procedures relevant to a given level. The corresponding tables have been discussed and approved at the European level within the Dynarad concerted action. It is proposed that the term 'conformal radiotherapy' be restricted to procedures where all steps are at least at level 2.

  14. Recursion relations for conformal blocks

    NASA Astrophysics Data System (ADS)

    Penedones, João; Trevisani, Emilio; Yamazaki, Masahito

    2016-09-01

    In the context of conformal field theories in general space-time dimension, we find all the possible singularities of the conformal blocks as functions of the scaling dimension Δ of the exchanged operator. In particular, we argue, using representation theory of parabolic Verma modules, that in odd spacetime dimension the singularities are only simple poles. We discuss how to use this information to write recursion relations that determine the conformal blocks. We first recover the recursion relation introduced in [1] for conformal blocks of external scalar operators. We then generalize this recursion relation for the conformal blocks associated to the four point function of three scalar and one vector operator. Finally we specialize to the case in which the vector operator is a conserved current.

  15. Reducing the Digital Divide through ICT Adoption: Factors, Barriers, and How ICT in Schools Can Help

    ERIC Educational Resources Information Center

    Tengtrakul, Pitikorn

    2013-01-01

    Through econometric analysis of data from multiple surveys, this study explores factors that affect ICT adoption and evaluates the extent to which ICT in schools affect the ICT adoption of surrounding communities, in order to provide a perspective that can help narrow the gap of digital divide. Understanding factors affecting ICT adoption may…

  16. Technological advances in adoptive immunotherapy.

    PubMed

    Oelke, Mathias; Krueger, Christine; Schneck, Jonathan P

    2005-01-01

    Adoptive immunotherapy is an attractive and elegant strategy for treating a variety of life-threatening diseases. Several approaches have been developed to generate antigen-specific CD4+ and CD8+ T cells for adoptive T-cell therapy in cancer and infectious diseases. Currently, many approaches are based on either the use of autologous peptide pulsed dendritic cells as antigen-presenting cells or nonspecific expansion of T cells. Unfortunately, current approaches lack the ability to serve as reproducible and economically viable methods. Several groups are developing new artificial approaches to overcome problems associated with dendritic cells and the nonspecific expansion of T-cell clones in order to make adoptive immunotherapy more feasible and effective. Thus, by increasing the availability of adoptive immunotherapy, we will be able to better determine the efficacy of the approaches in the treatment of a variety of diseases. In this review, we focus on technological advances that will facilitate adoptive immunotherapy. Specifically, we summarize current strategies which are either based on artificial antigen-presenting cells or on T-cell receptor gene transfer. PMID:15753966

  17. Spatial Separation of Molecular Conformers and Clusters

    PubMed Central

    Horke, Daniel; Trippel, Sebastian; Chang, Yuan-Pin; Stern, Stephan; Mullins, Terry; Kierspel, Thomas; Küpper, Jochen

    2014-01-01

    Gas-phase molecular physics and physical chemistry experiments commonly use supersonic expansions through pulsed valves for the production of cold molecular beams. However, these beams often contain multiple conformers and clusters, even at low rotational temperatures. We present an experimental methodology that allows the spatial separation of these constituent parts of a molecular beam expansion. Using an electric deflector the beam is separated by its mass-to-dipole moment ratio, analogous to a bender or an electric sector mass spectrometer spatially dispersing charged molecules on the basis of their mass-to-charge ratio. This deflector exploits the Stark effect in an inhomogeneous electric field and allows the separation of individual species of polar neutral molecules and clusters. It furthermore allows the selection of the coldest part of a molecular beam, as low-energy rotational quantum states generally experience the largest deflection. Different structural isomers (conformers) of a species can be separated due to the different arrangement of functional groups, which leads to distinct dipole moments. These are exploited by the electrostatic deflector for the production of a conformationally pure sample from a molecular beam. Similarly, specific cluster stoichiometries can be selected, as the mass and dipole moment of a given cluster depends on the degree of solvation around the parent molecule. This allows experiments on specific cluster sizes and structures, enabling the systematic study of solvation of neutral molecules. PMID:24457426

  18. Spatial separation of molecular conformers and clusters.

    PubMed

    Horke, Daniel; Trippel, Sebastian; Chang, Yuan-Pin; Stern, Stephan; Mullins, Terry; Kierspel, Thomas; Küpper, Jochen

    2014-01-09

    Gas-phase molecular physics and physical chemistry experiments commonly use supersonic expansions through pulsed valves for the production of cold molecular beams. However, these beams often contain multiple conformers and clusters, even at low rotational temperatures. We present an experimental methodology that allows the spatial separation of these constituent parts of a molecular beam expansion. Using an electric deflector the beam is separated by its mass-to-dipole moment ratio, analogous to a bender or an electric sector mass spectrometer spatially dispersing charged molecules on the basis of their mass-to-charge ratio. This deflector exploits the Stark effect in an inhomogeneous electric field and allows the separation of individual species of polar neutral molecules and clusters. It furthermore allows the selection of the coldest part of a molecular beam, as low-energy rotational quantum states generally experience the largest deflection. Different structural isomers (conformers) of a species can be separated due to the different arrangement of functional groups, which leads to distinct dipole moments. These are exploited by the electrostatic deflector for the production of a conformationally pure sample from a molecular beam. Similarly, specific cluster stoichiometries can be selected, as the mass and dipole moment of a given cluster depends on the degree of solvation around the parent molecule. This allows experiments on specific cluster sizes and structures, enabling the systematic study of solvation of neutral molecules.

  19. Conformal Fermi Coordinates

    SciTech Connect

    Dai, Liang; Pajer, Enrico; Schmidt, Fabian E-mail: Enrico.pajer@gmail.com

    2015-11-01

    Fermi Normal Coordinates (FNC) are a useful frame for isolating the locally observable, physical effects of a long-wavelength spacetime perturbation. Their cosmological application, however, is hampered by the fact that they are only valid on scales much smaller than the horizon. We introduce a generalization that we call Conformal Fermi Coordinates (CFC). CFC preserve all the advantages of FNC, but in addition are valid outside the horizon. They allow us to calculate the coupling of long- and short-wavelength modes on all scales larger than the sound horizon of the cosmological fluid, starting from the epoch of inflation until today, by removing the complications of the second order Einstein equations to a large extent, and eliminating all gauge ambiguities. As an application, we present a calculation of the effect of long-wavelength tensor modes on small scale density fluctuations. We recover previous results, but clarify the physical content of the individual contributions in terms of locally measurable effects and ''projection'' terms.

  20. Dynamics of protein conformations

    NASA Astrophysics Data System (ADS)

    Stepanova, Maria

    2010-10-01

    A novel theoretical methodology is introduced to identify dynamic structural domains and analyze local flexibility in proteins. The methodology employs a multiscale approach combining identification of essential collective coordinates based on the covariance analysis of molecular dynamics trajectories, construction of the Mori projection operator with these essential coordinates, and analysis of the corresponding generalized Langevin equations [M.Stepanova, Phys.Rev.E 76(2007)051918]. Because the approach employs a rigorous theory, the outcomes are physically transparent: the dynamic domains are associated with regions of relative rigidity in the protein, whereas off-domain regions are relatively soft. This also allows scoring the flexibility in the macromolecule with atomic-level resolution [N.Blinov, M.Berjanskii, D.S.Wishart, and M.Stepanova, Biochemistry, 48(2009)1488]. The applications include the domain coarse-graining and characterization of conformational stability in protein G and prion proteins. The results are compared with published NMR experiments. Potential applications for structural biology, bioinformatics, and drug design are discussed.

  1. Conformational dimorphism of isochroman-1-ones in the solid state

    NASA Astrophysics Data System (ADS)

    Babjaková, Eva; Hanulíková, Barbora; Dastychová, Lenka; Kuřitka, Ivo; Nečas, Marek; Vícha, Robert

    2014-12-01

    Isochroman-1-one derivatives, which are relatives of coumarins, display a broad spectrum of biological activity; therefore, these derivatives attract the attention of chemists. A series of new isochroman-1-ones were prepared by the reaction of benzyl-derived Grignard reagents with acyl chlorides. All of the prepared compounds were characterized using single-crystal X-ray diffraction as well as FT-IR, NMR and MS techniques. Single crystal X-ray diffraction analysis revealed that the isochromanones can adopt two distinct conformations in the solid state. For one of the compounds, two polymorphs with unique forms crystallized separately under different temperatures. The packing of all of the examined crystals is stabilized via weak intramolecular C-H⋯π and/or C-H⋯O interactions. Although the closed conformer was predominantly found in the actual crystals, the open conformer is thermochemically more stable for all of the examined compounds according to DFT calculations.

  2. Ring A conformation of aconine and pseudaconine in CDCl3.

    PubMed

    Deng, Hong-Ying; Chen, Qiao-Hong; Wang, Feng-Peng

    2014-06-01

    On the basis of intensive interpretation of the 1H NMR spectroscopic data, the ring A conformation of aconine (1) was speculated as twist boat in CDCl3, and as chair or twist boat in acetone-d6 and pyridine-d5. The ring A of pseudaconine (2) adopts the chair conformation in CDCl3, acetone-d6, and pyridine-ds. Accordingly, the boat conformation of ring A in these two diterpenoid alkaloids in CDCl3 reported in the literature [1] should be revised. The difference in 13C NMR data for the same compound (1 or 2) in two different solvents (CDCl3, pyridine-d5) can be attributed to solvent effects.

  3. Side-Chain Conformational Preferences Govern Protein-Protein Interactions.

    PubMed

    Watkins, Andrew M; Bonneau, Richard; Arora, Paramjit S

    2016-08-24

    Protein secondary structures serve as geometrically constrained scaffolds for the display of key interacting residues at protein interfaces. Given the critical role of secondary structures in protein folding and the dependence of folding propensities on backbone dihedrals, secondary structure is expected to influence the identity of residues that are important for complex formation. Counter to this expectation, we find that a narrow set of residues dominates the binding energy in protein-protein complexes independent of backbone conformation. This finding suggests that the binding epitope may instead be substantially influenced by the side-chain conformations adopted. We analyzed side-chain conformational preferences in residues that contribute significantly to binding. This analysis suggests that preferred rotamers contribute directly to specificity in protein complex formation and provides guidelines for peptidomimetic inhibitor design.

  4. Personality disorders in adopted versus non-adopted adults.

    PubMed

    Westermeyer, Joseph; Yoon, Gihyun; Amundson, Carla; Warwick, Marion; Kuskowski, Michael A

    2015-04-30

    The goal of this epidemiological study was to investigate lifetime history and odds ratios of personality disorders in adopted and non-adopted adults using a nationally representative sample. Data, drawn from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC), were compared in adopted (n=378) versus non-adopted (n=42,503) adults to estimate the odds of seven personality disorders using logistic regression analyses. The seven personality disorders were histrionic, antisocial, avoidant, paranoid, schizoid, obsessive-compulsive, and dependent personality disorder. Adoptees had a 1.81-fold increase in the odds of any personality disorder compared with non-adoptees. Adoptees had increased odds of histrionic, antisocial, avoidant, paranoid, schizoid, and obsessive-compulsive personality disorder compared with non-adoptees. Two risk factors associated with lifetime history of a personality disorder in adoptees compared to non-adoptees were (1) being in the age cohort 18-29 years (but no difference in the age 30-44 cohort), using the age 45 or older cohort as the reference and (2) having 12 years of education (but no difference in higher education groups), using the 0-11 years of education as the reference. These findings support the higher rates of personality disorders among adoptees compared to non-adoptees.

  5. Re an Adoption Application (Surrogacy)

    PubMed

    1987-03-01

    In England, it is illegal under the Adoption Act 1958 to pay or reward anyone in an effort to adopt a child. A family court was asked in this case whether a surrogacy arrangement involving the payment of 5,000 pounds violated the Act. The applicants, a husband and wife, were unable to have children and had entered into an informal arrangement with a woman who agreed to engage in sexual intercourse with the husband and bear a child for the couple in exchange for 10,000 pounds. Because the surrogate wrote a book about her experience from which she made money, and sincerely wanted to help out the childless couple, she accepted only half of her fee. Convinced that the surrogate arrangement was not commercial in nature, the court found no violation of English law, authorized the payment to the mother, and authorized adoption of the child by the father and his wife.

  6. Towards conformal loop quantum gravity

    NASA Astrophysics Data System (ADS)

    H-T Wang, Charles

    2006-03-01

    A discussion is given of recent developments in canonical gravity that assimilates the conformal analysis of gravitational degrees of freedom. The work is motivated by the problem of time in quantum gravity and is carried out at the metric and the triad levels. At the metric level, it is shown that by extending the Arnowitt-Deser-Misner (ADM) phase space of general relativity (GR), a conformal form of geometrodynamics can be constructed. In addition to the Hamiltonian and Diffeomorphism constraints, an extra first class constraint is introduced to generate conformal transformations. This phase space consists of York's mean extrinsic curvature time, conformal three-metric and their momenta. At the triad level, the phase space of GR is further enlarged by incorporating spin-gauge as well as conformal symmetries. This leads to a canonical formulation of GR using a new set of real spin connection variables. The resulting gravitational constraints are first class, consisting of the Hamiltonian constraint and the canonical generators for spin-gauge and conformorphism transformations. The formulation has a remarkable feature of being parameter-free. Indeed, it is shown that a conformal parameter of the Barbero-Immirzi type can be absorbed by the conformal symmetry of the extended phase space. This gives rise to an alternative approach to loop quantum gravity that addresses both the conceptual problem of time and the technical problem of functional calculus in quantum gravity.

  7. Logarithmic conformal field theory

    NASA Astrophysics Data System (ADS)

    Gainutdinov, Azat; Ridout, David; Runkel, Ingo

    2013-12-01

    Conformal field theory (CFT) has proven to be one of the richest and deepest subjects of modern theoretical and mathematical physics research, especially as regards statistical mechanics and string theory. It has also stimulated an enormous amount of activity in mathematics, shaping and building bridges between seemingly disparate fields through the study of vertex operator algebras, a (partial) axiomatisation of a chiral CFT. One can add to this that the successes of CFT, particularly when applied to statistical lattice models, have also served as an inspiration for mathematicians to develop entirely new fields: the Schramm-Loewner evolution and Smirnov's discrete complex analysis being notable examples. When the energy operator fails to be diagonalisable on the quantum state space, the CFT is said to be logarithmic. Consequently, a logarithmic CFT is one whose quantum space of states is constructed from a collection of representations which includes reducible but indecomposable ones. This qualifier arises because of the consequence that certain correlation functions will possess logarithmic singularities, something that contrasts with the familiar case of power law singularities. While such logarithmic singularities and reducible representations were noted by Rozansky and Saleur in their study of the U (1|1) Wess-Zumino-Witten model in 1992, the link between the non-diagonalisability of the energy operator and logarithmic singularities in correlators is usually ascribed to Gurarie's 1993 article (his paper also contains the first usage of the term 'logarithmic conformal field theory'). The class of CFTs that were under control at this time was quite small. In particular, an enormous amount of work from the statistical mechanics and string theory communities had produced a fairly detailed understanding of the (so-called) rational CFTs. However, physicists from both camps were well aware that applications from many diverse fields required significantly more

  8. CONFORMANCE IMPROVEMENT USING GELS

    SciTech Connect

    Randall S. Seright

    2002-02-28

    This technical progress report describes work performed from June 20 through December 19, 2001, for the project, ''Conformance Improvement Using Gels''. Interest has increased in some new polymeric products that purport to substantially reduce permeability to water while causing minimum permeability reduction to oil. In view of this interest, we are currently studying BJ's Aqua Con. Results from six corefloods revealed that the Aqua Con gelant consistently reduced permeability to water more than that to oil. However, the magnitude of the disproportionate permeability reduction varied significantly for the various experiments. Thus, as with most materials tested to date, the issue of reproducibility and control of the disproportionate permeability remains to be resolved. Concern exists about the ability of gels to resist washout after placement in fractures. We examined whether a width constriction in the middle of a fracture would cause different gel washout behavior upstream versus downstream of the constriction. Tests were performed using a formed Cr(III)-acetate-HPAM gel in a 48-in.-long fracture with three sections of equal length, but with widths of 0.08-, 0.02-, and 0.08-in., respectively. The pressure gradients during gel extrusion (i.e., placement) were similar in the two 0.08-in.-wide fracture sections, even though they were separated by a 0.02-in.-wide fracture section. The constriction associated with the middle fracture section may have inhibited gel washout during the first pulse of brine injection after gel placement. However, during subsequent phases of brine injection, the constriction did not inhibit washout in the upstream fracture section any more than in the downstream section.

  9. Why Adoption of Standards Matters

    ERIC Educational Resources Information Center

    Journal of Staff Development, 2016

    2016-01-01

    A total of 39 states have adopted, adapted, or endorsed the Standards for Professional Learning, including the standards issued in 2011 (labeled in red) and those published earlier (labeled in blue). Making a commitment to the standards is a commitment to continuous learning for all educators in a school.

  10. Internet Adoption: An Empirical Investigation

    ERIC Educational Resources Information Center

    Ma, Junzhao

    2011-01-01

    The Internet has brought significant changes to the retail industry because it revolutionizes how information is transmitted and accessed. The main objective of this research is to enhance our understanding of people's adoption of the Internet and its implications for retail competition. This dissertation consists of two essays. The first essay…

  11. Has the Academy Adopted TQM?

    ERIC Educational Resources Information Center

    Birnbaum, Robert; Deshotels, Judy

    1999-01-01

    A survey of 469 colleges and universities assessed the degree to which colleges and universities have adopted total quality management (TQM) or continuous quality improvement (CQI) techniques. Results suggest use of TQM/CQI is lower than predicted, at about 13% of institutions. Variations in extent of use of the approach are discussed. (MSE)

  12. The conformations of cyclic (1-->2)-beta-D-glucans: application of multidimensional clustering analysis to conformational data sets obtained by Metropolis Monte Carlo calculations.

    PubMed

    York, W S; Thomsen, J U; Meyer, B

    1993-10-01

    Sets containing up to 1.3 x 10(6) energetically accessible conformations of linear (1-->2)-beta-D-glucan oligosaccharides were obtained by Metropolis Monte Carlo (MMC) calculations performed with the GEGOP (GEometry of GlycOProteins) program. Quantitative analyses of the data sets (which were expressed in terms of the glycosidic dihedral angle coordinates) were obtained by two different clustering methods: (i) the three-distance hierarchical clustering method (3-DM), published by Jure Zupan, and (ii) a nonhierarchical clustering method (Population-Density Projection, PDP) which, through a segmentation analysis of two-dimensional projections of the population-density surface, establishes a partitioning of conformational space into a set of "cluster regions", followed by a clustering step where each conformation of the data set is assigned to one of these regions. Computer programs (MCLUST and PDPCLUST) were developed to perform the 3-DM and PDP analyses, respectively. The two types of analysis provided very similar sets of conformational families (clusters), which could be expressed as combinations of distinct conformations of the glycosidic torsional angles (phi, psi) centered at (50 degrees, 10 degrees) for conformation A, (40 degrees, 160 degrees) for conformation B, (55 degrees, -160 degrees) for conformation B', and (170 degrees, 10 degrees) for conformation C. The analysis provided the populations of the families, along with relative rates for transitions between families. Examination of the frequencies of the A, B, and C glycosidic bond conformations with respect to their relative positions in the sequence revealed the tendency of the (1-->2)-beta-D-glucan to adopt conformational repeating structures of the general form [AnB], where n = 3 or 6. These repeating structures combine in an energetically cooperative fashion to give low-energy cyclic conformations having, for example C5 symmetry [AAAB]5 for the eicosamer, and C3 symmetry [AAAAAAB]3 for the

  13. Logarithmic conformal field theory

    NASA Astrophysics Data System (ADS)

    Gainutdinov, Azat; Ridout, David; Runkel, Ingo

    2013-12-01

    Conformal field theory (CFT) has proven to be one of the richest and deepest subjects of modern theoretical and mathematical physics research, especially as regards statistical mechanics and string theory. It has also stimulated an enormous amount of activity in mathematics, shaping and building bridges between seemingly disparate fields through the study of vertex operator algebras, a (partial) axiomatisation of a chiral CFT. One can add to this that the successes of CFT, particularly when applied to statistical lattice models, have also served as an inspiration for mathematicians to develop entirely new fields: the Schramm-Loewner evolution and Smirnov's discrete complex analysis being notable examples. When the energy operator fails to be diagonalisable on the quantum state space, the CFT is said to be logarithmic. Consequently, a logarithmic CFT is one whose quantum space of states is constructed from a collection of representations which includes reducible but indecomposable ones. This qualifier arises because of the consequence that certain correlation functions will possess logarithmic singularities, something that contrasts with the familiar case of power law singularities. While such logarithmic singularities and reducible representations were noted by Rozansky and Saleur in their study of the U (1|1) Wess-Zumino-Witten model in 1992, the link between the non-diagonalisability of the energy operator and logarithmic singularities in correlators is usually ascribed to Gurarie's 1993 article (his paper also contains the first usage of the term 'logarithmic conformal field theory'). The class of CFTs that were under control at this time was quite small. In particular, an enormous amount of work from the statistical mechanics and string theory communities had produced a fairly detailed understanding of the (so-called) rational CFTs. However, physicists from both camps were well aware that applications from many diverse fields required significantly more

  14. Probing of different conformations of piperazine using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    SenGupta, Sumana; Maiti, Nandita; Chadha, Ridhima; Kapoor, Sudhir

    2014-06-01

    Piperazine exists in a number of energetically close structural conformations, and here, we investigated the dependence of their relative abundance on the surrounding conditions by using Raman and SERS spectroscopy in pure solid, aqueous solution and Ag hydrosol. The experimental results were interpreted by DFT calculations using B3LYP functional with aug-cc-pvdz/LANL2DZ basis sets. In the chair form of piperazine, which is more stable than the skewed boat by ∼8 kcal mol-1, the two N-H bonds can remain equatorial or axial, leading to three different conformations, eq-eq, eq-ax and ax-ax. The calculated Raman spectrum of the lowest energy eq-eq conformation corresponds well with the experimental spectrum in pure solid, indicating eq-eq to be predominant. But, the contribution of the eq-ax conformation was found to be maximum in aqueous solution. The SERS spectrum revealed that eq-ax conformation was preferably adopted as piperazine was adsorbed vertically through its axial N-atom over silver nanoparticle surface.

  15. Conformational states of the full-length glucagon receptor

    PubMed Central

    Yang, Linlin; Yang, Dehua; de Graaf, Chris; Moeller, Arne; West, Graham M.; Dharmarajan, Venkatasubramanian; Wang, Chong; Siu, Fai Y.; Song, Gaojie; Reedtz-Runge, Steffen; Pascal, Bruce D.; Wu, Beili; Potter, Clinton S.; Zhou, Hu; Griffin, Patrick R.; Carragher, Bridget; Yang, Huaiyu; Wang, Ming-Wei; Stevens, Raymond C.; Jiang, Hualiang

    2015-01-01

    Class B G protein-coupled receptors are composed of an extracellular domain (ECD) and a seven-transmembrane (7TM) domain, and their signalling is regulated by peptide hormones. Using a hybrid structural biology approach together with the ECD and 7TM domain crystal structures of the glucagon receptor (GCGR), we examine the relationship between full-length receptor conformation and peptide ligand binding. Molecular dynamics (MD) and disulfide crosslinking studies suggest that apo-GCGR can adopt both an open and closed conformation associated with extensive contacts between the ECD and 7TM domain. The electron microscopy (EM) map of the full-length GCGR shows how a monoclonal antibody stabilizes the ECD and 7TM domain in an elongated conformation. Hydrogen/deuterium exchange (HDX) studies and MD simulations indicate that an open conformation is also stabilized by peptide ligand binding. The combined studies reveal the open/closed states of GCGR and suggest that glucagon binds to GCGR by a conformational selection mechanism. PMID:26227798

  16. Conformation and interactions of dopamine hydrochloride in solution

    SciTech Connect

    Callear, Samantha K.; Imberti, Silvia; Johnston, Andrew; McLain, Sylvia E.

    2015-01-07

    The aqueous solution of dopamine hydrochloride has been investigated using neutron and X-ray total scattering data together with Monte-Carlo based modelling using Empirical Potential Structure Refinement. The conformation of the protonated dopamine molecule is presented and the results compared to the conformations found in crystal structures, dopamine-complexed protein crystal structures and predicted from theoretical calculations and pharmacophoric models. It is found that protonated dopamine adopts a range of conformations in solution, highlighting the low rotational energy barrier between different conformations, with the preferred conformation being trans-perpendicular. The interactions between each of the species present (protonated dopamine molecules, water molecules, and chloride anions) have been determined and are discussed with reference to interactions observed in similar systems both in the liquid and crystalline state, and predicted from theoretical calculations. The expected strong hydrogen bonds between the strong hydrogen bond donors and acceptors are observed, together with evidence of weaker CH hydrogen bonds and π interactions also playing a significant role in determining the arrangement of adjacent molecules.

  17. Conformational states of the full-length glucagon receptor

    NASA Astrophysics Data System (ADS)

    Yang, Linlin; Yang, Dehua; de Graaf, Chris; Moeller, Arne; West, Graham M.; Dharmarajan, Venkatasubramanian; Wang, Chong; Siu, Fai Y.; Song, Gaojie; Reedtz-Runge, Steffen; Pascal, Bruce D.; Wu, Beili; Potter, Clinton S.; Zhou, Hu; Griffin, Patrick R.; Carragher, Bridget; Yang, Huaiyu; Wang, Ming-Wei; Stevens, Raymond C.; Jiang, Hualiang

    2015-07-01

    Class B G protein-coupled receptors are composed of an extracellular domain (ECD) and a seven-transmembrane (7TM) domain, and their signalling is regulated by peptide hormones. Using a hybrid structural biology approach together with the ECD and 7TM domain crystal structures of the glucagon receptor (GCGR), we examine the relationship between full-length receptor conformation and peptide ligand binding. Molecular dynamics (MD) and disulfide crosslinking studies suggest that apo-GCGR can adopt both an open and closed conformation associated with extensive contacts between the ECD and 7TM domain. The electron microscopy (EM) map of the full-length GCGR shows how a monoclonal antibody stabilizes the ECD and 7TM domain in an elongated conformation. Hydrogen/deuterium exchange (HDX) studies and MD simulations indicate that an open conformation is also stabilized by peptide ligand binding. The combined studies reveal the open/closed states of GCGR and suggest that glucagon binds to GCGR by a conformational selection mechanism.

  18. Hierarchical Biomolecular Dynamics: Picosecond Hydrogen Bonding Regulates Microsecond Conformational Transitions.

    PubMed

    Buchenberg, Sebastian; Schaudinnus, Norbert; Stock, Gerhard

    2015-03-10

    Biomolecules exhibit structural dynamics on a number of time scales, including picosecond (ps) motions of a few atoms, nanosecond (ns) local conformational transitions, and microsecond (μs) global conformational rearrangements. Despite this substantial separation of time scales, fast and slow degrees of freedom appear to be coupled in a nonlinear manner; for example, there is theoretical and experimental evidence that fast structural fluctuations are required for slow functional motion to happen. To elucidate a microscopic mechanism of this multiscale behavior, Aib peptide is adopted as a simple model system. Combining extensive molecular dynamics simulations with principal component analysis techniques, a hierarchy of (at least) three tiers of the molecule's free energy landscape is discovered. They correspond to chiral left- to right-handed transitions of the entire peptide that happen on a μs time scale, conformational transitions of individual residues that take about 1 ns, and the opening and closing of structure-stabilizing hydrogen bonds that occur within tens of ps and are triggered by sub-ps structural fluctuations. Providing a simple mechanism of hierarchical dynamics, fast hydrogen bond dynamics is found to be a prerequisite for the ns local conformational transitions, which in turn are a prerequisite for the slow global conformational rearrangement of the peptide. As a consequence of the hierarchical coupling, the various processes exhibit a similar temperature behavior which may be interpreted as a dynamic transition. PMID:26579778

  19. Remote conformational control of a molecular switch via methylation and deprotonation.

    PubMed

    Knipe, Peter C; Jones, Ian M; Thompson, Sam; Hamilton, Andrew D

    2014-12-14

    Exacting control over conformation in response to an external stimulus is the central focus of molecular switching. Here we describe the synthesis of a series of diphenylacetylene-based molecular switches, and examine their response to covalent modification and deprotonation at remote phenolic positions. A complex interplay between multiple intramolecular hydrogen bond donors and acceptors determines the global conformation.

  20. CONFORMANCE IMPROVEMENT USING GELS

    SciTech Connect

    Randall S. Seright

    2004-09-30

    This report describes work performed during the third and final year of the project, ''Conformance Improvement Using Gels.'' Corefloods revealed throughput dependencies of permeability reduction by polymers and gels that were much more prolonged during oil flow than water flow. This behavior was explained using simple mobility ratio arguments. A model was developed that quantitatively fits the results and predicts ''clean up'' times for oil productivity when production wells are returned to service after application of a polymer or gel treatment. X-ray computed microtomography studies of gels in strongly water-wet Berea sandstone and strongly oil-wet porous polyethylene suggested that oil penetration through gel-filled pores occurs by a gel-dehydration mechanism, rather than gel-ripping or gel-displacement mechanisms. In contrast, analysis of data from the University of Kansas suggests that the gel-ripping or displacement mechanisms are more important in more permeable, strongly water-wet sandpacks. These findings help to explain why aqueous gels can reduce permeability to water more than to oil under different conditions. Since cement is the most commonly used material for water shutoff, we considered when gels are preferred over cements. Our analysis and experimental results indicated that cement cannot be expected to completely fill (top to bottom) a vertical fracture of any width, except near the wellbore. For vertical fractures with apertures less than 4 mm, the cement slurry will simply not penetrate very far into the fracture. For vertical fractures with apertures greater than 4 mm, the slurry may penetrate a substantial distance into the bottom part of the fracture. However, except near the wellbore, the upper part of the fracture will remain open due to gravity segregation. We compared various approaches to plugging fractures using gels, including (1) varying polymer content, (2) varying placement (extrusion) rate, (3) using partially formed gels, (4

  1. CONFORMANCE IMPROVEMENT USING GELS

    SciTech Connect

    Randall S. Seright

    2004-03-01

    This technical progress report describes work performed from September 1, 2003, through February 29, 2004, for the project, ''Conformance Improvement Using Gels.'' We examined the properties of several ''partially formed'' gels that were formulated with a combination of high and low molecular weight HPAM polymers. After placement in 4-mm-wide fractures, these gels required about 25 psi/ft for brine to breach the gel (the best performance to date in fractures this wide). After this breach, stabilized residual resistance factors decreased significantly with increased flow rate. Also, residual resistance factors were up to 9 times greater for water than for oil. Nevertheless, permeability reduction factors were substantial for both water and oil flow. Gel with 2.5% chopped fiberglass effectively plugged 4-mm-wide fractures if a 0.5-mm-wide constriction was present. The ability to screen-out at a constriction appears crucial for particulate incorporation to be useful in plugging fractures. In addition to fiberglass, we examined incorporation of polypropylene fibers into gels. Once dispersed in brine or gelant, the polypropylene fibers exhibited the least gravity segregation of any particulate that we have tested to date. In fractures with widths of at least 2 mm, 24-hr-old gels (0.5% high molecular weight HPAM) with 0.5% fiber did not exhibit progressive plugging during placement and showed extrusion pressure gradients similar to those of gels without the fiber. The presence of the fiber roughly doubled the gel's resistance to first breach by brine flow. The breaching pressure gradients were not as large as for gels made with high and low molecular weight polymers (mentioned above). However, their material requirements and costs (i.e., polymer and/or particulate concentrations) were substantially lower than for those gels. A partially formed gel made with 0.5% HPAM did not enter a 0.052-mm-wide fracture when applying a pressure gradient of 65 psi/ft. This result

  2. Radial coordinates for conformal blocks

    NASA Astrophysics Data System (ADS)

    Hogervorst, Matthijs; Rychkov, Slava

    2013-05-01

    We develop the theory of conformal blocks in CFTd expressing them as power series with Gegenbauer polynomial coefficients. Such series have a clear physical meaning when the conformal block is analyzed in radial quantization: individual terms describe contributions of descendants of a given spin. Convergence of these series can be optimized by a judicious choice of the radial quantization origin. We argue that the best choice is to insert the operators symmetrically. We analyze in detail the resulting “ρ-series” and show that it converges much more rapidly than for the commonly used variable z. We discuss how these conformal block representations can be used in the conformal bootstrap. In particular, we use them to derive analytically some bootstrap bounds whose existence was previously found numerically.

  3. Conformal mapping of rectangular heptagons

    SciTech Connect

    Bogatyrev, Andrei B

    2012-12-31

    A new effective approach to calculating the direct and inverse conformal mapping of rectangular polygons onto a half-plane is put forward; it is based on the use of Riemann theta functions. Bibliography: 14 titles.

  4. Lattice Simulations and Infrared Conformality

    DOE PAGES

    Appelquist, Thomas; Fleming, George T.; Lin, Meifeng; Neil, Ethan T.; Schaich, David A

    2011-09-01

    We examine several recent lattice-simulation data sets, asking whether they are consistent with infrared conformality. We observe, in particular, that for an SU(3) gauge theory with 12 Dirac fermions in the fundamental representation, recent simulation data can be described assuming infrared conformality. Lattice simulations include a fermion mass m which is then extrapolated to zero, and we note that this data can be fit by a small-m expansion, allowing a controlled extrapolation. We also note that the conformal hypothesis does not work well for two theories that are known or expected to be confining and chirally broken, and that itmore » does work well for another theory expected to be infrared conformal.« less

  5. Solution NMR conformation of glycosaminoglycans.

    PubMed

    Pomin, Vitor H

    2014-04-01

    Nuclear magnetic resonance (NMR) spectroscopy has been giving a pivotal contribution to the progress of glycomics, mostly by elucidating the structural, dynamical, conformational and intermolecular binding aspects of carbohydrates. Particularly in the field of conformation, NOE resonances, scalar couplings, residual dipolar couplings, and chemical shift anisotropy offsets have been the principal NMR parameters utilized. Molecular dynamics calculations restrained by NMR-data input are usually employed in conjunction to generate glycosidic bond dihedral angles. Glycosaminoglycans (GAGs) are a special class of sulfated polysaccharides extensively studied worldwide. Besides regulating innumerous physiological processes, these glycans are also widely explored in the global market as either clinical or nutraceutical agents. The conformational aspects of GAGs are key regulators to the quality of interactions with the functional proteins involved in biological events. This report discusses the solution conformation of each GAG type analyzed by one or more of the above-mentioned methods.

  6. Scale invariance vs conformal invariance

    NASA Astrophysics Data System (ADS)

    Nakayama, Yu

    2015-03-01

    In this review article, we discuss the distinction and possible equivalence between scale invariance and conformal invariance in relativistic quantum field theories. Under some technical assumptions, we can prove that scale invariant quantum field theories in d = 2 space-time dimensions necessarily possess the enhanced conformal symmetry. The use of the conformal symmetry is well appreciated in the literature, but the fact that all the scale invariant phenomena in d = 2 space-time dimensions enjoy the conformal property relies on the deep structure of the renormalization group. The outstanding question is whether this feature is specific to d = 2 space-time dimensions or it holds in higher dimensions, too. As of January 2014, our consensus is that there is no known example of scale invariant but non-conformal field theories in d = 4 space-time dimensions under the assumptions of (1) unitarity, (2) Poincaré invariance (causality), (3) discrete spectrum in scaling dimensions, (4) existence of scale current and (5) unbroken scale invariance in the vacuum. We have a perturbative proof of the enhancement of conformal invariance from scale invariance based on the higher dimensional analogue of Zamolodchikov's c-theorem, but the non-perturbative proof is yet to come. As a reference we have tried to collect as many interesting examples of scale invariance in relativistic quantum field theories as possible in this article. We give a complementary holographic argument based on the energy-condition of the gravitational system and the space-time diffeomorphism in order to support the claim of the symmetry enhancement. We believe that the possible enhancement of conformal invariance from scale invariance reveals the sublime nature of the renormalization group and space-time with holography. This review is based on a lecture note on scale invariance vs conformal invariance, on which the author gave lectures at Taiwan Central University for the 5th Taiwan School on Strings and

  7. Recovering a representative conformational ensemble from underdetermined macromolecular structural data.

    PubMed

    Berlin, Konstantin; Castañeda, Carlos A; Schneidman-Duhovny, Dina; Sali, Andrej; Nava-Tudela, Alfredo; Fushman, David

    2013-11-01

    Structural analysis of proteins and nucleic acids is complicated by their inherent flexibility, conferred, for example, by linkers between their contiguous domains. Therefore, the macromolecule needs to be represented by an ensemble of conformations instead of a single conformation. Determining this ensemble is challenging because the experimental data are a convoluted average of contributions from multiple conformations. As the number of the ensemble degrees of freedom generally greatly exceeds the number of independent observables, directly deconvolving experimental data into a representative ensemble is an ill-posed problem. Recent developments in sparse approximations and compressive sensing have demonstrated that useful information can be recovered from underdetermined (ill-posed) systems of linear equations by using sparsity regularization. Inspired by these advances, we designed the Sparse Ensemble Selection (SES) method for recovering multiple conformations from a limited number of observations. SES is more general and accurate than previously published minimum-ensemble methods, and we use it to obtain representative conformational ensembles of Lys48-linked diubiquitin, characterized by the residual dipolar coupling data measured at several pH conditions. These representative ensembles are validated against NMR chemical shift perturbation data and compared to maximum-entropy results. The SES method reproduced and quantified the previously observed pH dependence of the major conformation of Lys48-linked diubiquitin, and revealed lesser-populated conformations that are preorganized for binding known diubiquitin receptors, thus providing insights into possible mechanisms of receptor recognition by polyubiquitin. SES is applicable to any experimental observables that can be expressed as a weighted linear combination of data for individual states.

  8. 29 CFR 500.105 - DOT standards adopted by the Secretary.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the purposes of this section has adopted from 49 CFR part 398 the following pertinent standards. (In... conform the language to these regulations): (1) Qualification of drivers or operators (Source: 49 CFR 398... meridian shall not be less than a total of 140 degrees; ability to distinguish colors red, green and...

  9. 29 CFR 500.105 - DOT standards adopted by the Secretary.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... the purposes of this section has adopted from 49 CFR part 398 the following pertinent standards. (In... conform the language to these regulations): (1) Qualification of drivers or operators (Source: 49 CFR 398... meridian shall not be less than a total of 140 degrees; ability to distinguish colors red, green and...

  10. 29 CFR 500.105 - DOT standards adopted by the Secretary.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the purposes of this section has adopted from 49 CFR part 398 the following pertinent standards. (In... conform the language to these regulations): (1) Qualification of drivers or operators (Source: 49 CFR 398...) Driving of motor vehicles (Source: 49 CFR 398.4)—(i) Compliance required. Every person shall comply...

  11. 29 CFR 500.105 - DOT standards adopted by the Secretary.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... the purposes of this section has adopted from 49 CFR part 398 the following pertinent standards. (In... conform the language to these regulations): (1) Qualification of drivers or operators (Source: 49 CFR 398...) Driving of motor vehicles (Source: 49 CFR 398.4)—(i) Compliance required. Every person shall comply...

  12. 29 CFR 500.105 - DOT standards adopted by the Secretary.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... the purposes of this section has adopted from 49 CFR part 398 the following pertinent standards. (In... conform the language to these regulations): (1) Qualification of drivers or operators (Source: 49 CFR 398...) Driving of motor vehicles (Source: 49 CFR 398.4)—(i) Compliance required. Every person shall comply...

  13. Delineating the conformational flexibility of trisaccharides from NMR spectroscopy experiments and computer simulations.

    PubMed

    Yang, Mingjun; Angles d'Ortoli, Thibault; Säwén, Elin; Jana, Madhurima; Widmalm, Göran; MacKerell, Alexander D

    2016-07-28

    The conformation of saccharides in solution is challenging to characterize in the context of a single well-defined three-dimensional structure. Instead, they are better represented by an ensemble of conformations associated with their structural diversity and flexibility. In this study, we delineate the conformational heterogeneity of five trisaccharides via a combination of experimental and computational techniques. Experimental NMR measurements target conformationally sensitive parameters, including J couplings and effective distances around the glycosidic linkages, while the computational simulations apply the well-calibrated additive CHARMM carbohydrate force field in combination with efficient enhanced sampling molecular dynamics simulation methods. Analysis of conformational heterogeneity is performed based on sampling of discreet states as defined by dihedral angles, on root-mean-square differences of Cartesian coordinates and on the extent of volume sampled. Conformational clustering, based on the glycosidic linkage dihedral angles, shows that accounting for the full range of sampled conformations is required to reproduce the experimental data, emphasizing the utility of the molecular simulations in obtaining an atomic detailed description of the conformational properties of the saccharides. Results show the presence of differential conformational preferences as a function of primary sequence and glycosidic linkage types. Significant differences in conformational ensembles associated with the anomeric configuration of a single glycosidic linkage reinforce the impact of such changes on the conformational properties of carbohydrates. The present structural insights of the studied trisaccharides represent a foundation for understanding the range of conformations adopted in larger oligosaccharides and how these molecules encode their conformational heterogeneity into the monosaccharide sequence. PMID:27346493

  14. Home Energy Displays. Consumer Adoption and Response

    SciTech Connect

    LaMarche, Janelle; Cheney, K.; Akers, C.; Roth, K.; Sachs, O.

    2012-12-01

    The focus of this project was to investigate the factors influencing consumer adoption of Home Energy Displays (HEDs) and to evaluate electricity consumption in households with basic HEDs versus enhanced feedback methods - web portals or alerts. The team hypothesized that providing flexible and relatable information to users, in addition to a basic HED, would make feedback more effective and achieve persistent energy savings. In Phase I, Fraunhofer conducted three user research studies and found preferences for aesthetically pleasing, easy to understand feedback that is accessible through multiple media and offered free of charge. The deployment of HEDs in 150 households planned for Phase II encountered major recruitment and HED field deployment problems. In light of these challenges, the team is pursuing a modified study investigating the energy savings of a web portal versus alert-based energy feedback instead of a physical HED.

  15. Embryo adoption: Some further considerations.

    PubMed

    Patterson, Colin

    2015-02-01

    Recent discussions of embryo adoption have sought to make sense of the teaching of the Congregation for the Doctrine of the Faith (CDF) document Dignitas personae which appeared to provide a negative judgment on such a practice. This article aims to provide a personalist account of the process of fertilization and implantation that might serve as the basis for the negative judgment of the CDF document. In doing so, it relies upon the idea that a person, including an embryo, is not to be considered in isolation, but always in relation to God and to others. This approach extends the substantialist conceptualizations commonly employed in discussions of this issue. More generally, the article seeks to highlight the value of a personalist re-framing for an understanding of the moral questions surrounding the beginning of life. Lay summary: This article seeks to make sense of what appears to be a clear-cut rejection, set out in the Congregation for the Doctrine of the Faith (CDF) document Dignitas personae, of the proposal for women to "adopt" surplus frozen embryos. It draws upon more recently developed modes of philosophical/theological reasoning to argue that, in human procreation, both fertilization and implantation represent constitutive dimensions of divine creative activity and so must be protected from manipulative technological intervention. Since embryo adoption requires this kind of technology, it makes sense for the Church document not to approve it. PMID:25698841

  16. CONFORMANCE IMPROVEMENT USING GELS

    SciTech Connect

    Randall S. Seright

    2003-09-01

    This report describes work performed during the second year of the project, ''Conformance Improvement Using Gels.'' The project has two objectives. The first objective is to identify gel compositions and conditions that substantially reduce flow through fractures that allow direct channeling between wells, while leaving secondary fractures open so that high fluid injection and production rates can be maintained. The second objective is to optimize treatments in fractured production wells, where the gel must reduce permeability to water much more than that to oil. Pore-level images from X-ray computed microtomography were re-examined for Berea sandstone and porous polyethylene. This analysis suggests that oil penetration through gel-filled pores occurs by a gel-dehydration mechanism, rather than a gel-ripping mechanism. This finding helps to explain why aqueous gels can reduce permeability to water more than to oil. We analyzed a Cr(III)-acetate-HPAM gel treatment in a production well in the Arbuckle formation. The availability of accurate pressure data before, during, and after the treatment was critical for the analysis. After the gel treatment, water productivity was fairly constant at about 20% of the pre-treatment value. However, oil productivity was stimulated by a factor of 18 immediately after the treatment. During the six months after the treatment, oil productivity gradually decreased to approach the pre-treatment value. To explain this behavior, we proposed that the fracture area open to oil flow was increased substantially by the gel treatment, followed by a gradual closing of the fractures during subsequent production. For a conventional Cr(III)-acetate-HPAM gel, the delay between gelant preparation and injection into a fracture impacts the placement, leakoff, and permeability reduction behavior. Formulations placed as partially formed gels showed relatively low pressure gradients during placement, and yet substantially reduced the flow capacity of

  17. Conformality lost: Broken symmetries in the early universe

    NASA Astrophysics Data System (ADS)

    Joyce, Austin

    In this dissertation, we introduce and investigate a general framework to describe the dynamics of the early universe. This mechanism is based on spontaneously broken conformal symmetry; we find that spectator fields in the theory can acquire a scale invariant spectrum of perturbations under generic conditions. Before introducing the conformal mechanism, we first consider the landscape of cosmologies involving a single scalar field which can address the canonical early universe puzzles. We find that, generically, single field non-inflationary solutions become strongly-coupled. We are therefore led to consider theories with multiple fields. We introduce the conformal mechanism via specific examples before constructing the most general effective theory for the conformal mechanism by utilizing the coset construction familiar from particle physics to construct the lagrangian for the Goldstone field of the broken conformal symmetry. This theory may be observationally distinguished from inflation by considering the non-linearly realized conformal symmetries. We systematically derive the Ward identities associated to the non-linearly realized symmetries, which relate (N + 1)-point correlation functions with a soft external Goldstone to N-point functions, and discuss observational implications, which cannot be mimicked by inflation. Finally, we consider violating the null energy condition (NEC) within the general framework considered. We show that the DBI conformal galileons, derived from the world-volume theory of a 3-brane moving in an Anti-de Sitter bulk, admit a background which violates the NEC. Unlike other known examples of NEC violation, such as ghost condensation and conformal galileons, this theory also admits a stable, Poincare-invariant vacuum. However, perturbations around deformations of this solution propagate superluminally.

  18. Linkage-specific conformational ensembles of non-canonical polyubiquitin chains.

    PubMed

    Castañeda, Carlos A; Chaturvedi, Apurva; Camara, Christina M; Curtis, Joseph E; Krueger, Susan; Fushman, David

    2016-02-17

    Polyubiquitination is a critical protein post-translational modification involved in a variety of processes in eukaryotic cells. The molecular basis for selective recognition of the polyubiquitin signals by cellular receptors is determined by the conformations polyubiquitin chains adopt; this has been demonstrated for K48- and K63-linked chains. Recent studies of the so-called non-canonical chains (linked via K6, K11, K27, K29, or K33) suggest they play important regulatory roles in growth, development, and immune system pathways, but biophysical studies are needed to elucidate the physical/structural basis of their interactions with receptors. A first step towards this goal is characterization of the conformations these chains adopt in solution. We assembled diubiquitins (Ub2) comprised of every lysine linkage. Using solution NMR measurements, small-angle neutron scattering (SANS), and in silico ensemble generation, we determined population-weighted conformational ensembles that shed light on the structure and dynamics of the non-canonical polyubiquitin chains. We found that polyubiquitin is conformationally heterogeneous, and each chain type exhibits unique conformational ensembles. For example, K6-Ub2 and K11-Ub2 (at physiological salt concentration) are in dynamic equilibrium between at least two conformers, where one exhibits a unique Ub/Ub interface, distinct from that observed in K48-Ub2 but similar to crystal structures of these chains. Conformers for K29-Ub2 and K33-Ub2 resemble recent crystal structures in the ligand-bound state. Remarkably, a number of diubiquitins adopt conformers similar to K48-Ub2 or K63-Ub2, suggesting potential overlap of biological function among different lysine linkages. These studies highlight the potential power of determining function from elucidation of conformational states.

  19. To conform or not to conform: spontaneous conformity diminishes the sensitivity to monetary outcomes.

    PubMed

    Yu, Rongjun; Sun, Sai

    2013-01-01

    When people have different opinions in a group, they often adjust their own attitudes and behaviors to match the group opinion, known as social conformity. The affiliation account of normative conformity states that people conform to norms in order to 'fit in', whereas the accuracy account of informative conformity posits that the motive to learn from others produces herding. Here, we test another possibility that following the crowd reduces the experienced negative emotion when the group decision turns out to be a bad one. Using event related potential (ERP) combined with a novel group gambling task, we found that participants were more likely to choose the option that was predominately chosen by other players in previous trials, although there was little explicit normative pressure at the decision stage and group choices were not informative. When individuals' choices were different from others, the feedback related negativity (FRN), an ERP component sensitive to losses and errors, was enhanced, suggesting that being independent is aversive. At the outcome stage, the losses minus wins FRN effect was significantly reduced following conformity choices than following independent choices. Analyses of the P300 revealed similar patterns both in the response and outcome period. Our study suggests that social conformity serves as an emotional buffer that protects individuals from experiencing strong negative emotion when the outcomes are bad.

  20. Fluctuation Flooding Method (FFM) for accelerating conformational transitions of proteins

    NASA Astrophysics Data System (ADS)

    Harada, Ryuhei; Takano, Yu; Shigeta, Yasuteru

    2014-03-01

    A powerful conformational sampling method for accelerating structural transitions of proteins, "Fluctuation Flooding Method (FFM)," is proposed. In FFM, cycles of the following steps enhance the transitions: (i) extractions of largely fluctuating snapshots along anisotropic modes obtained from trajectories of multiple independent molecular dynamics (MD) simulations and (ii) conformational re-sampling of the snapshots via re-generations of initial velocities when re-starting MD simulations. In an application to bacteriophage T4 lysozyme, FFM successfully accelerated the open-closed transition with the 6 ns simulation starting solely from the open state, although the 1-μs canonical MD simulation failed to sample such a rare event.

  1. Conformational features and recognition properties of a conformationally blocked calix[7]arene derivative.

    PubMed

    Gaeta, Carmine; Talotta, Carmen; Farina, Francesco; Campi, Gaetano; Camalli, Mercedes; Neri, Placido

    2012-01-23

    The shaping of a calix[7]arene macrocycle into cone-like structure 3, through exhaustive alkylation of doubly bridged calix[7]arene derivative 2 with bulky groups, has been investigated. Conformational details about the structure adopted by calix[7]arene derivative 3 in solution have been obtained by using chemical shift surface maps, as previously reported by our group. Thus, chemical shift contour plots indicated that 3 adopted a cone-shaped structure in solution analogous to that adopted by the known p-tert-butylcalix[7]arene heptacarboxylic acid derivative 4. Interestingly, the X-ray structure of derivative 3 showed a high degree of similarity to the theoretical structure, which confirmed the validity of the contour plots method. The preorganized calix[7]arene host 3 showed interesting recognition abilities toward both organic and alkali cations. In fact, an unprecedented endo-cavity complexation of linear and branched alkyl ammonium cations with a larger calix[7]arene host was evidenced. A comparable affinity for branched tBuNH(3)(+) and linear nBuNH(3)(+) guests was observed.

  2. In-Group Conformity Sustains Different Foraging Traditions in Capuchin Monkeys (Cebus apella)

    PubMed Central

    Dindo, Marietta; Whiten, Andrew; de Waal, Frans B. M.

    2009-01-01

    Background Decades of research have revealed rich cultural repertoires encompassing multiple traditions in wild great apes, a picture crucially complemented by experimental simulations with captive apes. Studies with wild capuchin monkeys, the most encephalized simian species, have indicated a New World convergence on these cultural phenomena, involving multiple traditions and tool use. However, experimental studies to date are in conflict with such findings in concluding that capuchins, like other monkeys, show minimal capacities for social learning. Methodology/Principal Findings Here we report a new experimental approach in which the alpha male of each of two groups of capuchins was trained to open an artificial foraging device in a quite different way, using either a slide or lift action, then reunited with his group. In each group a majority of monkeys, 8 of 11 and 13 of 14, subsequently mastered the task. Seventeen of the successful 21 monkeys discovered the alternative action to that seeded in the group, performing it a median of 4 times. Nevertheless, all 21 primarily adopted the technique seeded by their group's alpha male. Median proportions of slide versus lift were 0.96 for the group seeded with slide versus 0. 01 for the group seeded with lift. Conclusions/Significance These results suggest a striking effect of social conformity in learned behavioral techniques, consistent with field reports of capuchin traditions and convergent on the only other species in which such cultural phenomena have been reported, chimpanzees and humans. PMID:19924242

  3. p97 Disease Mutations Modulate Nucleotide-Induced Conformation to Alter Protein-Protein Interactions.

    PubMed

    Bulfer, Stacie L; Chou, Tsui-Fen; Arkin, Michelle R

    2016-08-19

    The AAA+ ATPase p97/VCP adopts at least three conformations that depend on the binding of ADP and ATP and alter the orientation of the N-terminal protein-protein interaction (PPI) domain into "up" and "down" conformations. Point mutations that cause multisystem proteinopathy 1 (MSP1) are found at the interface of the N domain and D1-ATPase domain and potentially alter the conformational preferences of p97. Additionally, binding of "adaptor" proteins to the N-domain regulates p97's catalytic activity. We propose that p97/adaptor PPIs are coupled to p97 conformational states. We evaluated the binding of nucleotides and the adaptor proteins p37 and p47 to wild-type p97 and MSP1 mutants. Notably, p47 and p37 bind 8-fold more weakly to the ADP-bound conformation of wild-type p97 compared to the ATP-bound conformation. However, MSP1 mutants lose this nucleotide-induced conformational coupling because they destabilize the ADP-bound, "down" conformation of the N-domain. Loss in conformation coupling to PPIs could contribute to the mechanism of MSP1. PMID:27267671

  4. Intra- and intermolecular forces dependent main chain conformations of esters of α,β-dehydroamino acids

    NASA Astrophysics Data System (ADS)

    Siodłak, Dawid; Bujak, Maciej; Staś, Monika

    2013-09-01

    Esters of dehydroamino acids occur in nature. To investigate their conformational properties, the low-temperature structures of Ac-ΔAla-OMe, Ac-ΔVal-OMe, Z-(Z)-ΔAbu-OMe, and Z-(Z)-ΔAbu-NHMe were studied by single-crystal X-ray diffraction. The ΔAla ester prefers the fully extended conformation C5. Both the ΔVal and (Z)-ΔAbu esters assume the conformation β, whereas the amide analogue of the latter prefers the conformation α. For the conformations found, DFT calculations using B3LYP/6-311++G(d,p) with the SCRF-PCM and M062X/6-311++G(d,p) with the SCRF-SMD method were applied to mimicking chloroform and water environment. The tendency of the ΔVal and (Z)-ΔAbu esters towards the conformation β, and their amide analogues towards the conformation α, with increase of the polarity of environment was found. The analysis of both intra- and intermolecular interactions including hydrogen bonds, carbonyl dipole attraction, and π-electron conjugation, enabled to understand and elucidate the conformational preferences of studied compounds. The studies show how the molecular structure, and in consequence, the conformation adopted by molecules is influenced by the different intra- and intermolecular forces.

  5. 40 CFR 93.154 - Conformity analysis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Conformity analysis. 93.154 Section 93...) DETERMINING CONFORMITY OF FEDERAL ACTIONS TO STATE OR FEDERAL IMPLEMENTATION PLANS Determining Conformity of General Federal Actions to State or Federal Implementation Plans § 93.154 Conformity analysis. Any...

  6. Fluorescence excitation spectrum and solvent-assisted conformational isomerization (SACI) of jet-cooled acetaminophen

    NASA Astrophysics Data System (ADS)

    Sohn, Woon Yong; Kang, Jeong Seok; Lee, So Young; Kang, Hyuk

    2013-08-01

    Fluorescence excitation spectrum of jet-cooled acetaminophen was obtained. When AAP was expanded with a buffer gas containing 0.3-1.1% of water, absorption peaks of the less stable trans conformer was significantly reduced by solvent-assisted conformational isomerization (SACI), which is confirmed by a separately measured UV-UV hole burning spectroscopy. It is also confirmed by quantum mechanical calculation and RRKM calculation that it is energetically and kinetically possible to induce SACI in AAP with water. The SACI mechanism suggests a possible pathway that acetaminophen can adopt an active conformation in vivo, which is need for molecular recognition and drug activity.

  7. Policy Issues in Gay and Lesbian Adoption.

    ERIC Educational Resources Information Center

    Sullivan, Ann

    1995-01-01

    Notes that adoption agencies have developed few specific policies on the issue of lesbian and gay adoption. Provides an overview of key considerations about homosexual adopters, including beliefs and values of agency professionals, the legal and social ramifications of adoption into a relationship not based on marriage, and possible consequences…

  8. 18 CFR 341.6 - Adoption rule.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Adoption rule. 341.6... SUBJECT TO SECTION 6 OF THE INTERSTATE COMMERCE ACT § 341.6 Adoption rule. (a) Change in name of carrier... such occurrence. The filing of adoption notices and adoption supplements requires no notice period....

  9. 18 CFR 341.6 - Adoption rule.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Adoption rule. 341.6... SUBJECT TO SECTION 6 OF THE INTERSTATE COMMERCE ACT § 341.6 Adoption rule. (a) Change in name of carrier... such occurrence. The filing of adoption notices and adoption supplements requires no notice period....

  10. 18 CFR 341.6 - Adoption rule.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Adoption rule. 341.6... SUBJECT TO SECTION 6 OF THE INTERSTATE COMMERCE ACT § 341.6 Adoption rule. (a) Change in name of carrier... such occurrence. The filing of adoption notices and adoption supplements requires no notice period....

  11. 18 CFR 341.6 - Adoption rule.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Adoption rule. 341.6... SUBJECT TO SECTION 6 OF THE INTERSTATE COMMERCE ACT § 341.6 Adoption rule. (a) Change in name of carrier... such occurrence. The filing of adoption notices and adoption supplements requires no notice period....

  12. 33 CFR 230.21 - Adoption.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... FOR IMPLEMENTING NEPA § 230.21 Adoption. See 40 CFR 1506.3. A district commander will normally adopt... recirculated as provided in 40 CFR 1506.3 (b) or (c), the adopted EIS with the supplement, if any, will be processed in accordance with this regulation. A district commander may also adopt another agency's EA/FONSI....

  13. 33 CFR 230.21 - Adoption.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... FOR IMPLEMENTING NEPA § 230.21 Adoption. See 40 CFR 1506.3. A district commander will normally adopt... recirculated as provided in 40 CFR 1506.3 (b) or (c), the adopted EIS with the supplement, if any, will be processed in accordance with this regulation. A district commander may also adopt another agency's EA/FONSI....

  14. 33 CFR 230.21 - Adoption.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... FOR IMPLEMENTING NEPA § 230.21 Adoption. See 40 CFR 1506.3. A district commander will normally adopt... recirculated as provided in 40 CFR 1506.3 (b) or (c), the adopted EIS with the supplement, if any, will be processed in accordance with this regulation. A district commander may also adopt another agency's EA/FONSI....

  15. 33 CFR 230.21 - Adoption.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... FOR IMPLEMENTING NEPA § 230.21 Adoption. See 40 CFR 1506.3. A district commander will normally adopt... recirculated as provided in 40 CFR 1506.3 (b) or (c), the adopted EIS with the supplement, if any, will be processed in accordance with this regulation. A district commander may also adopt another agency's EA/FONSI....

  16. 33 CFR 230.21 - Adoption.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... FOR IMPLEMENTING NEPA § 230.21 Adoption. See 40 CFR 1506.3. A district commander will normally adopt... recirculated as provided in 40 CFR 1506.3 (b) or (c), the adopted EIS with the supplement, if any, will be processed in accordance with this regulation. A district commander may also adopt another agency's EA/FONSI....

  17. Adoption and Single Parents: A Review.

    ERIC Educational Resources Information Center

    Groze, Vic

    1991-01-01

    Examines the literature about people who choose to become single adoptive parents. Reviews the demographic and personal characteristics of single parents who adopt, and summarizes the experiences of single parents with the children they adopt. Calls for further research on single parents who adopt special needs children. (GH)

  18. Adoption Factors of the Electronic Health Record: A Systematic Review

    PubMed Central

    2016-01-01

    Background The Health Information Technology for Economic and Clinical Health (HITECH) was a significant piece of legislation in America that served as a catalyst for the adoption of health information technology. Following implementation of the HITECH Act, Health Information Technology (HIT) experienced broad adoption of Electronic Health Records (EHR), despite skepticism exhibited by many providers for the transition to an electronic system. A thorough review of EHR adoption facilitator and barriers provides ongoing support for the continuation of EHR implementation across various health care structures, possibly leading to a reduction in associated economic expenditures. Objective The purpose of this review is to compile a current and comprehensive list of facilitators and barriers to the adoption of the EHR in the United States. Methods Authors searched Cumulative Index of Nursing and Allied Health Literature (CINAHL) and MEDLINE, 01/01/2012–09/01/2015, core clinical/academic journals, MEDLINE full text, and evaluated only articles germane to our research objective. Team members selected a final list of articles through consensus meetings (n=31). Multiple research team members thoroughly read each article to confirm applicability and study conclusions, thereby increasing validity. Results Group members identified common facilitators and barriers associated with the EHR adoption process. In total, 25 adoption facilitators were identified in the literature occurring 109 times; the majority of which were efficiency, hospital size, quality, access to data, perceived value, and ability to transfer information. A total of 23 barriers to adoption were identified in the literature, appearing 95 times; the majority of which were cost, time consuming, perception of uselessness, transition of data, facility location, and implementation issues. Conclusions The 25 facilitators and 23 barriers to the adoption of the EHR continue to reveal a preoccupation on cost, despite

  19. A longitudinal investigation of children internationally adopted at school age.

    PubMed

    Helder, Emily J; Mulder, Elizabeth; Gunnoe, Marjorie Linder

    2016-01-01

    Most existing research on children adopted internationally has focused on those adopted as infants and toddlers. The current study longitudinally tracked several outcomes, including cognitive, behavioral, emotional, attachment, and family functioning, in 25 children who had been internationally adopted at school age (M = 7.7 years old at adoption, SD = 3.4, range = 4–15 years). We examined the incidence of clinically significant impairments, significant change in outcomes over the three study points, and variables that predicted outcomes over time. Clinically significant impairments in sustained attention, full-scale intelligence, reading, language, executive functioning, externalizing problems, and parenting stress were common, with language and executive functioning impairments present at higher levels in the current study compared with past research focusing on children adopted as infants and toddlers. Over the three study points, significant improvements across most cognitive areas and attachment functioning were observed, though significant worsening in executive functioning and internalizing problems was present. Adoptive family-specific variables, such as greater maternal education, smaller family size, a parenting approach that encouraged age-expected behaviors, home schooling, and being the sole adopted child in the family were associated with greater improvement across several cognitive outcomes. In contrast, decreased parenting stress was predicted by having multiple adopted children and smaller family sizes were associated with greater difficulties with executive functioning. Child-specific variables were also linked to outcomes, with girls displaying worse attachment and poorer cognitive performance and with less time in orphanage care resulting in greater adoption success. Implications for future research and clinical applications are discussed.

  20. Adopted: A practical salinity scale

    NASA Astrophysics Data System (ADS)

    The Unesco/ICES/SCOR/IAPSO Joint Panel on Oceanographic Tables and Standards has recommended the adoption of a Practical Salinity Scale, 1978, and a corresponding new International Equation of State of Seawater, 1980. A full account of the research leading to their recommendation is available in the series Unesco Technical Papers in Marine Science.The parent organizations have accepted the panel's recommendations and have set January 1, 1982, as the date when the new procedures, formulae, and tables should replace those now in use.

  1. Adoptive cell therapy for sarcoma

    PubMed Central

    Mata, Melinda; Gottschalk, Stephen

    2015-01-01

    Current therapy for sarcomas, though effective in treating local disease, is often ineffective for patients with recurrent or metastatic disease. To improve outcomes, novel approaches are needed and cell therapy has the potential to meet this need since it does not rely on the cytotoxic mechanisms of conventional therapies. The recent successes of T-cell therapies for hematological malignancies have led to renewed interest in exploring cell therapies for solid tumors such as sarcomas. In this review, we will discuss current cell therapies for sarcoma with special emphasis on genetic approaches to improve the effector function of adoptively transferred cells. PMID:25572477

  2. UN adopts Law of Sea

    NASA Astrophysics Data System (ADS)

    Richman, Barbara T.

    After more than 8 years of diplomatic wrangling, the United Nations Convention on the Law of the Sea was adopted on April 30 by a vote of 130 to 4. The United States, Israel, Turkey, and Venezuela voted against the treaty; 17 nations—including the Soviet Union, West Germany, and Britain—abstained.The treaty, which would give nations the exclusive rights to natural resources in the continental shelf up to approximately 650 km offshore, will be signed in December. The treaty becomes effective 1 year after at least 60 nations ratify it.

  3. Studies on the Conformational Features of Neomycin-B and its Molecular Recognition by RNA and Bacterial Defense Proteins

    NASA Astrophysics Data System (ADS)

    Asensio, Juan Luis; Bastida, Agatha; Jiménez-Barbero, Jesús

    According to NMR and molecular dynamics simulations, the conformational behavior of natural aminoglycosides is characterized by a remarkable flexibility, with different conformations, even non-exo-anomeric ones, in fast exchange. Very probably, this feature allows the adaptation of these ligands to the spatial and electronic requirements of different receptors. The large diversity of structures adopted by aminoglycosides in the binding pocket of the different RNA receptors and the distinct enzymes involved in bacterial resistance are consistent with this view. This conformational diversity can, in certain favorable cases, be exploited in the design of new antibiotic derivatives not susceptible to enzymatic inactivation, by designing tailor-made conformationally locked aminoglycosides.

  4. Universality class in conformal inflation

    SciTech Connect

    Kallosh, Renata; Linde, Andrei E-mail: alinde@stanford.edu

    2013-07-01

    We develop a new class of chaotic inflation models with spontaneously broken conformal invariance. Observational consequences of a broad class of such models are stable with respect to strong deformations of the scalar potential. This universality is a critical phenomenon near the point of enhanced symmetry, SO(1,1), in case of conformal inflation. It appears because of the exponential stretching of the moduli space and the resulting exponential flattening of scalar potentials upon switching from the Jordan frame to the Einstein frame in this class of models. This result resembles stretching and flattening of inhomogeneities during inflationary expansion. It has a simple interpretation in terms of velocity versus rapidity near the Kähler cone in the moduli space, similar to the light cone of special theory of relativity. This effect makes inflation possible even in the models with very steep potentials. We describe conformal and superconformal versions of this cosmological attractor mechanism.

  5. [Adoptive parents' satisfaction with the adoption experience and with its impact on family life].

    PubMed

    Sánchez-Sandoval, Yolanda

    2011-11-01

    In this study, we discuss the relevance of adoptive families' satisfaction in the assessment of adoption processes. The effects of adoption on a sample group of 272 adoptive families are analyzed. Most families show high levels of satisfaction as to: their decision to adopt, the features of their adopted children and how adoption has affected them as individuals and as a family. Statistical analyses show that these families can have different satisfaction levels depending on certain features of the adoptees, of the adoptive families or of their educational style. Life satisfaction of the adoptees is also related to how their adoptive parents evaluate the adoption.

  6. [Adoptive parents' satisfaction with the adoption experience and with its impact on family life].

    PubMed

    Sánchez-Sandoval, Yolanda

    2011-11-01

    In this study, we discuss the relevance of adoptive families' satisfaction in the assessment of adoption processes. The effects of adoption on a sample group of 272 adoptive families are analyzed. Most families show high levels of satisfaction as to: their decision to adopt, the features of their adopted children and how adoption has affected them as individuals and as a family. Statistical analyses show that these families can have different satisfaction levels depending on certain features of the adoptees, of the adoptive families or of their educational style. Life satisfaction of the adoptees is also related to how their adoptive parents evaluate the adoption. PMID:22047850

  7. Embryo adoption: Some further considerations

    PubMed Central

    Patterson, Colin

    2015-01-01

    Recent discussions of embryo adoption have sought to make sense of the teaching of the Congregation for the Doctrine of the Faith (CDF) document Dignitas personae which appeared to provide a negative judgment on such a practice. This article aims to provide a personalist account of the process of fertilization and implantation that might serve as the basis for the negative judgment of the CDF document. In doing so, it relies upon the idea that a person, including an embryo, is not to be considered in isolation, but always in relation to God and to others. This approach extends the substantialist conceptualizations commonly employed in discussions of this issue. More generally, the article seeks to highlight the value of a personalist re-framing for an understanding of the moral questions surrounding the beginning of life. Lay summary: This article seeks to make sense of what appears to be a clear-cut rejection, set out in the Congregation for the Doctrine of the Faith (CDF) document Dignitas personae, of the proposal for women to “adopt” surplus frozen embryos. It draws upon more recently developed modes of philosophical/theological reasoning to argue that, in human procreation, both fertilization and implantation represent constitutive dimensions of divine creative activity and so must be protected from manipulative technological intervention. Since embryo adoption requires this kind of technology, it makes sense for the Church document not to approve it. PMID:25698841

  8. A sampling approach for protein backbone fragment conformations.

    PubMed

    Yu, J Y; Zhang, W

    2013-01-01

    In protein structure prediction, backbone fragment bias information can narrow down the conformational space of the whole polypeptide chain significantly. Unlike existing methods that use fragments as building blocks, the paper presents a probabilistic sampling approach for protein backbone torsion angles by modelling angular correlation of (phi, psi) with a directional statistics distribution. Given a protein sequence and secondary structure information, this method samples backbone fragments conformations by using a backtrack sampling algorithm for the hidden Markov model with multiple inputs and a single output. The proposed approach is applied to a fragment library, and some well-known structural motifs are sampled very well on the optimal path. Computational results show that the method can help to obtain native-like backbone fragments conformations. PMID:23777175

  9. A topological and conformational stability alphabet for multipass membrane proteins.

    PubMed

    Feng, Xiang; Barth, Patrick

    2016-03-01

    Multipass membrane proteins perform critical signal transduction and transport across membranes. How transmembrane helix (TMH) sequences encode the topology and conformational flexibility regulating these functions remains poorly understood. Here we describe a comprehensive analysis of the sequence-structure relationships at multiple interacting TMHs from all membrane proteins with structures in the Protein Data Bank (PDB). We found that membrane proteins can be deconstructed in interacting TMH trimer units, which mostly fold into six distinct structural classes of topologies and conformations. Each class is enriched in recurrent sequence motifs from functionally unrelated proteins, revealing unforeseen consensus and evolutionary conserved networks of stabilizing interhelical contacts. Interacting TMHs' topology and local protein conformational flexibility were remarkably well predicted in a blinded fashion from the identified binding-hotspot motifs. Our results reveal universal sequence-structure principles governing the complex anatomy and plasticity of multipass membrane proteins that may guide de novo structure prediction, design, and studies of folding and dynamics. PMID:26780406

  10. Fe-heme conformations in ferric myoglobin.

    PubMed Central

    Longa, S D; Pin, S; Cortès, R; Soldatov, A V; Alpert, B

    1998-01-01

    X-ray absorption near-edge structure (XANES) spectra of ferric myoglobin from horse heart have been acquired as a function of pH (between 5.3 and 11.3). At pH = 11.3 temperature-dependent spectra (between 20 and 293 K) have been collected as well. Experimental data solve three main conformations of the Fe-heme: the first, at low pH, is related to high-spin aquomet-myoglobin (Mb+OH2). The other two, at pH 11.3, are related to hydroxymet-myoglobin (Mb+OH-), and are in thermal equilibrium, corresponding to high- and low-spin Mb+OH-. The structure of the three Fe-heme conformations has been assigned according to spin-resolved multiple scattering simulations and fitting of the XANES data. The chemical transition between Mb+OH2 and high-spin Mb+OH-, and the spin transition of Mb+OH-, are accompanied by changes of the Fe coordination sphere due to its movement toward the heme plane, coupled to an increase of the axial asymmetry. PMID:9826636

  11. Conformation-sensitive capillary electrophoresis.

    PubMed

    Ashton, Emma Jane

    2011-01-01

    Conformation-sensitive capillary electrophoresis (CSCE) is a rapid, high-throughput screening method that can be applied to any region of a genome for detection of sequence variants. Slab gel-based conformation-sensitive gel electrophoresis was first described by Ganguly et al., and the transfer from slab gels to capillaries for higher throughput was reported by Rozycka et al. CSCE is based on the principle that DNA homoduplexes and heteroduplexes migrate at different rates during electrophoresis under mildly denaturing conditions. Fragments showing an altered peak morphology compared to the wild type are then sequenced to determine the precise nature of the sequence variant detected.

  12. Interaction of multiple biomimetic antimicrobial polymers with model bacterial membranes

    SciTech Connect

    Baul, Upayan Vemparala, Satyavani; Kuroda, Kenichi

    2014-08-28

    Using atomistic molecular dynamics simulations, interaction of multiple synthetic random copolymers based on methacrylates on prototypical bacterial membranes is investigated. The simulations show that the cationic polymers form a micellar aggregate in water phase and the aggregate, when interacting with the bacterial membrane, induces clustering of oppositely charged anionic lipid molecules to form clusters and enhances ordering of lipid chains. The model bacterial membrane, consequently, develops lateral inhomogeneity in membrane thickness profile compared to polymer-free system. The individual polymers in the aggregate are released into the bacterial membrane in a phased manner and the simulations suggest that the most probable location of the partitioned polymers is near the 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG) clusters. The partitioned polymers preferentially adopt facially amphiphilic conformations at lipid-water interface, despite lacking intrinsic secondary structures such as α-helix or β-sheet found in naturally occurring antimicrobial peptides.

  13. [Adoption: an alternative to assisted reproductive techniques?].

    PubMed

    Blanchy, S

    2011-09-01

    Information on adoption must be given to couples who seek treatment for medically-assisted procreation. But is adoption a real alternative? What are the chances for a couple who consults to see its desire for adoption be achieved according to its own situation, the characteristics of the child he wants, and the general situation of adoption? Can adoption, just like assisted procreation, often described by the couples as a "obstacle course", go parallel? Or should one try adoption once assisted reproduction failed? Is the couple willing to suffer the social and legal control of adoption after having supported the medical control of the ART? In all cases, the reality is that two out of three couples engaged in assisted reproduction will have a child whereas scarcely more than one candidate to adoption will be offered to adopt a child after three or four-years procedure.

  14. Asymmetric conformational maturation of HIV-1 reverse transcriptase

    PubMed Central

    Zheng, Xunhai; Perera, Lalith; Mueller, Geoffrey A; DeRose, Eugene F; London, Robert E

    2015-01-01

    HIV-1 reverse transcriptase utilizes a metamorphic polymerase domain that is able to adopt two alternate structures that fulfill catalytic and structural roles, thereby minimizing its coding requirements. This ambiguity introduces folding challenges that are met by a complex maturation process. We have investigated this conformational maturation using NMR studies of methyl-labeled RT for the slower processes in combination with molecular dynamics simulations for rapid processes. Starting from an inactive conformation, the p66 precursor undergoes a unimolecular isomerization to a structure similar to its active form, exposing a large hydrophobic surface that facilitates initial homodimer formation. The resulting p66/p66' homodimer exists as a conformational heterodimer, after which a series of conformational adjustments on different time scales can be observed. Formation of the inter-subunit RH:thumb' interface occurs at an early stage, while maturation of the connection' and unfolding of the RH' domains are linked and occur on a much slower time scale. DOI: http://dx.doi.org/10.7554/eLife.06359.001 PMID:26037594

  15. Chain conformational and physicochemical properties of fucoidans from sea cucumber.

    PubMed

    Xu, Xiaoqi; Xue, Changhu; Chang, Yaoguang; Wang, Jun; Jiang, Kunhao

    2016-11-01

    Although fucoidans from sea cucumber (SC-FUCs) have been proven as potential bioactive polysaccharides and functional food ingridents, their chain conformation and physicochemical properties were still poorly understood. This study investigated the chain conformation of fucoidans from sea cucumber Acaudina molpadioides (Am-FUC), Isostichopus badionotus (Ib-FUC) and Apostichopus japonicus (Aj-FUC), of which primary structure has been recently clarified. Chain conformation parameters demonstrated that studied SC-FUCs adopted random coil conformation in 150mM NaCl solution (pH 7.4). Based on the worm-like cylinder model and atomic force microscopy, the chain stiffness of SC-FUCs was further evaluated as Am-FUC≈Ib-FUC>Aj-FUC. It was suggested that the existence of branch structure increased the chain flexibility, while sulfated pattern exerted limited influence. SC-FUCs demonstrated shear-thinning rheological behavior and negative charge. Am-FUC possessed a higher thermostability than Ib-FUC and Aj-FUC. These results have important implications for understanding the molecular characteristics of SC-FUCs, which could facilitate their further application.

  16. Chain conformational and physicochemical properties of fucoidans from sea cucumber.

    PubMed

    Xu, Xiaoqi; Xue, Changhu; Chang, Yaoguang; Wang, Jun; Jiang, Kunhao

    2016-11-01

    Although fucoidans from sea cucumber (SC-FUCs) have been proven as potential bioactive polysaccharides and functional food ingridents, their chain conformation and physicochemical properties were still poorly understood. This study investigated the chain conformation of fucoidans from sea cucumber Acaudina molpadioides (Am-FUC), Isostichopus badionotus (Ib-FUC) and Apostichopus japonicus (Aj-FUC), of which primary structure has been recently clarified. Chain conformation parameters demonstrated that studied SC-FUCs adopted random coil conformation in 150mM NaCl solution (pH 7.4). Based on the worm-like cylinder model and atomic force microscopy, the chain stiffness of SC-FUCs was further evaluated as Am-FUC≈Ib-FUC>Aj-FUC. It was suggested that the existence of branch structure increased the chain flexibility, while sulfated pattern exerted limited influence. SC-FUCs demonstrated shear-thinning rheological behavior and negative charge. Am-FUC possessed a higher thermostability than Ib-FUC and Aj-FUC. These results have important implications for understanding the molecular characteristics of SC-FUCs, which could facilitate their further application. PMID:27516290

  17. Conformational homogeneity in molecular recognition by proteolytic enzymes.

    PubMed

    Tyndall, J D; Fairlie, D P

    1999-01-01

    Crystal structures for several hundred protease-inhibitor complexes have been analysed and their superimpositions have been used to demonstrate a universal relationship between inhibitor/substrate conformation and molecular recognition by all aspartic, serine, cysteine and metallo proteases. Proteases universally recognize an extended beta strand conformation in all their peptidic (and non-peptidic) inhibitors and substrate analogues without significant exceptions. This conformational homogeneity is illustrated here for a subset of 180 protease-inhibitor structures which are displayed as (a) structural overlays of multiple inhibitors for each of eight aspartic, eight serine, six metallo and five cysteine proteases; (b) single inhibitors each bound to different proteases; and (c) Ramachandran plots of peptide or pseudo-peptide dihedral angle pairs which demonstrate beta strands (Phi -54 degrees to -173 degrees, Psi 24 degrees to 174 degrees ) like those normally found paired in proteins as beta sheets. However, unlike beta sheets, alpha and 3(10) helices, beta and gamma turns, where the folded main chain amide components are intramolecularly hydrogen bonded and thus unavailable for interaction with proteins, an inhibitor/substrate in an isolated beta strand conformation provides maximum exposure of its hydrogen bonding donors/acceptors and side chain components to a putative protease receptor. This analysis highlights the advantages of a strand conformation over other elements of secondary structure for protease recognition and may lead to generic strategies for inhibitor design.

  18. Electronic Dental Records System Adoption.

    PubMed

    Abramovicz-Finkelsztain, Renata; Barsottini, Claudia G N; Marin, Heimar Fatima

    2015-01-01

    The use of Electronic Dental Records (EDRs) and management software has become more frequent, following the increase in prevelance of new technologies and computers in dental offices. The purpose of this study is to identify and evaluate the use of EDRs by the dental community in the São Paulo city area. A quantitative case study was performed using a survey on the phone. A total of 54 offices were contacted and only one declinedparticipation in this study. Only one office did not have a computer. EDRs were used in 28 offices and only four were paperless. The lack of studies in this area suggests the need for more usability and implementation studies on EDRs so that we can improve EDR adoption by the dental community.

  19. Determination of the Influence of Side-Chain Conformation on Glycosylation Selectivity using Conformationally Restricted Donors.

    PubMed

    Dharuman, Suresh; Crich, David

    2016-03-18

    The synthesis of a series of conformationally locked mannopyranosyl thioglycosides in which the C6-O6 bond adopts either the gauche,gauche, gauche,trans, or trans,gauche conformation is described, and their influence on glycosylation stereoselectivity investigated. Two 4,6-O-benzylidene-protected mannosyl thioglycosides carrying axial or equatorial methyl groups at the 6-position were also synthesized and the selectivity of their glycosylation reactions studied to enable a distinction to be made between steric and stereoelectronic effects. The presence of an axial methoxy group at C6 in the bicyclic donor results in a decreased preference for formation of the β-mannoside, whereas an axial methyl group has little effect on selectivity. The result is rationalized in terms of through-space stabilization of a transient intermediate oxocarbenium ion by the axial methoxy group resulting in a higher degree of SN 1-like character in the glycosylation reaction. Comparisons are made with literature examples and exceptions are discussed in terms of pervading steric effects layered on top of the basic stereoelectronic effect.

  20. Tetrazole acetic acid: tautomers, conformers, and isomerization.

    PubMed

    Araujo-Andrade, C; Reva, I; Fausto, R

    2014-02-14

    Monomers of (tetrazol-5-yl)-acetic acid (TAA) were obtained by sublimation of the crystalline compound and the resulting vapors were isolated in cryogenic nitrogen matrices at 13 K. The conformational and tautomeric composition of TAA in the matrix was characterized by infrared spectroscopy and vibrational calculations carried out at the B3LYP/6-311++G(d,p) level. TAA may adopt two tautomeric modifications, 1H- and 2H-, depending on the position of the annular hydrogen atom. Two-dimensional potential energy surfaces (PESs) of TAA were theoretically calculated at the MP2/6-311++G(d,p) level, for each tautomer. Four and six symmetry-unique minima were located on these PESs, for 1H- and 2H-TAA, respectively. The energetics of the detected minima was subsequently refined by calculations at the QCISD level. Two 1H- and three 2H-conformers fall within the 0-8 kJ mol(-1) energy range and should be appreciably populated at the sublimation temperature (∼330 K). Observation of only one conformer for each tautomer (1ccc and 2pcc) is explained in terms of calculated barriers to conformational rearrangements. All conformers with the cis O=COH moiety are separated by low barriers (less than 10 kJ mol(-1)) and collapse to the most stable 1ccc (1H-) and 2pcc (2H-) forms during deposition of the matrix. On the trans O=COH surfaces, the relative energies are very high (between 12 and 27 kJ mol(-1)). The trans forms are not thermally populated at the sublimation conditions and were not detected in matrices. One high-energy form in each tautomer, 1cct (1H-) and 2pct (2H-), was found to differ from the most stable form only by rotation of the OH group and separated from other forms by high barriers. This opened a perspective for their stabilization in a matrix. 1cct and 2pct were generated in the matrices selectively by means of narrow-band near-infrared (NIR) irradiations of the samples at 6920 and 6937 cm(-1), where the first OH stretching overtone vibrations of 1ccc and 2pcc occur

  1. Tetrazole acetic acid: Tautomers, conformers, and isomerization

    SciTech Connect

    Araujo-Andrade, C.; Reva, I. Fausto, R.

    2014-02-14

    Monomers of (tetrazol-5-yl)-acetic acid (TAA) were obtained by sublimation of the crystalline compound and the resulting vapors were isolated in cryogenic nitrogen matrices at 13 K. The conformational and tautomeric composition of TAA in the matrix was characterized by infrared spectroscopy and vibrational calculations carried out at the B3LYP/6-311++G(d,p) level. TAA may adopt two tautomeric modifications, 1H- and 2H-, depending on the position of the annular hydrogen atom. Two-dimensional potential energy surfaces (PESs) of TAA were theoretically calculated at the MP2/6-311++G(d,p) level, for each tautomer. Four and six symmetry-unique minima were located on these PESs, for 1H- and 2H-TAA, respectively. The energetics of the detected minima was subsequently refined by calculations at the QCISD level. Two 1H- and three 2H-conformers fall within the 0–8 kJ mol{sup −1} energy range and should be appreciably populated at the sublimation temperature (∼330 K). Observation of only one conformer for each tautomer (1ccc and 2pcc) is explained in terms of calculated barriers to conformational rearrangements. All conformers with the cis O=COH moiety are separated by low barriers (less than 10 kJ mol{sup −1}) and collapse to the most stable 1ccc (1H-) and 2pcc (2H-) forms during deposition of the matrix. On the trans O=COH surfaces, the relative energies are very high (between 12 and 27 kJ mol{sup −1}). The trans forms are not thermally populated at the sublimation conditions and were not detected in matrices. One high-energy form in each tautomer, 1cct (1H-) and 2pct (2H-), was found to differ from the most stable form only by rotation of the OH group and separated from other forms by high barriers. This opened a perspective for their stabilization in a matrix. 1cct and 2pct were generated in the matrices selectively by means of narrow-band near-infrared (NIR) irradiations of the samples at 6920 and 6937 cm{sup −1}, where the first OH stretching overtone

  2. Temperature: Human Regulating, Ants Conforming

    ERIC Educational Resources Information Center

    Clopton, Joe R.

    2007-01-01

    Biological processes speed up as temperature rises. Procedures for demonstrating this with ants traveling on trails, and data gathered by students on the Argentine ant ("Linepithema humile") are presented. The concepts of temperature regulation and conformity are detailed with a focus on the processes rather than on terms that label the organisms.

  3. Conformal coating using parylene polymers.

    PubMed

    Noordegraaf, J

    1997-01-01

    Parylene, a conformal polymer film, is being used increasingly in Europe to provide environmental and dielectric isolation. Application areas include electronic circuitry, sensors, and medical substrates. This article describes the variants of parylene and their characteristics, together with the process and applications of parylene coating. PMID:10167681

  4. The conformational analysis of 2-halocyclooctanones.

    PubMed

    Rozada, Thiago C; Gauze, Gisele F; Rosa, Fernanda A; Favaro, Denize C; Rittner, Roberto; Pontes, Rodrigo M; Basso, Ernani A

    2015-02-25

    The establishment of the most stable structures of eight membered rings is a challenging task to the field of conformational analysis. In this work, a series of 2-halocyclooctanones were synthesized (including fluorine, chlorine, bromine and iodine derivatives) and submitted to conformational studies using a combination of theoretical calculation and infrared spectroscopy. For each compound, four conformations were identified as the most important ones. These conformations are derived from the chair-boat conformation of cyclooctanone. The pseudo-equatorial (with respect to the halogen) conformer is preferred in vacuum and in low polarity solvents for chlorine, bromine and iodine derivatives. For 2-fluorocyclooctanone, the preferred conformation in vacuum is pseudo-axial. In acetonitrile, the pseudo-axial conformer becomes the most stable for the chlorine derivative. According to NBO calculations, the conformational preference is not dictated by electron delocalization, but by classical electrostatic repulsions.

  5. Remodeling of Lipid Vesicles into Cylindrical Micelles by α-Synuclein in an Extended α-Helical Conformation*

    PubMed Central

    Mizuno, Naoko; Varkey, Jobin; Kegulian, Natalie C.; Hegde, Balachandra G.; Cheng, Naiqian; Langen, Ralf; Steven, Alasdair C.

    2012-01-01

    α-Synuclein (αS) is a protein with multiple conformations and interactions. Natively unfolded in solution, αS accumulates as amyloid in neurological tissue in Parkinson disease and interacts with membranes under both physiological and pathological conditions. Here, we used cryoelectron microscopy in conjunction with electron paramagnetic resonance (EPR) and other techniques to characterize the ability of αS to remodel vesicles. At molar ratios of 1:5 to 1:40 for protein/lipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol), large spherical vesicles are converted into cylindrical micelles ∼50 Å in diameter. Other lipids of the same charge (negative) exhibit generally similar behavior, although bilayer tubes of 150–500 Å in width are also produced, depending on the lipid acyl chains. At higher protein/lipid ratios, discoid particles, 70–100 Å across, are formed. EPR data show that, on cylindrical micelles, αS adopts an extended amphipathic α-helical conformation, with its long axis aligned with the tube axis. The observed geometrical relationship between αS and the micelle suggests that the wedging of its long α-helix into the outer leaflet of a membrane may cause curvature and an anisotropic partition of lipids, leading to tube formation. PMID:22767608

  6. Adoption of Children with Disabilities: An Exploration of the Issues for Adoptive Families

    ERIC Educational Resources Information Center

    Good, Gretchen A.

    2016-01-01

    This systematic literature review is an exploration of issues for adoptive families throughout the adoption process and into the various phases of the life of the adoptive family. Although there has been much recent research related to adoption, in general, very little adoption literature addresses the often unspoken needs of families who want to…

  7. In Their Own Words: Adopted Persons' Experiences of Adoption Disclosure and Discussion in Their Families

    ERIC Educational Resources Information Center

    Wydra, Maria; O'Brien, Karen M.; Merson, Erica S.

    2012-01-01

    This study explored adoption disclosure in a sample of 18 adult adoptees who were adopted as infants. A qualitative analysis of semistructured interviews with adoptees was used to learn about participants' experiences of adoption disclosure. The majority always knew they were adopted, were able to talk openly with parents about adoption, and had…

  8. Cyclic AMP Analog Blocks Kinase Activation by Stabilizing Inactive Conformation: Conformational Selection Highlights a New Concept in Allosteric Inhibitor Design*

    PubMed Central

    Badireddy, Suguna; Yunfeng, Gao; Ritchie, Mark; Akamine, Pearl; Wu, Jian; Kim, Choel W.; Taylor, Susan S.; Qingsong, Lin; Swaminathan, Kunchithapadam; Anand, Ganesh S.

    2011-01-01

    The regulatory (R) subunit of protein kinase A serves to modulate the activity of protein kinase A in a cAMP-dependent manner and exists in two distinct and structurally dissimilar, end point cAMP-bound “B” and C-subunit-bound “H”-conformations. Here we report mechanistic details of cAMP action as yet unknown through a unique approach combining x-ray crystallography with structural proteomics approaches, amide hydrogen/deuterium exchange and ion mobility mass spectrometry, applied to the study of a stereospecific cAMP phosphorothioate analog and antagonist((Rp)-cAMPS). X-ray crystallography shows cAMP-bound R-subunit in the B form but surprisingly the antagonist Rp-cAMPS-bound R-subunit crystallized in the H conformation, which was previously assumed to be induced only by C-subunit-binding. Apo R-subunit crystallized in the B form as well but amide exchange mass spectrometry showed large differences between apo, agonist and antagonist-bound states of the R-subunit. Further ion mobility reveals the apo R-subunit as an ensemble of multiple conformations with collisional cross-sectional areas spanning both the agonist and antagonist-bound states. Thus contrary to earlier studies that explained the basis for cAMP action through “induced fit” alone, we report evidence for conformational selection, where the ligand-free apo form of the R-subunit exists as an ensemble of both B and H conformations. Although cAMP preferentially binds the B conformation, Rp-cAMPS interestingly binds the H conformation. This reveals the unique importance of the equatorial oxygen of the cyclic phosphate in mediating conformational transitions from H to B forms highlighting a novel approach for rational structure-based drug design. Ideal inhibitors such as Rp-cAMPS are those that preferentially “select” inactive conformations of target proteins by satisfying all “binding” constraints alone without inducing conformational changes necessary for activation. PMID:21081668

  9. Conformational preferences of 1,4,7-trithiacyclononane: a molecular mechanics and density functional theory study.

    PubMed

    Jagannadh, Bulusu; Reddy, Surasani Sumathi; Thangavelu, Ramagounder P

    2004-02-01

    Conformational preferences of 1,4,7-trithiacyclononane were studied using a highly efficient sampling technique based on local nonstochastic deformations and the MM2(91) force field. The results show that conformers that the molecule adopts in the crystal state were found to be low-energy conformers (LECs) within 5 kcal mol(-1) of the global minimum. A conformation with C1 symmetry was the global minimum and the C3 and C2 conformations were calculated to be 0.03 and 1.78 kcal mol(-1) higher in energy, respectively. The structures were further minimized using Density Functional Theory (DFT) calculations with two different functionals. The C2 and the C1 conformations were found to be LECs with the C3 conformation more than 4.0 kcal mol(-1) above the global minimum. The relative energies and structural ordering obtained using the BP86 functional are in agreement with the previously reported relative energies calculated using second-order Moller-Plesset (MP2) ab initio calculations. With the energy ordering being dependent on the molecular mechanics force field used, the approach of MM-->DFT (searching exhaustively the available conformational space at the MM level followed by generating the energy ordering through DFT calculations) appears to be appropriate for thiacrown ethers.

  10. Fake conformal symmetry in unimodular gravity

    NASA Astrophysics Data System (ADS)

    Oda, Ichiro

    2016-08-01

    We study Weyl symmetry (local conformal symmetry) in unimodular gravity. It is shown that the Noether currents for both Weyl symmetry and global scale symmetry vanish exactly as in conformally invariant scalar-tensor gravity. We clearly explain why in the class of conformally invariant gravitational theories, the Noether currents vanish by starting with conformally invariant scalar-tensor gravity. Moreover, we comment on both classical and quantum-mechanical equivalences in Einstein's general relativity, conformally invariant scalar-tensor gravity, and the Weyl-transverse gravity. Finally, we discuss the Weyl current in the conformally invariant scalar action and see that it is also vanishing.

  11. S-Shaped Conformation of the Quaterthiophene Molecular Backbone in Two-Dimensional Bisterpyridine-Derivative Self-Assembled Nanoarchitecture.

    PubMed

    Kervella, Yann; Shilova, Ekaterina; Latil, Sylvain; Jousselme, Bruno; Silly, Fabien

    2015-12-15

    The conformation and the two-dimensional self-assembly of 4'-(3',4″-dihexyloxy-5,2':5',2″:5″,2‴-quaterthien-2,5‴-diyl)-bis(2,2':6',2″-terpyridine) molecules are theoretically and experimentally investigated. This molecular building block forms a hydrogen-bonded chiral supramolecular nanoarchitecture on graphite at the solid/liquid interface. Scanning tunneling microscopy (STM) shows that the molecule adopts an S-shaped conformation in this structure. DFTB+ calculations reveal that this conformation is not the lowest-energy conformation. The molecular nanoarchitecture appears to be stabilized by hydrogen bonding as well as van der Waals interactions. I-, L-, and D-shaped molecular conformations are, however, locally observed at the domain boundary, but these conformations do not self-assemble into organized 2D structures. PMID:26624809

  12. Synthesis and bioactivity of a side chain bridged paclitaxel: A test of the T-Taxol conformation.

    PubMed

    Hodge, Mathis; Chen, Qiao-Hong; Bane, Susan; Sharma, Shubhada; Loew, Maura; Banerjee, Abhijit; Alcaraz, Ana A; Snyder, James P; Kingston, David G I

    2009-05-15

    A knowledge of the bioactive tubulin-binding conformation of paclitaxel (Taxol()) is crucial to a full understanding of the bioactivity of this important anticancer drug, and potentially also to the design of simplified analogs. The bioactive conformation has been shown to be best approximated by the T-Taxol conformation. As a further test of this conclusion, the paclitaxel analog 4 was designed as a compound which has all the chemical functionality necessary for activity, but which cannot adopt the T-Taxol conformation. The synthesis and bioassay of 4 confirmed its lack of activity, and thus provided further support for the T-Taxol conformation as the bioactive tubulin-binding conformation.

  13. Conformational analysis of oleandomycin and its 8-methylene-9-oxime derivative by NMR and molecular modelling.

    PubMed

    Novak, Predrag; Tomisić, Zrinka Banić; Tepes, Predrag; Lazarevski, Gorjana; Plavec, Janez; Turkalj, Gordana

    2005-01-01

    Conformations of the 14-membered macrolide antibiotic oleandomycin and its 8-methylene-9-oxime derivative were determined in various solvents. The experimental NMR data--coupling constants and NOE contacts--were compared with the results of molecular modelling--molecular mechanics calculations and molecular dynamics simulations. The conformational changes, on the right-hand side of the 14-membered ring, affected mostly the 3JH2,H3 values and NOE crosspeaks H3 or H4 to H11. Oleandomycin was found to be present predominantly in the C3-C5 folded-in conformations in DMSO-d6 solution, whereas in buffered D2O, acetone-d6 and CDCl3, there was a mixture of folded-in and folded-out conformational families. The predominant conformation of the 8-methylene-oleandomycin-9-oxime derivative in solution was a folded-out one although different amounts of folded-in conformation were also present depending on the solvent. Oleandrose and desosamine sugar moieties adopted the usual and expected chair conformation. The conformation around the glycosidic bonds, governing the relative orientation of sugars vs. the lactone ring, showed a certain flexibility within two conformationally close families. We believe that by combining the experimental NMR data and the molecular modelling techniques, as reported in this paper, we have made significant progress in understanding the conformational behaviour and properties of macrolides. Our belief is based on our own current studies on oleandomycins as well as on the previously reported results and best practices concerning other macrolides. A rational for macrolide conformational studies and advances in methodology has been suggested accordingly. PMID:15602597

  14. Conformational States of Macromolecular Assemblies Explored by Integrative Structure Calculation

    PubMed Central

    Thalassinos, Konstantinos; Pandurangan, Arun Prasad; Xu, Min; Alber, Frank; Topf, Maya

    2013-01-01

    Summary A detailed description of macromolecular assemblies in multiple conformational states can be very valuable for understanding cellular processes. At present, structural determination of most assemblies in different biologically relevant conformations cannot be achieved by a single technique and thus requires an integrative approach that combines information from multiple sources. Different techniques require different computational methods to allow efficient and accurate data processing and analysis. Here, we summarize the latest advances and future challenges in computational methods that help the interpretation of data from two techniques—mass spectrometry and three-dimensional cryo-electron microscopy (with focus on alignment and classification of heterogeneous subtomograms from cryo-electron tomography). We evaluate how new developments in these two broad fields will lead to further integration with atomic structures to broaden our picture of the dynamic behavior of assemblies in their native environment. PMID:24010709

  15. Impact of Adoption on Birth Parents

    MedlinePlus

    ... This relationship, as well as the birth parent’s perception of his or her identity, may change over ... McRoy, R. G., & Grotevant, H. D. (2000). Birthmother perceptions of the psychologically present adopted child: Adoption openness ...

  16. When to Tell Your Child About Adoption

    MedlinePlus

    ... adopted youngsters need to be told about their origins, ideally even before middle childhood. Introducing the Information ... needs to have an honest understanding of his origin. Adopted children who have not been told seem ...

  17. National Foster Care and Adoption Directory Search

    MedlinePlus

    ... on the Placement of Children (ICPC) Administrator - Provides legal and fiscal oversight for ICPC, which regulates the interstate movement of children in foster care, adoption, residential treatment, or juvenile justice programs. This person should be contacted by adoption ...

  18. The Place of Genetic Counselling in Adoption.

    ERIC Educational Resources Information Center

    Hockey, Athel; Bain, Jill

    1982-01-01

    An approach combining social worker and geneticist expertise in adoption is outlined in the study involving 180 families. Genetic counseling has shown to be an essential safeguard to the preservation of the adoptive family unit. (Author/SW)

  19. Macro influencers of electronic health records adoption.

    PubMed

    Raghavan, Vijay V; Chinta, Ravi; Zhirkin, Nikita

    2015-01-01

    While adoption rates for electronic health records (EHRs) have improved, the reasons for significant geographical differences in EHR adoption within the USA have remained unclear. To understand the reasons for these variations across states, we have compiled from secondary sources a profile of different states within the USA, based on macroeconomic and macro health-environment factors. Regression analyses were performed using these indicator factors on EHR adoption. The results showed that internet usage and literacy are significantly associated with certain measures of EHR adoption. Income level was not significantly associated with EHR adoption. Per capita patient days (a proxy for healthcare need intensity within a state) is negatively correlated with EHR adoption rate. Health insurance coverage is positively correlated with EHR adoption rate. Older physicians (>60 years) tend to adopt EHR systems less than their younger counterparts. These findings have policy implications on formulating regionally focused incentive programs.

  20. Probing protein multidimensional conformational fluctuations by single-molecule multiparameter photon stamping spectroscopy.

    PubMed

    Lu, Maolin; Lu, H Peter

    2014-10-16

    Conformational motions of proteins are highly dynamic and intrinsically complex. To capture the temporal and spatial complexity of conformational motions and further to understand their roles in protein functions, an attempt is made to probe multidimensional conformational dynamics of proteins besides the typical one-dimensional FRET coordinate or the projected conformational motions on the one-dimensional FRET coordinate. T4 lysozyme hinge-bending motions between two domains along α-helix have been probed by single-molecule FRET. Nevertheless, the domain motions of T4 lysozyme are rather complex involving multiple coupled nuclear coordinates and most likely contain motions besides hinge-bending. It is highly likely that the multiple dimensional protein conformational motions beyond the typical enzymatic hinged-bending motions have profound impact on overall enzymatic functions. In this report, we have developed a single-molecule multiparameter photon stamping spectroscopy integrating fluorescence anisotropy, FRET, and fluorescence lifetime. This spectroscopic approach enables simultaneous observations of both FRET-related site-to-site conformational dynamics and molecular rotational (or orientational) motions of individual Cy3-Cy5 labeled T4 lysozyme molecules. We have further observed wide-distributed rotational flexibility along orientation coordinates by recording fluorescence anisotropy and simultaneously identified multiple intermediate conformational states along FRET coordinate by monitoring time-dependent donor lifetime, presenting a whole picture of multidimensional conformational dynamics in the process of T4 lysozyme open-close hinge-bending enzymatic turnover motions under enzymatic reaction conditions. By analyzing the autocorrelation functions of both lifetime and anisotropy trajectories, we have also observed the dynamic and static inhomogeneity of T4 lysozyme multidimensional conformational fluctuation dynamics, providing a fundamental

  1. Conformational States of HIV-1 Reverse Transcriptase for Nucleotide Incorporation vs Pyrophosphorolysis-Binding of Foscarnet.

    PubMed

    Das, Kalyan; Balzarini, Jan; Miller, Matthew T; Maguire, Anita R; DeStefano, Jeffrey J; Arnold, Eddy

    2016-08-19

    HIV-1 reverse transcriptase (RT) catalytically incorporates individual nucleotides into a viral DNA strand complementing an RNA or DNA template strand; the polymerase active site of RT adopts multiple conformational and structural states while performing this task. The states associated are dNTP binding at the N site, catalytic incorporation of a nucleotide, release of a pyrophosphate, and translocation of the primer 3'-end to the P site. Structural characterization of each of these states may help in understanding the molecular mechanisms of drug activity and resistance and in developing new RT inhibitors. Using a 38-mer DNA template-primer aptamer as the substrate mimic, we crystallized an RT/dsDNA complex that is catalytically active, yet translocation-incompetent in crystals. The ability of RT to perform dNTP binding and incorporation in crystals permitted obtaining a series of structures: (I) RT/DNA (P-site), (II) RT/DNA/AZTTP ternary, (III) RT/AZT-terminated DNA (N-site), and (IV) RT/AZT-terminated DNA (N-site)/foscarnet complexes. The stable N-site complex permitted the binding of foscarnet as a pyrophosphate mimic. The Mg(2+) ions dissociated after catalytic addition of AZTMP in the pretranslocated structure III, whereas ions A and B had re-entered the active site to bind foscarnet in structure IV. The binding of foscarnet involves chelation with the Mg(2+) (B) ion and interactions with K65 and R72. The analysis of interactions of foscarnet and the recently discovered nucleotide-competing RT inhibitor (NcRTI) α-T-CNP in two different conformational states of the enzyme provides insights for developing new classes of polymerase active site RT inhibitors. PMID:27192549

  2. Conformal Gravity rotation curves with a conformal Higgs halo

    NASA Astrophysics Data System (ADS)

    Horne, Keith

    2016-06-01

    We discuss the effect of a conformally coupled Higgs field on conformal gravity (CG) predictions for the rotation curves of galaxies. The Mannheim-Kazanas (MK) metric is a valid vacuum solution of CG's fourth-order Poisson equation if and only if the Higgs field has a particular radial profile, S(r) = S0 a/(r + a), decreasing from S0 at r = 0 with radial scalelength a. Since particle rest masses scale with S(r)/S0, their world lines do not follow time-like geodesics of the MK metric gμν, as previously assumed, but rather those of the Higgs-frame MK metric tilde{g}_{μ ν }=Ω ^2 g_{μ ν }, with the conformal factor Ω(r) = S(r)/S0. We show that the required stretching of the MK metric exactly cancels the linear potential that has been invoked to fit galaxy rotation curves without dark matter. We also formulate, for spherical structures with a Higgs halo S(r), the CG equations that must be solved for viable astrophysical tests of CG using galaxy and cluster dynamics and lensing.

  3. Conformally flat static spherically symmetric perfect-fluid distribution in Einstein-Cartan theory

    NASA Astrophysics Data System (ADS)

    Kalyanshetti, S. B.; Waghmode, B. B.

    1983-06-01

    We consider the static, conformally flat spherically symmetric perfect-fluid distribution in Einstein-Cartan theory and obtain the field equations. These field equations are solved by adopting Hehl's approach with the assumption that the spins of the particles composing the fluid are all aligned in the radial direction only and the reality conditions are discussed.

  4. Learning Goals of AACSB-Accredited Undergraduate Business Programs: Predictors of Conformity versus Differentiation

    ERIC Educational Resources Information Center

    Brink, Kyle E.; Palmer, Timothy B.; Costigan, Robert D.

    2014-01-01

    Learning goals are central to assurance of learning. Yet little is known about what goals are used by business programs or how they are established. On the one hand, business schools are encouraged to develop their own unique learning goals. However, business schools also face pressures that would encourage conformity by adopting goals used by…

  5. 40 CFR 93.161 - Conformity evaluation for Federal installations with facility-wide emission budgets.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... installations with facility-wide emission budgets. 93.161 Section 93.161 Protection of Environment ENVIRONMENTAL... Implementation Plans § 93.161 Conformity evaluation for Federal installations with facility-wide emission budgets... installations subject to Federal oversight develop and adopt a facility-wide emission budget to be used...

  6. A Narrative Inquiry of International Adoption Stories

    ERIC Educational Resources Information Center

    Pryor, Christin; Pettinelli, J. Douglas

    2011-01-01

    The international adoption entrance story is an unexplored topic in the adoption literature. The stories that families tell of beginning life with their new children has important implications for the development of an autobiographical narrative of an adopted child. A coherent autobiographical narrative is vital for healthy childhood development.…

  7. 32 CFR 584.4 - Adoption proceedings.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 3 2012-07-01 2009-07-01 true Adoption proceedings. 584.4 Section 584.4... CUSTODY, AND PATERNITY § 584.4 Adoption proceedings. (a) General. This chapter does not apply to those... normally may not be put up for adoption without the consent of the parents. Therefore, communications...

  8. 14 CFR 221.160 - Adoption notice.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Adoption notice. 221.160 Section 221.160... REGULATIONS TARIFFS Adoption Publications Required To Show Change in Carrier's Name or Transfer of Operating Control § 221.160 Adoption notice. (a) When the name of a carrier is changed or when its operating...

  9. 25 CFR 75.18 - Adoption.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Adoption. 75.18 Section 75.18 Indians BUREAU OF INDIAN... OF CHEROKEE INDIANS, NORTH CAROLINA § 75.18 Adoption. The Tribal Council of the Eastern Band of Cherokee Indians shall be empowered to enact ordinances governing the adoption of new members....

  10. 40 CFR 1506.3 - Adoption.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 33 2011-07-01 2011-07-01 false Adoption. 1506.3 Section 1506.3 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY OTHER REQUIREMENTS OF NEPA § 1506.3 Adoption. (a) An agency may adopt a Federal draft or final environmental impact statement or portion...

  11. 40 CFR 1506.3 - Adoption.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Adoption. 1506.3 Section 1506.3 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY OTHER REQUIREMENTS OF NEPA § 1506.3 Adoption. (a) An agency may adopt a Federal draft or final environmental impact statement or portion...

  12. 32 CFR 584.4 - Adoption proceedings.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 3 2013-07-01 2013-07-01 false Adoption proceedings. 584.4 Section 584.4... CUSTODY, AND PATERNITY § 584.4 Adoption proceedings. (a) General. This chapter does not apply to those... normally may not be put up for adoption without the consent of the parents. Therefore, communications...

  13. 47 CFR 61.171 - Adoption notice.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 3 2013-10-01 2013-10-01 false Adoption notice. 61.171 Section 61.171 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) TARIFFS Adoption of Tariffs and Other Documents of Predecessor Carriers § 61.171 Adoption notice. When a...

  14. 14 CFR 221.160 - Adoption notice.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Adoption notice. 221.160 Section 221.160... REGULATIONS TARIFFS Adoption Publications Required To Show Change in Carrier's Name or Transfer of Operating Control § 221.160 Adoption notice. (a) When the name of a carrier is changed or when its operating...

  15. 25 CFR 75.18 - Adoption.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Adoption. 75.18 Section 75.18 Indians BUREAU OF INDIAN... OF CHEROKEE INDIANS, NORTH CAROLINA § 75.18 Adoption. The Tribal Council of the Eastern Band of Cherokee Indians shall be empowered to enact ordinances governing the adoption of new members....

  16. 14 CFR 221.160 - Adoption notice.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Adoption notice. 221.160 Section 221.160... REGULATIONS TARIFFS Adoption Publications Required To Show Change in Carrier's Name or Transfer of Operating Control § 221.160 Adoption notice. (a) When the name of a carrier is changed or when its operating...

  17. 47 CFR 61.171 - Adoption notice.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Adoption notice. 61.171 Section 61.171 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) TARIFFS Adoption of Tariffs and Other Documents of Predecessor Carriers § 61.171 Adoption notice. When a...

  18. 40 CFR 1506.3 - Adoption.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 34 2012-07-01 2012-07-01 false Adoption. 1506.3 Section 1506.3 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY OTHER REQUIREMENTS OF NEPA § 1506.3 Adoption. (a) An agency may adopt a Federal draft or final environmental impact statement or portion...

  19. 40 CFR 1506.3 - Adoption.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 34 2013-07-01 2013-07-01 false Adoption. 1506.3 Section 1506.3 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY OTHER REQUIREMENTS OF NEPA § 1506.3 Adoption. (a) An agency may adopt a Federal draft or final environmental impact statement or portion...

  20. 14 CFR 221.160 - Adoption notice.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Adoption notice. 221.160 Section 221.160... REGULATIONS TARIFFS Adoption Publications Required To Show Change in Carrier's Name or Transfer of Operating Control § 221.160 Adoption notice. (a) When the name of a carrier is changed or when its operating...

  1. 32 CFR 584.4 - Adoption proceedings.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 3 2014-07-01 2014-07-01 false Adoption proceedings. 584.4 Section 584.4... CUSTODY, AND PATERNITY § 584.4 Adoption proceedings. (a) General. This chapter does not apply to those... normally may not be put up for adoption without the consent of the parents. Therefore, communications...

  2. 14 CFR 221.160 - Adoption notice.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Adoption notice. 221.160 Section 221.160... REGULATIONS TARIFFS Adoption Publications Required To Show Change in Carrier's Name or Transfer of Operating Control § 221.160 Adoption notice. (a) When the name of a carrier is changed or when its operating...

  3. 47 CFR 61.171 - Adoption notice.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 3 2012-10-01 2012-10-01 false Adoption notice. 61.171 Section 61.171 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) TARIFFS Adoption of Tariffs and Other Documents of Predecessor Carriers § 61.171 Adoption notice. When a...

  4. 40 CFR 1506.3 - Adoption.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Adoption. 1506.3 Section 1506.3 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY OTHER REQUIREMENTS OF NEPA § 1506.3 Adoption. (a) An agency may adopt a Federal draft or final environmental impact statement or portion...

  5. 32 CFR 584.4 - Adoption proceedings.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 3 2011-07-01 2009-07-01 true Adoption proceedings. 584.4 Section 584.4... CUSTODY, AND PATERNITY § 584.4 Adoption proceedings. (a) General. This chapter does not apply to those... normally may not be put up for adoption without the consent of the parents. Therefore, communications...

  6. 47 CFR 61.171 - Adoption notice.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 3 2011-10-01 2011-10-01 false Adoption notice. 61.171 Section 61.171 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) TARIFFS Adoption of Tariffs and Other Documents of Predecessor Carriers § 61.171 Adoption notice. When a...

  7. 25 CFR 75.18 - Adoption.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Adoption. 75.18 Section 75.18 Indians BUREAU OF INDIAN... OF CHEROKEE INDIANS, NORTH CAROLINA § 75.18 Adoption. The Tribal Council of the Eastern Band of Cherokee Indians shall be empowered to enact ordinances governing the adoption of new members....

  8. 47 CFR 61.171 - Adoption notice.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 3 2014-10-01 2014-10-01 false Adoption notice. 61.171 Section 61.171 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) TARIFFS Adoption of Tariffs and Other Documents of Predecessor Carriers § 61.171 Adoption notice. When a...

  9. 25 CFR 75.18 - Adoption.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Adoption. 75.18 Section 75.18 Indians BUREAU OF INDIAN... OF CHEROKEE INDIANS, NORTH CAROLINA § 75.18 Adoption. The Tribal Council of the Eastern Band of Cherokee Indians shall be empowered to enact ordinances governing the adoption of new members....

  10. 25 CFR 75.18 - Adoption.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Adoption. 75.18 Section 75.18 Indians BUREAU OF INDIAN... OF CHEROKEE INDIANS, NORTH CAROLINA § 75.18 Adoption. The Tribal Council of the Eastern Band of Cherokee Indians shall be empowered to enact ordinances governing the adoption of new members....

  11. International Adoption: Current Status and Future Prospects.

    ERIC Educational Resources Information Center

    Bartholet, Elizabeth

    1993-01-01

    Laws regulating adoption are varied and complex in countries that offer children for international adoption (IA), while United States Immigration laws pose additional obstacles to Americans wishing to adopt foreign-born children. Declarations by the United Nations and the development of a convention on IA by the Hague Conference offer some hope…

  12. The Adopted Adolescent. Selected Papers Number 55.

    ERIC Educational Resources Information Center

    Banning, Anne

    This review of studies on clinical and nonclinical populations explores outcomes of adoption and developmental issues for adolescents, and in particular, developmental problems for adopted adolescents. Studies on nonclinical populations demonstrate that adoption is a highly successful form of substitute care. Prospective longitudinal studies show…

  13. Adoption Bibliography and Multi-Ethnic Sourcebook.

    ERIC Educational Resources Information Center

    Van Why, Elizabeth Wharton, Comp.

    Designed for parents who have adopted or who contemplate adoption, and for educational, legal, medical, social, and theological professionals, this bibliography and source book contains over 1250 citations relating to adoption. The book is divided into two parts. The first section is a bibliography of articles, personal narratives, dissertations,…

  14. Public Entrepreneurs and the Adoption of Broad-Based Merit Aid beyond the Southeastern United States

    ERIC Educational Resources Information Center

    Ingle, William Kyle; Petroff, Ruth Ann

    2013-01-01

    The concentration of broad-based merit aid adoption in the southeastern United States has been well noted in the literature. However, there are states that have adopted broad-based merit aid programs outside of the Southeast. Guided by multiple theoretical frameworks, including innovation diffusion theory (e.g., Gray, 1973, 1994; Rogers, 2003),…

  15. Conformal Window and Correlation Functions in Lattice Conformal QCD

    NASA Astrophysics Data System (ADS)

    Iwasaki, Y.

    We discuss various aspects of Conformal Field Theories on the Lattice. We mainly investigate the SU(3) gauge theory with Nf degenerate fermions in the fundamental representation, employing the one-plaquette gauge action and the Wilson fermion action. First we make a brief review of our previous works on the phase structure of lattice gauge theories in terms of the gauge coupling constant and the quark mass. We thereby clarify the reason why we conjecture that the conformal window is 7 ≤ Nf ≤ 16. Secondly, we introduce a new concept, "conformal theories with IR cutof" and point out that any numerical simulation on a lattice is bounded by an IR cutoff ∧IR. Then we make predictions that when Nf is within the conformal window, the propagator of a meson G(t) behaves at large t, as G(t) = c exp (-mHt)/tα, that is, a modified Yukawa-type decay form, instead of the usual exponential decay form exp (-mHt), in the small quark mass region. This holds on an any lattice for any coupling constant g, as far as g is between 0 and g*, where g* is the IR fixed point. We verify that numerical results really satisfy the predictions for the Nf = 7 case and the Nf = 16 case. Thirdly, we discuss small number of flavors (Nf = 2 ˜ 6) QCD at finite temperatures. We point out theoretically and verify numerically that the correlation functions at T/Tc > 1 exhibit the characteristics of the conformal function with IR cutoff, an exponential decay with power correction. Investigating our numerical data by a new method which we call the "local-analysis" of propagators, we observe that the Nf = 7 case and the Nf = 2 at T ˜ 2Tc case are similar to each other, while the Nf = 16 case and the Nf = 2 at T = 102 ˜ 105Tc cases are similar to each other. Further, we observe our data are consistent with the picture that the Nf = 7 case and the Nf = 2 at T ˜ 2Tc case are close to the meson unparticle model. On the other hand, the Nf = 16 case and the Nf = 2 at T = 102 ˜ 105Tc cases are close to

  16. Conformal triality of the Kepler problem

    NASA Astrophysics Data System (ADS)

    Cariglia, Marco

    2016-08-01

    We show that the Kepler problem is projectively equivalent to null geodesic motion on the conformal compactification of Minkowski-4 space. This space realises the conformal triality of Minkowski, dS and AdS spaces.

  17. Gauge natural formulation of conformal gravity

    SciTech Connect

    Campigotto, M.; Fatibene, L.

    2015-03-15

    We consider conformal gravity as a gauge natural theory. We study its conservation laws and superpotentials. We also consider the Mannheim and Kazanas spherically symmetric vacuum solution and discuss conserved quantities associated to conformal and diffeomorphism symmetries.

  18. Killing Initial Data on spacelike conformal boundaries

    NASA Astrophysics Data System (ADS)

    Paetz, Tim-Torben

    2016-08-01

    We analyze Killing Initial Data on Cauchy surfaces in conformally rescaled vacuum space-times satisfying Friedrich's conformal field equations. As an application, we derive the KID equations on a spacelike ℐ-.

  19. [Conformal radiotherapy of brain tumors].

    PubMed

    Haie-Meder, C; Beaudré, A; Breton, C; Biron, B; Cordova, A; Dubray, B; Mazeron, J J

    1999-01-01

    Conformal irradiation of brain tumours is based on the three-dimensional reconstruction of the targeted volumes and at-risk organ images, the three-dimensional calculation of the dose distribution and a treatment device (immobilisation, beam energy, collimation, etc.) adapted to the high precision required by the procedure. Each step requires an appropriate methodology and a quality insurance program. Specific difficulties in brain tumour management are related to GTV and CTV definition depending upon the histological type, the quality of the surgical resection and the medical team. Clinical studies have reported dose escalation trials, mostly in high-grade gliomas and tumours at the base of the skull. Clinical data are now providing a better knowledge of the tolerance of normal tissues. As for small tumours, the implementation of beam intensity modulation is likely to narrow the gap between conformal and stereotaxic radiotherapy. PMID:10572510

  20. The Conformational Behaviour of Glucosamine

    NASA Astrophysics Data System (ADS)

    Peña, Isabel; Kolesniková, Lucie; Cabezas, Carlos; Bermúdez, Celina; Berdakin, Matías; Simao, Alcides; Alonso, José L.

    2014-06-01

    A laser ablation method has been successfully used to vaporize the bioactive amino monosaccharide D-glucosamine. Three cyclic α-4C1 pyranose forms have been identified using a combination of CP-FTMW and LA-MB-FTMW spectroscopy. Stereoelectronic hyperconjugative factors, like those associated with anomeric or gauche effects, as well as the cooperative OH\\cdotsO, OH\\cdotsN and NH\\cdotsO chains, extended along the entire molecule, are the main factors driving the conformational behavior. All observed conformers exhibit a counter-clockwise arrangement (cc) of the network of intramolecular hydrogen bonds. The results are compared with those recently obtained for D-glucose. J. L. Alonso, M. A. Lozoya, I. Peña, J. C. López, C. Cabezas, S. Mata, S. Blanco, Chem. Sci. 2014, 5, 515.

  1. The conformational cycle of kinesin.

    PubMed Central

    Cross, R A; Crevel, I; Carter, N J; Alonso, M C; Hirose, K; Amos, L A

    2000-01-01

    The stepping mechanism of kinesin can be thought of as a programme of conformational changes. We briefly review protein chemical, electron microscopic and transient kinetic evidence for conformational changes, and working from this evidence, outline a model for the mechanism. In the model, both kinesin heads initially trap Mg x ADP. Microtubule binding releases ADP from one head only (the trailing head). Subsequent ATP binding and hydrolysis by the trailing head progressively accelerate attachment of the leading head, by positioning it closer to its next site. Once attached, the leading head releases its ADP and exerts a sustained pull on the trailing head. The rate of closure of the molecular gate which traps ADP on the trailing head governs its detachment rate. A speculative but crucial coordinating feature is that this rate is strain sensitive, slowing down under negative strain and accelerating under positive strain. PMID:10836499

  2. Holographic multiverse and conformal invariance

    SciTech Connect

    Garriga, Jaume; Vilenkin, Alexander E-mail: vilenkin@cosmos.phy.tufts.edu

    2009-11-01

    We consider a holographic description of the inflationary multiverse, according to which the wave function of the universe is interpreted as the generating functional for a lower dimensional Euclidean theory. We analyze a simple model where transitions between inflationary vacua occur through bubble nucleation, and the inflating part of spacetime consists of de Sitter regions separated by thin bubble walls. In this model, we present some evidence that the dual theory is conformally invariant in the UV.

  3. Anomalous dimensions of conformal baryons

    NASA Astrophysics Data System (ADS)

    Pica, Claudio; Sannino, Francesco

    2016-10-01

    We determine the anomalous dimensions of baryon operators for the three-color theory as functions of the number of massless flavors within the conformal window to the maximum known order in perturbation theory. We show that the anomalous dimension of the baryon is controllably small, within the δ expansion, for a wide range of number of flavors. We also find that this is always smaller than the anomalous dimension of the fermion mass operator. These findings challenge the partial compositeness paradigm.

  4. Stabilizing the boat conformation of cyclohexane rings

    SciTech Connect

    Dasgupta, S.; Goddard, W.A. III; Moldowan, J.M.; Carlson, R.M.K.; Goddard, W.A. III.

    1995-06-21

    In calculating the energetics for various conformers of the A, B, and C series of hopanoid hydrocarbons present in mature oil reservoirs, we find that the B series prefers the boat conformation (by 1.3-2.5 kcal/mol) for the D cyclohexane ring. We analyze the structural elements responsible for stabilizing this boat conformation, identify the key features, and illustrate how one might stabilize boat conformations of other systems. 5 refs., 3 figs., 2 tabs.

  5. Home Energy Displays: Consumer Adoption and Response

    SciTech Connect

    LaMarche, J.; Cheney, K.; Akers, C.; Roth, K.; Sachs, O.

    2012-12-01

    The focus of this project was to investigate the factors influencing consumer adoption of Home Energy Displays (HEDs) and to evaluate electricity consumption in households with basic HEDs versus enhanced feedback methods - web portals or alerts. We hypothesized that providing flexible and relatable information to users, in addition to a basic HED, would make feedback more effective and achieve persistent energy savings. In Phase I, we conducted three user research studies and found preferences for aesthetically pleasing, easy to understand feedback that is accessible through multiple media and offered free of charge. The deployment of HEDs in 150 households planned for Phase II encountered major recruitment and HED field deployment problems. First, after extensive outreach campaigns to apartment complexes with 760 units, only 8% of building's tenants elected to receive a free HED in their homes as part of the field study. Second, the HED used, a leading market model, had a spectrum of problems, including gateway miscommunications, failure to post to a data-hosting third party, and display malfunctions. In light of these challenges, we are pursuing a modified study investigating the energy savings of a web portal versus alert-based energy feedback instead of a physical HED.

  6. Update on international adoption: focus on Russia.

    PubMed

    McGuinness, Teena M; Robinson, Cheryl Broadus

    2011-06-01

    American families will continue to adopt children from foreign countries; the desire to have a child transcends national boundaries. Sadly, not all adoptions have happy outcomes. A recent and well-reported incident involved an American mother, who, exasperated with her adopted son's severe behavioral problems, returned him to Russia, alone, on an aircraft. Other tragic reports involve internationally adopted children who have died at the hands of their American parents. This article provides an overview of the consequences of institutionalization as a risk factor for behavioral health of children; implications for nursing care of adoptive families follow. PMID:21598869

  7. Anomalies, conformal manifolds, and spheres

    NASA Astrophysics Data System (ADS)

    Gomis, Jaume; Hsin, Po-Shen; Komargodski, Zohar; Schwimmer, Adam; Seiberg, Nathan; Theisen, Stefan

    2016-03-01

    The two-point function of exactly marginal operators leads to a universal contribution to the trace anomaly in even dimensions. We study aspects of this trace anomaly, emphasizing its interpretation as a sigma model, whose target space {M} is the space of conformal field theories (a.k.a. the conformal manifold). When the underlying quantum field theory is supersymmetric, this sigma model has to be appropriately supersymmetrized. As examples, we consider in some detail {N}=(2,2) and {N}=(0,2) supersymmetric theories in d = 2 and {N}=2 supersymmetric theories in d = 4. This reasoning leads to new information about the conformal manifolds of these theories, for example, we show that the manifold is Kähler-Hodge and we further argue that it has vanishing Kähler class. For {N}=(2,2) theories in d = 2 and {N}=2 theories in d = 4 we also show that the relation between the sphere partition function and the Kähler potential of {M} follows immediately from the appropriate sigma models that we construct. Along the way we find several examples of potential trace anomalies that obey the Wess-Zumino consistency conditions, but can be ruled out by a more detailed analysis.

  8. Conformal Invariance of Graphene Sheets.

    PubMed

    Giordanelli, I; Posé, N; Mendoza, M; Herrmann, H J

    2016-03-10

    Suspended graphene sheets exhibit correlated random deformations that can be studied under the framework of rough surfaces with a Hurst (roughness) exponent 0.72 ± 0.01. Here, we show that, independent of the temperature, the iso-height lines at the percolation threshold have a well-defined fractal dimension and are conformally invariant, sharing the same statistical properties as Schramm-Loewner evolution (SLEκ) curves with κ = 2.24 ± 0.07. Interestingly, iso-height lines of other rough surfaces are not necessarily conformally invariant even if they have the same Hurst exponent, e.g. random Gaussian surfaces. We have found that the distribution of the modulus of the Fourier coefficients plays an important role on this property. Our results not only introduce a new universality class and place the study of suspended graphene membranes within the theory of critical phenomena, but also provide hints on the long-standing question about the origin of conformal invariance in iso-height lines of rough surfaces.

  9. Limit cycles and conformal invariance

    NASA Astrophysics Data System (ADS)

    Fortin, Jean-François; Grinstein, Benjamín; Stergiou, Andreas

    2013-01-01

    There is a widely held belief that conformal field theories (CFTs) require zero beta functions. Nevertheless, the work of Jack and Osborn implies that the beta functions are not actually the quantites that decide conformality, but until recently no such behavior had been exhibited. Our recent work has led to the discovery of CFTs with nonzero beta functions, more precisely CFTs that live on recurrent trajectories, e.g., limit cycles, of the beta-function vector field. To demonstrate this we study the S function of Jack and Osborn. We use Weyl consistency conditions to show that it vanishes at fixed points and agrees with the generator Q of limit cycles on them. Moreover, we compute S to third order in perturbation theory, and explicitly verify that it agrees with our previous determinations of Q. A byproduct of our analysis is that, in perturbation theory, unitarity and scale invariance imply conformal invariance in four-dimensional quantum field theories. Finally, we study some properties of these new, "cyclic" CFTs, and point out that the a-theorem still governs the asymptotic behavior of renormalization-group flows.

  10. The Conformational Landscape of Serinol

    NASA Astrophysics Data System (ADS)

    Sanz, M. Eugenia; Loru, Donatella; Peña, Isabel; Alonso, José L.

    2014-06-01

    The rotational spectrum of the amino alcohol serinol CH_2OH--CH(NH_2)--CH_2OH, which constitutes the hydrophilic head of the lipid sphingosine, has been investigated using chirped-pulsed Fourier transform microwave spectroscopy in combination with laser ablation Five different forms of serinol have been observed and conclusively identified by the comparison between the experimental values of their rotational and 14N quadrupole coupling constants and those predicted by ab initio calculations. In all observed conformers several hydrogen bonds are established between the two hydroxyl groups and the amino groups in a chain or circular arrangement. The most abundant conformer is stabilised by O--H···N and N--H···O hydrogen bonds forming a chain rather than a cycle. One of the detected conformers presents a tunnelling motion of the hydrogen atoms of the functional groups similar to that observed in glycerol. S. Mata, I. Peña, C. Cabezas, J. C. López, J. L. Alonso, J. Mol. Spectrosc. 2012, 280, 91 V. V. Ilyushin, R. A. Motiyenko, F. J. Lovas, D. F. Plusquellic, J. Mol. Spectrosc. 2008, 251, 129.

  11. Anomalies, conformal manifolds, and spheres

    DOE PAGES

    Gomis, Jaume; Hsin, Po-Shen; Komargodski, Zohar; Schwimmer, Adam; Seiberg, Nathan; Theisen, Stefan

    2016-03-04

    The two-point function of exactly marginal operators leads to a universal contribution to the trace anomaly in even dimensions. We study aspects of this trace anomaly, emphasizing its interpretation as a sigma model, whose target space $M$ is the space of conformal field theories (a.k.a. the conformal manifold). When the underlying quantum field theory is supersymmetric, this sigma model has to be appropriately supersymmetrized. As examples, we consider in some detail $N$ = (2; 2) and $N$ = (0; 2) supersymmetric theories in d = 2 and $N$ = 2 supersymmetric theories in d = 4. This reasoning leads tomore » new information about the conformal manifolds of these theories, for example, we show that the manifold is K ahler-Hodge and we further argue that it has vanishing K ahler class. For $N$ = (2; 2) theories in d = 2 and N = 2 theories in d = 4 we also show that the relation between the sphere partition function and the K ahler potential of $M$ follows immediately from the appropriate sigma models that we construct. Ultimately, along the way we find several examples of potential trace anomalies that obey the Wess-Zumino consistency conditions, but can be ruled out by a more detailed analysis.« less

  12. Electrophysiological precursors of social conformity.

    PubMed

    Shestakova, Anna; Rieskamp, Jörg; Tugin, Sergey; Ossadtchi, Alexey; Krutitskaya, Janina; Klucharev, Vasily

    2013-10-01

    Humans often change their beliefs or behavior due to the behavior or opinions of others. This study explored, with the use of human event-related potentials (ERPs), whether social conformity is based on a general performance-monitoring mechanism. We tested the hypothesis that conflicts with a normative group opinion evoke a feedback-related negativity (FRN) often associated with performance monitoring and subsequent adjustment of behavior. The experimental results show that individual judgments of facial attractiveness were adjusted in line with a normative group opinion. A mismatch between individual and group opinions triggered a frontocentral negative deflection with the maximum at 200 ms, similar to FRN. Overall, a conflict with a normative group opinion triggered a cascade of neuronal responses: from an earlier FRN response reflecting a conflict with the normative opinion to a later ERP component (peaking at 380 ms) reflecting a conforming behavioral adjustment. These results add to the growing literature on neuronal mechanisms of social influence by disentangling the conflict-monitoring signal in response to the perceived violation of social norms and the neural signal of a conforming behavioral adjustment.

  13. Conformal Invariance of Graphene Sheets

    PubMed Central

    Giordanelli, I.; Posé, N.; Mendoza, M.; Herrmann, H. J.

    2016-01-01

    Suspended graphene sheets exhibit correlated random deformations that can be studied under the framework of rough surfaces with a Hurst (roughness) exponent 0.72 ± 0.01. Here, we show that, independent of the temperature, the iso-height lines at the percolation threshold have a well-defined fractal dimension and are conformally invariant, sharing the same statistical properties as Schramm-Loewner evolution (SLEκ) curves with κ = 2.24 ± 0.07. Interestingly, iso-height lines of other rough surfaces are not necessarily conformally invariant even if they have the same Hurst exponent, e.g. random Gaussian surfaces. We have found that the distribution of the modulus of the Fourier coefficients plays an important role on this property. Our results not only introduce a new universality class and place the study of suspended graphene membranes within the theory of critical phenomena, but also provide hints on the long-standing question about the origin of conformal invariance in iso-height lines of rough surfaces. PMID:26961723

  14. Electrophysiological precursors of social conformity.

    PubMed

    Shestakova, Anna; Rieskamp, Jörg; Tugin, Sergey; Ossadtchi, Alexey; Krutitskaya, Janina; Klucharev, Vasily

    2013-10-01

    Humans often change their beliefs or behavior due to the behavior or opinions of others. This study explored, with the use of human event-related potentials (ERPs), whether social conformity is based on a general performance-monitoring mechanism. We tested the hypothesis that conflicts with a normative group opinion evoke a feedback-related negativity (FRN) often associated with performance monitoring and subsequent adjustment of behavior. The experimental results show that individual judgments of facial attractiveness were adjusted in line with a normative group opinion. A mismatch between individual and group opinions triggered a frontocentral negative deflection with the maximum at 200 ms, similar to FRN. Overall, a conflict with a normative group opinion triggered a cascade of neuronal responses: from an earlier FRN response reflecting a conflict with the normative opinion to a later ERP component (peaking at 380 ms) reflecting a conforming behavioral adjustment. These results add to the growing literature on neuronal mechanisms of social influence by disentangling the conflict-monitoring signal in response to the perceived violation of social norms and the neural signal of a conforming behavioral adjustment. PMID:22683703

  15. The development and adjustment of 7-year-old children adopted in infancy.

    PubMed

    Stams, G J; Juffer, F; Rispens, J; Hoksbergen, R A

    2000-11-01

    The present study (N = 159) provides evidence of an increased risk for behavior problems of infant-placed 7-year-old internationally, transracially adopted children in the Netherlands. However, parents reported more behavior problems for adopted boys than for adopted girls. Notably, about 30% of the adopted children were classified as clinical on the CBCL scale for total problems, which is a much larger percentage than the 10% found in the normative population. It was suggested that these results could be explained by the operation of multiple risk factors before and after adoption placement, e.g. the child's genetic disposition, pre-natal and pre-adoption care, or the child's cognitive understanding of adoption in middle childhood. Also, results suggest that maternal sensitive responsiveness in adoptive families declines in the transition from early to middle childhood. In contrast to the home setting, the adopted children showed favorable behavioral and socioemotional adjustment at school, while their academic achievement and intelligence were in the normal range or above average. In particular Korean children had high IQs: 31% of these children obtained an intelligence score above 120. It was suggested that adoptive parents seem to offer their children sufficient or even more than average cognitive stimulation. Furthermore, adopted girls scored higher in optimal ego-control, social competence, and peer group popularity than nonadopted girls from the general population: 30% of the adopted girls were rated as popular by their classmates, which compares favorably to the 13% found in the general school population. PMID:11099119

  16. Adoptive immunotherapy of advanced melanoma.

    PubMed

    Shapira-Frommer, Ronnie; Schachter, Jacob

    2012-09-01

    Adoptive cell therapy (ACT) has emerged as an effective therapy for patients with metastatic melanoma. Since the first introduction of the protocol in 1988 [1], major improvements have been achieved with response rates of 40%-72% among patients who were resistant to previous treatment lines. Both cell product and conditioning regimen are major determinants of treatment efficacy; therefore, developing ACT protocols explore diverse ways to establish autologous intra-tumoral lymphocyte cultures or peripheral effector cells as well as different lymphodepleting regimens. While a proof of feasibility and a proof of concept had been established with previous published results, ACT will need to move beyond single-center experiences, to confirmatory, multi-center studies. If ACT is to move into widespread practice, it will be necessary to develop reproducible high quality cell production methods and accepted lymphodepleting regimen. Two new drugs, ipilimumab (Yervoy, Bristol-Myers Squibb) and vemurafenib (Zelboraf, Roche), were approved in 2011 for the treatment of metastatic melanoma based on positive phase III trials. Both drugs show a clear overall survival benefit, so the timing of when to use ACT will need to be carefully thought out. In contrast to these 2 new, commercially available outpatient treatments, ACT is a personally-specified product and labor-intensive therapy that demands both acquisition of high standard laboratory procedures and close clinical inpatient monitoring during treatment. It is unique among other anti-melanoma treatments, providing the potential for a durable response following a single, self-limited treatment. This perspective drives the efforts to make this protocol accessible for more patients and to explore modifications that may optimize treatment results.

  17. On the cohomology of Leibniz conformal algebras

    NASA Astrophysics Data System (ADS)

    Zhang, Jiao

    2015-04-01

    We construct a new cohomology complex of Leibniz conformal algebras with coefficients in a representation instead of a module. The low-dimensional cohomology groups of this complex are computed. Meanwhile, we construct a Leibniz algebra from a Leibniz conformal algebra and prove that the category of Leibniz conformal algebras is equivalent to the category of equivalence classes of formal distribution Leibniz algebras.

  18. 40 CFR 52.799 - Transportation conformity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Transportation conformity. 52.799... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.799 Transportation conformity. On June 4, 2010, Indiana submitted the Transportation Conformity Consultation SIP consisting...

  19. 40 CFR 52.799 - Transportation conformity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Transportation conformity. 52.799... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.799 Transportation conformity. On June 4, 2010, Indiana submitted the Transportation Conformity Consultation SIP consisting...

  20. 40 CFR 52.799 - Transportation conformity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Transportation conformity. 52.799... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.799 Transportation conformity. On June 4, 2010, Indiana submitted the Transportation Conformity Consultation SIP consisting...

  1. 40 CFR 52.799 - Transportation conformity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Transportation conformity. 52.799... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.799 Transportation conformity. On June 4, 2010, Indiana submitted the Transportation Conformity Consultation SIP consisting...

  2. [Attachment and Adoption: Diagnostics, Psychopathology, and Therapy].

    PubMed

    Brisch, Karl-Heinz

    2015-01-01

    This presentation describes the development of attachment between adopted children and their adoptive parents with a focus on the particular issues seen in international adoptions. The questions of settling in, trauma in the country of origin, and the motivations of the adoptive parents will be discussed. Diagnosis and various psychopathological manifestations will be examined, as will outpatient and inpatient modes of therapy. The treatment of children of various ages will be covered along with the necessity for intensive counseling and psychotherapy for the adoptive parents. This will enable the parents to work through early trauma, which will give them and their adopted child the basis for developing healthy attachment patterns. This in turn will enable the child to mature and integrate into society. Possibilities of prevention are discussed. Many of the approaches discussed here regarding attachment and adoption may be applied to foster children and their foster parents. PMID:26645775

  3. [Attachment and Adoption: Diagnostics, Psychopathology, and Therapy].

    PubMed

    Brisch, Karl-Heinz

    2015-01-01

    This presentation describes the development of attachment between adopted children and their adoptive parents with a focus on the particular issues seen in international adoptions. The questions of settling in, trauma in the country of origin, and the motivations of the adoptive parents will be discussed. Diagnosis and various psychopathological manifestations will be examined, as will outpatient and inpatient modes of therapy. The treatment of children of various ages will be covered along with the necessity for intensive counseling and psychotherapy for the adoptive parents. This will enable the parents to work through early trauma, which will give them and their adopted child the basis for developing healthy attachment patterns. This in turn will enable the child to mature and integrate into society. Possibilities of prevention are discussed. Many of the approaches discussed here regarding attachment and adoption may be applied to foster children and their foster parents.

  4. Real-space visualization of conformation-independent oligothiophene electronic structure

    NASA Astrophysics Data System (ADS)

    Taber, Benjamen N.; Kislitsyn, Dmitry A.; Gervasi, Christian F.; Mills, Jon M.; Rosenfield, Ariel E.; Zhang, Lei; Mannsfeld, Stefan C. B.; Prell, James S.; Briseno, Alejandro L.; Nazin, George V.

    2016-05-01

    We present scanning tunneling microscopy and spectroscopy (STM/STS) investigations of the electronic structures of different alkyl-substituted oligothiophenes on the Au(111) surface. STM imaging showed that on Au(111), oligothiophenes adopted distinct straight and bent conformations. By combining STS maps with STM images, we visualize, in real space, particle-in-a-box-like oligothiophene molecular orbitals. We demonstrate that different planar conformers with significant geometrical distortions of oligothiophene backbones surprisingly exhibit very similar electronic structures, indicating a low degree of conformation-induced electronic disorder. The agreement of these results with gas-phase density functional theory calculations implies that the oligothiophene interaction with the Au(111) surface is generally insensitive to molecular conformation.

  5. Conformational studies of γ-turn in pseudopeptides containing α-amino acid and conformationally constrained meta amino benzoic acid/meta nitro aniline

    NASA Astrophysics Data System (ADS)

    Dutt Konar, Anita

    2013-03-01

    Reverse turns (commonly β-turns and γ-turns), a common motif in proteins and peptides, have attracted attention due to their relevance in a wide variety of biological processes. In an attempt to artificially imitate and stabilize these turns in short acyclic peptides, a series of N-terminally protected pseudopeptides comprising of an α-amino acid and conformationally constrained meta amino benzoic acid (mABA)/meta nitro aniline (mNA) (peptides I-VI) have been synthesized. The molecules were well characterized by various spectroscopic techniques and subjected to a systematic conformational analysis. Our experimental results reveal that only pseudopeptides I and II with methyl as the sidechain, tertiary butyloxy carbonyl as the N-terminal protecting group and (mABA)/(mNA) at the C-terminus adopt γ-turn conformations in solid state as well as in solution. Even slight modification of any of the stated conditions donot support the formation of this γ-turn architecture in the solid state. Interestingly, the peptides III-V which displays extended conformation in solid state forms γ-turn structure in solution. Thus this result reflects the importance of co-operative steric interactions amongst various amino acid residues in stabilizing a particular conformation in peptides in different phases (solid and solution). This report may open a new avenue in introducing γ-turn motifs within the bioactive conformation of selected peptides.

  6. 43 CFR 4750.4-2 - Adoption fee.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... wild horses and burros? You must pay an adoption fee for each wild horse or burro you adopt. Usually... adoption events for wild horses or burros. At competitive adoptions, qualified adopters set adoption fees... Director may reduce or waive the fee when wild horses or burros are un-adoptable at the base adoption...

  7. 43 CFR 4750.4-2 - Adoption fee.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... wild horses and burros? You must pay an adoption fee for each wild horse or burro you adopt. Usually... adoption events for wild horses or burros. At competitive adoptions, qualified adopters set adoption fees... Director may reduce or waive the fee when wild horses or burros are un-adoptable at the base adoption...

  8. 43 CFR 4750.4-2 - Adoption fee.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... wild horses and burros? You must pay an adoption fee for each wild horse or burro you adopt. Usually... adoption events for wild horses or burros. At competitive adoptions, qualified adopters set adoption fees... Director may reduce or waive the fee when wild horses or burros are un-adoptable at the base adoption...

  9. 43 CFR 4750.4-2 - Adoption fee.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... wild horses and burros? You must pay an adoption fee for each wild horse or burro you adopt. Usually... adoption events for wild horses or burros. At competitive adoptions, qualified adopters set adoption fees... Director may reduce or waive the fee when wild horses or burros are un-adoptable at the base adoption...

  10. Conformational influence of the ribose 2'-hydroxyl group: crystal structures of DNA-RNA chimeric duplexes

    NASA Technical Reports Server (NTRS)

    Egli, M.; Usman, N.; Rich, A.

    1993-01-01

    We have crystallized three double-helical DNA-RNA chimeric duplexes and determined their structures by X-ray crystallography at resolutions between 2 and 2.25 A. The two self-complementary duplexes [r(G)d(CGTATACGC)]2 and [d(GCGT)r(A)d(TACGC)]2, as well as the Okazaki fragment d(GGGTATACGC).r(GCG)d(TATACCC), were found to adopt A-type conformations. The crystal structures are non-isomorphous, and the crystallographic environments for the three chimeras are different. A number of intramolecular interactions of the ribose 2'-hydroxyl groups contribute to the stabilization of the A-conformation. Hydrogen bonds between 2'-hydroxyls and 5'-oxygens or phosphate oxygens, in addition to the previously observed hydrogen bonds to 1'-oxygens of adjacent riboses and deoxyriboses, are observed in the DNA-RNA chimeric duplexes. The crystalline chimeric duplexes do not show a transition between the DNA A- and B-conformations. CD spectra suggest that the Okazaki fragment assumes an A-conformation in solution as well. In this molecule the three RNA residues may therefore lock the complete decamer in the A-conformation. Crystals of an all-DNA strand with the same sequence as the self-complementary chimeras show a morphology which is different from those of the chimera crystals. Moreover, the oligonucleotide does not match any of the sequence characteristics of DNAs usually adopting the A-conformation in the crystalline state (e.g., octamers with short alternating stretches of purines and pyrimidines). In DNA-RNA chimeric duplexes, it is therefore possible that a single RNA residue can drive the conformational equilibrium toward the A-conformation.

  11. Economic incentives and foster child adoption.

    PubMed

    Argys, Laura; Duncan, Brian

    2013-06-01

    Every year, a large number of children in the United States enter the foster care system. Many of them are eventually reunited with their biological parents or quickly adopted. A significant number, however, face long-term foster care, and some of these children are eventually adopted by their foster parents. The decision by foster parents to adopt their foster child carries significant economic consequences, including for feiting foster care payments while also assuming responsibility for medical, legal, and educational expenses, to name a few. Since 1980, U.S. states have begun to offer adoption subsidies to offset some of these expenses, significantly lowering the cost of adopting a child who is in the foster care system. This article presents empirical evidence of the role that these economic incentives play in foster parents' decision of when, or if, to adopt their foster child. We find that adoption subsidies increase adoptions through two distinct price mechanisms: by lowering the absolute cost of adoption, and by lowering the relative cost of adoption versus long-term foster care.

  12. Changes in Motivation for Adoption, Value Orientations and Behavior in Three Generations of Adoptive Parents.

    ERIC Educational Resources Information Center

    Hoksbergen, Rene A. C.

    1998-01-01

    Hypothesizes that in this century a pattern of three generations of adoptive parents has developed, differing in motives and attitudes toward adoption: traditional-closed, open-idealistic, and materialistic-realistic. Maintains that adoption has lost its taboo character, domestic adoption is decreasing or has almost vanished (Scandinavia,…

  13. Alternative Conformations of Cytochrome c: Structure, Function, and Detection.

    PubMed

    Hannibal, Luciana; Tomasina, Florencia; Capdevila, Daiana A; Demicheli, Verónica; Tórtora, Verónica; Alvarez-Paggi, Damián; Jemmerson, Ronald; Murgida, Daniel H; Radi, Rafael

    2016-01-26

    Cytochrome c (cyt c) is a cationic hemoprotein of ∼100 amino acid residues that exhibits exceptional functional versatility. While its primary function is electron transfer in the respiratory chain, cyt c is also recognized as a key component of the intrinsic apoptotic pathway, the mitochondrial oxidative protein folding machinery, and presumably as a redox sensor in the cytosol, along with other reported functions. Transition to alternative conformations and gain-of-peroxidase activity are thought to further enable the multiple functions of cyt c and its translocation across cellular compartments. In vitro, direct interactions of cyt c with cardiolipin, post-translational modifications such as tyrosine nitration, phosphorylation, methionine sulfoxidation, mutations, and even fine changes in electrical fields lead to a variety of conformational states that may be of biological relevance. The identification of these alternative conformations and the elucidation of their functions in vivo continue to be a major challenge. Here, we unify the knowledge of the structural flexibility of cyt c that supports functional moonlighting and review biochemical and immunochemical evidence confirming that cyt c undergoes conformational changes during normal and altered cellular homeostasis.

  14. Supramolecular hydrogels based on short peptides linked with conformational switch.

    PubMed

    Huang, Yucheng; Qiu, Zhenjun; Xu, Yanmei; Shi, Junfeng; Lin, Hongkun; Zhang, Yan

    2011-04-01

    Short peptides appropriately linked with an azobenzene conformational switch were found to be motif and pH dependant supramolecular hydrogelators. The hydrogelation properties of the short peptides linked with the conformational switch were studied in detail with respect to dependence on amino acid residue, pH and salt effect. The presence of amino acids with aromatic side chains such as Phe and Tyr was found to be favorable for the short peptides to gel water at an appropriate pH range. Cationic amino acid residues such as Arg and Lys in the short peptides were found to be unfavorable for hydrogelation. pH and salt effect were also found to be important factors for the hydrogelation properties of the short peptides. A series of short peptides with bioactive sequences were linked with the conformational switch and their hydrogelation properties were investigated. Photoresponsive supramolecular hydrogels were realized based on the E-/Z- transition of the conformational switch upon light irradiation. Proper combination of amino acid residues in the short peptides resulted in smart supramolecular hydrogels with responses to multiple stimuli.

  15. Necessary Condition for Emergent Symmetry from the Conformal Bootstrap

    NASA Astrophysics Data System (ADS)

    Nakayama, Yu; Ohtsuki, Tomoki

    2016-09-01

    We use the conformal bootstrap program to derive the necessary conditions for emergent symmetry enhancement from discrete symmetry (e.g., Zn ) to continuous symmetry [e.g., U (1 )] under the renormalization group flow. In three dimensions, in order for Z2 symmetry to be enhanced to U (1 ) symmetry, the conformal bootstrap program predicts that the scaling dimension of the order parameter field at the infrared conformal fixed point must satisfy Δ1>1.08 . We also obtain the similar necessary conditions for Z3 symmetry with Δ1>0.580 and Z4 symmetry with Δ1>0.504 from the simultaneous conformal bootstrap analysis of multiple four-point functions. As applications, we show that our necessary conditions impose severe constraints on the nature of the chiral phase transition in QCD, the deconfinement criticality in Néel valence bond solid transitions, and anisotropic deformations in critical O (n ) models. We prove that some fixed points proposed in the literature are unstable under the perturbation that cannot be forbidden by the discrete symmetry. In these situations, the second-order phase transition with enhanced symmetry cannot happen.

  16. Alternative Conformations of Cytochrome c: Structure, Function, and Detection.

    PubMed

    Hannibal, Luciana; Tomasina, Florencia; Capdevila, Daiana A; Demicheli, Verónica; Tórtora, Verónica; Alvarez-Paggi, Damián; Jemmerson, Ronald; Murgida, Daniel H; Radi, Rafael

    2016-01-26

    Cytochrome c (cyt c) is a cationic hemoprotein of ∼100 amino acid residues that exhibits exceptional functional versatility. While its primary function is electron transfer in the respiratory chain, cyt c is also recognized as a key component of the intrinsic apoptotic pathway, the mitochondrial oxidative protein folding machinery, and presumably as a redox sensor in the cytosol, along with other reported functions. Transition to alternative conformations and gain-of-peroxidase activity are thought to further enable the multiple functions of cyt c and its translocation across cellular compartments. In vitro, direct interactions of cyt c with cardiolipin, post-translational modifications such as tyrosine nitration, phosphorylation, methionine sulfoxidation, mutations, and even fine changes in electrical fields lead to a variety of conformational states that may be of biological relevance. The identification of these alternative conformations and the elucidation of their functions in vivo continue to be a major challenge. Here, we unify the knowledge of the structural flexibility of cyt c that supports functional moonlighting and review biochemical and immunochemical evidence confirming that cyt c undergoes conformational changes during normal and altered cellular homeostasis. PMID:26720007

  17. Prediction of conformationally dependent atomic multipole moments in carbohydrates.

    PubMed

    Cardamone, Salvatore; Popelier, Paul L A

    2015-12-15

    The conformational flexibility of carbohydrates is challenging within the field of computational chemistry. This flexibility causes the electron density to change, which leads to fluctuating atomic multipole moments. Quantum Chemical Topology (QCT) allows for the partitioning of an "atom in a molecule," thus localizing electron density to finite atomic domains, which permits the unambiguous evaluation of atomic multipole moments. By selecting an ensemble of physically realistic conformers of a chemical system, one evaluates the various multipole moments at defined points in configuration space. The subsequent implementation of the machine learning method kriging delivers the evaluation of an analytical function, which smoothly interpolates between these points. This allows for the prediction of atomic multipole moments at new points in conformational space, not trained for but within prediction range. In this work, we demonstrate that the carbohydrates erythrose and threose are amenable to the above methodology. We investigate how kriging models respond when the training ensemble incorporating multiple energy minima and their environment in conformational space. Additionally, we evaluate the gains in predictive capacity of our models as the size of the training ensemble increases. We believe this approach to be entirely novel within the field of carbohydrates. For a modest training set size of 600, more than 90% of the external test configurations have an error in the total (predicted) electrostatic energy (relative to ab initio) of maximum 1 kJ mol(-1) for open chains and just over 90% an error of maximum 4 kJ mol(-1) for rings.

  18. A new clustering of antibody CDR loop conformations

    PubMed Central

    North, Benjamin; Lehmann, Andreas; Dunbrack, Roland L.

    2010-01-01

    Previous analyses of the complementarity determining regions (CDRs) of antibodies have focused on a small number of “canonical” conformations for each loop. This is primarily the result of the work of Chothia and colleagues, most recently in 1997. Because of the widespread utility of antibodies, we have revisited the clustering of conformations of the six CDR loops with the much larger amount of structural information currently available. In this work, we were careful to use a high-quality data set by eliminating low-resolution structures and CDRs with high B-factors or high conformational energies. We used a distance function based on directional statistics and an effective clustering algorithm using affinity propagation. With this data set of over 300 non-redundant antibody structures, we were able to cover 28 CDR-length combinations (e.g., L1 length 11, or “L1-11” in our nomenclature) for L1, L2, L3, H1 and H2. The Chothia analysis covered only 20 CDR-lengths. Only four of these had more than one conformational cluster, of which two could easily be distinguished by gene source (mouse/human; κ/λ) and one purely by the presence and positions of Pro residues (L3-9). Thus using the Chothia analysis does not require the complicated set of “structure-determining residues” that is often assumed. Of our 28 CDR-lengths, 15 of them have multiple conformational clusters including ten for which Chothia had only one canonical class. We have a total of 72 clusters for the non-H3 CDRs; approximately 85% of the non-H3 sequences can be assigned to a conformational cluster based on gene source and/or sequence. We found that earlier predictions of “bulged” vs. “non-bulged” conformations based on the presence or absence of anchor residues Arg/Lys94 and Asp101 of H3 have not held up, since all four combinations lead to a majority of conformations that are bulged. Thus the earlier analyses have been significantly enhanced by the increased data. We believe the

  19. Conformance Testing: Measurement Decision Rules

    NASA Technical Reports Server (NTRS)

    Mimbs, Scott M.

    2010-01-01

    The goal of a Quality Management System (QMS) as specified in ISO 9001 and AS9100 is to provide assurance to the customer that end products meet specifications. Measuring devices, often called measuring and test equipment (MTE), are used to provide the evidence of product conformity to specified requirements. Unfortunately, processes that employ MTE can become a weak link to the overall QMS if proper attention is not given to the measurement process design, capability, and implementation. Documented "decision rules" establish the requirements to ensure measurement processes provide the measurement data that supports the needs of the QMS. Measurement data are used to make the decisions that impact all areas of technology. Whether measurements support research, design, production, or maintenance, ensuring the data supports the decision is crucial. Measurement data quality can be critical to the resulting consequences of measurement-based decisions. Historically, most industries required simplistic, one-size-fits-all decision rules for measurements. One-size-fits-all rules in some cases are not rigorous enough to provide adequate measurement results, while in other cases are overly conservative and too costly to implement. Ideally, decision rules should be rigorous enough to match the criticality of the parameter being measured, while being flexible enough to be cost effective. The goal of a decision rule is to ensure that measurement processes provide data with a sufficient level of quality to support the decisions being made - no more, no less. This paper discusses the basic concepts of providing measurement-based evidence that end products meet specifications. Although relevant to all measurement-based conformance tests, the target audience is the MTE end-user, which is anyone using MTE other than calibration service providers. Topics include measurement fundamentals, the associated decision risks, verifying conformance to specifications, and basic measurement

  20. Conformance Verification of Privacy Policies

    NASA Astrophysics Data System (ADS)

    Fu, Xiang

    Web applications are both the consumers and providers of information. To increase customer confidence, many websites choose to publish their privacy protection policies. However, policy conformance is often neglected. We propose a logic based framework for formally specifying and reasoning about the implementation of privacy protection by a web application. A first order extension of computation tree logic is used to specify a policy. A verification paradigm, built upon a static control/data flow analysis, is presented to verify if a policy is satisfied.

  1. Chromosome Conformation Capture in Drosophila.

    PubMed

    Li, Hua-Bing

    2016-01-01

    Linear chromatin fiber is packed inside the nuclei as a complex three-dimensional structure, and the organization of the chromatin has important roles in the appropriate spatial and temporal regulation of gene expression. To understand how chromatin organizes inside nuclei, and how regulatory proteins physically interact with genes, chromosome conformation capture (3C) technique provides a powerful and sensitive tool to detect both short- and long-range DNA-DNA interaction. Here I describe the 3C technique to detect the DNA-DNA interactions mediated by insulator proteins that are closely related to PcG in Drosophila, which is also broadly applicable to other systems. PMID:27659987

  2. Conformational Transitions in Molecular Systems

    NASA Astrophysics Data System (ADS)

    Bachmann, M.; Janke, W.

    2008-11-01

    Proteins are the "work horses" in biological systems. In almost all functions specific proteins are involved. They control molecular transport processes, stabilize the cell structure, enzymatically catalyze chemical reactions; others act as molecular motors in the complex machinery of molecular synthetization processes. Due to their significance, misfolds and malfunctions of proteins typically entail disastrous diseases, such as Alzheimer's disease and bovine spongiform encephalopathy (BSE). Therefore, the understanding of the trinity of amino acid composition, geometric structure, and biological function is one of the most essential challenges for the natural sciences. Here, we glance at conformational transitions accompanying the structure formation in protein folding processes.

  3. Toward TeV Conformality

    SciTech Connect

    Appelquist, T; Avakian, A; Babich, R; Brower, R C; Cheng, M; Clark, M A; Cohen, S D; Fleming, G T; Kiskis, J; Neil, E T; Osborn, J C; Rebbi, C; Schaich, D; Soltz, R; Vranas, P

    2009-11-30

    We study the chiral condensate <{bar {psi}}{psi}> for an SU(3) gauge theory with N{sub f} massless Dirac fermions in the fundamental representation when N{sub f} is increased from 2 to 6. For N{sub f} = 2, our lattice simulations of <{bar {psi}}{psi}>/F{sup 3}, where F is the Nambu-Goldstone-boson decay constant, agree with the measured QCD value. For N{sub f} = 6, this ratio shows significant enhancement, presaging an even larger enhancement anticipated as N{sub f} increases further, toward the critical value for transition from confinement to infrared conformality.

  4. Cellular Cations Control Conformational Switching of Inositol Pyrophosphate Analogues.

    PubMed

    Hager, Anastasia; Wu, Mingxuan; Wang, Huanchen; Brown, Nathaniel W; Shears, Stephen B; Veiga, Nicolás; Fiedler, Dorothea

    2016-08-22

    The inositol pyrophosphate messengers (PP-InsPs) are emerging as an important class of cellular regulators. These molecules have been linked to numerous biological processes, including insulin secretion and cancer cell migration, but how they trigger such a wide range of cellular responses has remained unanswered in many cases. Here, we show that the PP-InsPs exhibit complex speciation behaviour and propose that a unique conformational switching mechanism could contribute to their multifunctional effects. We synthesised non-hydrolysable bisphosphonate analogues and crystallised the analogues in complex with mammalian PPIP5K2 kinase. Subsequently, the bisphosphonate analogues were used to investigate the protonation sequence, metal-coordination properties, and conformation in solution. Remarkably, the presence of potassium and magnesium ions enabled the analogues to adopt two different conformations near physiological pH. Understanding how the intrinsic chemical properties of the PP-InsPs can contribute to their complex signalling outputs will be essential to elucidate their regulatory functions. PMID:27460418

  5. Building Adoption of Visual Analytics Software

    SciTech Connect

    Chinchor, Nancy; Cook, Kristin A.; Scholtz, Jean

    2012-01-05

    Adoption of technology is always difficult. Issues such as having the infrastructure necessary to support the technology, training for users, integrating the technology into current processes and tools, and having the time, managerial support, and necessary funds need to be addressed. In addition to these issues, the adoption of visual analytics tools presents specific challenges that need to be addressed. This paper discusses technology adoption challenges and approaches for visual analytics technologies.

  6. [Choosing the name in international adoption].

    PubMed

    van Effenterre, Aude; Harf, Aurélie; Skandrani, Sandra; Taïeb, Olivier; Moro, Marie Rose

    2014-01-01

    In the context of international adoption, the question is raised of the links which the adoptive parents may or may not maintain with the culture of the child's birth country. The name which the adoptive parents choose reflects this questioning. A study was carried out into this subject with parents and children in order to gain a better understanding of the feelings of belonging, filiation and affiliation in these situations.

  7. Probing ion channel conformational dynamics using simultaneous single-molecule ultrafast spectroscopy and patch-clamp electric recording

    NASA Astrophysics Data System (ADS)

    Harms, Greg; Orr, Galya; Lu, H. Peter

    2004-03-01

    An approach to probing single-molecule ion channel kinetics and conformational dynamics, patch-clamp confocal fluorescence microscopy (PCCFM), uses simultaneous ultrafast fluorescence spectroscopy and single-channel electric current recording. PCCFM is applied to determine single-channel conformational dynamics by probing single-pair fluorescence resonant energy transfer, fluorescence self-quenching, and anisotropy of the dye-labeled gramicidin ion channel incorporated in an artificial lipid bilayer. Hidden conformational changes were observed, which strongly suggests that multiple intermediate conformation states are involved in gramicidin ion channel dynamics.

  8. Crystal structures and conformational analyses of three pyranochromene derivatives

    PubMed Central

    Swaminathan, K.; Sethusankar, K.; Kumar, G. Siva; Bakthadoss, M.

    2015-01-01

    The title compounds, C27H20O6, (I) [systematic name: methyl 7-oxo-14-phenyl-1H,7H,14H-pyrano[3,2-c:5,4-c′]dichromene-14a(6bH)-carboxyl­ate], C24H22O5, (II) [systematic name: methyl 1-oxo-6-phenyl-2,3,4,12b-tetra­hydro-1H,6H-chromeno[3,4-c]chromene-6a(7H)-carboxyl­ate], and C25H23N3O4, (III) [systematic name: 6-(4-ethyl­phen­yl)-2,4-dimethyl-1,3-dioxo-2,3,4,12b-tetra­hydro-1H,6H-chromeno[4′,3′:4,5]pyrano[2,3-d]pyrimidine-6a(7H)-carbo­nitrile], are pyran­ochromene derivatives. The central pyran rings (B) of compounds (I) and (III) adopt half-chair conformations, whereas that of compound (II) adopts a sofa conformation. The pyran rings (A) of the chromene ring systems of compounds (II) and (III) adopt half-chair conformations, while that of compound (I) adopts a sofa conformation. The mean plane of the central pyran rings (B) make dihedral angles of 70.02 (6), 61.52 (6) and 69.12 (7)°, respectively, with the mean planes of the chromene moieties (C+A) of compounds (I), (II) and (III). The bicyclic coumarin ring system (C+A+B+E) in compound (I) is almost planar (r.m.s. deviation = 0.042 Å). The carbo­nitrile side chain in compound (III) is very nearly linear, with the C—C N angle being 176.6 (2)°. The cyclo­hexene ring (E), fused with the central pyran ring (B) in compound (II) adopts a sofa conformation. In the mol­ecular structures of compounds (II) and (III), there are C—H⋯O short contacts, which generate S(7) ring motifs. In the crystal structures of the title compounds, mol­ecules are linked by C—H⋯O hydrogen bonds, which generate mol­ecular sheets parallel to the ab plane, with R 4 3(28) loops in (I), inversion dimers with R 2 2(10) loops in (II) and chains along [010] with R 2 2(12) ring motifs in (III). In the crystal structures of (I) and (III), there are also C—H⋯π inter­actions present, leading to the formation of a three-dimensional framework in (II) and to sheets parallel to (101) in (III). PMID:26396757

  9. Measuring and Increasing Adoption Rates of Cookstoves in a Humanitarian Crisis.

    PubMed

    Wilson, Daniel L; Coyle, Jeremy; Kirk, Angeli; Rosa, Javier; Abbas, Omnia; Adam, Mohammed Idris; Gadgil, Ashok J

    2016-08-01

    Traditional smoky cooking fires are one of today's greatest environmental threats to human life. These fires, used by 40% of the global population, cause 3.9 million annual premature deaths. "Clean cookstoves" have potential to improve this situation; however, most cookstove programs do not employ objective measurement of adoption to inform design, marketing, subsidies, finance, or dissemination practices. Lack of data prevents insights and may contribute to consistently low adoption rates. In this study, we used sensors and surveys to measure objective versus self-reported adoption of freely-distributed cookstoves in an internally displaced persons camp in Darfur, Sudan. Our data insights demonstrate how to effectively measure and promote adoption, especially in a humanitarian crisis. With sensors, we measured that 71% of participants were cookstove "users" compared to 95% of respondents reporting the improved cookstove was their "primary cookstove." No line of survey questioning, whether direct or indirect, predicted sensor-measured usage. For participants who rarely or never used their cookstoves after initial dissemination ("non-users"), we found significant increases in adoption after a simple followup survey (p = 0.001). The followup converted 83% of prior "non-users" to "users" with average daily adoption of 1.7 cooking hours over 2.2 meals. This increased adoption, which we posit resulted from cookstove familiarization and social conformity, was sustained for a 2-week observation period post intervention. PMID:27435285

  10. Measuring and Increasing Adoption Rates of Cookstoves in a Humanitarian Crisis.

    PubMed

    Wilson, Daniel L; Coyle, Jeremy; Kirk, Angeli; Rosa, Javier; Abbas, Omnia; Adam, Mohammed Idris; Gadgil, Ashok J

    2016-08-01

    Traditional smoky cooking fires are one of today's greatest environmental threats to human life. These fires, used by 40% of the global population, cause 3.9 million annual premature deaths. "Clean cookstoves" have potential to improve this situation; however, most cookstove programs do not employ objective measurement of adoption to inform design, marketing, subsidies, finance, or dissemination practices. Lack of data prevents insights and may contribute to consistently low adoption rates. In this study, we used sensors and surveys to measure objective versus self-reported adoption of freely-distributed cookstoves in an internally displaced persons camp in Darfur, Sudan. Our data insights demonstrate how to effectively measure and promote adoption, especially in a humanitarian crisis. With sensors, we measured that 71% of participants were cookstove "users" compared to 95% of respondents reporting the improved cookstove was their "primary cookstove." No line of survey questioning, whether direct or indirect, predicted sensor-measured usage. For participants who rarely or never used their cookstoves after initial dissemination ("non-users"), we found significant increases in adoption after a simple followup survey (p = 0.001). The followup converted 83% of prior "non-users" to "users" with average daily adoption of 1.7 cooking hours over 2.2 meals. This increased adoption, which we posit resulted from cookstove familiarization and social conformity, was sustained for a 2-week observation period post intervention.

  11. Conformational gating of DNA conductance

    PubMed Central

    Artés, Juan Manuel; Li, Yuanhui; Qi, Jianqing; Anantram, M. P.; Hihath, Joshua

    2015-01-01

    DNA is a promising molecule for applications in molecular electronics because of its unique electronic and self-assembly properties. Here we report that the conductance of DNA duplexes increases by approximately one order of magnitude when its conformation is changed from the B-form to the A-form. This large conductance increase is fully reversible, and by controlling the chemical environment, the conductance can be repeatedly switched between the two values. The conductance of the two conformations displays weak length dependencies, as is expected for guanine-rich sequences, and can be fit with a coherence-corrected hopping model. These results are supported by ab initio electronic structure calculations that indicate that the highest occupied molecular orbital is more disperse in the A-form DNA case. These results demonstrate that DNA can behave as a promising molecular switch for molecular electronics applications and also provide additional insights into the huge dispersion of DNA conductance values found in the literature. PMID:26648400

  12. Metrics with Galilean conformal isometry

    SciTech Connect

    Bagchi, Arjun; Kundu, Arnab

    2011-03-15

    The Galilean conformal algebra (GCA) arises in taking the nonrelativistic limit of the symmetries of a relativistic conformal field theory in any dimensions. It is known to be infinite dimensional in all spacetime dimensions. In particular, the 2d GCA emerges out of a scaling limit of linear combinations of two copies of the Virasoro algebra. In this paper, we find metrics in dimensions greater than 2 which realize the finite 2d GCA (the global part of the infinite algebra) as their isometry by systematically looking at a construction in terms of cosets of this finite algebra. We list all possible subalgebras consistent with some physical considerations motivated by earlier work in this direction and construct all possible higher-dimensional nondegenerate metrics. We briefly study the properties of the metrics obtained. In the standard one higher-dimensional ''holographic'' setting, we find that the only nondegenerate metric is Minkowskian. In four and five dimensions, we find families of nontrivial metrics with a rather exotic signature. A curious feature of these metrics is that all but one of them are Ricci-scalar flat.

  13. Charged gravastars admitting conformal motion

    NASA Astrophysics Data System (ADS)

    Usmani, A. A.; Rahaman, F.; Ray, Saibal; Nandi, K. K.; Kuhfittig, Peter K. F.; Rakib, Sk. A.; Hasan, Z.

    2011-07-01

    We propose a new model of a gravastar admitting conformal motion. While retaining the framework of the Mazur-Mottola model, the gravastar is assumed to be internally charged, with an exterior defined by a Reissner-Nordström instead of a Schwarzschild line element. The solutions, obtained by exploiting an assumed conformal Killing vector, involve (i) the interior region, (ii) the shell, and (iii) the exterior region of the sphere. Of these three cases the first one is of primary interest since the total gravitational mass here turns out to be an electromagnetic mass under some specific conditions. This suggests that the interior de Sitter vacuum of a charged gravastar is essentially an electromagnetic mass model that must generate gravitational mass which provides a stable configuration by balancing the repulsive pressure arising from charge with its attractive gravity to avert a singularity. Therefore the present model, like the Mazur-Mottola model, results in the construction of a compact astrophysical object, as an alternative to a black hole. We have also analyzed various other aspects such as the stress energy tensor in the thin shell and the entropy of the system.

  14. Conformational gating of DNA conductance.

    PubMed

    Artés, Juan Manuel; Li, Yuanhui; Qi, Jianqing; Anantram, M P; Hihath, Joshua

    2015-01-01

    DNA is a promising molecule for applications in molecular electronics because of its unique electronic and self-assembly properties. Here we report that the conductance of DNA duplexes increases by approximately one order of magnitude when its conformation is changed from the B-form to the A-form. This large conductance increase is fully reversible, and by controlling the chemical environment, the conductance can be repeatedly switched between the two values. The conductance of the two conformations displays weak length dependencies, as is expected for guanine-rich sequences, and can be fit with a coherence-corrected hopping model. These results are supported by ab initio electronic structure calculations that indicate that the highest occupied molecular orbital is more disperse in the A-form DNA case. These results demonstrate that DNA can behave as a promising molecular switch for molecular electronics applications and also provide additional insights into the huge dispersion of DNA conductance values found in the literature. PMID:26648400

  15. Quantifying macromolecular conformational transition pathways

    NASA Astrophysics Data System (ADS)

    Seyler, Sean; Kumar, Avishek; Thorpe, Michael; Beckstein, Oliver

    2015-03-01

    Diverse classes of proteins function through large-scale conformational changes that are challenging for computer simulations. A range of fast path-sampling techniques have been used to generate transitions, but it has been difficult to compare paths from (and assess the relative strengths of) different methods. We introduce a comprehensive method (pathway similarity analysis, PSA) for quantitatively characterizing and comparing macromolecular pathways. The Hausdorff and Fréchet metrics (known from computational geometry) are used to quantify the degree of similarity between polygonal curves in configuration space. A strength of PSA is its use of the full information available from the 3 N-dimensional configuration space trajectory without requiring additional specific knowledge about the system. We compare a sample of eleven different methods for the closed-to-open transitions of the apo enzyme adenylate kinase (AdK) and also apply PSA to an ensemble of 400 AdK trajectories produced by dynamic importance sampling MD and the Geometrical Pathways algorithm. We discuss the method's potential to enhance our understanding of transition path sampling methods, validate them, and help guide future research toward deeper physical insights into conformational transitions.

  16. Conformal inflation coupled to matter

    SciTech Connect

    Brax, Philippe

    2014-05-01

    We formulate new conformal models of inflation and dark energy which generalise the Higgs-Dilaton scenario. We embed these models in unimodular gravity whose effect is to break scale invariance in the late time Universe. In the early Universe, inflation occurs close to a maximum of both the scalar potential and the scalar coupling to the Ricci scalar in the Jordan frame. At late times, the dilaton, which decouples from the dynamics during inflation, receives a potential term from unimodular gravity and leads to the acceleration of the Universe. We address two central issues in this scenario. First we show that the Damour-Polyalov mechanism, when non-relativistic matter is present prior to the start of inflation, sets the initial conditions for inflation at the maximum of the scalar potential. We then show that conformal invariance implies that matter particles are not coupled to the dilaton in the late Universe at the classical level. When fermions acquire masses at low energy, scale invariance is broken and quantum corrections induce a coupling between the dilaton and matter which is still small enough to evade the gravitational constraints in the solar system.

  17. Modeling conformational changes in cyclosporin A.

    PubMed Central

    O'Donohue, M. F.; Burgess, A. W.; Walkinshaw, M. D.; Treutlein, H. R.

    1995-01-01

    NMR and X-ray structures for the immunosuppressant cyclosporin A (CsA) reveal a remarkable difference between the unbound (free) conformation in organic solvents and the conformation bound to cyclophilin. We have performed computer simulations of the molecular dynamics of CsA under a variety of conditions and confirmed the stability of these two conformations at room temperature in water and in vacuum. However, when the free conformation was modeled in vacuum at 600 K, a transition pathway leading to the bound conformation was observed. This involved a change in the cis MeLeu-9 peptide bond to a trans conformation and the movement of the side chains forming the dominant hydrophobic cluster (residues MeBmt-1, MeLeu-4, MeLeu-6, and MeLeu-10) to the opposite side of the plane formed by the backbone atoms in the molecular ring. The final conformation had a backbone RMS deviation from the bound conformation of 0.53 A and was as stable in dynamics simulations as the bound conformation. Our calculations allowed us to make a detailed analysis of a transition pathway between the free and the bound conformations of CsA and to identify two distinct regions of coordinated movement in CsA, both of which underwent transitions independently. PMID:8535256

  18. A quantitative measure for protein conformational heterogeneity

    PubMed Central

    Lyle, Nicholas; Das, Rahul K.; Pappu, Rohit V.

    2013-01-01

    Conformational heterogeneity is a defining characteristic of proteins. Intrinsically disordered proteins (IDPs) and denatured state ensembles are extreme manifestations of this heterogeneity. Inferences regarding globule versus coil formation can be drawn from analysis of polymeric properties such as average size, shape, and density fluctuations. Here we introduce a new parameter to quantify the degree of conformational heterogeneity within an ensemble to complement polymeric descriptors. The design of this parameter is guided by the need to distinguish between systems that couple their unfolding-folding transitions with coil-to-globule transitions and those systems that undergo coil-to-globule transitions with no evidence of acquiring a homogeneous ensemble of conformations upon collapse. The approach is as follows: Each conformation in an ensemble is converted into a conformational vector where the elements are inter-residue distances. Similarity between pairs of conformations is quantified using the projection between the corresponding conformational vectors. An ensemble of conformations yields a distribution of pairwise projections, which is converted into a distribution of pairwise conformational dissimilarities. The first moment of this dissimilarity distribution is normalized against the first moment of the distribution obtained by comparing conformations from the ensemble of interest to conformations drawn from a Flory random coil model. The latter sets an upper bound on conformational heterogeneity thus ensuring that the proposed measure for intra-ensemble heterogeneity is properly calibrated and can be used to compare ensembles for different sequences and across different temperatures. The new measure of conformational heterogeneity will be useful in quantitative studies of coupled folding and binding of IDPs and in de novo sequence design efforts that are geared toward controlling the degree of heterogeneity in unbound forms of IDPs. PMID:24089719

  19. Envisaging the adoption process to strengthen gay- and lesbian-headed families: recommendations for adoption professionals.

    PubMed

    Matthews, John D; Cramer, Elizabeth P

    2006-01-01

    Although a growing number of child placement agencies are serving lesbians and gay men, a dearth of literature exists for adoption agency policies and practices related to working with this population. This article explores the unique characteristics and strengths of prospective gay and lesbian adoptive parents throughout each of the three phases of the adoption process-preplacement, placement, and postplacement-as well as provides suggestions for adoption professionals working with gays and lesbians. Data from a recent qualitative study of single, gay adoptive fathers are used to illustrate examples and expose areas of potential strengths of adoptive parents not generally explored in the preplacement or preparatory stage. Special attention also is given to the continuing needs of adoptive families headed by gays and lesbians after adoptive placement. Specifically explored are the needs for developing linkages with similar families, as well as providing resources designed to promote successful outcomes of adopted children raised by gays and lesbians.

  20. Predictors of race, adoption, and sexual orientation related socialization of adoptive parents of young children.

    PubMed

    Goldberg, Abbie E; Smith, JuliAnna Z

    2016-04-01

    Using a sample of 125 lesbian, gay, and heterosexual adoptive parent couples with young children (M = 6.32 years), this study examined predictors of direct socialization (preparation for adoptism, racism, and heterosexism) and indirect socialization (modeling interactions by responding to outsiders' inquiries about their child's adoptive status, racial background, or family structure). In terms of direct socialization, parents of older children tended to engage in more socialization around adoptism and heterosexism, and parents of daughters tended to engage in more socialization around racism and heterosexism. Greater perceived child interest in adoption was related to more direct socialization around adoptism. Parents of color reported more direct socialization around racism. Having a child of color was related to more direct socialization around heterosexism. Regarding indirect socialization, sexual minority parents reported more socialization around adoption and race. Greater perceived child interest in adoption was related to more indirect adoption socialization. Being more "out" was related to more indirect socialization around parent sexual orientation.

  1. Healthy depictions? Depicting adoption and adoption news events on broadcast news.

    PubMed

    Kline, Susan L; Chatterjee, Karishma; Karel, Amanda I

    2009-01-01

    Given that the public uses the media to learn about adoption as a family form, this study analyzes U.S. television news coverage of adoption between 2001 and 2005 (N = 309 stories), to identify the types of news events covered about adoption. A majority of news stories covered fraud, crime, legal disputes, and negative international adoption cases. Adoptees as defective or unhealthy were depicted more in negative news event stories, birth parents appeared less overall, and adoptive parents were most likely to have healthy depictions in positively oriented adoption experience, big family, and reunion stories. Although three quarters of the stories used primary adoption participants as news sources, one-third of the negative event stories did not contain healthy depictions of adoption participants. The authors discuss ways journalists and researchers might improve adoption news coverage.

  2. ADOPT: A Historically Validated Light Duty Vehicle Consumer Choice Model

    SciTech Connect

    Brooker, A.; Gonder, J.; Lopp, S.; Ward, J.

    2015-05-04

    The Automotive Deployment Option Projection Tool (ADOPT) is a light-duty vehicle consumer choice and stock model supported by the U.S. Department of Energy’s Vehicle Technologies Office. It estimates technology improvement impacts on U.S. light-duty vehicles sales, petroleum use, and greenhouse gas emissions. ADOPT uses techniques from the multinomial logit method and the mixed logit method estimate sales. Specifically, it estimates sales based on the weighted value of key attributes including vehicle price, fuel cost, acceleration, range and usable volume. The average importance of several attributes changes nonlinearly across its range and changes with income. For several attributes, a distribution of importance around the average value is used to represent consumer heterogeneity. The majority of existing vehicle makes, models, and trims are included to fully represent the market. The Corporate Average Fuel Economy regulations are enforced. The sales feed into the ADOPT stock model. It captures key aspects for summing petroleum use and greenhouse gas emissions This includes capturing the change in vehicle miles traveled by vehicle age, the creation of new model options based on the success of existing vehicles, new vehicle option introduction rate limits, and survival rates by vehicle age. ADOPT has been extensively validated with historical sales data. It matches in key dimensions including sales by fuel economy, acceleration, price, vehicle size class, and powertrain across multiple years. A graphical user interface provides easy and efficient use. It manages the inputs, simulation, and results.

  3. Sweet and bitter taste: structure and conformations of two aspartame dipeptide analogues.

    PubMed

    Benedetti, E; Gavuzzo, E; Santini, A; Kent, D R; Zhu, Y F; Zhu, Q; Mahr, C; Goodman, M

    1995-01-01

    The synthesis and X-ray diffraction analysis of two dipeptide taste ligands have been carried out as part of our study of the molecular basis of taste. The compounds L-aspartyl-D-alpha-methylphenylalanine methyl ester [L-Asp-D-(alpha Me)Phe-OMe] and L-aspartyl-D-alanyl-2,2,5, 5-tetramethylcyclopentanyl ester [L-Asp-D-Ala-OTMCP] elicit bitter and sweet taste, respectively. The C-terminal residues of the two analogues adopt distinctly different conformations in the solid state. The aspartyl moiety assumes the same conformation found in other dipeptide taste ligands with the side-chain carboxylate and the amino groups forming a zwitterionic ring with a conformation defined by psi, chi 1 = 157.7 degrees, -61.5 degrees for L-Asp-D-Ala-OTMCP and 151.0 degrees, -68.8 degrees for L-Asp-D-(alpha Me)Phe-OMe. In the second residue, a left-handed helical conformation is observed for the (alpha Me)Phe residue of L-Asp-D-(alpha Me)Phe-OMe with phi 2 = 49.0 degrees and psi 2 = 47.9 degrees, while the Ala residue of L-Asp-D-Ala-OTMCP adopts a semi-extended conformation characterized by dihedral angles phi 2 = 62.8 degrees and psi 2 = -139.9 degrees. The solid-state structure of the bitter L-Asp-D-(alpha Me)Phe-OMe is extended: while the crystal structure of the sweet L-Asp-D-OTMCP roughly adopts the typical L-shaped structure shown by other sweeteners. The data of L-Asp-D-(alpha Me)Phe-OMe are compared with those of its diastereoisomer L-Asp-L-(alpha Me)Phe-OMe. Conformational analysis of the two taste ligands in solution by NMR and computer simulations agrees well with our model for sweet and bitter tastes. PMID:9223014

  4. Sweet and bitter taste: structure and conformations of two aspartame dipeptide analogues.

    PubMed

    Benedetti, E; Gavuzzo, E; Santini, A; Kent, D R; Zhu, Y F; Zhu, Q; Mahr, C; Goodman, M

    1995-01-01

    The synthesis and X-ray diffraction analysis of two dipeptide taste ligands have been carried out as part of our study of the molecular basis of taste. The compounds L-aspartyl-D-alpha-methylphenylalanine methyl ester [L-Asp-D-(alpha Me)Phe-OMe] and L-aspartyl-D-alanyl-2,2,5, 5-tetramethylcyclopentanyl ester [L-Asp-D-Ala-OTMCP] elicit bitter and sweet taste, respectively. The C-terminal residues of the two analogues adopt distinctly different conformations in the solid state. The aspartyl moiety assumes the same conformation found in other dipeptide taste ligands with the side-chain carboxylate and the amino groups forming a zwitterionic ring with a conformation defined by psi, chi 1 = 157.7 degrees, -61.5 degrees for L-Asp-D-Ala-OTMCP and 151.0 degrees, -68.8 degrees for L-Asp-D-(alpha Me)Phe-OMe. In the second residue, a left-handed helical conformation is observed for the (alpha Me)Phe residue of L-Asp-D-(alpha Me)Phe-OMe with phi 2 = 49.0 degrees and psi 2 = 47.9 degrees, while the Ala residue of L-Asp-D-Ala-OTMCP adopts a semi-extended conformation characterized by dihedral angles phi 2 = 62.8 degrees and psi 2 = -139.9 degrees. The solid-state structure of the bitter L-Asp-D-(alpha Me)Phe-OMe is extended: while the crystal structure of the sweet L-Asp-D-OTMCP roughly adopts the typical L-shaped structure shown by other sweeteners. The data of L-Asp-D-(alpha Me)Phe-OMe are compared with those of its diastereoisomer L-Asp-L-(alpha Me)Phe-OMe. Conformational analysis of the two taste ligands in solution by NMR and computer simulations agrees well with our model for sweet and bitter tastes.

  5. Single molecule insights on conformational selection and induced fit mechanism.

    PubMed

    Hatzakis, Nikos S

    2014-02-01

    Biomolecular interactions regulate a plethora of vital cellular processes, including signal transduction, metabolism, catalysis and gene regulation. Regulation is encoded in the molecular properties of the constituent proteins; distinct conformations correspond to different functional outcomes. To describe the molecular basis of this behavior, two main mechanisms have been advanced: 'induced fit' and 'conformational selection'. Our understanding of these models relies primarily on NMR, computational studies and kinetic measurements. These techniques report the average behavior of a large ensemble of unsynchronized molecules, often masking intrinsic dynamic behavior of proteins and biologically significant transient intermediates. Single molecule measurements are emerging as a powerful tool for characterizing protein function. They offer the direct observation and quantification of the activity, abundance and lifetime of multiple states and transient intermediates in the energy landscape, that are typically averaged out in non-synchronized ensemble measurements. Here we survey new insights from single molecule studies that advance our understanding of the molecular mechanisms underlying biomolecular recognition. PMID:24342874

  6. Characterizing human retinotopic mapping with conformal geometry: a preliminary study

    NASA Astrophysics Data System (ADS)

    Ta, Duyan; Shi, Jie; Barton, Brian; Brewer, Alyssa; Lu, Zhong-Lin; Wang, Yalin

    2014-03-01

    Functional magnetic resonance imaging (fMRI) has been widely used to measure the retinotopic organization of early visual cortex in the human brain. Previous studies have identified multiple visual field maps (VFMs) based on statistical analysis of fMRI signals, but the resulting geometry has not been fully characterized with mathematical models. Here we test whether VFMs V1 and V2 obey the least restrictive of all geometric mappings; that is, whether they are anglepreserving and therefore maintain conformal mapping. We measured retinotopic organization in individual subjects using standard traveling-wave fMRI methods. Visual stimuli consisted of black and white, drifting checkerboards comprising rotating wedges and expanding rings to measure the cortical representations of polar angle and eccentricity, respectively. These representations were then projected onto a 3D cortical mesh of each hemisphere. By generating a mapped unit disk that is conformal of the VFMs using spherical stereographic projection and computing the parameterized coordinates of the eccentricity and polar angle gradients, we computed Beltrami coefficients to check whether the mapping from the visual field to the V1 and V2 cortical representations is conformal. We find that V1 and V2 exhibit local conformality. Our analysis of the Beltrami coefficient shows that selected regions of V1 and V2 that contain reasonably smooth eccentricity and polar angle gradients do show significant local conformality, warranting further investigation of this approach for analysis of early and higher visual cortex. These results suggest that such a mathematical model can be used to characterize the early VFMs in human visual cortex.

  7. 75 FR 68166 - National Adoption Month, 2010

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-04

    ... From the Federal Register Online via the Government Publishing Office TD04NO10.016 [FR Doc. 2010... the United States of America the two hundred and thirty-fifth. (Presidential Sig.) [FR Doc. 2010-28117... small. National Adoption Day is a day of hope and happiness when courthouses finalize the adoptions...

  8. Predicting Language Outcomes for Internationally Adopted Children

    ERIC Educational Resources Information Center

    Glennen, Sharon L.

    2007-01-01

    Purpose: Language and speech are difficult to assess in newly arrived internationally adopted children. The purpose of this study was to determine if assessments completed when toddlers were first adopted could predict language outcomes at age 2. Local norms were used to develop early intervention guidelines that were evaluated against age 2…

  9. Covering Adoption: General Depictions in Broadcast News

    ERIC Educational Resources Information Center

    Kline, Susan L.; Karel, Amanda I.; Chatterjee, Karishma

    2006-01-01

    Using theories of stigma (Goffman, 1963) and media frames (Iyengar, 1991), 292 news stories pertaining to adoption that appeared on major broadcast networks between 2001 and 2004 were analyzed. Media coverage of adoptees contained more problematic than positive depictions. Although birth parents were not always depicted, adoptive parent and…

  10. Issues in Adoption and Foster Care.

    ERIC Educational Resources Information Center

    Hepworth, H. Philip

    This speech presents an overview of issues and trends in the provision of foster care and adoption services in Canada. The number of children "in care" in Canada (in foster homes, institutions, or adoptive homes) appears to have peaked around 1969 and declined thereafter. Information on contraceptives and the availaibility of abortions are seen as…

  11. Why Wasn't This Child Adopted?

    ERIC Educational Resources Information Center

    Raspberry, William

    1982-01-01

    Critizes the public child care policy with regard to adoption services through the story of "Joey", a black child in his teens. Shortly after his birth, Joey was sent by his teenage mother to a city agency for adoption and until now no real effort has been made to place him in a permanent home. (Author/MP)

  12. 43 CFR 10010.20 - Adoption.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Adoption. 10010.20 Section 10010.20 Public Lands: Interior Regulations Relating to Public Lands (Continued) UTAH RECLAMATION MITIGATION AND... Environmental Assessments § 10010.20 Adoption. (a) An EA prepared for a proposal before the Commission...

  13. 43 CFR 10010.20 - Adoption.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Adoption. 10010.20 Section 10010.20 Public Lands: Interior Regulations Relating to Public Lands (Continued) UTAH RECLAMATION MITIGATION AND... Environmental Assessments § 10010.20 Adoption. (a) An EA prepared for a proposal before the Commission...

  14. 43 CFR 10010.20 - Adoption.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Adoption. 10010.20 Section 10010.20 Public Lands: Interior Regulations Relating to Public Lands (Continued) UTAH RECLAMATION MITIGATION AND... Environmental Assessments § 10010.20 Adoption. (a) An EA prepared for a proposal before the Commission...

  15. A Research and Development Adoption Model

    ERIC Educational Resources Information Center

    Hull, Ronald E.

    1974-01-01

    An elaboration of the adoption phase of the Clark and Guba R and D model. A brief discussion of the normative structures of the organizations and organizational boundary permeability provides the rationale for a set of suggested procedures for adoption of innovations at the school building level. (Author)

  16. Fuzzy Cognitive Map Modelling Educational Software Adoption

    ERIC Educational Resources Information Center

    Hossain, Sarmin; Brooks, Laurence

    2008-01-01

    Educational software adoption across UK secondary schools is seen as unsatisfactory. Based on stakeholders' perceptions, this paper uses fuzzy cognitive maps (FCMs) to model this adoption context. It discusses the development of the FCM model, using a mixed-methods approach and drawing on participants from three UK secondary schools. The study…

  17. Adoption of Improved Agricultural Practices in Uruguay.

    ERIC Educational Resources Information Center

    Rucks, Carlos Alberto

    Conducted in Uruguay during 1965-68, this study compared adoption rates for selected agricultural practices between one area which received an extension program and one which did not; and sought relationships between selected characteristics of individual farmers and the adoption of new practices. Data came from interviews with 69 experimental and…

  18. 32 CFR 584.4 - Adoption proceedings.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... situations were a soldier is trying to adopt a child. It applies to those situations where another person is trying to adopt a legitimate or illegitimate child of a soldier. A child born in or out of wedlock... has stated that he or she is not the natural parent of the child. (v) Since the soldier is not...

  19. Adopting the Caregiver Role: A Family Legacy.

    ERIC Educational Resources Information Center

    Piercy, Kathleen W.; Chapman, Jeffery G.

    2001-01-01

    A qualitative study was done to investigate how adult children become caregivers to older parents with functional impairments and what roles their own children adopt in their family's care arrangement. Interviews revealed five influences on children and grandchildren's adoption of caregiver roles: expectations; family rules; religious training;…

  20. Conservation Tillage: Monitoring Adoption with Satellite Imagery

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Conservation tillage is a commonly adopted best management practice for improving soil quality and reducing erosion. However, there are currently no methods in place to monitor conservation tillage adoption at the watershed scale. The primary objective of this study was to evaluate the utility of ...

  1. 76 FR 68613 - National Adoption Month, 2011

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-04

    ... Sig.) [FR Doc. 2011-28839 Filed 11-3-11; 11:15 am] Billing code 3295-F2-P ... Documents#0;#0; ] Proclamation 8744 of November 1, 2011 National Adoption Month, 2011 By the President of... basic support, and still more children abroad live without families. During National Adoption Month,...

  2. 78 FR 66609 - National Adoption Month, 2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-05

    .... (Presidential Sig.) [FR Doc. 2013-26669 Filed 11-4-13; 11:15 am] Billing code 3295-F4 ... Documents#0;#0; ] Proclamation 9049 of October 31, 2013 National Adoption Month, 2013 By the President of... million children and teenagers. During National Adoption Month, we celebrate these families and...

  3. 77 FR 66517 - National Adoption Month, 2012

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-06

    ... Sig.) [FR Doc. 2012-27190 Filed 11-5-12; 8:45 am] Billing code 3295-F3 ... Documents#0;#0; ] Proclamation 8896 of November 1, 2012 National Adoption Month, 2012 By the President of... knowing the love and protection of a permanent family. During National Adoption Month, we give voice...

  4. Nurturing Development of Foster and Adopted Children

    ERIC Educational Resources Information Center

    Nowak-Fabrykowski, Krystyna Teresa

    2015-01-01

    The goal of this study is to investigate early childhood teachers' perspective of teaching foster and adopted children. The main purpose is to seek suggestions how teachers can nurture the development of foster and adopted children. A 6 question survey was sent to 44 teachers pursuing graduate studies in early childhood education. Of this 50%…

  5. States Adopt Standards at Fast Clip

    ERIC Educational Resources Information Center

    Gewertz, Catherine

    2010-01-01

    Nearly half the states have adopted a new set of common academic standards, barely a month after their final release and, in most cases, with little opposition. As of July 9, 23 states had decided to replace their mathematics and English/language arts standards with the common set. Another flurry of adoptions is expected by Aug. 2, since the $4…

  6. Wrongful Adoption: Law, Policy and Practice.

    ERIC Educational Resources Information Center

    Freundlich, Madelyn; Peterson, Lisa

    The past decade has seen an increase in cases where adoptive parents fail to receive accurate or complete information about a child's physical, emotional, or developmental problems or about the child's birth family and history. In these cases adoptive parents are confronted with extremely expensive medical care or mental health care. This…

  7. Faculty Adoption of Active Learning Classrooms

    ERIC Educational Resources Information Center

    Van Horne, Sam; Murniati, Cecilia Titiek

    2016-01-01

    Although post-secondary educational institutions are incorporating more active learning classrooms (ALCs) that support collaborative learning, researchers have less often examined the cultural obstacles to adoption of those environments. In this qualitative research study, we adopted the conceptual framework of activity theory to examine the…

  8. Side chain conformational averaging in human dihydrofolate reductase.

    PubMed

    Tuttle, Lisa M; Dyson, H Jane; Wright, Peter E

    2014-02-25

    The three-dimensional structures of the dihydrofolate reductase enzymes from Escherichia coli (ecDHFR or ecE) and Homo sapiens (hDHFR or hE) are very similar, despite a rather low level of sequence identity. Whereas the active site loops of ecDHFR undergo major conformational rearrangements during progression through the reaction cycle, hDHFR remains fixed in a closed loop conformation in all of its catalytic intermediates. To elucidate the structural and dynamic differences between the human and E. coli enzymes, we conducted a comprehensive analysis of side chain flexibility and dynamics in complexes of hDHFR that represent intermediates in the major catalytic cycle. Nuclear magnetic resonance relaxation dispersion experiments show that, in marked contrast to the functionally important motions that feature prominently in the catalytic intermediates of ecDHFR, millisecond time scale fluctuations cannot be detected for hDHFR side chains. Ligand flux in hDHFR is thought to be mediated by conformational changes between a hinge-open state when the substrate/product-binding pocket is vacant and a hinge-closed state when this pocket is occupied. Comparison of X-ray structures of hinge-open and hinge-closed states shows that helix αF changes position by sliding between the two states. Analysis of χ1 rotamer populations derived from measurements of (3)JCγCO and (3)JCγN couplings indicates that many of the side chains that contact helix αF exhibit rotamer averaging that may facilitate the conformational change. The χ1 rotamer adopted by the Phe31 side chain depends upon whether the active site contains the substrate or product. In the holoenzyme (the binary complex of hDHFR with reduced nicotinamide adenine dinucleotide phosphate), a combination of hinge opening and a change in the Phe31 χ1 rotamer opens the active site to facilitate entry of the substrate. Overall, the data suggest that, unlike ecDHFR, hDHFR requires minimal backbone conformational rearrangement as

  9. Measuring the mechanical properties of molecular conformers

    NASA Astrophysics Data System (ADS)

    Jarvis, S. P.; Taylor, S.; Baran, J. D.; Champness, N. R.; Larsson, J. A.; Moriarty, P.

    2015-09-01

    Scanning probe-actuated single molecule manipulation has proven to be an exceptionally powerful tool for the systematic atomic-scale interrogation of molecular adsorbates. To date, however, the extent to which molecular conformation affects the force required to push or pull a single molecule has not been explored. Here we probe the mechanochemical response of two tetra(4-bromophenyl)porphyrin conformers using non-contact atomic force microscopy where we find a large difference between the lateral forces required for manipulation. Remarkably, despite sharing very similar adsorption characteristics, variations in the potential energy surface are capable of prohibiting probe-induced positioning of one conformer, while simultaneously permitting manipulation of the alternative conformational form. Our results are interpreted in the context of dispersion-corrected density functional theory calculations which reveal significant differences in the diffusion barriers for each conformer. These results demonstrate that conformational variation significantly modifies the mechanical response of even simple porpyhrins, potentially affecting many other flexible molecules.

  10. Applying direct observation to model workflow and assess adoption.

    PubMed

    Unertl, Kim M; Weinger, Matthew B; Johnson, Kevin B

    2006-01-01

    Lack of understanding about workflow can impair health IT system adoption. Observational techniques can provide valuable information about clinical workflow. A pilot study using direct observation was conducted in an outpatient chronic disease clinic. The goals of the study were to assess workflow and information flow and to develop a general model of workflow and information behavior. Over 55 hours of direct observation showed that the pilot site utilized many of the features of the informatics systems available to them, but also employed multiple non-electronic artifacts and workarounds. Gaps existed between clinic workflow and informatics tool workflow, as well as between institutional expectations of informatics tool use and actual use. Concurrent use of both paper-based and electronic systems resulted in duplication of effort and inefficiencies. A relatively short period of direct observation revealed important information about workflow and informatics tool adoption.

  11. Conformal Electromagnetic Particle in Cell: A Review

    SciTech Connect

    Meierbachtol, Collin S.; Greenwood, Andrew D.; Verboncoeur, John P.; Shanker, Balasubramaniam

    2015-10-26

    We review conformal (or body-fitted) electromagnetic particle-in-cell (EM-PIC) numerical solution schemes. Included is a chronological history of relevant particle physics algorithms often employed in these conformal simulations. We also provide brief mathematical descriptions of particle-tracking algorithms and current weighting schemes, along with a brief summary of major time-dependent electromagnetic solution methods. Several research areas are also highlighted for recommended future development of new conformal EM-PIC methods.

  12. Conformal frame dependence of inflation

    SciTech Connect

    Domènech, Guillem; Sasaki, Misao E-mail: misao@yukawa.kyoto-u.ac.jp

    2015-04-01

    Physical equivalence between different conformal frames in scalar-tensor theory of gravity is a known fact. However, assuming that matter minimally couples to the metric of a particular frame, which we call the matter Jordan frame, the matter point of view of the universe may vary from frame to frame. Thus, there is a clear distinction between gravitational sector (curvature and scalar field) and matter sector. In this paper, focusing on a simple power-law inflation model in the Einstein frame, two examples are considered; a super-inflationary and a bouncing universe Jordan frames. Then we consider a spectator curvaton minimally coupled to a Jordan frame, and compute its contribution to the curvature perturbation power spectrum. In these specific examples, we find a blue tilt at short scales for the super-inflationary case, and a blue tilt at large scales for the bouncing case.

  13. Conformal approach to cylindrical DLA

    NASA Astrophysics Data System (ADS)

    Taloni, A.; Caglioti, E.; Loreto, V.; Pietronero, L.

    2006-09-01

    We extend the conformal mapping approach elaborated for the radial diffusion limited aggregation model (DLA) to cylindrical geometry. We introduce in particular a complex function which allows a cylindrical cluster to be grown using as an intermediate step a radial aggregate. The aggregate grown exhibits the same self-affine features as the original cylindrical DLA. The specific choice of the transformation allows us to study the relationship between the radial and the cylindrical geometry. In particular the cylindrical aggregate can be seen as a radial aggregate with particles of size increasing with the radius. On the other hand, the radial aggregate can be seen as a cylindrical aggregate with particles of size decreasing with the height. This framework, which shifts the point of view from the geometry to the size of the particles, can open the way to more quantitative studies on the relationship between radial and cylindrical DLA.

  14. Conformable eddy current array delivery

    NASA Astrophysics Data System (ADS)

    Summan, Rahul; Pierce, Gareth; Macleod, Charles; Mineo, Carmelo; Riise, Jonathan; Morozov, Maxim; Dobie, Gordon; Bolton, Gary; Raude, Angélique; Dalpé, Colombe; Braumann, Johannes

    2016-02-01

    The external surface of stainless steel containers used for the interim storage of nuclear material may be subject to Atmospherically Induced Stress Corrosion Cracking (AISCC). The inspection of such containers poses a significant challenge due to the large quantities involved; therefore, automating the inspection process is of considerable interest. This paper reports upon a proof-of-concept project concerning the automated NDT of a set of test containers containing artificially generated AISCCs. An Eddy current array probe with a conformable padded surface from Eddyfi was used as the NDT sensor and end effector on a KUKA KR5 arc HW robot. A kinematically valid cylindrical raster scan path was designed using the KUKA|PRC path planning software. Custom software was then written to interface measurement acquisition from the Eddyfi hardware with the motion control of the robot. Preliminary results and analysis are presented from scanning two canisters.

  15. Approaching Conformality with Ten Flavors

    SciTech Connect

    Appelquist, Thomas; Brower, Richard C.; Buchoff, Michael I.; Cheng, Michael; Cohen, Saul D.; Fleming, George T.; Kiskis, Joe; Lin, Meifeng; Na, Heechang; Neil, Ethan T.; Osborn, James C.

    2012-04-01

    We present first results for lattice simulations, on a single volume, of the low-lying spectrum of an SU(3) Yang-Mills gauge theory with N{sub f} = 10 light fermions in the fundamental representation. Fits to the fermion mass dependence of various observables are found to be globally consistent with the hypothesis that this theory is within or just outside the strongly-coupled edge of the conformal window, with mass anomalous dimension {gamma}* {approx} 1 over the range of scales simulated. We stress that we cannot rule out the possibility of spontaneous chiral-symmetry breaking at scales well below our infrared cutoff. We discuss important systematic effects, including finite-volume corrections, and consider directions for future improvement.

  16. Electromagnetic characterization of conformal antennas

    NASA Technical Reports Server (NTRS)

    Volakis, John L.; Kempel, Leo C.; Alexanian, Angelos; Jin, J. M.; Yu, C. L.; Woo, Alex C.

    1992-01-01

    The ultimate objective of this project is to develop a new technique which permits an accurate simulation of microstrip patch antennas or arrays with various feed, superstrate and/or substrate configurations residing in a recessed cavity whose aperture is planar, cylindrical or otherwise conformed to the substructure. The technique combines the finite element and boundary integral methods to formulate a system suitable for solution via the conjugate gradient method in conjunction with the fast Fourier transform. The final code is intended to compute both scattering and radiation patterns of the structure with an affordable memory demand. With upgraded capabilities, the four included papers examined the radar cross section (RCS), input impedance, gain, and resonant frequency of several rectangular configurations using different loading and substrate/superstrate configurations.

  17. Rotational Spectroscopy Unveils Eleven Conformers of Adrenaline

    NASA Astrophysics Data System (ADS)

    Cabezas, C.; Cortijo, V.; Mata, S.; Lopez, J. C.; Alonso, J. L.

    2013-06-01

    Recent improvements in our LA-MB-FTMW instrumentation have allowed the characterization of eleven and eight conformers for the neurotransmitters adrenaline and noradrenaline respectively. The observation of this rich conformational behavior is in accordance with the recent observation of seven conformers for dopamine and in sharp contrast with the conformational reduction proposed for catecholamines. C. Cabezas, I. Peña, J. C. López, J. L. Alonso J. Phys. Chem. Lett. 2013, 4, 486. H. Mitsuda, M. Miyazaki, I. B. Nielsen, P. Carcabal,C. Dedonder, C. Jouvet, S. Ishiuchi, M. Fujii J. Phys. Chem. Lett. 2010, 1, 1130.

  18. Pyrrolidine nucleotide analogs with a tunable conformation

    PubMed Central

    Poštová Slavětínská, Lenka; Rejman, Dominik

    2014-01-01

    Summary Conformational preferences of the pyrrolidine ring in nucleotide analogs 7–14 were investigated by means of NMR and molecular modeling. The effect of the relative configuration of hydroxy and nucleobase substituents as well as the effect of the alkylation or acylation of the pyrrolidine nitrogen atom on the conformation of the pyrrolidine ring were studied. The results of a conformational analysis show that the alkylation/acylation can be effectively used for tuning the pyrrolidine conformation over the whole pseudorotation cycle. PMID:25246956

  19. Fabrication challenges associated with conformal optics

    NASA Astrophysics Data System (ADS)

    Schaefer, John; Eichholtz, Richard A.; Sulzbach, Frank C.

    2001-09-01

    A conformal optic is typically an optical window that conforms smoothly to the external shape of a system platform to improve aerodynamics. Conformal optics can be on-axis, such as an ogive missile dome, or off-axis, such as in a free form airplane wing. A common example of conformal optics is the automotive head light window that conforms to the body of the car aerodynamics and aesthetics. The unusual shape of conformal optics creates tremendous challenges for design, manufacturing, and testing. This paper will discuss fabrication methods that have been successfully demonstrated to produce conformal missile domes and associated wavefront corrector elements. It will identify challenges foreseen with more complex free-form configurations. Work presented in this paper was directed by the Precision Conformal Optics Consortium (PCOT). PCOT is comprised of both industrial and academic members who teamed to develop and demonstrate conformal optical systems suitable for insertion into future military programs. The consortium was funded under DARPA agreement number MDA972-96-9-08000.

  20. [International adoption: children's health risk evolution].

    PubMed

    Dartiguenave, C

    2012-05-01

    The socioeconomic and sanitary conditions in many countries make it necessary to weigh as precisely as possible the uncertainties which might affect the health of internationally adopted children, which is one of the key drivers to adoption decision. Indeed, health troubles are more and more frequent among children proposed by countries, at a time when there are fewer children to be adopted. Hence the institutions and the actors in the field of international adoption are compelled to frequently update their professional practices, so as to cope both with the declining offer for adoptable children and with the increasing pressure from the birth countries of children to make host countries adopt children with high age or with special needs. It also requires from the administrations the will to provide better initial information and to implement the demand for an agreement. Meanwhile, in spite of those growing constraints, adopting families have been more and more risk adverse during the latest decades, this being a common trend in our developed countries.

  1. Net charge per residue modulates conformational ensembles of intrinsically disordered proteins

    PubMed Central

    Mao, Albert H.; Crick, Scott L.; Vitalis, Andreas; Chicoine, Caitlin L.; Pappu, Rohit V.

    2010-01-01

    Intrinsically disordered proteins (IDPs) adopt heterogeneous ensembles of conformations under physiological conditions. Understanding the relationship between amino acid sequence and conformational ensembles of IDPs can help clarify the role of disorder in physiological function. Recent studies revealed that polar IDPs favor collapsed ensembles in water despite the absence of hydrophobic groups—a result that holds for polypeptide backbones as well. By studying highly charged polypeptides, a different archetype of IDPs, we assess how charge content modulates the intrinsic preference of polypeptide backbones for collapsed structures. We characterized conformational ensembles for a set of protamines in aqueous milieus using molecular simulations and fluorescence measurements. Protamines are arginine-rich IDPs involved in the condensation of chromatin during spermatogenesis. Simulations based on the ABSINTH implicit solvation model predict the existence of a globule-to-coil transition, with net charge per residue serving as the discriminating order parameter. The transition is supported by quantitative agreement between simulation and experiment. Local conformational preferences partially explain the observed trends of polymeric properties. Our results lead to the proposal of a schematic protein phase diagram that should enable prediction of polymeric attributes for IDP conformational ensembles using easily calculated physicochemical properties of amino acid sequences. Although sequence composition allows the prediction of polymeric properties, interresidue contact preferences of protamines with similar polymeric attributes suggest that certain details of conformational ensembles depend on the sequence. This provides a plausible mechanism for specificity in the functions of IDPs. PMID:20404210

  2. Substrate-Induced Conformational Changes Occur in All Cleaved Forms of Caspase-6

    SciTech Connect

    S Vaidya; E Velazquez-Delgado; G Abbruzzese; J Hardy

    2011-12-31

    Caspase-6 is an apoptotic cysteine protease that also governs disease progression in Huntington's and Alzheimer's diseases. Caspase-6 is of great interest as a target for treatment of these neurodegenerative diseases; however, the molecular basis of caspase-6 function and regulation remains poorly understood. In the recently reported structure of caspase-6, the 60's and 130's helices at the base of the substrate-binding groove extend upward, in a conformation entirely different from that of any other caspase. Presently, the central question about caspase-6 structure and function is whether the extended conformation is the catalytically competent conformation or whether the extended helices must undergo a large conformational rearrangement in order to bind substrate. We have generated a series of caspase-6 cleavage variants, including a novel constitutively two-chain form, and determined crystal structures of caspase-6 with and without the intersubunit linker. This series allows evaluation of the role of the prodomain and intersubunit linker on caspase-6 structure and function before and after substrate binding. Caspase-6 is inherently more stable than closely related caspases. Cleaved caspase-6 with both the prodomain and the linker present is the most stable, indicating that these two regions act in concert to increase stability, but maintain the extended conformation in the unliganded state. Moreover, these data suggest that caspase-6 undergoes a significant conformational change upon substrate binding, adopting a structure that is more like canonical caspases.

  3. Direct Neutron Scattering Measurements of Grafted Polymer Chain Conformations from Functionalized Nanoparticles

    NASA Astrophysics Data System (ADS)

    Hore, Michael J. A.; Hammouda, Boualem

    2014-03-01

    The conformations of grafted polymers play an important role in determining the physical properties of polymer nanocomposites. Small-angle neutron scattering (SANS) is performed to quantify the conformation of poly(methyl methacrylate)(Mw > 27,000 g/mol) and polystyrene chains (Mw > 57,000 g/mol) which are attached to iron oxide nanoparticles (Rnp = 2 . 5 nm, σ = 0 . 73 chains/nm2) and small fractal aggregates (R ~ 11 nm, σ = 0 . 2 chains/nm2), respectively. Unlike light scattering or microscopy, SANS can directly measure the grafted polymer chain conformations. In a homopolymer melt, we find the grafted chains adopt stretched conformations near the nanoparticle surface, and transition to ideal, random coils past a cutoff distance rc, in agreement with scaling arguments in the literature. We find the conformation of the polymer chains is largely unaffected by the ratio of the degree of polymerization of the matrix (P) to that of the brush (N). Finally, we extend this work to measure grafted polymer conformation in solution as a function of solvent quality, and find the grafted chains behave as swollen coils with an excluded volume parameter ν that decreases as the solvent cools to the Θ temperature.

  4. Molecular dynamics simulations of conformation changes of HIV-1 regulatory protein on graphene

    NASA Astrophysics Data System (ADS)

    Zhao, Daohui; Li, Libo; He, Daohang; Zhou, Jian

    2016-07-01

    The fragment of viral protein R (Vpr), Vpr13-33, plays an important role in regulating nuclear importing of HIV genes through channel formation in which it adopts a leucine-zipper-like alpha-helical conformation. A recent experimental study reported that helical Vpr13-33 would transform to β-sheet or random coil structures and aggregate on the surface of graphene or graphene oxide through hydrophobic interactions. Due to experimental limitations, however, there is still a considerable lack of understanding on the adsorption dynamics at the early stage of the conformational transition at water-graphene interface and the underlying driving force at molecular level. In this study, atomistic molecular dynamics simulations were used to explore the conformation transition phenomena. Vpr13-33 kept α-helical structure in solution, but changed to β-sheet structure when strongly adsorbed onto graphene. Preferential adsorption of Vpr13-33 on graphene is dominated by hydrophobic interactions. The cluster analysis identified the most significant populated conformation and the early stage of structure conversion from α-helical to β-sheet was found, but the full β-sheet propagation was not observed. Free energy landscape analysis further complemented the transformation analysis of peptide conformations. These findings are consistent with experimental results, and give a molecular level interpretation for the reduced cytotoxicity of Vpr13-33 to some extent upon graphene exposure. Meanwhile, this study provides some significant insights into the detailed mechanism of graphene-induced protein conformation transition.

  5. Conformational landscapes of DNA polymerase I and mutator derivatives establish fidelity checkpoints for nucleotide insertion.

    PubMed

    Hohlbein, Johannes; Aigrain, Louise; Craggs, Timothy D; Bermek, Oya; Potapova, Olga; Shoolizadeh, Pouya; Grindley, Nigel D F; Joyce, Catherine M; Kapanidis, Achillefs N

    2013-01-01

    The fidelity of DNA polymerases depends on conformational changes that promote the rejection of incorrect nucleotides before phosphoryl transfer. Here, we combine single-molecule FRET with the use of DNA polymerase I and various fidelity mutants to highlight mechanisms by which active-site side chains influence the conformational transitions and free-energy landscape that underlie fidelity decisions in DNA synthesis. Ternary complexes of high fidelity derivatives with complementary dNTPs adopt mainly a fully closed conformation, whereas a conformation with a FRET value between those of open and closed is sparsely populated. This intermediate-FRET state, which we attribute to a partially closed conformation, is also predominant in ternary complexes with incorrect nucleotides and, strikingly, in most ternary complexes of low-fidelity derivatives for both correct and incorrect nucleotides. The mutator phenotype of the low-fidelity derivatives correlates well with reduced affinity for complementary dNTPs and highlights the partially closed conformation as a primary checkpoint for nucleotide selection.

  6. Self-perpetuating changes in Sup35 protein conformation as a mechanism of heredity in yeast.

    PubMed

    Serio, T R; Cashikar, A G; Kowal, A S; Sawicki, G J; Lindquist, S L

    2001-01-01

    Recently, a novel mode of inheritance has been described in the yeast Saccharomyces cerevisiae. The mechanism is based on the prion hypothesis, which posits that self-perpetuating changes in the conformation of single protein, PrP, underlie the severe neurodegeneration associated with the transmissible spongiform enchephalopathies in mammals. In yeast, two prions, [URE3] and [PSI+], have been identified, but these factors confer unique phenotypes rather than disease to the organism. In each case, the prion-associated phenotype has been linked to alternative conformations of the Ure2 and Sup35 proteins. Remarkably, Ure2 and Sup35 proteins existing in the alternative conformations have the unique capacity to transmit this physical state to the newly synthesized protein in vivo. Thus, a mechanism exists to ensure replication of the conformational information that underlies protein-only inheritance. We have characterized the mechanism by which Sup35 conformational information is replicated in vitro. The assembly of amyloid fibres by a region of Sup35 encompassing the N-terminal 254 amino acids faithfully recapitulates the in vivo propagation of [PSI+]. Mutations that alter [PSI+] inheritance in vivo change the kinetics of amyloid assembly in vitro in a complementary fashion, and lysates from [PSI+] cells, but not [psi-] cells, accelerate assembly in vitro. Using this system we propose a mechanism by which the alternative conformation of Sup35 is adopted by an unstructured oilgomeric intermediate at the time of assembly.

  7. Parallel Process Issues for Lesbian and Gay Adoptive Parents and Their Adopted Children

    ERIC Educational Resources Information Center

    Matthews, John D.; Cramer, Elizabeth P.

    2005-01-01

    Gays and lesbians, both single and coupled, are increasingly turning to adoption to create or expand their families. This manuscript specifically addresses the continuing needs of adoptees and adoptive parents by exploring key issues in the life course of gays and lesbians and their adopted children, and identifying potential parallel development…

  8. 20 CFR 404.733 - Evidence you are the legally adopting parent or legally adopted child.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... or legally adopted child. 404.733 Section 404.733 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Evidence Evidence for Child's and Parent's Benefits § 404.733 Evidence you are the legally adopting parent or legally adopted child. If you are...

  9. Factors Influencing the Adoption Decision: An Analysis of Adopters and Nonadopters.

    ERIC Educational Resources Information Center

    King, Robert N.; Rollins, Timothy

    1995-01-01

    An agricultural innovation (nitrogen testing) had been used by 127 of a sample of 220 farmers. Adoption of the technique was influenced by information and change agents' attitudes. Adopters were also motivated by cost savings. Both adopters and nonadopters either did not have or use soil sampling skills needed to perform the test correctly.…

  10. Open Adoption of Infants: Adoptive Parents' Perceptions of Advantages and Disadvantages.

    ERIC Educational Resources Information Center

    Siegel, Deborah H.

    1993-01-01

    Conducted qualitative study of adoptive parents' (n=21 couples) reactions to recent open adoptions of their infants. Findings indicated overwhelmingly positive feelings about open adoption. Respondents often noted that issue of openness was eclipsed by other concerns: coping with infertility, finding a baby, dealing with personnel, and dealing…

  11. 20 CFR 404.733 - Evidence you are the legally adopting parent or legally adopted child.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... or legally adopted child. 404.733 Section 404.733 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Evidence Evidence for Child's and Parent's Benefits § 404.733 Evidence you are the legally adopting parent or legally adopted child. If you are...

  12. Cultural Tourism in Transnational Adoption: "Staged Authenticity" and Its Implications for Adopted Children

    ERIC Educational Resources Information Center

    Quiroz, Pamela Anne

    2012-01-01

    The discursive practices of adoptive parents in two online transnational adoption forums (2006-2008) and observations of five international adoption workshops suggest that what Heather Jacobson described as "culture keeping", the cultural socialization of children that retains a sense of native group identity, is more aptly characterized as…

  13. Korean Adoptee Identity: Adoptive and Ethnic Identity Profiles of Adopted Korean Americans

    ERIC Educational Resources Information Center

    Beaupre, Adam J.; Reichwald, Reed; Zhou, Xiang; Raleigh, Elizabeth; Lee, Richard M.

    2015-01-01

    Adopted Korean adolescents face the task of grappling with their identity as Koreans and coming to terms with their adoptive status. In order to explore these dual identities, the authors conducted a person-centered study of the identity profiles of 189 adopted Korean American adolescents. Using cluster analytic procedures, the study examined…

  14. A Study of Self-Esteem in Adopted Non-adopted Adolescents.

    ERIC Educational Resources Information Center

    Steward, Robbie J.; Lynn, Betty Jane

    This study tested the hypothesis that adopted adolescents have lower self-esteem than do non-adopted adolescents. Male and female students (N=159) between the ages of 18 and 22 were conveniently sampled from college undergraduate populations. Forty-four of the participants reported adoptive status. Each participant completed the Coopersmith…

  15. Pricing Health Behavior Interventions to Promote Adoption

    PubMed Central

    Ribisl, Kurt M.; Leeman, Jennifer; Glasser, Allison M.

    2015-01-01

    The relatively high cost of delivering many public health interventions limits their potential for broad public impact by reducing their likelihood of adoption and maintenance over time. Practitioners identify cost as the primary factor for which interventions they select to implement, but researchers rarely disseminate cost information or consider its importance when developing new interventions. A new approach is proposed, whereby intervention developers assess what individuals and agencies adopting their interventions are willing to pay and then design interventions that are responsive to this price range. The ultimate goal is to develop effective and affordable interventions, called lean interventions, which are widely adopted and have greater public health impact. PMID:24842743

  16. Intercountry adoption: a review of the evidence.

    PubMed

    Tizard, B

    1991-07-01

    Studies of the outcome of intercountry adoption are reviewed in the context of its history and politics. Intercountry adoption is a post-World War II phenomenon, and has become largely a service for childless couples in the West. Many Third World countries, and some Western social workers, are bitterly opposed to the practice, on both political and psychological grounds. Outcome studies have produced results similar to those found in studies of incountry adoption, although, to date, insufficient attention has been paid to issues of identity and racism. The policy implications of these studies will depend on political considerations, as well as the research evidence.

  17. Oligomerization, Conformational Stability and Thermal Unfolding of Harpin, HrpZPss and Its Hypersensitive Response-Inducing C-Terminal Fragment, C-214-HrpZPss

    PubMed Central

    Tarafdar, Pradip K.; Vedantam, Lakshmi Vasudev; Sankhala, Rajeshwer S.; Purushotham, Pallinti; Podile, Appa Rao; Swamy, Musti J.

    2014-01-01

    HrpZ—a harpin from Pseudomonas syringae—is a highly thermostable protein that exhibits multifunctional abilities e.g., it elicits hypersensitive response (HR), enhances plant growth, acts as a virulence factor, and forms pores in plant plasma membranes as well as artificial membranes. However, the molecular mechanism of its biological activity and high thermal stability remained poorly understood. HR inducing abilities of non-overlapping short deletion mutants of harpins put further constraints on the ability to establish structure-activity relationships. We characterized HrpZPss from Pseudomonas syringae pv. syringae and its HR inducing C-terminal fragment with 214 amino acids (C-214-HrpZPss) using calorimetric, spectroscopic and microscopic approaches. Both C-214-HrpZPss and HrpZPss were found to form oligomers. We propose that leucine-zipper-like motifs may take part in the formation of oligomeric aggregates, and oligomerization could be related to HR elicitation. CD, DSC and fluorescence studies showed that the thermal unfolding of these proteins is complex and involves multiple steps. The comparable conformational stability at 25°C (∼10.0 kcal/mol) of HrpZPss and C-214-HrpZPss further suggest that their structures are flexible, and the flexibility allows them to adopt proper conformation for multifunctional abilities. PMID:25502017

  18. An Atomistic View of Amyloidogenic Self-assembly: Structure and Dynamics of Heterogeneous Conformational States in the Pre-nucleation Phase

    PubMed Central

    Matthes, Dirk; Gapsys, Vytautas; Brennecke, Julian T.; de Groot, Bert L.

    2016-01-01

    The formation of well-defined filamentous amyloid structures involves a polydisperse collection of oligomeric states for which relatively little is known in terms of structural organization. Here we use extensive, unbiased explicit solvent molecular dynamics (MD) simulations to investigate the structural and dynamical features of oligomeric aggregates formed by a number of highly amyloidogenic peptides at atomistic resolution on the μs time scale. A consensus approach has been adopted to analyse the simulations in multiple force fields, yielding an in-depth characterization of pre-fibrillar oligomers and their global and local structure properties. A collision cross section analysis revealed structurally heterogeneous aggregate ensembles for the individual oligomeric states that lack a single defined quaternary structure during the pre-nucleation phase. To gain insight into the conformational space sampled in early aggregates, we probed their substructure and found emerging β-sheet subunit layers and a multitude of ordered intermolecular β-structure motifs with growing aggregate size. Among those, anti-parallel out-of-register β-strands compatible with toxic β-barrel oligomers were particularly prevalent already in smaller aggregates and formed prior to ordered fibrillar structure elements. Notably, also distinct fibril-like conformations emerged in the oligomeric state and underscore the notion that pre-nucleated oligomers serve as a critical intermediate step on-pathway to fibrils. PMID:27616019

  19. An Atomistic View of Amyloidogenic Self-assembly: Structure and Dynamics of Heterogeneous Conformational States in the Pre-nucleation Phase

    NASA Astrophysics Data System (ADS)

    Matthes, Dirk; Gapsys, Vytautas; Brennecke, Julian T.; de Groot, Bert L.

    2016-09-01

    The formation of well-defined filamentous amyloid structures involves a polydisperse collection of oligomeric states for which relatively little is known in terms of structural organization. Here we use extensive, unbiased explicit solvent molecular dynamics (MD) simulations to investigate the structural and dynamical features of oligomeric aggregates formed by a number of highly amyloidogenic peptides at atomistic resolution on the μs time scale. A consensus approach has been adopted to analyse the simulations in multiple force fields, yielding an in-depth characterization of pre-fibrillar oligomers and their global and local structure properties. A collision cross section analysis revealed structurally heterogeneous aggregate ensembles for the individual oligomeric states that lack a single defined quaternary structure during the pre-nucleation phase. To gain insight into the conformational space sampled in early aggregates, we probed their substructure and found emerging β-sheet subunit layers and a multitude of ordered intermolecular β-structure motifs with growing aggregate size. Among those, anti-parallel out-of-register β-strands compatible with toxic β-barrel oligomers were particularly prevalent already in smaller aggregates and formed prior to ordered fibrillar structure elements. Notably, also distinct fibril-like conformations emerged in the oligomeric state and underscore the notion that pre-nucleated oligomers serve as a critical intermediate step on-pathway to fibrils.

  20. An Atomistic View of Amyloidogenic Self-assembly: Structure and Dynamics of Heterogeneous Conformational States in the Pre-nucleation Phase.

    PubMed

    Matthes, Dirk; Gapsys, Vytautas; Brennecke, Julian T; de Groot, Bert L

    2016-01-01

    The formation of well-defined filamentous amyloid structures involves a polydisperse collection of oligomeric states for which relatively little is known in terms of structural organization. Here we use extensive, unbiased explicit solvent molecular dynamics (MD) simulations to investigate the structural and dynamical features of oligomeric aggregates formed by a number of highly amyloidogenic peptides at atomistic resolution on the μs time scale. A consensus approach has been adopted to analyse the simulations in multiple force fields, yielding an in-depth characterization of pre-fibrillar oligomers and their global and local structure properties. A collision cross section analysis revealed structurally heterogeneous aggregate ensembles for the individual oligomeric states that lack a single defined quaternary structure during the pre-nucleation phase. To gain insight into the conformational space sampled in early aggregates, we probed their substructure and found emerging β-sheet subunit layers and a multitude of ordered intermolecular β-structure motifs with growing aggregate size. Among those, anti-parallel out-of-register β-strands compatible with toxic β-barrel oligomers were particularly prevalent already in smaller aggregates and formed prior to ordered fibrillar structure elements. Notably, also distinct fibril-like conformations emerged in the oligomeric state and underscore the notion that pre-nucleated oligomers serve as a critical intermediate step on-pathway to fibrils. PMID:27616019