Sample records for domain swapping experiments
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Structure of Pseudoknot PK26 Shows 3D Domain Swapping in an RNA
NASA Technical Reports Server (NTRS)
Lietzke, Susan E; Barnes, Cindy L.
1998-01-01
3D domain swapping provides a facile pathway for the evolution of oligomeric proteins and allosteric mechanisms and a means for using monomer-oligomer equilibria to regulate biological activity. The term "3D domain swapping" describes the exchange of identical domains between two protein monomers to create an oligomer. 3D domain swapping has, so far, only been recognized in proteins. In this study, the structure of the pseudoknot PK26 is reported and it is a clear example of 3D domain swapping in RNA. PK26 was chosen for study because RNA pseudoknots are required structures in several biological processes and they arise frequently in in vitro selection experiments directed against protein targets. PK26 specifically inhibits HIV-1 reverse transcriptase with nanomolar affinity. We have now determined the 3.1 A resolution crystal structure of PK26 and find that it forms a 3D domain swapped dimer. PK26 shows extensive base pairing between and within strands. Formation of the dimer requires the linker region between the pseudoknot folds to adopt a unique conformation that allows a base within a helical stem to skip one base in the stacking register. Rearrangement of the linker would permit a monomeric pseudoknot to form. This structure shows how RNA can use 3D domain swapping to build large scale oligomers like the putative hexamer in the packaging RNA of bacteriophage Phi29.
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Huang, Yongqi; Gao, Meng; Su, Zhengding
2018-02-01
Three-dimensional (3D) domain swapping is a mechanism to form protein oligomers. It has been proposed that several factors, including proline residues in the hinge region, may affect the occurrence of 3D domain swapping. Although introducing prolines into the hinge region has been found to promote domain swapping for some proteins, the opposite effect has also been observed in several studies. So far, how proline affects 3D domain swapping remains elusive. In this work, based on a large set of 3D domain-swapped structures, we performed a systematic analysis to explore the correlation between the presence of proline in the hinge region and the occurrence of 3D domain swapping. We further analyzed the conformations of proline and pre-proline residues to investigate the roles of proline in 3D domain swapping. We found that more than 40% of the domain-swapped structures contained proline residues in the hinge region. Unexpectedly, conformational transitions of proline residues were rarely observed upon domain swapping. Our analyses showed that hinge regions containing proline residues preferred more extended conformations, which may be beneficial for the occurrence of domain swapping by facilitating opening of the exchanged segments.
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Upadhyay, Atul Kumar; Sowdhamini, Ramanathan
2016-01-01
3D-domain swapping is one of the mechanisms of protein oligomerization and the proteins exhibiting this phenomenon have many biological functions. These proteins, which undergo domain swapping, have acquired much attention owing to their involvement in human diseases, such as conformational diseases, amyloidosis, serpinopathies, proteionopathies etc. Early realisation of proteins in the whole human genome that retain tendency to domain swap will enable many aspects of disease control management. Predictive models were developed by using machine learning approaches with an average accuracy of 78% (85.6% of sensitivity, 87.5% of specificity and an MCC value of 0.72) to predict putative domain swapping in protein sequences. These models were applied to many complete genomes with special emphasis on the human genome. Nearly 44% of the protein sequences in the human genome were predicted positive for domain swapping. Enrichment analysis was performed on the positively predicted sequences from human genome for their domain distribution, disease association and functional importance based on Gene Ontology (GO). Enrichment analysis was also performed to infer a better understanding of the functional importance of these sequences. Finally, we developed hinge region prediction, in the given putative domain swapped sequence, by using important physicochemical properties of amino acids.
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Das, Payel; King, Jonathan A.; Zhou, Ruhong
2011-01-01
The prevalent eye disease age-onset cataract is associated with aggregation of human γD-crystallins, one of the longest-lived proteins. Identification of the γ-crystallin precursors to aggregates is crucial for developing strategies to prevent and reverse cataract. Our microseconds of atomistic molecular dynamics simulations uncover the molecular structure of the experimentally detected aggregation-prone folding intermediate species of monomeric native γD-crystallin with a largely folded C-terminal domain and a mostly unfolded N-terminal domain. About 30 residues including a, b, and c strands from the Greek Key motif 4 of the C-terminal domain experience strong solvent exposure of hydrophobic residues as well as partial unstructuring upon N-terminal domain unfolding. Those strands comprise the domain–domain interface crucial for unusually high stability of γD-crystallin. We further simulate the intermolecular linkage of these monomeric aggregation precursors, which reveals domain-swapped dimeric structures. In the simulated dimeric structures, the N-terminal domain of one monomer is frequently found in contact with residues 135–164 encompassing the a, b, and c strands of the Greek Key motif 4 of the second molecule. The present results suggest that γD-crystallin may polymerize through successive domain swapping of those three C-terminal β-strands leading to age-onset cataract, as an evolutionary cost of its very high stability. Alanine substitutions of the hydrophobic residues in those aggregation-prone β-strands, such as L145 and M147, hinder domain swapping as a pathway toward dimerization. These findings thus provide critical molecular insights onto the initial stages of age-onset cataract, which is important for understanding protein aggregation diseases. PMID:21670251
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Non-3D domain swapped crystal structure of truncated zebrafish alphaA crystallin
Laganowsky, A; Eisenberg, D
2010-01-01
In previous work on truncated alpha crystallins (Laganowsky et al., Protein Sci 2010; 19:1031–1043), we determined crystal structures of the alpha crystallin core, a seven beta-stranded immunoglobulin-like domain, with its conserved C-terminal extension. These extensions swap into neighboring cores forming oligomeric assemblies. The extension is palindromic in sequence, binding in either of two directions. Here, we report the crystal structure of a truncated alphaA crystallin (AAC) from zebrafish (Danio rerio) revealing C-terminal extensions in a non three-dimensional (3D) domain swapped, “closed” state. The extension is quasi-palindromic, bound within its own zebrafish core domain, lying in the opposite direction to that of bovine AAC, which is bound within an adjacent core domain (Laganowsky et al., Protein Sci 2010; 19:1031–1043). Our findings establish that the C-terminal extension of alpha crystallin proteins can be either 3D domain swapped or non-3D domain swapped. This duality provides another molecular mechanism for alpha crystallin proteins to maintain the polydispersity that is crucial for eye lens transparency. PMID:20669149
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Segment swapping aided the evolution of enzyme function: The case of uroporphyrinogen III synthase.
Szilágyi, András; Györffy, Dániel; Závodszky, Péter
2017-01-01
In an earlier study, we showed that two-domain segment-swapped proteins can evolve by domain swapping and fusion, resulting in a protein with two linkers connecting its domains. We proposed that a potential evolutionary advantage of this topology may be the restriction of interdomain motions, which may facilitate domain closure by a hinge-like movement, crucial for the function of many enzymes. Here, we test this hypothesis computationally on uroporphyrinogen III synthase, a two-domain segment-swapped enzyme essential in porphyrin metabolism. To compare the interdomain flexibility between the wild-type, segment-swapped enzyme (having two interdomain linkers) and circular permutants of the same enzyme having only one interdomain linker, we performed geometric and molecular dynamics simulations for these species in their ligand-free and ligand-bound forms. We find that in the ligand-free form, interdomain motions in the wild-type enzyme are significantly more restricted than they would be with only one interdomain linker, while the flexibility difference is negligible in the ligand-bound form. We also estimated the entropy costs of ligand binding associated with the interdomain motions, and find that the change in domain connectivity due to segment swapping results in a reduction of this entropy cost, corresponding to ∼20% of the total ligand binding free energy. In addition, the restriction of interdomain motions may also help the functional domain-closure motion required for catalysis. This suggests that the evolution of the segment-swapped topology facilitated the evolution of enzyme function for this protein by influencing its dynamic properties. Proteins 2016; 85:46-53. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
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Mou, Yun; Huang, Po-Ssu; Thomas, Leonard M; Mayo, Stephen L
2015-08-14
In standard implementations of computational protein design, a positive-design approach is used to predict sequences that will be stable on a given backbone structure. Possible competing states are typically not considered, primarily because appropriate structural models are not available. One potential competing state, the domain-swapped dimer, is especially compelling because it is often nearly identical with its monomeric counterpart, differing by just a few mutations in a hinge region. Molecular dynamics (MD) simulations provide a computational method to sample different conformational states of a structure. Here, we tested whether MD simulations could be used as a post-design screening tool to identify sequence mutations leading to domain-swapped dimers. We hypothesized that a successful computationally designed sequence would have backbone structure and dynamics characteristics similar to that of the input structure and that, in contrast, domain-swapped dimers would exhibit increased backbone flexibility and/or altered structure in the hinge-loop region to accommodate the large conformational change required for domain swapping. While attempting to engineer a homodimer from a 51-amino-acid fragment of the monomeric protein engrailed homeodomain (ENH), we had instead generated a domain-swapped dimer (ENH_DsD). MD simulations on these proteins showed increased B-factors derived from MD simulation in the hinge loop of the ENH_DsD domain-swapped dimer relative to monomeric ENH. Two point mutants of ENH_DsD designed to recover the monomeric fold were then tested with an MD simulation protocol. The MD simulations suggested that one of these mutants would adopt the target monomeric structure, which was subsequently confirmed by X-ray crystallography. Copyright © 2015. Published by Elsevier Ltd.
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Dimer formation through domain swapping in the crystal structure of the Grb2-SH2-Ac-pYVNV complex.
Schiering, N; Casale, E; Caccia, P; Giordano, P; Battistini, C
2000-11-07
Src homology 2 (SH2) domains are key modules in intracellular signal transduction. They link activated cell surface receptors to downstream targets by binding to phosphotyrosine-containing sequence motifs. The crystal structure of a Grb2-SH2 domain-phosphopeptide complex was determined at 2.4 A resolution. The asymmetric unit contains four polypeptide chains. There is an unexpected domain swap so that individual chains do not adopt a closed SH2 fold. Instead, reorganization of the EF loop leads to an open, nonglobular fold, which associates with an equivalent partner to generate an intertwined dimer. As in previously reported crystal structures of canonical Grb2-SH2 domain-peptide complexes, each of the four hybrid SH2 domains in the two domain-swapped dimers binds the phosphopeptide in a type I beta-turn conformation. This report is the first to describe domain swapping for an SH2 domain. While in vivo evidence of dimerization of Grb2 exists, our SH2 dimer is metastable and a physiological role of this new form of dimer formation remains to be demonstrated.
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Assar, Zahra; Nossoni, Zahra; Wang, Wenjing; Santos, Elizabeth M; Kramer, Kevin; McCornack, Colin; Vasileiou, Chrysoula; Borhan, Babak; Geiger, James H
2016-09-06
Human Cellular Retinol Binding Protein II (hCRBPII), a member of the intracellular lipid-binding protein family, is a monomeric protein responsible for the intracellular transport of retinol and retinal. Herein we report that hCRBPII forms an extensive domain-swapped dimer during bacterial expression. The domain-swapped region encompasses almost half of the protein. The dimer represents a novel structural architecture with the mouths of the two binding cavities facing each other, producing a new binding cavity that spans the length of the protein complex. Although wild-type hCRBPII forms the dimer, the propensity for dimerization can be substantially increased via mutation at Tyr60. The monomeric form of the wild-type protein represents the thermodynamically more stable species, making the domain-swapped dimer a kinetically trapped entity. Hypothetically, the wild-type protein has evolved to minimize dimerization of the folding intermediate through a critical hydrogen bond (Tyr60-Glu72) that disfavors the dimeric form. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Stabilization, Characterization, and Selective Removal of Cystatin C Amyloid Oligomers*
Östner, Gustav; Lindström, Veronica; Hjort Christensen, Per; Kozak, Maciej; Abrahamson, Magnus; Grubb, Anders
2013-01-01
The pathophysiological process in amyloid disorders usually involves the transformation of a functional monomeric protein via potentially toxic oligomers into amyloid fibrils. The structure and properties of the intermediary oligomers have been difficult to study due to their instability and dynamic equilibrium with smaller and larger species. In hereditary cystatin C amyloid angiopathy, a cystatin C variant is deposited in arterial walls and cause brain hemorrhage in young adults. In the present investigation, we use redox experiments of monomeric cystatin C, stabilized against domain swapping by an intramolecular disulfide bond, to generate stable oligomers (dimers, trimers, tetramers, decamers, and high molecular weight oligomers). These oligomers were characterized concerning size by gel filtration, polyacrylamide gel electrophoresis, and mass spectrometry, shape by electron and atomic force microscopy, and, function by assays of their capacity to inhibit proteases. The results showed the oligomers to be highly ordered, domain-swapped assemblies of cystatin C and that the oligomers could not build larger oligomers, or fibrils, without domain swapping. The stabilized oligomers were used to induce antibody formation in rabbits. After immunosorption, using immobilized monomeric cystatin C, and elution from columns with immobilized cystatin C oligomers, oligomer-specific antibodies were obtained. These could be used to selectively remove cystatin C dimers from biological fluids containing both dimers and monomers. PMID:23629649
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Structure of the EMMPRIN N-terminal domain 1: Dimerization via [beta]-strand swapping
DOE Office of Scientific and Technical Information (OSTI.GOV)
Luo, Jinquan; Teplyakov, Alexey; Obmolova, Galina
2010-09-27
Extracellular matrix metalloproteinase inducer (EMMPRIN), also known as Hab18G, CD147, Basigin, M6, and neurothelin, is a membrane glycoprotein expressed on the surface of various cell types and many cancer cells. EMMPRIN stimulates adjacent fibroblasts and tumor cells to produce matrix metalloproteinases and plays an important role in tumor invasion and metastasis, angiogenesis, spermatogensis and fertilization, cell-cell adhesion and communication, and other biological processes (reviewed in Ref. 1 and references therein). It was demonstrated that the EMMPRIN extracellular domain (ECD), which structurally belongs to the IgG superfamily, can form homo-oligomers in a cis dependent manner and the N-terminal domain 1 (residuesmore » 22-101) was necessary and sufficient to mediate this interaction. The crystal structure of the ECD of recombinant human EMMPRIN (Hab18G/CD147) expressed in E. coli was reported at 2.8 {angstrom} resolution (Yu et al. 2008). The construct consists of residues 22-205 of the mature protein and has both an N-terminal IgC2 domain (ND1, residues 22-101) and a C-terminal IgC2 domain (ND2, residues 107-205). The two domains are joined by a five amino acid residue linker that constitutes a flexible hinge between the two domains. The crystal form has four copies of the molecule in the asymmetric unit, each of which has a different inter-domain angle that varies from 121{sup o} to 144{sup o}. The two domains each have a conserved disulfide bridge and both are comprised of two {beta}-sheets formed by strands EBA and GFCC, and DEBA and AGFCC for ND1 and ND2, respectively. Based on the crystal packing in this structure, the authors proposed that lateral packing between the two IgG domains of EMMPRIN ECD represents a potential mechanism for cell adhesion. Here we report the 2.0-{angstrom} crystal structure of the N-terminal domain of EMMPRIN ECD (ND1) expressed in mammalian cells. The overall structure of the domain is very similar to that in the full length ECD. Quite unexpectedly, ND1 forms a dimer mediated through the exchange of its last {beta}-strand (strand G). {beta}-strand swapping, which is a subset of 3D domain swapping, has been found to mediate cell-cell adhesion by cadherins. 3D domain swapping has been proposed to be a mechanism of protein oligomerization, aggregation, evolution of oligomeric proteins from single domains and amyloidogenesis. In domain swapped proteins, the same structural elements are involved in the final 3D structure, and so there is little overall energetic difference between the monomer and the swapped oligomers. However, there is often a high energy barrier for the conversion as it often goes through an unfolded state. It is also possible that strand-swapping occurs during folding of nascent polypeptide chains. Frequently, the exchange hinges contain proline-rich motifs which are often in high strain conformations. Domain swapping appears to be a strategy to resolve such local structural strain. The exchange hinge of ND1 contains a Pro-Glu-Pro tripeptide motif. Both of the proline residues adopt extended trans conformations, when compared with cis in the full-length ECD structure. Proline cis-trans isomerization may be the driving force for this exchange. Strand-exchanged dimerization may be a mechanism for the oligomerization of EMMPRIN ECD and its cis-dependent homophilic interactions in cell-cell adhesion.« less
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Guzman, L M; Weiss, D S; Beckwith, J
1997-01-01
FtsI, FtsL, and FtsQ are three membrane proteins required for assembly of the division septum in the bacterium Escherichia coli. Cells lacking any of these three proteins form long, aseptate filaments that eventually lyse. FtsI, FtsL, and FtsQ are not homologous but have similar overall structures: a small cytoplasmic domain, a single membrane-spanning segment (MSS), and a large periplasmic domain that probably encodes the primary functional activities of these proteins. The periplasmic domain of FtsI catalyzes transpeptidation and is involved in the synthesis of septal peptidoglycan. The precise functions of FtsL and FtsQ are not known. To ask whether the cytoplasmic domain and MSS of each protein serve only as a membrane anchor or have instead a more sophisticated function, we have used molecular genetic techniques to swap these domains among the three Fts proteins and one membrane protein not involved in cell division, MalF. In the cases of FtsI and FtsL, replacement of the cytoplasmic domain and/or MSS resulted in the loss of the ability to support cell division. For FtsQ, MSS swaps supported cell division but cytoplasmic domain swaps did not. We discuss several potential interpretations of these results, including that the essential domains of FtsI, FtsL, and FtsQ have a role in regulating the localization and/or activity of these proteins to ensure that septum formation occurs at the right place in the cell and at the right time during the division cycle. PMID:9260951
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu, Cong; Sawaya, Michael R.; Eisenberg, David
{beta}{sub 2}-microglobulin ({beta}{sub 2}-m) is the light chain of the type I major histocompatibility complex. It deposits as amyloid fibrils within joints during long-term hemodialysis treatment. Despite the devastating effects of dialysis-related amyloidosis, full understanding of how fibrils form from soluble {beta}{sub 2}-m remains elusive. Here we show that {beta}{sub 2}-m can oligomerize and fibrillize via three-dimensional domain swapping. Isolating a covalently bound, domain-swapped dimer from {beta}{sub 2}-m oligomers on the pathway to fibrils, we were able to determine its crystal structure. The hinge loop that connects the swapped domain to the core domain includes the fibrillizing segment LSFSKD, whosemore » atomic structure we also determined. The LSFSKD structure reveals a class 5 steric zipper, akin to other amyloid spines. The structures of the dimer and the zipper spine fit well into an atomic model for this fibrillar form of {beta}{sub 2}-m, which assembles slowly under physiological conditions.« less
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Domain-swapped T cell receptors improve the safety of TCR gene therapy
Bethune, Michael T; Gee, Marvin H; Bunse, Mario; Lee, Mark S; Gschweng, Eric H; Pagadala, Meghana S; Zhou, Jing; Cheng, Donghui; Heath, James R; Kohn, Donald B; Kuhns, Michael S; Uckert, Wolfgang; Baltimore, David
2016-01-01
T cells engineered to express a tumor-specific αβ T cell receptor (TCR) mediate anti-tumor immunity. However, mispairing of the therapeutic αβ chains with endogenous αβ chains reduces therapeutic TCR surface expression and generates self-reactive TCRs. We report a general strategy to prevent TCR mispairing: swapping constant domains between the α and β chains of a therapeutic TCR. When paired, domain-swapped (ds)TCRs assemble with CD3, express on the cell surface, and mediate antigen-specific T cell responses. By contrast, dsTCR chains mispaired with endogenous chains cannot properly assemble with CD3 or signal, preventing autoimmunity. We validate this approach in cell-based assays and in a mouse model of TCR gene transfer-induced graft-versus-host disease. We also validate a related approach whereby replacement of αβ TCR domains with corresponding γδ TCR domains yields a functional TCR that does not mispair. This work enables the design of safer TCR gene therapies for cancer immunotherapy. DOI: http://dx.doi.org/10.7554/eLife.19095.001 PMID:27823582
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The HPr Proteins from the Thermophile Bacillus stearothermophilus Can Form Domain-swapped Dimers
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sridharan, Sudharsan; Razvi, Abbas; Scholtz, J. Martin
2010-07-20
The study of proteins from extremophilic organisms continues to generate interest in the field of protein folding because paradigms explaining the enhanced stability of these proteins still elude us and such studies have the potential to further our knowledge of the forces stabilizing proteins. We have undertaken such a study with our model protein HPr from a mesophile, Bacillus subtilis, and a thermophile, Bacillus stearothermophilus. We report here the high-resolution structures of the wild-type HPr protein from the thermophile and a variant, F29W. The variant proved to crystallize in two forms: a monomeric form with a structure very similar tomore » the wild-type protein as well as a domain-swapped dimer. Interestingly, the structure of the domain-swapped dimer for HPr is very different from that observed for a homologous protein, Crh, from B. subtilis. The existence of a domain-swapped dimer has implications for amyloid formation and is consistent with recent results showing that the HPr proteins can form amyloid fibrils. We also characterized the conformational stability of the thermophilic HPr proteins using thermal and solvent denaturation methods and have used the high-resolution structures in an attempt to explain the differences in stability between the different HPr proteins. Finally, we present a detailed analysis of the solution properties of the HPr proteins using a variety of biochemical and biophysical methods.« less
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Applying MDA to SDR for Space to Model Real-time Issues
NASA Technical Reports Server (NTRS)
Blaser, Tammy M.
2007-01-01
NASA space communications systems have the challenge of designing SDRs with highly-constrained Size, Weight and Power (SWaP) resources. A study is being conducted to assess the effectiveness of applying the MDA Platform-Independent Model (PIM) and one or more Platform-Specific Models (PSM) specifically to address NASA space domain real-time issues. This paper will summarize our experiences with applying MDA to SDR for Space to model real-time issues. Real-time issues to be examined, measured, and analyzed are: meeting waveform timing requirements and efficiently applying Real-time Operating System (RTOS) scheduling algorithms, applying safety control measures, and SWaP verification. Real-time waveform algorithms benchmarked with the worst case environment conditions under the heaviest workload will drive the SDR for Space real-time PSM design.
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Chen, Chien Peter; Posy, Shoshana; Ben-Shaul, Avinoam; Shapiro, Lawrence; Honig, Barry H.
2005-01-01
Cadherins constitute a family of cell-surface proteins that mediate intercellular adhesion through the association of protomers presented from juxtaposed cells. Differential cadherin expression leads to highly specific intercellular interactions in vivo. This cell–cell specificity is difficult to understand at the molecular level because individual cadherins within a given subfamily are highly similar to each other both in sequence and structure, and they dimerize with remarkably low binding affinities. Here, we provide a molecular model that accounts for these apparently contradictory observations. The model is based in part on the fact that cadherins bind to one another by “swapping” the N-terminal β-strands of their adhesive domains. An inherent feature of strand swapping (or, more generally, the domain swapping phenomenon) is that “closed” monomeric conformations act as competitive inhibitors of dimer formation, thus lowering affinities even when the dimer interface has the characteristics of high-affinity complexes. The model describes quantitatively how small affinity differences between low-affinity cadherin dimers are amplified by multiple cadherin interactions to establish large specificity effects at the cellular level. It is shown that cellular specificity would not be observed if cadherins bound with high affinities, thus emphasizing the crucial role of strand swapping in cell–cell adhesion. Numerical estimates demonstrate that the strength of cellular adhesion is extremely sensitive to the concentration of cadherins expressed at the cell surface. We suggest that the domain swapping mechanism is used by a variety of cell-adhesion proteins and that related mechanisms to control affinity and specificity are exploited in other systems. PMID:15937105
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Insights into Strand Exchange in BTB Domain Dimers from the Crystal Structures of FAZF and Miz1
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stogios, Peter J.; Cuesta-Seijo, Jose Antonio; Chen, Lu
2010-09-22
The BTB domain is a widely distributed protein-protein interaction motif that is often found at the N-terminus of zinc finger transcription factors. Previous crystal structures of BTB domains have revealed tightly interwound homodimers, with the N-terminus from one chain forming a two-stranded anti-parallel {beta}-sheet with a strand from the other chain. We have solved the crystal structures of the BTB domains from Fanconi anemia zinc finger (FAZF) and Miz1 (Myc-interacting zinc finger 1) to resolutions of 2.0 {angstrom} and 2.6 {angstrom}, respectively. Unlike previous examples of BTB domain structures, the FAZF BTB domain is a nonswapped dimer, with each N-terminalmore » {beta}-strand associated with its own chain. As a result, the dimerization interface in the FAZF BTB domain is about half as large as in the domain-swapped dimers. The Miz1 BTB domain resembles a typical swapped BTB dimer, although it has a shorter N-terminus that is not able to form the interchain sheet. Using cysteine cross-linking, we confirmed that the promyelocytic leukemia zinc finger (PLZF) BTB dimer is strand exchanged in solution, while the FAZF BTB dimer is not. A phylogenic tree of the BTB fold based on both sequence and structural features shows that the common ancestor of the BTB domain in BTB-ZF (bric a brac, tramtrack, broad-complex zinc finger) proteins was a domain-swapped dimer. The differences in the N-termini seen in the FAZF and Miz1 BTB domains appear to be more recent developments in the structural evolution of the domain.« less
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Murciano-Calles, Javier; Güell-Bosch, Jofre; Villegas, Sandra; Martinez, Jose C
2016-01-12
PDZ domains are protein-protein interaction modules sharing the same structural arrangement. To discern whether they display common features in their unfolding/misfolding behaviour we have analyzed in this work the unfolding thermodynamics, together with the misfolding kinetics, of the PDZ fold using three archetypical examples: the second and third PDZ domains of the PSD95 protein and the Erbin PDZ domain. Results showed that all domains passed through a common intermediate, which populated upon unfolding, and that this in turn drove the misfolding towards worm-like fibrillar structures. Thus, the unfolding/misfolding behaviour appears to be shared within these domains. We have also analyzed how this landscape can be modified upon the inclusion of extra-elements, as it is in the nNOS PDZ domain, or the organization of swapped species, as happens in the second PDZ domain of the ZO2 protein. Although the intermediates still formed upon thermal unfolding, the misfolding was prevented to varying degrees.
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Prodomain–growth factor swapping in the structure of pro-TGF-β1
Xu, Shutong; Dong, Xianchi; Lu, Chafen; Springer, Timothy A.
2018-01-01
TGF-β is synthesized as a proprotein that dimerizes in the endoplasmic reticulum. After processing in the Golgi to cleave the N-terminal prodomain from the C-terminal growth factor (GF) domain in each monomer, pro-TGF-β is secreted and stored in latent complexes. It is unclear which prodomain and GF monomer are linked before proprotein convertase cleavage and how much conformational change occurs following cleavage. We have determined a structure of pro-TGF-β1 with the proprotein convertase cleavage site mutated to mimic the structure of the TGF-β1 proprotein. Structure, mutation, and model building demonstrate that the prodomain arm domain in one monomer is linked to the GF that interacts with the arm domain in the other monomer in the dimeric structure (i.e. the prodomain arm domain and GF domain in each monomer are swapped). Swapping has important implications for the mechanism of biosynthesis in the TGF-β family and is relevant to the mechanism for preferential formation of heterodimers over homodimers for some members of the TGF-β family. Our structure, together with two previous ones, also provides insights into which regions of the prodomain–GF complex are highly structurally conserved and which are perturbed by crystal lattice contacts. PMID:29109152
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Pasta, Saloni Yatin; Raman, Bakthisaran; Ramakrishna, Tangirala; Rao, Ch Mohan
2002-11-29
Several small heat shock proteins contain a well conserved alpha-crystallin domain, flanked by an N-terminal domain and a C-terminal extension, both of which vary in length and sequence. The structural and functional role of the C-terminal extension of small heat shock proteins, particularly of alphaA- and alphaB-crystallins, is not well understood. We have swapped the C-terminal extensions between alphaA- and alphaB-crystallins and generated two novel chimeric proteins, alphaABc and alphaBAc. We have investigated the domain-swapped chimeras for structural and functional alterations. We have used thermal and non-thermal models of protein aggregation and found that the chimeric alphaB with the C-terminal extension of alphaA-crystallin, alphaBAc, exhibits dramatically enhanced chaperone-like activity. Interestingly, however, the chimeric alphaA with the C-terminal extension of alphaB-crystallin, alphaABc, has almost lost its activity. Pyrene solubilization and bis-1-anilino-8-naphthalenesulfonate binding studies show that alphaBAc exhibits more solvent-exposed hydrophobic pockets than alphaA, alphaB, or alphaABc. Significant tertiary structural changes are revealed by tryptophan fluorescence and near-UV CD studies upon swapping the C-terminal extensions. The far-UV CD spectrum of alphaBAc differs from that of alphaB-crystallin whereas that of alphaABc overlaps with that of alphaA-crystallin. Gel filtration chromatography shows alteration in the size of the proteins upon swapping the C-terminal extensions. Our study demonstrates that the unstructured C-terminal extensions play a crucial role in the structure and chaperone activity, in addition to generally believed electrostatic "solubilizer" function.
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Spadaccini, Roberta; Ercole, Carmine; Gentile, Maria A.; Sanfelice, Domenico; Boelens, Rolf; Wechselberger, Rainer; Batta, Gyula; Bernini, Andrea; Niccolai, Neri; Picone, Delia
2012-01-01
Three-dimensional domain swapping is a common phenomenon in pancreatic-like ribonucleases. In the aggregated state, these proteins acquire new biological functions, including selective cytotoxicity against tumour cells. RNase A is able to dislocate both N- and C-termini, but usually this process requires denaturing conditions. In contrast, bovine seminal ribonuclease (BS-RNase), which is a homo-dimeric protein sharing 80% of sequence identity with RNase A, occurs natively as a mixture of swapped and unswapped isoforms. The presence of two disulfides bridging the subunits, indeed, ensures a dimeric structure also to the unswapped molecule. In vitro, the two BS-RNase isoforms interconvert under physiological conditions. Since the tendency to swap is often related to the instability of the monomeric proteins, in these paper we have analysed in detail the stability in solution of the monomeric derivative of BS-RNase (mBS) by a combination of NMR studies and Molecular Dynamics Simulations. The refinement of NMR structure and relaxation data indicate a close similarity with RNase A, without any evidence of aggregation or partial opening. The high compactness of mBS structure is confirmed also by H/D exchange, urea denaturation, and TEMPOL mapping of the protein surface. The present extensive structural and dynamic investigation of (monomeric) mBS did not show any experimental evidence that could explain the known differences in swapping between BS-RNase and RNase A. Hence, we conclude that the swapping in BS-RNase must be influenced by the distinct features of the dimers, suggesting a prominent role for the interchain disulfide bridges. PMID:22253705
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de Ronde, Dryas; Pasquier, Adrien; Ying, Su; Butterbach, Patrick; Lohuis, Dick; Kormelink, Richard
2014-02-01
Recently, Tomato spotted wilt virus (TSWV) nonstructural protein NSs has been identified unambiguously as an avirulence (Avr) determinant for Tomato spotted wilt (Tsw)-based resistance. The observation that NSs from two natural resistance-breaking isolates had lost RNA silencing suppressor (RSS) activity and Avr suggested a link between the two functions. To test this, a large set of NSs mutants was generated by alanine substitutions in NSs from resistance-inducing wild-type strains (NSs(RI) ), amino acid reversions in NSs from resistance-breaking strains (NSs(RB)), domain deletions and swapping. Testing these mutants for their ability to suppress green fluorescent protein (GFP) silencing and to trigger a Tsw-mediated hypersensitive response (HR) revealed that the two functions can be separated. Changes in the N-terminal domain were found to be detrimental for both activities and indicated the importance of this domain, additionally supported by domain swapping between NSs(RI) and NSs(RB). Swapping domains between the closely related Tospovirus Groundnut ringspot virus (GRSV) NSs and TSWV NSs(RI) showed that Avr functionality could not simply be transferred between species. Although deletion of the C-terminal domain rendered NSs completely dysfunctional, only a few single-amino-acid mutations in the C-terminus affected both functions. Mutation of a GW/WG motif (position 17/18) rendered NSs completely dysfunctional for RSS and Avr activity, and indicated a putative interaction between NSs and Argonaute 1 (AGO1), and its importance in TSWV virulence and viral counter defence against RNA interference. © 2013 BSPP AND JOHN WILEY & SONS LTD.
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Extensive deamidation of RNase A inhibits its oligomerization through 3D domain swapping.
Fagagnini, Andrea; Montioli, Riccardo; Caloiu, Andra; Ribó, Marc; Laurents, Douglas V; Gotte, Giovanni
2017-01-01
Bovine pancreatic ribonuclease A (RNase A) is the monomeric prototype of the so-called secretory 'pancreatic-type' RNase super-family. Like the naturally domain-swapped dimeric bovine seminal variant, BS-RNase, and its glycosylated RNase B isoform, RNase A forms N- and C-terminal 3D domain-swapped oligomers after lyophilization from acid solutions, or if subjected to thermal denaturation at high protein concentration. All mentioned RNases can undergo deamidation at Asn67, forming Asp or isoAsp derivatives that modify the protein net charge and consequently its enzymatic activity. In addition, deamidation slightly affects RNase B self-association through the 3D domain swapping (3D-DS) mechanism. We report here the influence of extensive deamidation on RNase A tendency to oligomerize through 3D-DS. In particular, deamidation of Asn67 alone slightly decreases the propensity of the protein to oligomerize, with the Asp derivative being less affected than the isoAsp one. Contrarily, the additional Asp and/or isoAsp conversion of residues other than N67 almost nullifies RNase A oligomerization capability. In addition, Gln deamidation, although less kinetically favorable, may affect RNase A self-association. Using 2D and 3D NMR we identified the Asn/Gln residues most prone to undergo deamidation. Together with CD spectroscopy, NMR also indicates that poly-deamidated RNase A generally maintains its native tertiary structure. Again, we investigated in silico the effect of the residues undergoing deamidation on RNase A dimers structures. Finally, the effect of deamidation on RNase A oligomerization is discussed in comparison with studies on deamidation-prone proteins involved in amyloid formation. Copyright © 2016. Published by Elsevier B.V.
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Crystal structure of the UBR-box from UBR6/FBXO11 reveals domain swapping mediated by zinc binding.
Muñoz-Escobar, Juliana; Kozlov, Guennadi; Gehring, Kalle
2017-10-01
The UBR-box is a 70-residue zinc finger domain present in the UBR family of E3 ubiquitin ligases that directly binds N-terminal degradation signals in substrate proteins. UBR6, also called FBXO11, is an UBR-box containing E3 ubiquitin ligase that does not bind N-terminal signals. Here, we present the crystal structure of the UBR-box domain from human UBR6. The dimeric crystal structure reveals a unique form of domain swapping mediated by zinc coordination, where three independent protein chains come together to regenerate the topology of the monomeric UBR-box fold. Analysis of the structure suggests that the absence of N-terminal residue binding arises from the lack of an amino acid binding pocket. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.
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Structural analysis of NADPH depleted bovine liver catalase and its inhibitor complexes
Sugadev, Ragumani; Ponnuswamy, M.N.; Sekar, K.
2011-01-01
To study the functional role of NADPH during mammalian catalase inhibition, the X-ray crystal structures of NADPH-depleted bovine liver catalase and its inhibitor complexes, cyanide and azide, determined at 2.8Å resolution. From the complex structures it is observed that subunits with and without an inhibitor/catalytic water molecule are linked by N-terminal domain swapping. Comparing mammalian- and fungal- catalases, we speculate that NADPH-depleted mammalian catalases may function as a domain-swapped dimer of dimers, especially during inactivation by inhibitors like cyanide and azide. We further speculate that in mammalian catalases the N-terminal hinge-loop region and α-helix is the structural element that senses NADPH binding. Although the above arguments are speculative and need further verification, as a whole our studies have opened up a new possibility, viz. that mammalian catalase acts as a domain-swapped dimer of dimers, especially during inhibitor binding. To generalize this concept to the formation of the inactive state in mammalian catalases in the absence of tightly bound NADPH molecules needs further exploration. The present study adds one more intriguing fact to the existing mysteries of mammalian catalases. PMID:21968615
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Using simulation to prepare for clinical practice.
Morgan, James; Green, Victoria; Blair, John
2018-02-01
A significant proportion of medical students feel underprepared for clinical practice, especially in skills such as decision making, prioritisation and prescribing. Changes to medical curricula, including assistantships and shadowing, provide supervised practise, but students remain unable to fully take responsibility for patient care. Simulation may assist in addressing this deficit. A simulation course entitled 'Simulated ward round and professional skills' (SWAPS) was developed to improve student preparation for clinical practice. Preliminary work surveyed 22 foundation doctors to identify perceived areas of weakness and to guide the learning outcomes of the course. Following the design and development of the course, 133 final-year medical students were observed completing a 60-minute simulation scenario aimed at providing experiential learning in a ward environment, reflecting professional practice. Students received structured feedback and completed pre- and post-course questionnaires to evaluate changes in confidence over the learning domains. Qualitative feedback was also collected. A significant proportion of medical students feel underprepared for clinical practice RESULTS: The p values were significant in all assessed domains, indicating a perceived improvement in confidence following the SWAPS course. Qualitative feedback highlighted the perceived utility of the course in exposing students to clinical ward-based scenarios infrequently encountered in their medical curriculum. Students praised the personal feedback received and realism of the simulation. This paper contributes to the growing body of literature supporting the use of simulation to replicate a ward round and the daily roles of a junior doctor. The SWAPS course seems to empower students to take responsibility for clinical decision making and experience some of the realities of foundation training in a simulated setting. © 2017 John Wiley & Sons Ltd and The Association for the Study of Medical Education.
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Highly efficient entanglement swapping and teleportation at telecom wavelength
Jin, Rui-Bo; Takeoka, Masahiro; Takagi, Utako; Shimizu, Ryosuke; Sasaki, Masahide
2015-01-01
Entanglement swapping at telecom wavelengths is at the heart of quantum networking in optical fiber infrastructures. Although entanglement swapping has been demonstrated experimentally so far using various types of entangled photon sources both in near-infrared and telecom wavelength regions, the rate of swapping operation has been too low to be applied to practical quantum protocols, due to limited efficiency of entangled photon sources and photon detectors. Here we demonstrate drastic improvement of the efficiency at telecom wavelength by using two ultra-bright entangled photon sources and four highly efficient superconducting nanowire single photon detectors. We have attained a four-fold coincidence count rate of 108 counts per second, which is three orders higher than the previous experiments at telecom wavelengths. A raw (net) visibility in a Hong-Ou-Mandel interference between the two independent entangled sources was 73.3 ± 1.0% (85.1 ± 0.8%). We performed the teleportation and entanglement swapping, and obtained a fidelity of 76.3% in the swapping test. Our results on the coincidence count rates are comparable with the ones ever recorded in teleportation/swapping and multi-photon entanglement generation experiments at around 800 nm wavelengths. Our setup opens the way to practical implementation of device-independent quantum key distribution and its distance extension by the entanglement swapping as well as multi-photon entangled state generation in telecom band infrastructures with both space and fiber links. PMID:25791212
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Highly efficient entanglement swapping and teleportation at telecom wavelength.
Jin, Rui-Bo; Takeoka, Masahiro; Takagi, Utako; Shimizu, Ryosuke; Sasaki, Masahide
2015-03-20
Entanglement swapping at telecom wavelengths is at the heart of quantum networking in optical fiber infrastructures. Although entanglement swapping has been demonstrated experimentally so far using various types of entangled photon sources both in near-infrared and telecom wavelength regions, the rate of swapping operation has been too low to be applied to practical quantum protocols, due to limited efficiency of entangled photon sources and photon detectors. Here we demonstrate drastic improvement of the efficiency at telecom wavelength by using two ultra-bright entangled photon sources and four highly efficient superconducting nanowire single photon detectors. We have attained a four-fold coincidence count rate of 108 counts per second, which is three orders higher than the previous experiments at telecom wavelengths. A raw (net) visibility in a Hong-Ou-Mandel interference between the two independent entangled sources was 73.3 ± 1.0% (85.1 ± 0.8%). We performed the teleportation and entanglement swapping, and obtained a fidelity of 76.3% in the swapping test. Our results on the coincidence count rates are comparable with the ones ever recorded in teleportation/swapping and multi-photon entanglement generation experiments at around 800 nm wavelengths. Our setup opens the way to practical implementation of device-independent quantum key distribution and its distance extension by the entanglement swapping as well as multi-photon entangled state generation in telecom band infrastructures with both space and fiber links.
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Chan, Y H; Cheng, C H K; Chan, K M
2007-03-01
Using goldfish as a model, the structure-function relationship of goldfish growth hormone was studied using the strategy of homologous domain swapping. Chimeric mutants were constructed by exchanging homologous regions between goldfish growth hormone (gfGH II) and goldfish prolactin (gfPRL) with their cloned complementary DNAs. Six mutants, with their domain-swapped, were generated to have different combinations of three target regions, including the helix a, helix d and the large section in between these helices (possess the helices b, c and other random coiled regions). After expression in E. coli and refolding, these mutants were characterized by using competitive receptor binding assay (RRA) and growth hormone responding promoter activation assay. The different activity profiles of mutants in Spi 2.1 gene promoter assays from that in RRA shows that, for gfGH, receptor binding dose not confer receptor signal activations. When either helices a or d of gfGH was maintained with other helices replaced by their gfPRL counterparts, both receptor binding and hence gene activation activities are reduced. In mutants with helices b and c in gfGH maintained, containing the gfGH middle section, and helices a and d swapped with gfPRL, the had reduced RRA activities but the promoter activation activities retained. In conclusion, as in the case of human GH, the gfGH molecule possesses two functional sites: one of them is composed of discontinuous epitopes located on the target regions of this study and is for receptor binding; another site is located on the middle section of the molecule that helices a and d are not involved, and it is for activation of GH receptor and intracellular signals.
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Spin Hall and Spin Swapping Torques in Diffusive Ferromagnets
NASA Astrophysics Data System (ADS)
Pauyac, Christian Ortiz; Chshiev, Mairbek; Manchon, Aurelien; Nikolaev, Sergey A.
2018-04-01
A complete set of the generalized drift-diffusion equations for a coupled charge and spin dynamics in ferromagnets in the presence of extrinsic spin-orbit coupling is derived from the quantum kinetic approach, covering major transport phenomena, such as the spin and anomalous Hall effects, spin swapping, spin precession, and relaxation processes. We argue that the spin swapping effect in ferromagnets is enhanced due to spin polarization, while the overall spin texture induced by the interplay of spin-orbital and spin precession effects displays a complex spatial dependence that can be exploited to generate torques and nucleate or propagate domain walls in centrosymmetric geometries without the use of external polarizers, as opposed to the conventional understanding of spin-orbit mediated torques.
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Quantum Entanglement Swapping between Two Multipartite Entangled States
NASA Astrophysics Data System (ADS)
Su, Xiaolong; Tian, Caixing; Deng, Xiaowei; Li, Qiang; Xie, Changde; Peng, Kunchi
2016-12-01
Quantum entanglement swapping is one of the most promising ways to realize the quantum connection among local quantum nodes. In this Letter, we present an experimental demonstration of the entanglement swapping between two independent multipartite entangled states, each of which involves a tripartite Greenberger-Horne-Zeilinger (GHZ) entangled state of an optical field. The entanglement swapping is implemented deterministically by means of a joint measurement on two optical modes coming from the two multipartite entangled states respectively and the classical feedforward of the measurement results. After entanglement swapping the two independent multipartite entangled states are merged into a large entangled state in which all unmeasured quantum modes are entangled. The entanglement swapping between a tripartite GHZ state and an Einstein-Podolsky-Rosen entangled state is also demonstrated and the dependence of the resultant entanglement on transmission loss is investigated. The presented experiment provides a feasible technical reference for constructing more complicated quantum networks.
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Quantum Entanglement Swapping between Two Multipartite Entangled States.
Su, Xiaolong; Tian, Caixing; Deng, Xiaowei; Li, Qiang; Xie, Changde; Peng, Kunchi
2016-12-09
Quantum entanglement swapping is one of the most promising ways to realize the quantum connection among local quantum nodes. In this Letter, we present an experimental demonstration of the entanglement swapping between two independent multipartite entangled states, each of which involves a tripartite Greenberger-Horne-Zeilinger (GHZ) entangled state of an optical field. The entanglement swapping is implemented deterministically by means of a joint measurement on two optical modes coming from the two multipartite entangled states respectively and the classical feedforward of the measurement results. After entanglement swapping the two independent multipartite entangled states are merged into a large entangled state in which all unmeasured quantum modes are entangled. The entanglement swapping between a tripartite GHZ state and an Einstein-Podolsky-Rosen entangled state is also demonstrated and the dependence of the resultant entanglement on transmission loss is investigated. The presented experiment provides a feasible technical reference for constructing more complicated quantum networks.
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Chakrabarti, Apratim; Panter, Stephen N; Harrison, Kate; Jones, Jonathan D G; Jones, David A
2009-10-01
The tomato Cf-9 and Cf-9B genes both confer resistance to the leaf mold fungus Cladosporium fulvum but only Cf-9 confers seedling resistance and recognizes the avirulence (Avr) protein Avr9 produced by C. fulvum. Using domain swaps, leucine-rich repeats (LRR) 5 to 15 of Cf-9 were shown to be required for Cf-9-specific resistance to C. fulvum in tomato, and the entire N-terminus up to LRR15 of Cf-9B was shown to be required for Cf-9B-specific resistance. Finer domain swaps showed that nine amino-acid differences in LRR 13 to 15 provided sufficient Cf-9-specific residues in a Cf-9B context for recognition of Avr9 in Nicotiana tabacum or sufficient Cf-9B residues in a Cf-9 context for a novel necrotic response caused by the expression of Cf-9B in N. benthamiana. The responses conferred by LRR 13 to 15 were enhanced by addition of LRR 10 to 12, and either region of Cf-9B was found to cause necrosis in N. benthamiana when the other was replaced by Cf-9 sequence in a Cf-9B context. As a consequence, the domain swap with LRR 13 to 15 of Cf-9 in a Cf-9B context gained the dual ability to recognize Avr9 and cause necrosis in N. benthamiana. Intriguingly, two Cf-9B-specific domain swaps gave differing results for necrosis assays in N. benthamiana compared with disease resistance assays in transgenic tomato. The different domain requirements in these two cases suggest that the two assays detect unrelated ligands or detect related ligands in slightly different ways. A heat-sensitive necrosis-inducing factor present in N. benthamiana intercellular washing fluids was found to cause a necrotic response in N. tabacum plants carrying Hcr9-9A, Cf-9B, and Cf-9 but not in plants carrying only Cf-9. We postulate that this necrosis-inducing factor is recognized by Cf-9B either directly as a ligand or indirectly as a regulator of Cf-9B autoactivity.
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Fallahi Motlagh, Behzad; Sadeghi, Ali
2017-01-01
The aim of this study was to correlate macular thickness and visual field parameters in early glaucoma. A total of 104 eyes affected with early glaucoma were examined in a cross-sectional, prospective study. Visual field testing using both standard automated perimetry (SAP) and shortwave automated perimetry (SWAP) was performed. Global visual field parameters, including mean deviation (MD) and pattern standard deviation (PSD), were recorded and correlated with spectral domain optical coherence tomography (SD-OCT)-measured macular thickness and asymmetry. Average macular thickness correlated significantly with all measures of visual field including MD-SWAP (r = 0.42), MD-SAP (r = 0.41), PSD-SWAP (r = -0.23), and PSD-SAP (r = -0.21), with P-values <0.001 for all correlations. The mean MD scores (using both SWAP and SAP) were significantly higher in the eyes with thin than in those with intermediate average macular thickness. Intraeye (superior macula thickness - inferior macula thickness) asymmetries correlated significantly with both PSD-SWAP (r = 0.63, P < 0.001) and PSD-SAP (r = 0.26, P = 0.01) scores. This study revealed a significant correlation between macular thickness and visual field parameters in early glaucoma. The results of this study should make macular thickness measurements even more meaningful to glaucoma specialists.
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Patient SWAP-200 personality dimensions and FFM traits: Do they predict therapist responses?
Tanzilli, Annalisa; Lingiardi, Vittorio; Hilsenroth, Mark
2018-05-01
The main aim of this study was to examine the relationship between therapists' emotional responses and patients' personality evaluated by 3 dimensional diagnostic approaches empirically derived from the Shedler-Westen Assessment Procedure-200 (SWAP-200; Westen & Shedler, 1999a, 1999b): Two of these rely on the 5-factor model (FFM) domains, that were assessed with different SWAP-200 FFM versions developed by Shedler and Westen (SW-FFM scales; 2004) and McCrae, Löckenhoff, and Costa (MLC-FFM scales; 2005); the third approach is based on a multifaceted model of personality syndromes (SWAP personality dimension scales; see Shedler & Westen, 2004). A national sample of psychiatrists and psychologists (N = 166) of various theoretical orientations completed the Therapist Response Questionnaire (TRQ; Zittel Conklin & Westen, 2003) to identify patterns of therapist response, and the SWAP-200 to assess personality regarding a patient currently in their care. The findings showed good levels of construct validity between the SW-FFM and MLC-FFM scales, with the exception of the Openness trait. Moreover, specific SW-FFM and MLC-FFM scales were significantly associated with distinct SWAP personality dimension scales according in a conceptually meaningful nomological network. Although there were significant, theoretically coherent, and systematic relationships between therapists' responses and patients' personality features, overall the contribution of the SW-FFM and MLC-FFM traits in predicting therapists' responses was less sizable than the SWAP personality dimensions. These results seem to confirm the diagnostic and therapeutic value of countertransference as an essential tool in understanding psychological traits/dimensions that underlie the patients' psychopathology, both from within and outside of the FFM. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
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Smaldone, Giovanni; Vigorita, Marilisa; Ruggiero, Alessia; Balasco, Nicole; Dattelbaum, Jonathan D; D'Auria, Sabato; Del Vecchio, Pompea; Graziano, Giuseppe; Vitagliano, Luigi
2016-07-01
The Arginine Binding Protein isolated from Thermotoga maritima (TmArgBP) is a protein endowed with several peculiar properties. We have previously shown that TmArgBP dimerization is a consequence of the swapping of the C-terminal helix. Here we explored the structural determinants of TmArgBP domain swapping and oligomerization. In particular, we report a mutational analysis of the residue Pro235, which is located in the hinge region of the swapping dimer. This residue was either replaced with a Gly-Lys dipeptide (TmArgBP(P235GK)) or a Gly residue (TmArgBP(P235G)). Different forms of these mutants were generated and extensively characterized using biophysical techniques. For both TmArgBP(P235GK) and TmArgBP(P235G) mutants, the occurrence of multiple oligomerization states (monomers, dimers and trimers) was detected. The formation of well-folded monomeric forms for these mutants indicates that the dimerization through C-terminal domain swapping observed in wild-type TmArgBP is driven by conformational restraints imposed by the presence of Pro235 in the hinge region. Molecular dynamics studies corroborate this observation by showing that Gly235 assumes conformational states forbidden for Pro residues in the TmArgBP(P235G) monomer. Unexpectedly, the trimeric forms present: (a) peculiar circular dichroism spectra, (b) a great susceptibility to heating, and (c) the ability to bind the Thioflavin T dye. The present findings clearly demonstrate that single-point mutations have an important impact on the TmArgBP oligomerization process. In a wider context, they also indicate that proteins endowed with an intrinsic propensity to swap have an easy access to states with altered structural and, possibly, functional properties. Copyright © 2016. Published by Elsevier B.V.
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Soyk, Sebastian; Simková, Klára; Zürcher, Evelyne; Luginbühl, Leonie; Brand, Luise H; Vaughan, Cara K; Wanke, Dierk; Zeeman, Samuel C
2014-04-01
Plant BZR1-BAM transcription factors contain a β-amylase (BAM)-like domain, characteristic of proteins involved in starch breakdown. The enzyme-derived domains appear to be noncatalytic, but they determine the function of the two Arabidopsis thaliana BZR1-BAM isoforms (BAM7 and BAM8) during transcriptional initiation. Removal or swapping of the BAM domains demonstrates that the BAM7 BAM domain restricts DNA binding and transcriptional activation, while the BAM8 BAM domain allows both activities. Furthermore, we demonstrate that BAM7 and BAM8 interact on the protein level and cooperate during transcriptional regulation. Site-directed mutagenesis of residues in the BAM domain of BAM8 shows that its function as a transcriptional activator is independent of catalysis but requires an intact substrate binding site, suggesting it may bind a ligand. Microarray experiments with plants overexpressing truncated versions lacking the BAM domain indicate that the pseudo-enzymatic domain increases selectivity for the preferred cis-regulatory element BBRE (BZR1-BAM Responsive Element). Side specificity toward the G-box may allow crosstalk to other signaling networks. This work highlights the importance of the enzyme-derived domain of BZR1-BAMs, supporting their potential role as metabolic sensors. © 2014 American Society of Plant Biologists. All rights reserved.
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Bailey, Michelle; Chauhan, Chitra; Liu, Canhui; Unnasch, Thomas R
2011-03-01
Previous studies of Brugia malayi promoters have suggested that they are unusual in that they lack the CAAT or TATAA boxes that are often emblematic of eucaryotic core promoter domains. Instead, the region surrounding the spliced leader (SL) addition site appears to function as the core promoter domain in B. malayi. To test the hypothesis that polymorphisms in this SL addition domain are important determinants of promoter activity, a series of domain swap mutants were prepared replacing the SL addition domain of the B. malayi 13kDa large subunit ribosomal protein (BmRPL13) with those of other ribosomal protein (RP) promoters exhibiting a wide range of activities. These constructs were then tested for promoter activity in a homologous transient transfection system. On average, polymorphisms in the SL addition domain were found to be responsible for 80% of the variation in promoter activity exhibited by the RP promoters tested. Essentially all of this effect could be attributable to polymorphisms in the 10nt located directly upstream of the SL addition site. A comparison of the sequence of this domain to the promoter activity exhibited by the domain swap mutants suggested that promoter activity was related to the number of T residues present in the coding strand of the upstream domain. Confirming this, mutation of the upstream domain of the promoter of the BmRPS4 gene to a homogeneous stretch of 10 T residues resulted in a significant increase in promoter activity. Copyright © 2010 Elsevier B.V. All rights reserved.
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Fault tolerance in a supercomputer through dynamic repartitioning
Chen, Dong; Coteus, Paul W.; Gara, Alan G.; Takken, Todd E.
2007-02-27
A multiprocessor, parallel computer is made tolerant to hardware failures by providing extra groups of redundant standby processors and by designing the system so that these extra groups of processors can be swapped with any group which experiences a hardware failure. This swapping can be under software control, thereby permitting the entire computer to sustain a hardware failure but, after swapping in the standby processors, to still appear to software as a pristine, fully functioning system.
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SWAp dynamics in a decentralized context: experiences from Uganda.
Jeppsson, Anders
2002-12-01
This paper examines the role of the Ministry of Health (MoH) in Uganda in the process of developing a Sector-Wide Approach (SWAp) within the health sector. Power dynamics are integral to any understanding of development assistance, and SWAps bring with them new opportunities for the deployment of influence. The SWAp process has changed the interaction between the donors and the Government, and the perspective of this interaction has shifted from various technical areas to the entire health sector. It is argued that although the decentralization of the public sector has transferred considerable responsibilities and duties from the central level to the districts, significant power, defined as a social construct, has been generated by the MoH in the very process of developing SWAps. The MoH has been able to exercise significant influence on defining the content and boundaries of the SWAp process, as well as the direction it is taking. This development has largely followed blueprints drawn by donors. Through the institutional framework associated with SWAps, the MoH has redefined the interaction between the central level and the districts as well as between the MoH and the donors. While the SWAp process is now moving from the planning to the implementation phase in Uganda, we see a number of new, changing, ambiguous and contradictory strategies emerging.
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Gautam, Avneesh Kumar; Panse, Yogesh; Ghosh, Payel; Reza, Malik Johid; Mullick, Jayati; Sahu, Arvind
2015-01-01
The complement system has evolved to annul pathogens, but its improper regulation is linked with diseases. Efficient regulation of the system is primarily provided by a family of proteins termed regulators of complement activation (RCA). The knowledge of precise structural determinants of RCA proteins critical for imparting the regulatory activities and the molecular events underlying the regulatory processes, nonetheless, is still limited. Here, we have dissected the structural requirements of RCA proteins that are crucial for one of their two regulatory activities, the cofactor activity (CFA), by using the Kaposi’s sarcoma-associated herpesvirus RCA homolog Kaposica as a model protein. We have scanned the entire Kaposica molecule by sequential mutagenesis using swapping and site-directed mutagenesis, which identified residues critical for its interaction with C3b and factor I. Mapping of these residues onto the modeled structure of C3b–Kaposica–factor I complex supported the mutagenesis data. Furthermore, the model suggested that the C3b-interacting residues bridge the CUB (complement C1r-C1s, Uegf, Bmp1) and MG2 (macroglobulin-2) domains of C3b. Thus, it seems that stabilization of the CUB domain with respect to the core of the C3b molecule is central for its CFA. Identification of CFA-critical regions in Kaposica guided experiments in which the equivalent regions of membrane cofactor protein were swapped into decay-accelerating factor. This strategy allowed CFA to be introduced into decay-accelerating factor, suggesting that viral and human regulators use a common mechanism for CFA. PMID:26420870
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Spin-Swapping Transport and Torques in Ultrathin Magnetic Bilayers
NASA Astrophysics Data System (ADS)
Saidaoui, Hamed Ben Mohamed; Manchon, A.
2016-07-01
Planar spin transport in disordered ultrathin magnetic bilayers comprising a ferromagnet and a normal metal (typically used for spin pumping, spin Seebeck and spin-orbit torque experiments) is investigated theoretically. Using a tight-binding model that puts the extrinsic spin Hall effect and spin swapping on equal footing, we show that the nature of spin-orbit coupled transport dramatically depends on the ratio between the layer thickness d and the mean free path λ . While the spin Hall effect dominates in the diffusive limit (d ≫λ ), spin swapping dominates in the Knudsen regime (d ≲λ ). A remarkable consequence is that spin swapping induces a substantial fieldlike torque in the Knudsen regime.
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LRAT-specific domain facilitates vitamin A metabolism by domain swapping in HRASLS3
Golczak, Marcin; Sears, Avery E.; Kiser, Philip D.; ...
2014-11-10
Cellular uptake of vitamin A, production of visual chromophore and triglyceride homeostasis in adipocytes depend on two representatives of the vertebrate N1pC/P60 protein family, lecithin:retinol acyltransferase (LRAT) and HRAS-like tumor suppressor 3 (HRASLS3). Both proteins function as lipid-metabolizing enzymes but differ in their substrate preferences and dominant catalytic activity. The mechanism of this catalytic diversity is not understood. In this paper, by using a gain-of-function approach, we identified a specific sequence responsible for the substrate specificity of N1pC/P60 proteins. A 2.2-Å crystal structure of the HRASLS3-LRAT chimeric enzyme in a thioester catalytic intermediate state revealed a major structural rearrangement accompaniedmore » by three-dimensional domain swapping dimerization not observed in native HRASLS proteins. Structural changes affecting the active site environment contributed to slower hydrolysis of the catalytic intermediate, supporting efficient acyl transfer. Finally, these findings reveal structural adaptation that facilitates selective catalysis and mechanism responsible for diverse substrate specificity within the LRAT-like enzyme family.« less
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DNA binding by FOXP3 domain-swapped dimer suggests mechanisms of long-range chromosomal interactions
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, Y.; Chen, C.; Zhang, Z.
2015-01-07
FOXP3 is a lineage-specific transcription factor that is required for regulatory T cell development and function. In this study, we determined the crystal structure of the FOXP3 forkhead domain bound to DNA. The structure reveals that FOXP3 can form a stable domain-swapped dimer to bridge DNA in the absence of cofactors, suggesting that FOXP3 may play a role in long-range gene interactions. To test this hypothesis, we used circular chromosome conformation capture coupled with high throughput sequencing (4C-seq) to analyze FOXP3-dependent genomic contacts around a known FOXP3-bound locus, Ptpn22. Our studies reveal that FOXP3 induces significant changes in the chromatinmore » contacts between the Ptpn22 locus and other Foxp3-regulated genes, reflecting a mechanism by which FOXP3 reorganizes the genome architecture to coordinate the expression of its target genes. Our results suggest that FOXP3 mediates long-range chromatin interactions as part of its mechanisms to regulate specific gene expression in regulatory T cells.« less
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[Optimization of the pseudorandom input signals used for the forced oscillation technique].
Liu, Xiaoli; Zhang, Nan; Liang, Hong; Zhang, Zhengbo; Li, Deyu; Wang, Weidong
2017-10-01
The forced oscillation technique (FOT) is an active pulmonary function measurement technique that was applied to identify the mechanical properties of the respiratory system using external excitation signals. FOT commonly includes single frequency sine, pseudorandom and periodic impulse excitation signals. Aiming at preventing the time-domain amplitude overshoot that might exist in the acquisition of combined multi sinusoidal pseudorandom signals, this paper studied the phase optimization of pseudorandom signals. We tried two methods including the random phase combination and time-frequency domain swapping algorithm to solve this problem, and used the crest factor to estimate the effect of optimization. Furthermore, in order to make the pseudorandom signals met the requirement of the respiratory system identification in 4-40 Hz, we compensated the input signals' amplitudes at the low frequency band (4-18 Hz) according to the frequency-response curve of the oscillation unit. Resuts showed that time-frequency domain swapping algorithm could effectively optimize the phase combination of pseudorandom signals. Moreover, when the amplitudes at low frequencies were compensated, the expected stimulus signals which met the performance requirements were obtained eventually.
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Delayed-Choice Experiments and the Metaphysics of Entanglement
NASA Astrophysics Data System (ADS)
Egg, Matthias
2013-09-01
Delayed-choice experiments in quantum mechanics are often taken to undermine a realistic interpretation of the quantum state. More specifically, Healey has recently argued that the phenomenon of delayed-choice entanglement swapping is incompatible with the view that entanglement is a physical relation between quantum systems. This paper argues against these claims. It first reviews two paradigmatic delayed-choice experiments and analyzes their metaphysical implications. It then applies the results of this analysis to the case of entanglement swapping, showing that such experiments pose no threat to realism about entanglement.
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Smaldone, Giovanni; Berisio, Rita; Balasco, Nicole; D'Auria, Sabato; Vitagliano, Luigi; Ruggiero, Alessia
2018-05-31
Thermotoga maritima Arginine Binding Protein (TmArgBP) is a valuable candidate for arginine biosensing in diagnostics. This protein is endowed with unusual structural properties that include an extraordinary thermal/chemical stability, a domain swapped structure that undergoes large tertiary and quaternary structural transition, and the ability to form non-canonical oligomeric species. As the intrinsic stability of TmArgBP allows for extensive protein manipulations, we here dissected its structure in two parts: its main body deprived of the swapping fragment (TmArgBP 20-233 ) and the C-terminal peptide corresponding to the helical swapping element. Both elements have been characterized independently or in combination using a repertoire of biophysical/structural techniques. Present investigations clearly indicate that TmArgBP 20-233 represents a better scaffold for arginine sensing compared to the wild-type protein. Moreover, our data demonstrate that the ligand-free and the ligand-bound forms respond very differently to this helix deletion. This drastic perturbation has an important impact on the ligand-bound form of TmArgBP 20-233 stability whereas it barely affects its ligand-free state. The crystallographic structures of these forms provide a rationale to this puzzling observation. Indeed, the arginine-bound state is very rigid and virtually unchanged upon protein truncation. On the other hand, the flexible ligand-free TmArgBP 20-233 is able to adopt a novel state as a consequence of the helix deletion. Therefore, the flexibility of the ligand-free form endows this state with a remarkable robustness upon severe perturbations. In this scenario, TmArgBP dissection highlights an intriguing connection between destabilizing/stabilizing effects and the overall flexibility that could operate also in other proteins. Copyright © 2018 Elsevier B.V. All rights reserved.
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Austerity and the "sector-wide approach" to health: The Mozambique experience.
Pfeiffer, James; Gimbel, Sarah; Chilundo, Baltazar; Gloyd, Stephen; Chapman, Rachel; Sherr, Kenneth
2017-08-01
Fiscal austerity policies imposed by the IMF have reduced investments in social services, leaving post-independence nations like Mozambique struggling to recover from civil war and high disease burden. By 2000, a sector-wide approach (SWAp) was promoted to maximize aid effectiveness. 'Like-minded' bilateral donors, from Europe and Canada, promoted a unified approach to health sector support focusing on joint planning, common basket funding, and streamlined monitoring and evaluation to improve sector coordination, amplify country ownership, and build sustainable health systems. Notable donors - including US government and the Global Fund - did not participate in the SWAp, and increased vertical funding weakened the SWAp in favor of non-governmental organizations (NGOs). In spite of some success in harmonizing aid to the health sector, the SWAp experience in Mozambique demonstrates how continued austerity regimes that severely constrain public spending will continue to undermine health system strengthening in Africa, even in the midst of high levels of foreign aid with the ostensible purpose of strengthening those systems. The SWAp story provides a poignant illustration of how continued austerity will impede progress toward Sustainable Development Goal 3 (SDG 3); "Achieve universal health coverage, including financial risk protection, access to quality essential health-care services and access to safe, effective, quality and affordable essential medicines and vaccines for all". However, the SWAp continues to offer an alternative model to health system support that can provide a foundation for resistance to renewed austerity measures. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Katz, Michael; Hilsenroth, Mark J
2017-11-01
The Social Anxiety/Avoidance Scale was recently added to the Shedler Westen Assessment Procedure (SWAP), and requires independent validation. This study used data drawn from a larger ongoing project in order to retrospectively examine its convergent validity with two self-report attachment measures: Relationship Questionnaire (RQ) and Experiences in Close Relationships Questionnaire-Revised (ECR-R). Fifty-two patients completed the RQ and the ECR-R before beginning psychotherapy treatment. Clinicians rated the patients on the SWAP after six sessions. The SWAP Social Anxiety/Avoidance Scale (SWAP-SAAS) was negatively related to the RQ secure attachment prototype scale and positively related to the ECR-R attachment anxiety scale. Our findings provide initial support for the use of the SWAP-SAAS as a therapist-rated measure associated with lower patient-reported levels of fit with a secure attachment prototype and with higher patient-reported levels of attachment anxiety. Implications and suggestions for future research on the SWAP-SAAS, as well as for clinical work with socially anxious and avoidant patients, are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.
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Teh, Aik-Hong; Saito, Jennifer A.; Najimudin, Nazalan; Alam, Maqsudul
2015-01-01
Globins are haem-binding proteins with a conserved fold made up of α-helices and can possess diverse properties. A putative globin-coupled sensor from Methylacidiphilum infernorum, HGbRL, contains an N-terminal globin domain whose open and closed structures reveal an untypical dimeric architecture. Helices E and F fuse into an elongated helix, resulting in a novel site-swapped globin fold made up of helices A–E, hence the distal site, from one subunit and helices F–H, the proximal site, from another. The open structure possesses a large cavity binding an imidazole molecule, while the closed structure forms a unique Lys–His hexacoordinated species, with the first turn of helix E unravelling to allow Lys52(E10) to bind to the haem. Ligand binding induces reorganization of loop CE, which is stabilized in the closed form, and helix E, triggering a large conformational movement in the open form. These provide a mechanical insight into how a signal may be relayed between the globin domain and the C-terminal domain of HGbRL, a Roadblock/LC7 domain. Comparison with HGbI, a closely related globin, further underlines the high degree of structural versatility that the globin fold is capable of, enabling it to perform a diversity of functions. PMID:26094577
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Free energy landscapes for initiation and branching of protein aggregation.
Zheng, Weihua; Schafer, Nicholas P; Wolynes, Peter G
2013-12-17
Experiments on artificial multidomain protein constructs have probed the early stages of aggregation processes, but structural details of the species that initiate aggregation remain elusive. Using the associative-memory, water-mediated, structure and energy model known as AWSEM, a transferable coarse-grained protein model, we performed simulations of fused constructs composed of up to four copies of the Titin I27 domain or its mutant I27* (I59E). Free energy calculations enable us to quantify the conditions under which such multidomain constructs will spontaneously misfold. Consistent with experimental results, the dimer of I27 is found to be the smallest spontaneously misfolding construct. Our results show how structurally distinct misfolded states can be stabilized under different thermodynamic conditions, and this result provides a plausible link between the single-molecule misfolding experiments under native conditions and aggregation experiments under denaturing conditions. The conditions for spontaneous misfolding are determined by the interplay among temperature, effective local protein concentration, and the strength of the interdomain interactions. Above the folding temperature, fusing additional domains to the monomer destabilizes the native state, and the entropically stabilized amyloid-like state is favored. Because it is primarily energetically stabilized, the domain-swapped state is more likely to be important under native conditions. Both protofibril-like and branching structures are found in annealing simulations starting from extended structures, and these structures suggest a possible connection between the existence of multiple amyloidogenic segments in each domain and the formation of branched, amorphous aggregates as opposed to linear fibrillar structures.
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Sunita, S; Schwartz, Samantha L; Conn, Graeme L
2015-11-20
Double-stranded RNA (dsRNA)-activated protein kinase (PKR) is an important component of the innate immune system that presents a crucial first line of defense against viral infection. PKR has a modular architecture comprising a regulatory N-terminal dsRNA binding domain and a C-terminal kinase domain interposed by an unstructured ∼80-residue interdomain linker (IDL). Guided by sequence alignment, we created IDL deletions in human PKR (hPKR) and regulatory/kinase domain swap human-rat chimeric PKRs to assess the contributions of each domain and the IDL to regulation of the kinase activity by RNA. Using circular dichroism spectroscopy, limited proteolysis, kinase assays, and isothermal titration calorimetry, we show that each PKR protein is properly folded with similar domain boundaries and that each exhibits comparable polyinosinic-cytidylic (poly(rI:rC)) dsRNA activation profiles and binding affinities for adenoviral virus-associated RNA I (VA RNAI) and HIV-1 trans-activation response (TAR) RNA. From these results we conclude that the IDL of PKR is not required for RNA binding or mediating changes in protein conformation or domain interactions necessary for PKR regulation by RNA. In contrast, inhibition of rat PKR by VA RNAI and TAR RNA was found to be weaker than for hPKR by 7- and >300-fold, respectively, and each human-rat chimeric domain-swapped protein showed intermediate levels of inhibition. These findings indicate that PKR sequence or structural elements in the kinase domain, present in hPKR but absent in rat PKR, are exploited by viral non-coding RNAs to accomplish efficient inhibition of PKR. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
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Sato-Masumoto, Naoko; Ito, Michiho
2014-06-01
Geraniol and linalool are acyclic monoterpenes found in plant essential oils that have attracted much attention for their commercial use and in pharmaceutical studies. They are synthesized from geranyl diphosphate (GDP) by geraniol and linalool synthases, respectively. Both synthases are very similar at the amino acid level and share the same substrate; however, the position of the GDP to which they introduce hydroxyl groups is different. In this study, the mechanisms underlying the regiospecific hydroxylation of geraniol and linalool synthases were investigated using a domain swapping approach and site-directed mutagenesis in perilla. Sequences of the synthases were divided into ten domains (domains I to IV-4), and each corresponding domain was exchanged between both enzymes. It was shown that different regions were important for the formation of geraniol and linalool, namely, domains IV-1 and -4 for geraniol, and domains III-b, III-d, and IV-4 for linalool. These results suggested that the conformation of carbocation intermediates and their electron localization were seemingly to be different between geraniol and linalool synthases. Further, five amino acids in domain IV-4 were apparently indispensable for the formation of geraniol and linalool. According to three-dimensional structural models of the synthases, these five residues seemed to be responsible for the different spatial arrangement of the amino acid at H524 in the case of geraniol synthase, while N526 is the corresponding residue in linalool synthase. These results suggested that the side-chains of these five amino acids, in combination with several relevant domains, localized the positive charge in the carbocation intermediate to determine the position of the introduced hydroxyl group. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Kawelke, Steffen; Feussner, Ivo
2015-01-01
Wax esters are used as coatings or storage lipids in all kingdoms of life. They are synthesized from a fatty alcohol and an acyl-CoA by wax synthases. In order to get insights into the structure-function relationships of a wax synthase from Mus musculus, a domain swap experiment between the mouse acyl-CoA:wax alcohol acyltransferase (AWAT2) and the homologous mouse acyl-CoA:diacylglycerol O-acyltransferase 2 (DGAT2) was performed. This showed that the substrate specificity of AWAT2 is partially determined by two predicted transmembrane domains near the amino terminus of AWAT2. Upon exchange of the two domains for the respective part of DGAT2, the resulting chimeric enzyme was capable of incorporating up to 20% of very long acyl chains in the wax esters upon expression in S. cerevisiae strain H1246. The amount of very long acyl chains in wax esters synthesized by wild type AWAT2 was negligible. The effect was narrowed down to a single amino acid position within one of the predicted membrane domains, the AWAT2 N36R variant. Taken together, we provide first evidence that two predicted transmembrane domains in AWAT2 are involved in determining its acyl chain length specificity. PMID:26714272
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Akerboom, Jasper; Rivera, Jonathan D Vélez; Guilbe, María M Rodríguez; Malavé, Elisa C Alfaro; Hernandez, Hector H; Tian, Lin; Hires, S Andrew; Marvin, Jonathan S; Looger, Loren L; Schreiter, Eric R
2009-03-06
The genetically encoded calcium indicator GCaMP2 shows promise for neural network activity imaging, but is currently limited by low signal-to-noise ratio. We describe x-ray crystal structures as well as solution biophysical and spectroscopic characterization of GCaMP2 in the calcium-free dark state, and in two calcium-bound bright states: a monomeric form that dominates at intracellular concentrations observed during imaging experiments and an unexpected domain-swapped dimer with decreased fluorescence. This series of structures provides insight into the mechanism of Ca2+-induced fluorescence change. Upon calcium binding, the calmodulin (CaM) domain wraps around the M13 peptide, creating a new domain interface between CaM and the circularly permuted enhanced green fluorescent protein domain. Residues from CaM alter the chemical environment of the circularly permuted enhanced green fluorescent protein chromophore and, together with flexible inter-domain linkers, block solvent access to the chromophore. Guided by the crystal structures, we engineered a series of GCaMP2 point mutants to probe the mechanism of GCaMP2 function and characterized one mutant with significantly improved signal-to-noise. The mutation is located at a domain interface and its effect on sensor function could not have been predicted in the absence of structural data.
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Two-Hierarchy Entanglement Swapping for a Linear Optical Quantum Repeater
NASA Astrophysics Data System (ADS)
Xu, Ping; Yong, Hai-Lin; Chen, Luo-Kan; Liu, Chang; Xiang, Tong; Yao, Xing-Can; Lu, He; Li, Zheng-Da; Liu, Nai-Le; Li, Li; Yang, Tao; Peng, Cheng-Zhi; Zhao, Bo; Chen, Yu-Ao; Pan, Jian-Wei
2017-10-01
Quantum repeaters play a significant role in achieving long-distance quantum communication. In the past decades, tremendous effort has been devoted towards constructing a quantum repeater. As one of the crucial elements, entanglement has been created in different memory systems via entanglement swapping. The realization of j -hierarchy entanglement swapping, i.e., connecting quantum memory and further extending the communication distance, is important for implementing a practical quantum repeater. Here, we report the first demonstration of a fault-tolerant two-hierarchy entanglement swapping with linear optics using parametric down-conversion sources. In the experiment, the dominant or most probable noise terms in the one-hierarchy entanglement swapping, which is on the same order of magnitude as the desired state and prevents further entanglement connections, are automatically washed out by a proper design of the detection setting, and the communication distance can be extended. Given suitable quantum memory, our techniques can be directly applied to implementing an atomic ensemble based quantum repeater, and are of significant importance in the scalable quantum information processing.
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Two-Hierarchy Entanglement Swapping for a Linear Optical Quantum Repeater.
Xu, Ping; Yong, Hai-Lin; Chen, Luo-Kan; Liu, Chang; Xiang, Tong; Yao, Xing-Can; Lu, He; Li, Zheng-Da; Liu, Nai-Le; Li, Li; Yang, Tao; Peng, Cheng-Zhi; Zhao, Bo; Chen, Yu-Ao; Pan, Jian-Wei
2017-10-27
Quantum repeaters play a significant role in achieving long-distance quantum communication. In the past decades, tremendous effort has been devoted towards constructing a quantum repeater. As one of the crucial elements, entanglement has been created in different memory systems via entanglement swapping. The realization of j-hierarchy entanglement swapping, i.e., connecting quantum memory and further extending the communication distance, is important for implementing a practical quantum repeater. Here, we report the first demonstration of a fault-tolerant two-hierarchy entanglement swapping with linear optics using parametric down-conversion sources. In the experiment, the dominant or most probable noise terms in the one-hierarchy entanglement swapping, which is on the same order of magnitude as the desired state and prevents further entanglement connections, are automatically washed out by a proper design of the detection setting, and the communication distance can be extended. Given suitable quantum memory, our techniques can be directly applied to implementing an atomic ensemble based quantum repeater, and are of significant importance in the scalable quantum information processing.
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Structure of Bombyx mori densovirus 1, a silkworm pathogen.
Kaufmann, Bärbel; El-Far, Mohamed; Plevka, Pavel; Bowman, Valorie D; Li, Yi; Tijssen, Peter; Rossmann, Michael G
2011-05-01
Bombyx mori densovirus 1 (BmDNV-1), a major pathogen of silkworms, causes significant losses to the silk industry. The structure of the recombinant BmDNV-1 virus-like particle has been determined at 3.1-Å resolution using X-ray crystallography. It is the first near-atomic-resolution structure of a virus-like particle within the genus Iteravirus. The particles consist of 60 copies of the 55-kDa VP3 coat protein. The capsid protein has a β-barrel "jelly roll" fold similar to that found in many diverse icosahedral viruses, including archaeal, bacterial, plant, and animal viruses, as well as other parvoviruses. Most of the surface loops have little structural resemblance to other known parvovirus capsid proteins. In contrast to vertebrate parvoviruses, the N-terminal β-strand of BmDNV-1 VP3 is positioned relative to the neighboring 2-fold related subunit in a "domain-swapped" conformation, similar to findings for other invertebrate parvoviruses, suggesting domain swapping is an evolutionarily conserved structural feature of the Densovirinae.
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NASA Astrophysics Data System (ADS)
Chrabåszczewska, Magdalena; Maszota-Zieleniak, Martyna; Pietralik, Zuzanna; Taube, Michał; Rodziewicz-Motowidło, Sylwia; Szymańska, Aneta; Szutkowski, Kosma; Clemens, Daniel; Grubb, Anders; Kozak, Maciej
2018-05-01
Human cystatin C (HCC) is a cysteine protease inhibitor that takes a series of oligomeric forms in solution (e.g., dimers, trimers, tetramers, decamers, dodecamers, and other higher oligomers). The best-known form of cystatin C is the dimer, which arises as a result of a domain swapping mechanism. The formation of the HCC oligomeric forms, which is most likely due to this domain swapping mechanism, is associated with the aggregation of HCC into amyloid fibrils and deposits. To investigate the structure of a specific HCC oligomer, we developed a covalently stabilized trimer of HCC. An atomic model of this HCC trimer was proposed on the basis of molecular docking and molecular dynamics simulations. The most stable model of the HCC trimer obtained from the molecular dynamics simulations is characterized by a well-preserved secondary structure. The molecular size and structural parameters of the HCC trimer in solution were also confirmed by Small Angle Neutron Scattering and Nuclear Magnetic Resonance Diffusometry.
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Minimizing communication cost among distributed controllers in software defined networks
NASA Astrophysics Data System (ADS)
Arlimatti, Shivaleela; Elbreiki, Walid; Hassan, Suhaidi; Habbal, Adib; Elshaikh, Mohamed
2016-08-01
Software Defined Networking (SDN) is a new paradigm to increase the flexibility of today's network by promising for a programmable network. The fundamental idea behind this new architecture is to simplify network complexity by decoupling control plane and data plane of the network devices, and by making the control plane centralized. Recently controllers have distributed to solve the problem of single point of failure, and to increase scalability and flexibility during workload distribution. Even though, controllers are flexible and scalable to accommodate more number of network switches, yet the problem of intercommunication cost between distributed controllers is still challenging issue in the Software Defined Network environment. This paper, aims to fill the gap by proposing a new mechanism, which minimizes intercommunication cost with graph partitioning algorithm, an NP hard problem. The methodology proposed in this paper is, swapping of network elements between controller domains to minimize communication cost by calculating communication gain. The swapping of elements minimizes inter and intra communication cost among network domains. We validate our work with the OMNeT++ simulation environment tool. Simulation results show that the proposed mechanism minimizes the inter domain communication cost among controllers compared to traditional distributed controllers.
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Testbed Experiment for SPIDER: A Photonic Integrated Circuit-based Interferometric imaging system
NASA Astrophysics Data System (ADS)
Badham, K.; Duncan, A.; Kendrick, R. L.; Wuchenich, D.; Ogden, C.; Chriqui, G.; Thurman, S. T.; Su, T.; Lai, W.; Chun, J.; Li, S.; Liu, G.; Yoo, S. J. B.
The Lockheed Martin Advanced Technology Center (LM ATC) and the University of California at Davis (UC Davis) are developing an electro-optical (EO) imaging sensor called SPIDER (Segmented Planar Imaging Detector for Electro-optical Reconnaissance) that seeks to provide a 10x to 100x size, weight, and power (SWaP) reduction alternative to the traditional bulky optical telescope and focal-plane detector array. The substantial reductions in SWaP would reduce cost and/or provide higher resolution by enabling a larger-aperture imager in a constrained volume. Our SPIDER imager replaces the traditional optical telescope and digital focal plane detector array with a densely packed interferometer array based on emerging photonic integrated circuit (PIC) technologies that samples the object being imaged in the Fourier domain (i.e., spatial frequency domain), and then reconstructs an image. Our approach replaces the large optics and structures required by a conventional telescope with PICs that are accommodated by standard lithographic fabrication techniques (e.g., complementary metal-oxide-semiconductor (CMOS) fabrication). The standard EO payload integration and test process that involves precision alignment and test of optical components to form a diffraction limited telescope is, therefore, replaced by in-process integration and test as part of the PIC fabrication, which substantially reduces associated schedule and cost. In this paper we describe the photonic integrated circuit design and the testbed used to create the first images of extended scenes. We summarize the image reconstruction steps and present the final images. We also describe our next generation PIC design for a larger (16x area, 4x field of view) image.
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Chromatic interocular-switch rivalry.
Christiansen, Jens H; D'Antona, Anthony D; Shevell, Steven K
2017-05-01
Interocular-switch rivalry (also known as stimulus rivalry) is a kind of binocular rivalry in which two rivalrous images are swapped between the eyes several times a second. The result is stable periods of one image and then the other, with stable intervals that span many eye swaps (Logothetis, Leopold, & Sheinberg, 1996). Previous work used this close kin of binocular rivalry with rivalrous forms. Experiments here test whether chromatic interocular-switch rivalry, in which the swapped stimuli differ in only chromaticity, results in slow alternation between two colors. Swapping equiluminant rivalrous chromaticities at 3.75 Hz resulted in slow perceptual color alternation, with one or the other color often continuously visible for two seconds or longer (during which there were 15+ eye swaps). A well-known theory for sustained percepts from interocular-switch rivalry with form is inhibitory competition between binocular neurons driven by monocular neurons with matched orientation tuning in each eye; such binocular neurons would produce a stable response when a given orientation is swapped between the eyes. A similar model can account for the percepts here from chromatic interocular-switch rivalry and is underpinned by the neurophysiological finding that color-preferring binocular neurons are driven by monocular neurons from each eye with well-matched chromatic selectivity (Peirce, Solomon, Forte, & Lennie, 2008). In contrast to chromatic interocular-switch rivalry, luminance interocular-switch rivalry with swapped stimuli that differ in only luminance did not result in slowly alternating percepts of different brightnesses.
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Proline Residues as Switches in Conformational Changes Leading to Amyloid Fibril Formation
Taler-Verčič, Ajda; Hasanbašić, Samra; Berbić, Selma; Stoka, Veronika; Turk, Dušan; Žerovnik, Eva
2017-01-01
Here we discuss studies of the structure, folding, oligomerization and amyloid fibril formation of several proline mutants of human stefin B, which is a protein inhibitor of lysosomal cysteine cathepsins and a member of the cystatin family. The structurally important prolines in stefin B are responsible for the slow folding phases and facilitate domain swapping (Pro 74) and loop swapping (Pro 79). Moreover, our findings are compared to β2-microglobulin, a protein involved in dialysis-related amyloidosis. The assessment of the contribution of proline residues to the process of amyloid fibril formation may shed new light on the critical molecular events involved in conformational disorders. PMID:28272335
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Entanglement swapping with independent sources over an optical-fiber network
NASA Astrophysics Data System (ADS)
Sun, Qi-Chao; Mao, Ya-Li; Jiang, Yang-Fan; Zhao, Qi; Chen, Si-Jing; Zhang, Wei; Zhang, Wei-Jun; Jiang, Xiao; Chen, Teng-Yun; You, Li-Xing; Li, Li; Huang, Yi-Dong; Chen, Xian-Feng; Wang, Zhen; Ma, Xiongfeng; Zhang, Qiang; Pan, Jian-Wei
2017-03-01
Establishing entanglement between two remote systems by the method of entanglement swapping is an essential step for a long-distance quantum network. Here we report a field-test entanglement swapping experiment with two independent telecommunication band entangled photon-pair sources over an optical fiber network in Hefei. The two sources are located at two nodes that are 12.5 km apart and the Bell-state measurement is performed at a third location which is connected to the two source nodes with 14.7-km and 10.6-km optical fibers, respectively. The observed average visibility is 79.9 ±4.8 % , which is sufficient for the violation of Bell inequalities. Furthermore, with the swapped entanglement, we demonstrate a source-independent quantum key distribution, which is also immune to any detection attacks at the measurement site.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Kirouac, Kevin N.; Ling, Hong; UWO)
Human DNA polymerase iota (pol iota) is a unique member of Y-family polymerases, which preferentially misincorporates nucleotides opposite thymines (T) and halts replication at T bases. The structural basis of the high error rates remains elusive. We present three crystal structures of pol complexed with DNA containing a thymine base, paired with correct or incorrect incoming nucleotides. A narrowed active site supports a pyrimidine to pyrimidine mismatch and excludes Watson-Crick base pairing by pol. The template thymine remains in an anti conformation irrespective of incoming nucleotides. Incoming ddATP adopts a syn conformation with reduced base stacking, whereas incorrect dGTP andmore » dTTP maintain anti conformations with normal base stacking. Further stabilization of dGTP by H-bonding with Gln59 of the finger domain explains the preferential T to G mismatch. A template 'U-turn' is stabilized by pol and the methyl group of the thymine template, revealing the structural basis of T stalling. Our structural and domain-swapping experiments indicate that the finger domain is responsible for pol's high error rates on pyrimidines and determines the incorporation specificity.« less
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Simmering, Vanessa R; Wood, Chelsey M
2017-08-01
Working memory is a basic cognitive process that predicts higher-level skills. A central question in theories of working memory development is the generality of the mechanisms proposed to explain improvements in performance. Prior theories have been closely tied to particular tasks and/or age groups, limiting their generalizability. The cognitive dynamics theory of visual working memory development has been proposed to overcome this limitation. From this perspective, developmental improvements arise through the coordination of cognitive processes to meet demands of different behavioral tasks. This notion is described as real-time stability, and can be probed through experiments that assess how changing task demands impact children's performance. The current studies test this account by probing visual working memory for colors and shapes in a change detection task that compares detection of changes to new features versus swaps in color-shape binding. In Experiment 1, 3- to 4-year-old children showed impairments specific to binding swaps, as predicted by decreased real-time stability early in development; 5- to 6-year-old children showed a slight advantage on binding swaps, but 7- to 8-year-old children and adults showed no difference across trial types. Experiment 2 tested the proposed explanation of young children's binding impairment through added perceptual structure, which supported the stability and precision of feature localization in memory-a process key to detecting binding swaps. This additional structure improved young children's binding swap detection, but not new-feature detection or adults' performance. These results provide further evidence for the cognitive dynamics and real-time stability explanation of visual working memory development. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
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CMOS-APS Detectors for Solar Physics: Lessons Learned during the SWAP Preflight Calibration
NASA Astrophysics Data System (ADS)
de Groof, A.; Berghmans, D.; Nicula, B.; Halain, J.-P.; Defise, J.-M.; Thibert, T.; Schühle, U.
2008-05-01
CMOS-APS imaging detectors open new opportunities for remote sensing in solar physics beyond what classical CCDs can provide, offering far less power consumption, simpler electronics, better radiation hardness, and the possibility of avoiding a mechanical shutter. The SWAP telescope onboard the PROBA2 technology demonstration satellite of the European Space Agency will be the first actual implementation of a CMOS-APS detector for solar physics in orbit. One of the goals of the SWAP project is precisely to acquire experience with the CMOS-APS technology in a real-live space science context. Such a precursor mission is essential in the preparation of missions such as Solar Orbiter where the extra CMOS-APS functionalities will be hard requirements. The current paper concentrates on specific CMOS-APS issues that were identified during the SWAP preflight calibration measurements. We will discuss the different readout possibilities that the CMOS-APS detector of SWAP provides and their associated pros and cons. In particular we describe the “image lag” effect, which results in a contamination of each image with a remnant of the previous image. We have characterised this effect for the specific SWAP implementation and we conclude with a strategy on how to successfully circumvent the problem and actually take benefit of it for solar monitoring.
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17 CFR 240.3a68-2 - Requests for interpretation of swaps, security-based swaps, and mixed swaps.
Code of Federal Regulations, 2014 CFR
2014-04-01
... swaps, security-based swaps, and mixed swaps. 240.3a68-2 Section 240.3a68-2 Commodity and Securities..., Security-Based Swap, and Security-Based Swap Agreement; Mixed Swaps; Security-Based Swap Agreement Recordkeeping § 240.3a68-2 Requests for interpretation of swaps, security-based swaps, and mixed swaps. (a) In...
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17 CFR 240.3a68-2 - Requests for interpretation of swaps, security-based swaps, and mixed swaps.
Code of Federal Regulations, 2013 CFR
2013-04-01
... swaps, security-based swaps, and mixed swaps. 240.3a68-2 Section 240.3a68-2 Commodity and Securities..., Security-Based Swap, and Security-Based Swap Agreement; Mixed Swaps; Security-Based Swap Agreement Recordkeeping § 240.3a68-2 Requests for interpretation of swaps, security-based swaps, and mixed swaps. (a) In...
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Chromatic interocular-switch rivalry
Christiansen, Jens H.; D'Antona, Anthony D.; Shevell, Steven K.
2017-01-01
Interocular-switch rivalry (also known as stimulus rivalry) is a kind of binocular rivalry in which two rivalrous images are swapped between the eyes several times a second. The result is stable periods of one image and then the other, with stable intervals that span many eye swaps (Logothetis, Leopold, & Sheinberg, 1996). Previous work used this close kin of binocular rivalry with rivalrous forms. Experiments here test whether chromatic interocular-switch rivalry, in which the swapped stimuli differ in only chromaticity, results in slow alternation between two colors. Swapping equiluminant rivalrous chromaticities at 3.75 Hz resulted in slow perceptual color alternation, with one or the other color often continuously visible for two seconds or longer (during which there were 15+ eye swaps). A well-known theory for sustained percepts from interocular-switch rivalry with form is inhibitory competition between binocular neurons driven by monocular neurons with matched orientation tuning in each eye; such binocular neurons would produce a stable response when a given orientation is swapped between the eyes. A similar model can account for the percepts here from chromatic interocular-switch rivalry and is underpinned by the neurophysiological finding that color-preferring binocular neurons are driven by monocular neurons from each eye with well-matched chromatic selectivity (Peirce, Solomon, Forte, & Lennie, 2008). In contrast to chromatic interocular-switch rivalry, luminance interocular-switch rivalry with swapped stimuli that differ in only luminance did not result in slowly alternating percepts of different brightnesses. PMID:28510624
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Zang, Xuelian; Shi, Zhuanghua; Müller, Hermann J; Conci, Markus
2017-05-01
Learning of spatial inter-item associations can speed up visual search in everyday life, an effect referred to as contextual cueing (Chun & Jiang, 1998). Whereas previous studies investigated contextual cueing primarily using 2D layouts, the current study examined how 3D depth influences contextual learning in visual search. In two experiments, the search items were presented evenly distributed across front and back planes in an initial training session. In the subsequent test session, the search items were either swapped between the front and back planes (Experiment 1) or between the left and right halves (Experiment 2) of the displays. The results showed that repeated spatial contexts were learned efficiently under 3D viewing conditions, facilitating search in the training sessions, in both experiments. Importantly, contextual cueing remained robust and virtually unaffected following the swap of depth planes in Experiment 1, but it was substantially reduced (to nonsignificant levels) following the left-right side swap in Experiment 2. This result pattern indicates that spatial, but not depth, inter-item variations limit effective contextual guidance. Restated, contextual cueing (even under 3D viewing conditions) is primarily based on 2D inter-item associations, while depth-defined spatial regularities are probably not encoded during contextual learning. Hence, changing the depth relations does not impact the cueing effect.
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SWAP-Assembler 2: Optimization of De Novo Genome Assembler at Large Scale
DOE Office of Scientific and Technical Information (OSTI.GOV)
Meng, Jintao; Seo, Sangmin; Balaji, Pavan
2016-08-16
In this paper, we analyze and optimize the most time-consuming steps of the SWAP-Assembler, a parallel genome assembler, so that it can scale to a large number of cores for huge genomes with the size of sequencing data ranging from terabyes to petabytes. According to the performance analysis results, the most time-consuming steps are input parallelization, k-mer graph construction, and graph simplification (edge merging). For the input parallelization, the input data is divided into virtual fragments with nearly equal size, and the start position and end position of each fragment are automatically separated at the beginning of the reads. Inmore » k-mer graph construction, in order to improve the communication efficiency, the message size is kept constant between any two processes by proportionally increasing the number of nucleotides to the number of processes in the input parallelization step for each round. The memory usage is also decreased because only a small part of the input data is processed in each round. With graph simplification, the communication protocol reduces the number of communication loops from four to two loops and decreases the idle communication time. The optimized assembler is denoted as SWAP-Assembler 2 (SWAP2). In our experiments using a 1000 Genomes project dataset of 4 terabytes (the largest dataset ever used for assembling) on the supercomputer Mira, the results show that SWAP2 scales to 131,072 cores with an efficiency of 40%. We also compared our work with both the HipMER assembler and the SWAP-Assembler. On the Yanhuang dataset of 300 gigabytes, SWAP2 shows a 3X speedup and 4X better scalability compared with the HipMer assembler and is 45 times faster than the SWAP-Assembler. The SWAP2 software is available at https://sourceforge.net/projects/swapassembler.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Akerboom, Jasper; Velez Rivera, Jonathan D.; Rodriguez Guilbe, María M.
The genetically encoded calcium indicator GCaMP2 shows promise for neural network activity imaging, but is currently limited by low signal-to-noise ratio. We describe x-ray crystal structures as well as solution biophysical and spectroscopic characterization of GCaMP2 in the calcium-free dark state, and in two calcium-bound bright states: a monomeric form that dominates at intracellular concentrations observed during imaging experiments and an unexpected domain-swapped dimer with decreased fluorescence. This series of structures provides insight into the mechanism of Ca{sup 2+}-induced fluorescence change. Upon calcium binding, the calmodulin (CaM) domain wraps around the M13 peptide, creating a new domain interface between CaMmore » and the circularly permuted enhanced green fluorescent protein domain. Residues from CaM alter the chemical environment of the circularly permuted enhanced green fluorescent protein chromophore and, together with flexible inter-domain linkers, block solvent access to the chromophore. Guided by the crystal structures, we engineered a series of GCaMP2 point mutants to probe the mechanism of GCaMP2 function and characterized one mutant with significantly improved signal-to-noise. The mutation is located at a domain interface and its effect on sensor function could not have been predicted in the absence of structural data.« less
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Garcia, Mayra L.; Reynolds, Tracy D.; Mothes, Walther; Robek, Michael D.
2013-01-01
The hepatitis B virus (HBV) Core protein encodes a late (L)-domain like motif (129PPAYRPPNAP138) that has been purported to serve as a docking site for recruitment of host factors such as Nedd4 that can mediate viral particle release from infected cells. However, mutation of this region of Core typically disrupts nucleocapsid formation in the cytoplasm, making it difficult to ascertain if the Core PPAY motif constitutes a functional L-domain that mediates HBV release in the context of replicating virus. Since many viral L-domains are functionally interchangeable between different virus families, and such swapping experiments have been used as a tool to identify other viral sequences with L-domain activity, we generated chimeric constructs between murine leukemia virus (MLV) Gag and HBV Core to determine if the potential HBV L-domain motif is sufficient to stimulate virus release. We found that the HBV Core PPAY motif, but not the PNAP motif, demonstrates L-domain activity in the context of MLV replication to direct virus release and infectious virion production. Additionally, we found that overexpression of the cellular Nedd4 or WWP1 ubiquitin ligases stimulates release of a partially defective PPAY domain mutant, providing further evidence supporting a role for the Nedd4 ubiquitin ligase in promoting HBV release. These studies lend further insight into the mechanisms used by HBV to mediate its release from infected cells. PMID:24009707
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17 CFR 1.8 - Requests for interpretation of swaps, security-based swaps, and mixed swaps.
Code of Federal Regulations, 2014 CFR
2014-04-01
... swaps, security-based swaps, and mixed swaps. 1.8 Section 1.8 Commodity and Securities Exchanges... Requests for interpretation of swaps, security-based swaps, and mixed swaps. (a) In general. Any person may... Exchange Act and the rules and regulations promulgated thereunder; or (3) A mixed swap, as that term is...
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17 CFR 1.8 - Requests for interpretation of swaps, security-based swaps, and mixed swaps.
Code of Federal Regulations, 2013 CFR
2013-04-01
... swaps, security-based swaps, and mixed swaps. 1.8 Section 1.8 Commodity and Securities Exchanges... Requests for interpretation of swaps, security-based swaps, and mixed swaps. (a) In general. Any person may... Exchange Act and the rules and regulations promulgated thereunder; or (3) A mixed swap, as that term is...
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Morgan, Rhodri M. L.; Pal, Mohinder; Roe, S. Mark
A helix swap involving the fifth helix between two adjacently bound Tah1 molecules restores the normal binding environment of the conserved MEEVD peptide of Hsp90. Dimerization also explains how other monomeric TPR-domain proteins are excluded from forming inappropriate mixed co-chaperone complexes with Hsp90 and Tah1. Specific co-chaperone adaptors facilitate the recruitment of client proteins to the Hsp90 system. Tah1 binds the C-terminal conserved MEEVD motif of Hsp90, thus linking an eclectic set of client proteins to the R2TP complex for their assembly and regulation by Hsp90. Rather than the normal complement of seven α-helices seen in other tetratricopeptide repeat (TPR)more » domains, Tah1 unusually consists of the first five only. Consequently, the methionine of the MEEVD peptide remains exposed to solvent when bound by Tah1. In solution Tah1 appears to be predominantly monomeric, and recent structures have failed to explain how Tah1 appears to prevent the formation of mixed TPR domain-containing complexes such as Cpr6–(Hsp90){sub 2}–Tah1. To understand this further, the crystal structure of Tah1 in complex with the MEEVD peptide of Hsp90 was determined, which shows a helix swap involving the fifth α-helix between two adjacently bound Tah1 molecules. Dimerization of Tah1 restores the normal binding environment of the bound Hsp90 methionine residue by reconstituting a TPR binding site similar to that in seven-helix-containing TPR domain proteins. Dimerization also explains how other monomeric TPR-domain proteins are excluded from forming inappropriate mixed co-chaperone complexes.« less
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'Change4Life Smart Swaps': quasi-experimental evaluation of a natural experiment.
Wrieden, Wendy L; Levy, Louis B
2016-09-01
To evaluate the impact on food purchasing behaviour of the 'Change4Life Smart Swaps' campaign to encourage families to make small changes to lower-fat or lower-sugar versions of commonly eaten foods and drinks. Quasi-experimental study comparing the proportion of swaps made by an intervention group (267 families who had signed up to the 'Smart Swaps' campaign promoted through various media, including television and radio advertising in early 2014) and a comparison group (135 families resident in Wales, signed up for 'Change4Life' materials, but not directly exposed to the 'Smart Swaps' campaign). During weeks 1, 2 and 3 of the campaign participants were asked to record their purchases of dairy products, carbonated drinks and breakfast cereals, using a mobile phone app questionnaire, when making a purchase within the category. England and Wales. Families registered with 'Change4Life'. In weeks 2 and 3 a significantly higher percentage of the intervention group had made 'smart swaps' than the comparison group. After week 3, 58 % of participants had swapped to a lower-fat dairy product compared with 26 % of the comparison group (P<0·001), 32 % of the intervention group had purchased a lower-sugar drink compared with 19 % of the comparison group (P=0·01), and 24 % had made a change to a lower-sugar cereal compared with 12 % of the comparison group (P=0·009). In the short term a national campaign to change purchase habits towards healthier products may have some merit but the sustainability of change requires further investigation.
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Lu, Xu; Hamkalo, Barbara; Parseghian, Missag H.; Hansen, Jeffrey C.
2009-01-01
Linker histones bind to the nucleosomes and linker DNA of chromatin fibers, causing changes in linker DNA structure and stabilization of higher order folded and oligomeric chromatin structures. Linker histones affect chromatin structure acting primarily through their ~100 residue C-terminal domain (CTD). We have previously shown that the ability of the linker histone H1° to alter chromatin structure was localized to two discontinuous 24-/25-residue CTD regions (Lu, X., and Hansen, J. C. (2004) J Biol Chem 279, 8701–8707). To determine the biochemical basis for these results, we have characterized chromatin model systems assembled with endogenous mouse somatic H1 isoforms, or recombinant H1° CTD mutants in which the primary sequence has been scrambled, the amino acid composition mutated, or the location of various CTD regions swapped. Our results indicate that specific amino acid composition plays a fundamental role in molecular recognition and function by the H1 CTD. Additionally, these experiments support a new molecular model for CTD function, and provide a biochemical basis for the redundancy observed in H1 isoform knockout experiments in vivo. PMID:19072710
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Comparative Validity of the Shedler and Westen Assessment Procedure-200
ERIC Educational Resources Information Center
Mullins-Sweatt, Stephanie N.; Widiger, Thomas A.
2008-01-01
A predominant dimensional model of general personality structure is the five-factor model (FFM). Quite a number of alternative instruments have been developed to assess the domains of the FFM. The current study compares the validity of 2 alternative versions of the Shedler and Westen Assessment Procedure (SWAP-200) FFM scales, 1 that was developed…
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-09-13
...; File No. 4-611] Joint Public Roundtable To Discuss Data for Swaps and Security- Based Swaps, Swap Data Repositories, Security-Based Swap Data Repositories, and Real-Time Public Reporting AGENCY: Commodity Futures... public roundtable discussion at which invited participants will discuss data for swaps and security-based...
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17 CFR 45.3 - Swap data reporting: creation data.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 17 Commodity and Securities Exchanges 2 2014-04-01 2014-04-01 false Swap data reporting: creation... (CONTINUED) SWAP DATA RECORDKEEPING AND REPORTING REQUIREMENTS § 45.3 Swap data reporting: creation data. Registered entities and swap counterparties must report required swap creation data electronically to a swap...
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Sequential dynamics in visual short-term memory.
Kool, Wouter; Conway, Andrew R A; Turk-Browne, Nicholas B
2014-10-01
Visual short-term memory (VSTM) is thought to help bridge across changes in visual input, and yet many studies of VSTM employ static displays. Here we investigate how VSTM copes with sequential input. In particular, we characterize the temporal dynamics of several different components of VSTM performance, including: storage probability, precision, variability in precision, guessing, and swapping. We used a variant of the continuous-report VSTM task developed for static displays, quantifying the contribution of each component with statistical likelihood estimation, as a function of serial position and set size. In Experiments 1 and 2, storage probability did not vary by serial position for small set sizes, but showed a small primacy effect and a robust recency effect for larger set sizes; precision did not vary by serial position or set size. In Experiment 3, the recency effect was shown to reflect an increased likelihood of swapping out items from earlier serial positions and swapping in later items, rather than an increased rate of guessing for earlier items. Indeed, a model that incorporated responding to non-targets provided a better fit to these data than alternative models that did not allow for swapping or that tried to account for variable precision. These findings suggest that VSTM is updated in a first-in-first-out manner, and they bring VSTM research into closer alignment with classical working memory research that focuses on sequential behavior and interference effects.
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Sequential dynamics in visual short-term memory
Conway, Andrew R. A.; Turk-Browne, Nicholas B.
2014-01-01
Visual short-term memory (VSTM) is thought to help bridge across changes in visual input, and yet many studies of VSTM employ static displays. Here we investigate how VSTM copes with sequential input. In particular, we characterize the temporal dynamics of several different components of VSTM performance, including: storage probability, precision, variability in precision, guessing, and swapping. We used a variant of the continuous-report VSTM task developed for static displays, quantifying the contribution of each component with statistical likelihood estimation, as a function of serial position and set size. In Experiments 1 and 2, storage probability did not vary by serial position for small set sizes, but showed a small primacy effect and a robust recency effect for larger set sizes; precision did not vary by serial position or set size. In Experiment 3, the recency effect was shown to reflect an increased likelihood of swapping out items from earlier serial positions and swapping in later items, rather than an increased rate of guessing for earlier items. Indeed, a model that incorporated responding to non-targets provided a better fit to these data than alternative models that did not allow for swapping or that tried to account for variable precision. These findings suggest that VSTM is updated in a first-in-first-out manner, and they bring VSTM research into closer alignment with classical working memory research that focuses on sequential behavior and interference effects. PMID:25228092
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Advanced optical components for next-generation photonic networks
NASA Astrophysics Data System (ADS)
Yoo, S. J. B.
2003-08-01
Future networks will require very high throughput, carrying dominantly data-centric traffic. The role of Photonic Networks employing all-optical systems will become increasingly important in providing scalable bandwidth, agile reconfigurability, and low-power consumptions in the future. In particular, the self-similar nature of data traffic indicates that packet switching and burst switching will be beneficial in the Next Generation Photonic Networks. While the natural conclusion is to pursue Photonic Packet Switching and Photonic Burst Switching systems, there are significant challenges in realizing such a system due to practical limitations in optical component technologies. Lack of a viable all-optical memory technology will continue to drive us towards exploring rapid reconfigurability in the wavelength domain. We will introduce and discuss the advanced optical component technologies behind the Photonic Packet Routing system designed and demonstrated at UC Davis. The system is capable of packet switching and burst switching, as well as circuit switching with 600 psec switching speed and scalability to 42 petabit/sec aggregated switching capacity. By utilizing a combination of rapidly tunable wavelength conversion and a uniform-loss cyclic frequency (ULCF) arrayed waveguide grating router (AWGR), the system is capable of rapidly switching the packets in wavelength, time, and space domains. The label swapping module inside the Photonic Packet Routing system containing a Mach-Zehnder wavelength converter and a narrow-band fiber Bragg-grating achieves all-optical label swapping with optical 2R (potentially 3R) regeneration while maintaining optical transparency for the data payload. By utilizing the advanced optical component technologies, the Photonic Packet Routing system successfully demonstrated error-free, cascaded, multi-hop photonic packet switching and routing with optical-label swapping. This paper will review the advanced optical component technologies and their role in the Next Generation Photonic Networks.
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Molecular metamorphosis in polcalcin allergens by EF-hand rearrangements and domain swapping.
Magler, Iris; Nüss, Dorota; Hauser, Michael; Ferreira, Fatima; Brandstetter, Hans
2010-06-01
Polcalcins such as Bet v 4 and Phl p 7 are pollen allergens that are constructed from EF-hand motifs, which are very common and well characterized helix-loop-helix motifs with calcium-binding functions, as elementary building blocks. Being members of an exceptionally well-characterized protein superfamily, these allergens highlight the fundamental challenge in explaining what features distinguish allergens from nonallergenic proteins. We found that Bet v 4 and Phl p 7 undergo oligomerization transitions with characteristics that are markedly different from those typically found in proteins: transitions from monomers to dimers and to distinct higher oligomers can be induced by increasing temperature; similarly, low concentrations of destabilizing agents, e.g. SDS, induce oligomerization transitions of Bet v 4. The changes in the quaternary structure, termed molecular metamorphosis, are induced and controlled by a combination of EF-hand rearrangements and domain swapping rather than by the classical law of mass action. Using an EF-hand-pairing model, we provide a two-step model that consistently explains and substantiates the observed metamorphosis. Moreover, the unusual oligomerization behavior suggests a straightforward explanation of how allergens can accomplish the crosslinking of IgE on mast cells, a hallmark of allergens.
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17 CFR 45.10 - Reporting to a single swap data repository.
Code of Federal Regulations, 2012 CFR
2012-04-01
... the swap data repository to which the first report of required swap creation data is made pursuant to... designated contract market that reports required swap creation data as required by § 45.3 shall report all... of the swap data repository to which required swap creation data is reported by the swap execution...
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17 CFR 45.10 - Reporting to a single swap data repository.
Code of Federal Regulations, 2014 CFR
2014-04-01
..., which shall be the swap data repository to which the first report of required swap creation data is made... designated contract market that reports required swap creation data as required by § 45.3 shall report all... of the swap data repository to which required swap creation data is reported by the swap execution...
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17 CFR 45.10 - Reporting to a single swap data repository.
Code of Federal Regulations, 2013 CFR
2013-04-01
... the swap data repository to which the first report of required swap creation data is made pursuant to... designated contract market that reports required swap creation data as required by § 45.3 shall report all... of the swap data repository to which required swap creation data is reported by the swap execution...
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-02-08
... standards for swap dealers and major swap participants.'' On January 13, 2011, the Commission voted to issue... regarding internal business conduct standards for swap dealers and major swap participants. Prior notices of... comment on this issue. The Commission believes that the inclusion of this type of provision in the swap...
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-04-09
... COMMODITY FUTURES TRADING COMMISSION 17 CFR Part 23 RIN 3038-AC96 Confirmation, Portfolio Reconciliation, Portfolio Compression, and Swap Trading Relationship Documentation Requirements for Swap Dealers..., portfolio compression, and swap trading relationship documentation for Swap Dealers and Major Swap...
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Moes, Danièle; Hoffmann, Céline; Dieterle, Monika; Moreau, Flora; Neumann, Katrin; Papuga, Jessica; Furtado, Angela Tavares; Steinmetz, André; Thomas, Clément
2015-08-19
Actin-bundling Arabidopsis LIM proteins are subdivided into two subfamilies differing in their pH sensitivity. Widely-expressed WLIMs are active under low and high physiologically-relevant pH conditions, whereas pollen-enriched PLIMs are inactivated by pH values above 6.8. By a domain swapping approach we identified the C-terminal (Ct) domain of PLIMs as the domain responsible for pH responsiveness. Remarkably, this domain conferred pH sensitivity to LIM proteins, when provided "in trans" (i.e., as a single, independent, peptide), indicating that it operates through the interaction with another domain. An acidic 6xc-Myc peptide functionally mimicked the Ct domain of PLIMs and efficiently inhibited LIM actin bundling activity under high pH conditions. Together, our data suggest a model where PLIMs are regulated by an intermolecular interaction between their acidic Ct domain and another, yet unidentified, domain. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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Characterization of the RcsC sensor kinase from Erwinia amylovora and other Enterobacteria.
Wang, Dongping; Korban, Schuyler S; Pusey, P Lawrence; Zhao, Youfu
2011-06-01
RcsC is a hybrid sensor kinase which contains a sensor domain, a histidine kinase domain, and a receiver domain. We have previously demonstrated that, although the Erwinia amylovora rcsC mutant produces more amylovoran than the wild-type (WT) strain in vitro, the mutant remains nonpathogenic on both immature pear fruit and apple plants. In this study, we have comparatively characterized the Erwinia RcsC and its homologs from various enterobacteria. Results demonstrate that expression of the Erwinia rcsC gene suppresses amylovoran production in various amylovoran overproducing WT and mutant strains, thus suggesting the presence of a net phosphatase activity of Erwinia RcsC. Findings have also demonstrated that rcsC homologs from other enterobacteria could not rescue amylovoran production of the Erwinia rcsC mutant in vitro. However, virulence of the Erwinia rcsC mutant is partially restored by rcsC homologs from Pantoea stewartii, Yersinia pestis, and Salmonella enterica but not from Escherichia coli on apple shoots. Domain-swapping experiments have indicated that replacement of the E. coli RcsC sensor domain by those of Erwinia and Yersinia spp. partially restores virulence of the Erwinia rcsC mutant, whereas chimeric constructs containing the sensor domain of E. coli RcsC could not rescue virulence of the Erwinia rcsC mutant on apple. Interestingly, only chimeric constructs containing the histidine kinase and receiver domains of Erwinia RcsC are fully capable of rescuing amylovoran production. These results suggest that the sensor domain of RcsC may be important in regulating bacterial virulence, whereas the activity of the histidine kinase and receiver domains of Erwinia RcsC may be essential for amylovoran production in vitro.
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Vergara-Jaque, Ariela; Fenollar-Ferrer, Cristina; Kaufmann, Desirée; Forrest, Lucy R.
2015-01-01
Secondary active transporters are critical for neurotransmitter clearance and recycling during synaptic transmission and uptake of nutrients. These proteins mediate the movement of solutes against their concentration gradients, by using the energy released in the movement of ions down pre-existing concentration gradients. To achieve this, transporters conform to the so-called alternating-access hypothesis, whereby the protein adopts at least two conformations in which the substrate binding sites are exposed to one or other side of the membrane, but not both simultaneously. Structures of a bacterial homolog of neuronal glutamate transporters, GltPh, in several different conformational states have revealed that the protein structure is asymmetric in the outward- and inward-open states, and that the conformational change connecting them involves a elevator-like movement of a substrate binding domain across the membrane. The structural asymmetry is created by inverted-topology repeats, i.e., structural repeats with similar overall folds whose transmembrane topologies are related to each other by two-fold pseudo-symmetry around an axis parallel to the membrane plane. Inverted repeats have been found in around three-quarters of secondary transporter folds. Moreover, the (a)symmetry of these systems has been successfully used as a bioinformatic tool, called “repeat-swap modeling” to predict structural models of a transporter in one conformation using the known structure of the transporter in the complementary conformation as a template. Here, we describe an updated repeat-swap homology modeling protocol, and calibrate the accuracy of the method using GltPh, for which both inward- and outward-facing conformations are known. We then apply this repeat-swap homology modeling procedure to a concentrative nucleoside transporter, VcCNT, which has a three-dimensional arrangement related to that of GltPh. The repeat-swapped model of VcCNT predicts that nucleoside transport also occurs via an elevator-like mechanism. PMID:26388773
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Time-ordering dependence of measurements in teleportation
NASA Astrophysics Data System (ADS)
Bertlmann, Reinhold A.; Narnhofer, Heide; Thirring, Walter
2013-03-01
We trace back the phenomenon of "delayed-choice entanglement swapping" as it was realized in a recent experiment to the commutativity of the projection operators that are involved in the corresponding measurement process. We also propose an experimental set-up which depends on the order of successive measurements corresponding to noncommutative projection operators. In this case entanglement swapping is used to teleport a quantum state from Alice to Bob, where Bob has now the possibility to examine the noncommutativity within the quantum history.
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17 CFR 23.504 - Swap trading relationship documentation.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 17 Commodity and Securities Exchanges 1 2014-04-01 2014-04-01 false Swap trading relationship documentation. 23.504 Section 23.504 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP DEALERS AND MAJOR SWAP PARTICIPANTS Swap Documentation § 23.504 Swap trading relationship...
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17 CFR 23.504 - Swap trading relationship documentation.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 17 Commodity and Securities Exchanges 1 2013-04-01 2013-04-01 false Swap trading relationship documentation. 23.504 Section 23.504 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP DEALERS AND MAJOR SWAP PARTICIPANTS Swap Documentation § 23.504 Swap trading relationship...
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Code of Federal Regulations, 2014 CFR
2014-04-01
... such a swap) in an account segregated pursuant to section 4d(f) of the Act. Cleared Swaps Customer... derivatives clearing organization. A person shall be a Cleared Swaps Customer only with respect to its Cleared Swaps. Cleared Swaps Customer Account. This term refers to any account for the Cleared Swaps of Cleared...
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Code of Federal Regulations, 2012 CFR
2012-04-01
... such a swap) in an account segregated pursuant to section 4d(f) of the Act. Cleared Swaps Customer... derivatives clearing organization. A person shall be a Cleared Swaps Customer only with respect to its Cleared Swaps. Cleared Swaps Customer Account. This term refers to any account for the Cleared Swaps of Cleared...
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Code of Federal Regulations, 2013 CFR
2013-04-01
... such a swap) in an account segregated pursuant to section 4d(f) of the Act. Cleared Swaps Customer... derivatives clearing organization. A person shall be a Cleared Swaps Customer only with respect to its Cleared Swaps. Cleared Swaps Customer Account. This term refers to any account for the Cleared Swaps of Cleared...
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Quantum image median filtering in the spatial domain
NASA Astrophysics Data System (ADS)
Li, Panchi; Liu, Xiande; Xiao, Hong
2018-03-01
Spatial filtering is one principal tool used in image processing for a broad spectrum of applications. Median filtering has become a prominent representation of spatial filtering because its performance in noise reduction is excellent. Although filtering of quantum images in the frequency domain has been described in the literature, and there is a one-to-one correspondence between linear spatial filters and filters in the frequency domain, median filtering is a nonlinear process that cannot be achieved in the frequency domain. We therefore investigated the spatial filtering of quantum image, focusing on the design method of the quantum median filter and applications in image de-noising. To this end, first, we presented the quantum circuits for three basic modules (i.e., Cycle Shift, Comparator, and Swap), and then, we design two composite modules (i.e., Sort and Median Calculation). We next constructed a complete quantum circuit that implements the median filtering task and present the results of several simulation experiments on some grayscale images with different noise patterns. Although experimental results show that the proposed scheme has almost the same noise suppression capacity as its classical counterpart, the complexity analysis shows that the proposed scheme can reduce the computational complexity of the classical median filter from the exponential function of image size n to the second-order polynomial function of image size n, so that the classical method can be speeded up.
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17 CFR 49.9 - Duties of registered swap data repositories.
Code of Federal Regulations, 2014 CFR
2014-04-01
... privacy of any and all swap data and any other related information that the swap data repository receives... 17 Commodity and Securities Exchanges 2 2014-04-01 2014-04-01 false Duties of registered swap data... (CONTINUED) SWAP DATA REPOSITORIES § 49.9 Duties of registered swap data repositories. (a) Duties. To be...
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77 FR 35199 - Swap Data Recordkeeping and Reporting Requirements: Pre-Enactment and Transition Swaps
Federal Register 2010, 2011, 2012, 2013, 2014
2012-06-12
...The Commodity Futures Trading Commission (``Commission'' or ``CFTC'') is adopting rules to further implement the Commodity Exchange Act (``CEA'' or ``Act'') with respect to the new statutory framework regarding swap data recordkeeping and reporting established by the Dodd-Frank Wall Street Reform and Consumer Protection Act (``Dodd-Frank Act''). The Dodd-Frank Act, which amended the CEA, directs that rules adopted by the Commission shall provide for the reporting of data relating to swaps entered into before the date of enactment of the Dodd-Frank Act, the terms of which have not expired as of the date of enactment of the Dodd-Frank Act (``pre-enactment swaps'') and data relating to swaps entered into on or after the date of enactment of the Dodd-Frank Act and prior to the compliance date specified in the Commission's final swap data reporting rules (``transition swaps''). These final rules establish swap data recordkeeping and reporting requirements for pre-enactment swaps and transition swaps.
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Forwood, Suzanna E; Ahern, Amy L; Marteau, Theresa M; Jebb, Susan A
2015-06-25
Swaps are often used to encourage healthier food choices, but there is little evidence of their effectiveness. The current study assessed the impact of offering swaps on groceries purchased within a bespoke online supermarket; specifically the objective was to measure the impact on energy density (ED) of food purchases following the offer of lower ED alternatives (a) at point of selection or at checkout, and (b) with or without explicit consent to receive swap prompts. Participants were asked to complete a 12-item shopping task within an online shopping platform, developed for studying food purchasing. 1610 adults were randomly assigned to a no swap control condition or to one of four interventions: consented swaps at selection; consented swaps at checkout; imposed swaps at selection; or imposed swaps at checkout. Each swap presented two lower ED options from the same category as the participant's chosen food. Swap acceptance rate and purchased food ED were the primary outcomes. Of the mean 12.36 (SD 1.26) foods purchased, intervention participants were offered a mean of 4.1 (SD 1.68) swaps, with the potential to reduce the ED of purchased food (effect (95% CI): -83 kJ/100 g (-110 - -56), p = <0.0001). A median of one swap (IQR 0 to 2) was accepted, not significantly reducing the purchased food ED (effect (95% CI): -24 kJ/100 g (4 - -52), p = 0.094). More swaps were accepted when offered at selection than at checkout (OR (95% CI) = 1.224 (1.11 - 1.35), p < 0.0001), but no differences were seen with consent. Purchased food ED was unaffected by point of swap or consent, but reduced with number of swaps accepted (effect per swap (95% CI) = -24 kJ/100 g (-35 - -14), p < 0.0001). Within category swaps did not reduce the ED of food purchases reflecting the observation that the use of swaps within an on-line shopping platform offered small potential gains in ED and a minority was accepted.
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17 CFR 240.3a68-4 - Regulation of mixed swaps.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Regulation of mixed swaps. 240... Agreement; Mixed Swaps; Security-Based Swap Agreement Recordkeeping § 240.3a68-4 Regulation of mixed swaps. (a) In general. The term mixed swap has the meaning set forth in section 3(a)(68)(D) of the Act (15 U...
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Chen, Chih-Hong; Piraner, Dan; Gorenstein, Nina M; Geahlen, Robert L; Beth Post, Carol
2013-11-01
The association of spleen tyrosine kinase (Syk), a central tyrosine kinase in B cell signaling, with Vav SH2 domain is controlled by phosphorylation of two closely spaced tyrosines in Syk linker B: Y342 and Y346. Previous studies established both singly phosphorylated and doubly phosphorylated forms play a role in signaling. The structure of the doubly phosphorylated form identified a new recognition of phosphotyrosine whereby two phosphotyrosines bind simultaneously to the Vav SH2 domain, one in the canonical pTyr pocket and one in the specificity pocket on the opposite side of the central β-sheet. It is unknown if the specificity pocket can bind phosphotyrosine independent of phosphotyrosine binding the pTyr pocket. To address this gap in knowledge, we determined the structure of the complex between Vav1 SH2 and a peptide (SykLB-YpY) modeling the singly phosphorylated-Y346 form of Syk with unphosphorylated Y342. The nuclear magnetic resonance (NMR) data conclusively establish that recognition of phosphotyrosine is swapped between the two pockets; phosphorylated pY346 binds the specificity pocket of Vav1 SH2, and unphosphorylated Y342 occupies what is normally the pTyr binding pocket. Nearly identical changes in chemical shifts occurred upon binding all three forms of singly and doubly phosphorylated peptides; however, somewhat smaller shift perturbations for SykLB-YpY from residues in regions of high internal mobility suggest that internal motions are coupled to binding affinity. The differential recognition that includes this swapped binding of phosphotyrosine to the specificity pocket of Vav SH2 increases the repertoire of possible phosphotyrosine binding by SH2 domains in regulating protein-protein interactions in cellular signaling. Copyright © 2013 Wiley Periodicals, Inc.
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Engineering of chimeric eukaryotic/bacterial Rubisco large subunits in Escherichia coli.
Koay, Teng Wei; Wong, Hann Ling; Lim, Boon Hoe
2016-11-26
Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is a rate-limiting photosynthetic enzyme that catalyzes carbon fixation in the Calvin cycle. Much interest has been devoted to engineering this ubiquitous enzyme with the goal of increasing plant growth. However, experiments that have successfully produced improved Rubisco variants, via directed evolution in Escherichia coli, are limited to bacterial Rubisco because the eukaryotic holoenzyme cannot be produced in E. coli. The present study attempts to determine the specific differences between bacterial and eukaryotic Rubisco large subunit primary structure that are responsible for preventing heterologous eukaryotic holoenzyme formation in E. coli. A series of chimeric Synechococcus Rubiscos were created in which different sections of the large subunit were swapped with those of the homologous Chlamydomonas Rubisco. Chimeric holoenzymes that can form in vivo would indicate that differences within the swapped sections do not disrupt holoenzyme formation. Large subunit residues 1-97, 198-247 and 448-472 were successfully swapped without inhibiting holoenzyme formation. In all ten chimeras, protein expression was observed for the separate subunits at a detectable level. As a first approximation, the regions that can tolerate swapping may be targets for future engineering.
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Overall conformation of covalently stabilized domain-swapped dimer of human cystatin C in solution
NASA Astrophysics Data System (ADS)
Murawska, Magdalena; Szymańska, Aneta; Grubb, Anders; Kozak, Maciej
2017-11-01
Human cystatin C (HCC), a small protein, plays a crucial role in inhibition of cysteine proteases. The most common structural form of human cystatin C in crystals is a dimer, which has been evidenced both for the native protein and its mutants. In these structures, HCC dimers were formed through the mechanism of domain swapping. The structure of the monomeric form of human cystatin C was determined for V57N mutant and the mutant with the engineered disulfide bond (L47C)-(G69C) (known as stab1-HCC). On the basis of stab1-HCC, a number of covalently stabilized oligomers, including also dimers have been obtained. The aim of this study was to analyze the structure of the covalently stabilized dimer HCC in solution by the small angle X-ray scattering (SAXS) technique and synchrotron radiation. Experimental data confirmed that in solution this protein forms a dimer, which is characterized by the radius of gyration RG = 3.1 nm and maximum intramolecular distance Dmax = 10.3 nm. Using the ab initio method and program DAMMIN, we propose a low resolution structure of stabilized covalently cystatin C in solution. Stab-HCC dimer adopts in solution an elongated conformation, which is well reconstructed by the ab initio model.
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Tsujimoto, Yoshiaki; Tanaka, Motoki; Iwasaki, Nobuo; Ikuta, Rikizo; Miki, Shigehito; Yamashita, Taro; Terai, Hirotaka; Yamamoto, Takashi; Koashi, Masato; Imoto, Nobuyuki
2018-01-23
We experimentally demonstrate a high-fidelity entanglement swapping and a generation of the Greenberger-Horne-Zeilinger (GHZ) state using polarization-entangled photon pairs at telecommunication wavelength produced by spontaneous parametric down conversion with continuous-wave pump light. While spatially separated sources asynchronously emit photon pairs, the time-resolved photon detection guarantees the temporal indistinguishability of photons without active timing synchronizations of pump lasers and/or adjustment of optical paths. In the experiment, photons are sufficiently narrowed by fiber-based Bragg gratings with the central wavelengths of 1541 nm & 1580 nm, and detected by superconducting nanowire single-photon detectors with low timing jitters. The observed fidelities of the final states for entanglement swapping and the generated three-qubit state were 0.84 ± 0.04 and 0.70 ± 0.05, respectively.
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77 FR 50425 - Clearing Exemption for Swaps Between Certain Affiliated Entities
Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-21
... other categories of entities or corporate groups, such as non-swap dealers and non-major swap... exempt swaps between certain affiliated entities within a corporate group from the clearing requirement... meets the financial conditions associated with entering into non-cleared swaps. The Commission issued...
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17 CFR 23.602 - Diligent supervision.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 17 Commodity and Securities Exchanges 1 2014-04-01 2014-04-01 false Diligent supervision. 23.602... MAJOR SWAP PARTICIPANTS Duties of Swap Dealers and Major Swap Participants § 23.602 Diligent supervision. (a) Supervision. Each swap dealer and major swap participant shall establish and maintain a system to...
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17 CFR 23.602 - Diligent supervision.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 17 Commodity and Securities Exchanges 1 2013-04-01 2013-04-01 false Diligent supervision. 23.602... MAJOR SWAP PARTICIPANTS Duties of Swap Dealers and Major Swap Participants § 23.602 Diligent supervision. (a) Supervision. Each swap dealer and major swap participant shall establish and maintain a system to...
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17 CFR 49.19 - Core principles applicable to registered swap data repositories.
Code of Federal Regulations, 2013 CFR
2013-04-01
... registered swap data repositories. 49.19 Section 49.19 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP DATA REPOSITORIES § 49.19 Core principles applicable to registered swap data repositories. (a) Compliance with core principles. To be registered, and maintain registration, a swap data...
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17 CFR 49.19 - Core principles applicable to registered swap data repositories.
Code of Federal Regulations, 2012 CFR
2012-04-01
... registered swap data repositories. 49.19 Section 49.19 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP DATA REPOSITORIES § 49.19 Core principles applicable to registered swap data repositories. (a) Compliance with Core Principles. To be registered, and maintain registration, a swap data...
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17 CFR 49.12 - Swap data repository recordkeeping requirements.
Code of Federal Regulations, 2012 CFR
2012-04-01
... 17 Commodity and Securities Exchanges 1 2012-04-01 2012-04-01 false Swap data repository... COMMISSION SWAP DATA REPOSITORIES § 49.12 Swap data repository recordkeeping requirements. (a) A registered swap data repository shall maintain its books and records in accordance with the requirements of part...
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17 CFR 49.12 - Swap data repository recordkeeping requirements.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 17 Commodity and Securities Exchanges 1 2013-04-01 2013-04-01 false Swap data repository... COMMISSION SWAP DATA REPOSITORIES § 49.12 Swap data repository recordkeeping requirements. (a) A registered swap data repository shall maintain its books and records in accordance with the requirements of part...
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17 CFR 49.12 - Swap data repository recordkeeping requirements.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 17 Commodity and Securities Exchanges 2 2014-04-01 2014-04-01 false Swap data repository... COMMISSION (CONTINUED) SWAP DATA REPOSITORIES § 49.12 Swap data repository recordkeeping requirements. (a) A registered swap data repository shall maintain its books and records in accordance with the requirements of...
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17 CFR 45.5 - Unique swap identifiers.
Code of Federal Regulations, 2012 CFR
2012-04-01
... transmit a unique swap identifier as provided in paragraphs (a)(1) and (2) of this section. (1) Creation... prior to the reporting of required swap creation data. The unique swap identifier shall consist of a... execution facility or designated contract market with respect to unique swap identifier creation; and (ii...
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17 CFR 45.5 - Unique swap identifiers.
Code of Federal Regulations, 2013 CFR
2013-04-01
... transmit a unique swap identifier as provided in paragraphs (a)(1) and (2) of this section. (1) Creation... prior to the reporting of required swap creation data. The unique swap identifier shall consist of a... execution facility or designated contract market with respect to unique swap identifier creation; and (ii...
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17 CFR 45.5 - Unique swap identifiers.
Code of Federal Regulations, 2014 CFR
2014-04-01
... transmit a unique swap identifier as provided in paragraphs (a)(1) and (2) of this section. (1) Creation... prior to the reporting of required swap creation data. The unique swap identifier shall consist of a... execution facility or designated contract market with respect to unique swap identifier creation; and (ii...
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17 CFR 37.403 - Additional requirements for cash-settled swaps.
Code of Federal Regulations, 2014 CFR
2014-04-01
... requirements for cash-settled swaps. (a) For cash-settled swaps, the swap execution facility shall demonstrate that it monitors the pricing of the reference price used to determine cash flows or settlement; (b) For... cash-settled swaps. 37.403 Section 37.403 Commodity and Securities Exchanges COMMODITY FUTURES TRADING...
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75 FR 64643 - Reporting of Security-Based Swap Transaction Data
Federal Register 2010, 2011, 2012, 2013, 2014
2010-10-20
... information relating to pre-enactment security-based swaps to a registered security-based swap data repository... within 60 days after a registered security- based swap data repository commences operations to receive... repository,\\8\\ and security- based swap execution facility.\\9\\ The Commission has issued an advance notice of...
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17 CFR 45.4 - Swap data reporting: continuation data.
Code of Federal Regulations, 2014 CFR
2014-04-01
... swap data repository as set forth in this section. This obligation commences on the applicable... swap data set forth in part 43 of this chapter; and, where applicable, swap dealers, major swap... traders set forth in parts 17 and 18 of this chapter. (a) Continuation data reporting method. For each...
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17 CFR 45.4 - Swap data reporting: continuation data.
Code of Federal Regulations, 2013 CFR
2013-04-01
... swap data repository as set forth in this section. This obligation commences on the applicable... swap data set forth in part 43 of this chapter; and, where applicable, swap dealers, major swap... traders set forth in parts 17 and 18 of this chapter. (a) Continuation data reporting method. For each...
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17 CFR 45.4 - Swap data reporting: continuation data.
Code of Federal Regulations, 2012 CFR
2012-04-01
... swap data repository as set forth in this section. This obligation commences on the applicable... swap data set forth in part 43 of this chapter; and, where applicable, swap dealers, major swap... traders set forth in parts 17 and 18 of this chapter. (a) Continuation data reporting method. For each...
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77 FR 2613 - Registration of Swap Dealers and Major Swap Participants
Federal Register 2010, 2011, 2012, 2013, 2014
2012-01-19
...The Commodity Futures Trading Commission (Commission or CFTC) is adopting regulations under the Commodity Exchange Act (Act or CEA) that establish the process for the registration of swap dealers (SDs) and major swap participants (MSPs, and collectively with SDs, Swaps Entities) and that require Swaps Entities to become and remain members of a registered futures association (RFA). The Commission is also adopting regulations that define an ``associated person'' of an SD or MSP as a natural person and that implement the prohibition on a Swaps Entity permitting an associated person who is statutorily disqualified from registration from effecting or being involved in effecting swaps on behalf of the Swaps Entity. The Commission is adopting these regulations in accordance with section 4s of the CEA, which was recently added to the CEA by the Dodd-Frank Wall Street Reform and Consumer Protection Act (Dodd-Frank Act).
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-05-23
...In accordance with the Dodd-Frank Wall Street Reform and Consumer Protection Act of 2010 (``Dodd-Frank Act''), the Commodity Futures Trading Commission (``CFTC'') and the Securities and Exchange Commission (``SEC'') (collectively, the ``Commissions''), in consultation with the Board of Governors of the Federal Reserve System (``Board''), are adopting new rules and interpretive guidance under the Commodity Exchange Act (``CEA''), and the Securities Exchange Act of 1934 (``Exchange Act''), to further define the terms ``swap dealer,'' ``security-based swap dealer,'' ``major swap participant,'' ``major security-based swap participant,'' and ``eligible contract participant.''
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Gao, Yong-Gui; Suzuki, Hiroaki; Itou, Hiroshi; Zhou, Yong; Tanaka, Yoshikazu; Wachi, Masaaki; Watanabe, Nobuhisa; Tanaka, Isao; Yao, Min
2008-01-01
LldR (CGL2915) from Corynebacterium glutamicum is a transcription factor belonging to the GntR family, which is typically involved in the regulation of oxidized substrates associated with amino acid metabolism. In the present study, the crystal structure of LldR was determined at 2.05-Å resolution. The structure consists of N- and C-domains similar to those of FadR, but with distinct domain orientations. LldR and FadR dimers achieve similar structures by domain swapping, which was first observed in dimeric assembly of transcription factors. A structural feature of Zn2+ binding in the regulatory domain was also observed, as a difference from the FadR subfamily. DNA microarray and DNase I footprint analyses suggested that LldR acts as a repressor regulating cgl2917-lldD and cgl1934-fruK-ptsF operons, which are indispensable for l-lactate and fructose/sucrose utilization, respectively. Furthermore, the stoichiometries and affinities of LldR and DNAs were determined by isothermal titration calorimetry measurements. The transcriptional start site and repression of LldR on the cgl2917-lldD operon were analysed by primer extension assay. Mutation experiments showed that residues Lys4, Arg32, Arg42 and Gly63 are crucial for DNA binding. The location of the putative ligand binding cavity and the regulatory mechanism of LldR on its affinity for DNA were proposed. PMID:18988622
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Orlikowska, Marta; Jankowska, Elzbieta; Borek, Dominika
2012-03-15
Human cystatin C (hCC) is a low-molecular-mass protein (120 amino-acid residues, 13 343 Da) found in all nucleated cells. Its main physiological role is regulation of the activity of cysteine proteases. Biologically active hCC is a monomeric protein, but all crystallization efforts have resulted in a dimeric domain-swapped structure. Recently, two monomeric structures were reported for cystatin C variants. In one of them stabilization was achieved by abolishing the possibility of domain swapping by the introduction of an additional disulfide bridge connecting the two protein domains (Cys47-Cys69). In the second structure, reported by this group, the monomeric hCC fold wasmore » preserved by stabilization of the conformationally constrained loop (L1) by a single-amino-acid substitution (V57N). To further assess the influence of changes in the sequence and properties of loop L1 on the dimerization propensity of cystatin C, two additional hCC mutants were obtained: one with a residue favoured in {beta}-turns (V57D) and another with proline (V57P), a residue that is known to be a structural element that can rigidify but also broaden turns. Here, the expression, purification and crystallization of V57D and V57P variants of recombinant human cystatin C are described. Crystals were grown by the vapour-diffusion method. Several diffraction data sets were collected using a synchrotron source at the Advanced Photon Source, Argonne National Laboratory, Chicago, USA.« less
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2014-05-16
ISS040-E-000298 (16 May 2014) --- NASA astronaut Steve Swanson, Expedition 40 commander, works with the General Laboratory Active Cryogenic ISS Experiment Refrigerator (GLACIER) in the Destiny laboratory of the International Space Station.
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2014-05-16
ISS040-E-000297 (16 May 2014) --- NASA astronaut Steve Swanson, Expedition 40 commander, works with the General Laboratory Active Cryogenic ISS Experiment Refrigerator (GLACIER) in the Destiny laboratory of the International Space Station.
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2014-05-16
ISS040-E-000296 (16 May 2014) --- NASA astronaut Steve Swanson, Expedition 40 commander, works with the General Laboratory Active Cryogenic ISS Experiment Refrigerator (GLACIER) in the Destiny laboratory of the International Space Station.
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75 FR 63080 - Interim Final Rule for Reporting Pre-Enactment Swap Transactions
Federal Register 2010, 2011, 2012, 2013, 2014
2010-10-14
... registered swap data repository (``SDR'') \\1\\ or to the Commission by the compliance date to be established... to the terms of such swaps. \\1\\ The term ``swap data repository'' is defined in Section 1a(48) of the... the date of the enactment of this subsection shall be reported to a registered swap data repository or...
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All-quad meshing without cleanup
Rushdi, Ahmad A.; Mitchell, Scott A.; Mahmoud, Ahmed H.; ...
2016-08-22
Here, we present an all-quad meshing algorithm for general domains. We start with a strongly balanced quadtree. In contrast to snapping the quadtree corners onto the geometric domain boundaries, we move them away from the geometry. Then we intersect the moved grid with the geometry. The resulting polygons are converted into quads with midpoint subdivision. Moving away avoids creating any flat angles, either at a quadtree corner or at a geometry–quadtree intersection. We are able to handle two-sided domains, and more complex topologies than prior methods. The algorithm is provably correct and robust in practice. It is cleanup-free, meaning wemore » have angle and edge length bounds without the use of any pillowing, swapping, or smoothing. Thus, our simple algorithm is fast and predictable. This paper has better quality bounds, and the algorithm is demonstrated over more complex domains, than our prior version.« less
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All-quad meshing without cleanup
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rushdi, Ahmad A.; Mitchell, Scott A.; Mahmoud, Ahmed H.
Here, we present an all-quad meshing algorithm for general domains. We start with a strongly balanced quadtree. In contrast to snapping the quadtree corners onto the geometric domain boundaries, we move them away from the geometry. Then we intersect the moved grid with the geometry. The resulting polygons are converted into quads with midpoint subdivision. Moving away avoids creating any flat angles, either at a quadtree corner or at a geometry–quadtree intersection. We are able to handle two-sided domains, and more complex topologies than prior methods. The algorithm is provably correct and robust in practice. It is cleanup-free, meaning wemore » have angle and edge length bounds without the use of any pillowing, swapping, or smoothing. Thus, our simple algorithm is fast and predictable. This paper has better quality bounds, and the algorithm is demonstrated over more complex domains, than our prior version.« less
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Dirndorfer, Daniela; Seidel, Ralf P.; Nimrod, Guy; Miesbauer, Margit; Ben-Tal, Nir; Engelhard, Martin; Zimmermann, Richard; Winklhofer, Konstanze F.; Tatzelt, Jörg
2013-01-01
Different neuropeptide hormones, which are either too small to adopt a stable conformation or are predicted to be intrinsically disordered, are synthesized as larger precursors containing a prodomain in addition to an N-terminal signal peptide. We analyzed the biogenesis of three unstructured neuropeptide hormones and observed that translocation of these precursors into the lumen of the endoplasmic reticulum (ER) is critically dependent on the presence of the prodomain. The hormone domains could be deleted from the precursors without interfering with ER import and secretion, whereas constructs lacking the prodomain remained in the cytosol. Domain-swapping experiments revealed that the activity of the prodomains to promote productive ER import resides in their ability to adopt an α-helical structure. Removal of the prodomain from the precursor did not interfere with co-translational targeting of the nascent chain to the Sec61 translocon but with its subsequent productive translocation into the ER lumen. Our study reveals a novel function of prodomains to enable import of small or intrinsically disordered secretory proteins into the ER based on their ability to adopt an α-helical conformation. PMID:23532840
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Dirndorfer, Daniela; Seidel, Ralf P; Nimrod, Guy; Miesbauer, Margit; Ben-Tal, Nir; Engelhard, Martin; Zimmermann, Richard; Winklhofer, Konstanze F; Tatzelt, Jörg
2013-05-17
Different neuropeptide hormones, which are either too small to adopt a stable conformation or are predicted to be intrinsically disordered, are synthesized as larger precursors containing a prodomain in addition to an N-terminal signal peptide. We analyzed the biogenesis of three unstructured neuropeptide hormones and observed that translocation of these precursors into the lumen of the endoplasmic reticulum (ER) is critically dependent on the presence of the prodomain. The hormone domains could be deleted from the precursors without interfering with ER import and secretion, whereas constructs lacking the prodomain remained in the cytosol. Domain-swapping experiments revealed that the activity of the prodomains to promote productive ER import resides in their ability to adopt an α-helical structure. Removal of the prodomain from the precursor did not interfere with co-translational targeting of the nascent chain to the Sec61 translocon but with its subsequent productive translocation into the ER lumen. Our study reveals a novel function of prodomains to enable import of small or intrinsically disordered secretory proteins into the ER based on their ability to adopt an α-helical conformation.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Chang, Yu-Tzu; Shu, Chung-Li; Lai, Jing-Yang
Mouse embryo fibroblasts (MEFs) grow slowly after cultivation from animals, however, after an extended period of cultivation, their growth accelerates. We found that SWAP-70 deficient MEFs failed to increase growth rates. They maintain normal growth rates and proliferation cycles for at least 5 years. Complementing SWAP-70 deficiency in one of these MEF clones, MEF1F2, by expressing human SWAP-70 resulted in fast growth of the cells after further cultivation for a long period. The resulting cells show a transformation phenotype, since they grow on top of each other and do not show contact inhibition. This phenotype was reverted when sanguinarine, amore » putative SWAP-70 inhibitor, was added. Two SWAP-70 expressing clones were examined in detail. Even after cell density became very high their cdc2 and NFκB were still activated suggesting that they do not stop growing. One of the clones formed colonies in soft agar and formed tumors in nude mice. Lately, one more clone became transformed being able to make colonies in soft agar. We maintain 4 human SWAP-70 expressing MEF1F2 cell lines. Three out of 4 clones exhibited transforming phenotypes. The mouse SWAP-70 gene also promoted transformation of MEFs. Taken together our data suggest that SWAP-70 is not a typical oncogene, but is required for spontaneous transformation of MEFs. - Highlights: • Mouse embryo fibroblasts (MEFs) lacking SWAP-70 do not cause spontaneous transform. • Adding back of SWAP-70 to SWAP-70-deficient MEFs induces spontaneous transformation. • SWAP-70 is required for spontaneous transformation of MEFs.« less
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Mapping from multiple-control Toffoli circuits to linear nearest neighbor quantum circuits
NASA Astrophysics Data System (ADS)
Cheng, Xueyun; Guan, Zhijin; Ding, Weiping
2018-07-01
In recent years, quantum computing research has been attracting more and more attention, but few studies on the limited interaction distance between quantum bits (qubit) are deeply carried out. This paper presents a mapping method for transforming multiple-control Toffoli (MCT) circuits into linear nearest neighbor (LNN) quantum circuits instead of traditional decomposition-based methods. In order to reduce the number of inserted SWAP gates, a novel type of gate with the optimal LNN quantum realization was constructed, namely NNTS gate. The MCT gate with multiple control bits could be better cascaded by the NNTS gates, in which the arrangement of the input lines was LNN arrangement of the MCT gate. Then, the communication overhead measurement model on inserted SWAP gate count from the original arrangement to the new arrangement was put forward, and we selected one of the LNN arrangements with the minimum SWAP gate count. Moreover, the LNN arrangement-based mapping algorithm was given, and it dealt with the MCT gates in turn and mapped each MCT gate into its LNN form by inserting the minimum number of SWAP gates. Finally, some simplification rules were used, which can further reduce the final quantum cost of the LNN quantum circuit. Experiments on some benchmark MCT circuits indicate that the direct mapping algorithm results in fewer additional SWAP gates in about 50%, while the average improvement rate in quantum cost is 16.95% compared to the decomposition-based method. In addition, it has been verified that the proposed method has greater superiority for reversible circuits cascaded by MCT gates with more control bits.
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Irreversible Heavy Chain Transfer to Chondroitin*
Lauer, Mark E.; Hascall, Vincent C.; Green, Dixy E.; DeAngelis, Paul L.; Calabro, Anthony
2014-01-01
We have recently demonstrated that the transfer of heavy chains (HCs) from inter-α-inhibitor, via the enzyme TSG-6 (tumor necrosis factor-stimulated gene 6), to hyaluronan (HA) oligosaccharides is an irreversible event in which subsequent swapping of HCs between HA molecules does not occur. We now describe our results of HC transfer experiments to chondroitin sulfate A, chemically desulfated chondroitin, chemoenzymatically synthesized chondroitin, unsulfated heparosan, heparan sulfate, and alginate. Of these potential HC acceptors, only chemically desulfated chondroitin and chemoenzymatically synthesized chondroitin were HC acceptors. The kinetics of HC transfer to chondroitin was similar to HA. At earlier time points, HCs were more widely distributed among the different sizes of chondroitin chains. As time progressed, the HCs migrated to lower molecular weight chains of chondroitin. Our interpretation is that TSG-6 swaps the HCs from the larger, reversible sites on chondroitin chains, which function as HC acceptors, onto smaller chondroitin chains, which function as irreversible HC acceptors. HCs transferred to smaller chondroitin chains were unable to be swapped off the smaller chondroitin chains and transferred to HA. HCs transferred to high molecular weight HA were unable to be swapped onto chondroitin. We also present data that although chondroitin was a HC acceptor, HA was the preferred acceptor when chondroitin and HA were in the same reaction mixture. PMID:25135638
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Theos, Alexander C.; Watt, Brenda; Harper, Dawn C.; Janczura, Karolina J.; Theos, Sarah C.; Herman, Kathryn E.; Marks, Michael S.
2013-01-01
SUMMARY Proteolytic fragments of the pigment cell-specific glycoprotein, PMEL, form the amyloid fibrillar matrix underlying melanins in melanosomes. The fibrils form within multivesicular endosomes to which PMEL is selectively sorted and that serve as melanosome precursors. GPNMB is a tissue-restricted glycoprotein with substantial sequence homology to PMEL but no known function, and was proposed to localize to non-fibrillar domains of distinct melanosome subcompartments in melanocytes. Here we confirm that GPNMB localizes to compartments distinct from the PMEL-containing multivesicular premelanosomes or late endosomes in melanocytes and HeLa cells, respectively, and is largely absent from fibrils. Using domain swapping, the unique PMEL localization is ascribed to its PKD domain, whereas the homologous PKD domain of GPNMB lacks apparent sorting function. The difference likely reflects extensive modification of the GPNMB PKD domain by N-glycosylation, nullifying its sorting function. These results reveal the molecular basis for the distinct trafficking and morphogenetic properties of PMEL and GPNMB, and support a deterministic function of the PMEL PKD domain in both protein sorting and amyloidogenesis. PMID:23452376
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Ama1p-activated anaphase-promoting complex regulates the destruction of Cdc20p during meiosis II
Tan, Grace S.; Magurno, Jennifer; Cooper, Katrina F.
2011-01-01
The execution of meiotic divisions in Saccharomyces cerevisiae is regulated by anaphase-promoting complex/cyclosome (APC/C)–mediated protein degradation. During meiosis, the APC/C is activated by association with Cdc20p or the meiosis-specific activator Ama1p. We present evidence that, as cells exit from meiosis II, APC/CAma1 mediates Cdc20p destruction. APC/CAma1 recognizes two degrons on Cdc20p, the destruction box and destruction degron, with either domain being sufficient to mediate Cdc20p destruction. Cdc20p does not need to associate with the APC/C to bind Ama1p or be destroyed. Coimmunoprecipitation analyses showed that the diverged amino-terminal region of Ama1p recognizes both Cdc20p and Clb1p, a previously identified substrate of APC/CAma1. Domain swap experiments revealed that the C-terminal WD region of Cdh1p, when fused to the N-terminal region of Ama1p, could direct most of Ama1p functions, although at a reduced level. In addition, this fusion protein cannot complement the spore wall defect in ama1Δ strains, indicating that substrate specificity is also derived from the WD repeat domain. These findings provide a mechanism to temporally down-regulate APC/CCdc20 activity as the cells complete meiosis II and form spores. PMID:21118994
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Structural analysis of β-prism lectin from Colocasia esculenta (L.) S chott.
Vajravijayan, S; Pletnev, S; Pletnev, V Z; Nandhagopal, N; Gunasekaran, K
2016-10-01
The Mannose-binding β-Prism Colocasia esculenta lectin (β-PCL) was purified from tubers using ion exchange chromatography. The purified β-PCL appeared as a single band of ∼12kDa on SDS-PAGE. β-PCL crystallizes in trigonal space group P3121 and diffracted to a resolution of 2.1Å. The structure was solved using Molecular replacement using Crocus vernus lectin (PDB: 3MEZ) as a model. From the final refined model to an R-factor of 16.5% and an Rfree of 20.4%, it has been observed that the biological unit consists of two β-Prism domains augmented through C-terminals swap over to form one of faces for each domain. Cα superposition of individual domains of β-PCL with individual domains of other related structures and superposition of whole protein structures were carried out. The higher RMS deviation for the superposition of whole structures suggest that β-prism domains assume different orientation in each structure. Copyright © 2016 Elsevier B.V. All rights reserved.
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17 CFR 49.10 - Acceptance of data.
Code of Federal Regulations, 2014 CFR
2014-04-01
... technological protocols established by a swap data repository shall provide for the receipt of swap creation data, swap continuation data, real-time public reporting data, and all other data and information... swap data repository shall adopt policies and procedures, including technological protocols, which...
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Hirota, Shun; Ueda, Mariko; Hayashi, Yugo; Nagao, Satoshi; Kamikubo, Hironari; Kataoka, Mikio
2012-12-01
We have previously shown that polymerization of cytochrome c (cyt c) occurs by successively domain swapping its C-terminal α-helix in the presence of ethanol. However, the factors that govern the conversion process of monomers to domain-swapped oligomers remain unknown. We found that oligomeric cyt c is produced in the presence of ethanol and the oligomers precipitate due to low solubility. The optical absorption spectra revealed that in the presence of 30-40% ethanol, the Met-heme coordination in cyt c is dissociated. However, according to circular dichroism and small-angle X-ray scattering measurements, the α-helical structure of cyt c is maintained in solution with a little perturbation and the radius of gyration increases slightly but without dissociation of the C-terminal α-helix from the rest of the protein by the addition of ethanol. Solid-state nuclear magnetic resonance spectra showed that oligomeric cyt c in the precipitate also retains most of its α-helical structure. In the transmission electron microscopic image of the precipitate obtained by the addition of ethanol to cyt c, spherical particles with diameters of about 3 nm were detected. These results indicate that oligomeric cyt c forms through a state with the Met80 region locally unfolded, while maintaining the secondary structure, possibly an open monomer.
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17 CFR 49.26 - Disclosure requirements of swap data repositories.
Code of Federal Regulations, 2014 CFR
2014-04-01
... data repository's policies and procedures reasonably designed to protect the privacy of any and all... swap data repositories. 49.26 Section 49.26 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION (CONTINUED) SWAP DATA REPOSITORIES § 49.26 Disclosure requirements of swap data...
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-13
...In accordance with section 712(a)(8), section 712(d)(1), sections 712(d)(2)(B) and (C), sections 721(b) and (c), and section 761(b) of the Dodd-Frank Wall Street Reform and Consumer Protection Act (``Dodd-Frank Act''), the Commodity Futures Trading Commission (``CFTC'') and the Securities and Exchange Commission (``SEC'') (collectively, ``Commissions''), in consultation with the Board of Governors of the Federal Reserve System (``Board''), are jointly adopting new rules and interpretations under the Commodity Exchange Act (``CEA'') and the Securities Exchange Act of 1934 (``Exchange Act'') to further define the terms ``swap,'' ``security-based swap,'' and ``security-based swap agreement'' (collectively, ``Product Definitions''); regarding ``mixed swaps;'' and governing books and records with respect to ``security-based swap agreements.'' The CFTC requests comment on its interpretation concerning forwards with embedded volumetric optionality, contained in Section II.B.2.(b)(ii) of this release.
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75 FR 75207 - Regulation SBSR-Reporting and Dissemination of Security-Based Swap Information
Federal Register 2010, 2011, 2012, 2013, 2014
2010-12-02
...In accordance with Section 763 (``Section 763'') and Section 766 (``Section 766'') of Title VII (``Title VII'') of the Dodd-Frank Wall Street Reform and Consumer Protection Act (the ``Dodd-Frank Act''), the Securities and Exchange Commission (``SEC'' or ``Commission'') is proposing Regulation SBSR--Reporting and Dissemination of Security-Based Swap Information (``Regulation SBSR'') under the Securities Exchange Act of 1934 (``Exchange Act'').\\1\\ Proposed Regulation SBSR would provide for the reporting of security- based swap information to registered security-based swap data repositories or the Commission and the public dissemination of security-based swap transaction, volume, and pricing information. Registered security-based swap data repositories would be required to establish and maintain certain policies and procedures regarding how transaction data are reported and disseminated, and participants of registered security-based swap data repositories that are security- based swap dealers or major security-based swap participants would be required to establish and maintain policies and procedures that are reasonably designed to ensure that they comply with applicable reporting obligations. Finally, proposed Regulation SBSR also would require a registered SDR to register with the Commission as a securities information processor on existing Form SIP. ---------------------------------------------------------------------------
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17 CFR 49.19 - Core principles applicable to registered swap data repositories.
Code of Federal Regulations, 2014 CFR
2014-04-01
... registered swap data repositories. 49.19 Section 49.19 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION (CONTINUED) SWAP DATA REPOSITORIES § 49.19 Core principles applicable to registered swap data repositories. (a) Compliance with core principles. To be registered, and maintain...
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17 CFR 49.27 - Access and fees.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 49.27 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP DATA REPOSITORIES § 49.27 Access and fees. (a) Fair, open and equal access. (1) A registered swap data repository..., swap dealers, major swap participants and any other counterparties, on a fair, open and equal basis...
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17 CFR 49.27 - Access and fees.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 49.27 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION (CONTINUED) SWAP DATA REPOSITORIES § 49.27 Access and fees. (a) Fair, open and equal access. (1) A registered swap data repository..., swap dealers, major swap participants and any other counterparties, on a fair, open and equal basis...
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17 CFR 49.27 - Access and fees.
Code of Federal Regulations, 2012 CFR
2012-04-01
... 49.27 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP DATA REPOSITORIES § 49.27 Access and fees. (a) Fair, open and equal access. (1) A registered swap data repository..., swap dealers, major swap participants and any other counterparties, on a fair, open and equal basis...
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17 CFR 49.26 - Disclosure requirements of swap data repositories.
Code of Federal Regulations, 2013 CFR
2013-04-01
... TRADING COMMISSION SWAP DATA REPOSITORIES § 49.26 Disclosure requirements of swap data repositories... swap data repository shall furnish to the reporting entity a disclosure document that contains the... 17 Commodity and Securities Exchanges 1 2013-04-01 2013-04-01 false Disclosure requirements of...
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17 CFR 49.26 - Disclosure requirements of swap data repositories.
Code of Federal Regulations, 2012 CFR
2012-04-01
... TRADING COMMISSION SWAP DATA REPOSITORIES § 49.26 Disclosure requirements of swap data repositories... swap data repository shall furnish to the reporting entity a disclosure document that contains the... 17 Commodity and Securities Exchanges 1 2012-04-01 2012-04-01 false Disclosure requirements of...
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77 FR 31767 - Aggregation, Position Limits for Futures and Swaps
Federal Register 2010, 2011, 2012, 2013, 2014
2012-05-30
... physical commodity swaps that are economically equivalent to such contracts. In response to a petition for... on a designated contract market (``DCM''), as well as swaps that are economically equivalent to such... physical commodity swaps that are economically equivalent to such contracts (collectively with Core...
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75 FR 76139 - Real-Time Public Reporting of Swap Transaction Data
Federal Register 2010, 2011, 2012, 2013, 2014
2010-12-07
... Transaction Data; Proposed Rule #0;#0;Federal Register / Vol. 75 , No. 234 / Tuesday, December 7, 2010...-Time Public Reporting of Swap Transaction Data AGENCY: Commodity Futures Trading Commission. ACTION...-time public reporting of swap transaction and pricing data for all swap transactions. Additionally, the...
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17 CFR 49.16 - Privacy and confidentiality requirements of swap data repositories.
Code of Federal Regulations, 2014 CFR
2014-04-01
... FUTURES TRADING COMMISSION (CONTINUED) SWAP DATA REPOSITORIES § 49.16 Privacy and confidentiality... procedures to protect the privacy and confidentiality of any and all SDR Information (except for swap data... of accepting swap data from reporting entities, require the waiver of any privacy rights by such...
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Code of Federal Regulations, 2012 CFR
2012-04-01
... Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP DATA REPOSITORIES § 49.2... indirectly, controls, is controlled by, or is under common control with, the swap data repository. (2) Asset... “commercial use” means the use of swap data held and maintained by a registered swap data repository for a...
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Code of Federal Regulations, 2013 CFR
2013-04-01
... Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP DATA REPOSITORIES § 49.2... indirectly, controls, is controlled by, or is under common control with, the swap data repository. (2) Asset... “commercial use” means the use of swap data held and maintained by a registered swap data repository for a...
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78 FR 20848 - Swap Dealers and Major Swap Participants; Clerical or Ministerial Employees
Federal Register 2010, 2011, 2012, 2013, 2014
2013-04-08
... COMMODITY FUTURES TRADING COMMISSION 17 CFR Part 23 RIN 3038-AE00 Swap Dealers and Major Swap Participants; Clerical or Ministerial Employees AGENCY: Commodity Futures Trading Commission. ACTION: Proposed rule. SUMMARY: The Commodity Futures Trading Commission (Commission or CFTC) is proposing to amend its...
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78 FR 64173 - Swap Dealers and Major Swap Participants; Clerical or Ministerial Employees
Federal Register 2010, 2011, 2012, 2013, 2014
2013-10-28
... COMMODITY FUTURES TRADING COMMISSION 17 CFR Part 23 RIN 3038-AE00 Swap Dealers and Major Swap Participants; Clerical or Ministerial Employees AGENCY: Commodity Futures Trading Commission. ACTION: Final rule. SUMMARY: The Commodity Futures Trading Commission is adopting an amendment to its regulations to...
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Mitchell, Carter A; Shi, Ce; Aldrich, Courtney C; Gulick, Andrew M
2012-04-17
Many bacteria use large modular enzymes for the synthesis of polyketide and peptide natural products. These multidomain enzymes contain integrated carrier domains that deliver bound substrates to multiple catalytic domains, requiring coordination of these chemical steps. Nonribosomal peptide synthetases (NRPSs) load amino acids onto carrier domains through the activity of an upstream adenylation domain. Our lab recently determined the structure of an engineered two-domain NRPS containing fused adenylation and carrier domains. This structure adopted a domain-swapped dimer that illustrated the interface between these two domains. To continue our investigation, we now examine PA1221, a natural two-domain protein from Pseudomonas aeruginosa. We have determined the amino acid specificity of this new enzyme and used domain specific mutations to demonstrate that loading the downstream carrier domain within a single protein molecule occurs more quickly than loading of a nonfused carrier domain intermolecularly. Finally, we have determined crystal structures of both apo- and holo-PA1221 proteins, the latter using a valine-adenosine vinylsulfonamide inhibitor that traps the adenylation domain-carrier domain interaction. The protein adopts an interface similar to that seen with the prior adenylation domain-carrier protein construct. A comparison of these structures with previous structures of multidomain NRPSs suggests that a large conformational change within the NRPS adenylation domains guides the carrier domain into the active site for thioester formation.
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Biophysical investigation of type A PutAs reveals a conserved core oligomeric structure
DOE Office of Scientific and Technical Information (OSTI.GOV)
Korasick, David A.; Singh, Harkewal; Pemberton, Travis A.
2017-08-01
Many enzymes form homooligomers, yet the functional significance of self-association is seldom obvious. Herein, we examine the connection between oligomerization and catalytic function for proline utilization A (PutA) enzymes. PutAs are bifunctional enzymes that catalyze both reactions of proline catabolism. Type A PutAs are the smallest members of the family, possessing a minimal domain architecture consisting of N-terminal proline dehydrogenase and C-terminal l-glutamate-γ-semialdehyde dehydrogenase modules. Type A PutAs form domain-swapped dimers, and in one case (Bradyrhizobium japonicum PutA), two of the dimers assemble into a ring-shaped tetramer. Whereas the dimer has a clear role in substrate channeling, the functional significancemore » of the tetramer is unknown. To address this question, we performed structural studies of four-type A PutAs from two clades of the PutA tree. The crystal structure of Bdellovibrio bacteriovorus PutA covalently inactivated by N-propargylglycine revealed a fold and substrate-channeling tunnel similar to other PutAs. Small-angle X-ray scattering (SAXS) and analytical ultracentrifugation indicated that Bdellovibrio PutA is dimeric in solution, in contrast to the prediction from crystal packing of a stable tetrameric assembly. SAXS studies of two other type A PutAs from separate clades also suggested that the dimer predominates in solution. To assess whether the tetramer of B. japonicum PutA is necessary for catalytic function, a hot spot disruption mutant that cleanly produces dimeric protein was generated. The dimeric variant exhibited kinetic parameters similar to the wild-type enzyme. These results implicate the domain-swapped dimer as the core structural and functional unit of type A PutAs.« less
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-06-07
... COMMODITY FUTURES TRADING COMMISSION 17 CFR Part 1 RIN 3038-AD46 SECURITIES AND EXCHANGE...-Based Swap Agreement Recordkeeping AGENCY: Commodity Futures Trading Commission; Securities and Exchange... Futures Trading Commission and the Securities and Exchange Commission published a document in the Federal...
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-11-23
... risks associated with the use of models to derive market valuations or otherwise calculate or evaluate... swap dealers and major swap participants registered with the Commission with regard to: Risk management...) \\3\\ to establish a comprehensive regulatory framework to reduce risk, increase transparency, and...
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17 CFR 45.3 - Swap data reporting: creation data.
Code of Federal Regulations, 2013 CFR
2013-04-01
... to the reporting obligations with respect to real time reporting of swap data set forth in part 43 of... economic terms data for the swap, within the applicable reporting deadline set forth in paragraph (b)(1)(i..., must report all primary economic terms data for the swap, within the applicable reporting deadline set...
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17 CFR 45.3 - Swap data reporting: creation data.
Code of Federal Regulations, 2012 CFR
2012-04-01
... to the reporting obligations with respect to real time reporting of swap data set forth in part 43 of... economic terms data for the swap, within the applicable reporting deadline set forth in paragraph (b)(1)(i..., must report all primary economic terms data for the swap, within the applicable reporting deadline set...
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-07-08
...-fraud provisions, as well as exempt these security-based swaps from Exchange Act registration... interest involving security-based swaps.\\31\\ We have also proposed anti-fraud and anti-manipulation rules... Against Fraud, Manipulation, and Deception in Connection with Security-Based Swaps, Release No. 34-63236...
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Hirabayashi, Yoshihiro; Kawakami, Takayuki; Suzuki, Hideo; Igarashi, Takashi; Saitoh, Kazuhiko; Seo, Norimasa
2005-09-01
Syringe swap is an important problem in anesthetic care, causing harm to patients. We examined the effect of colored syringe and a colored sheet on the incidence of syringe swaps during anesthetic management. We determined the color code. The blue-syringe contains local anesthetics; yellow-syringe, sympathomimetic drugs; and white-syringe with a red label fixed opposite the scale, muscle relaxants. The colored sheet displays the photographs of the syringe with drug name, dose and volume. The colored syringe and colored sheet were supplied for use from February 2004. We compared the incidence of syringe swaps during the period from February 2004 to January 2005 with that from February 2003 to January 2004. Although five syringe swaps were recorded from February 2003 to January 2004, in 5901 procedures, we encountered no syringe swaps from February 2004 to January 2005, in 6078 procedures. The colored syringe and colored sheet significantly decreased the incidence of syringe swaps during anesthetic management (P <0.05). The use of the sheet together with colored syringes can prevent syringe swaps during anesthesia.
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Zhuravlev, Pavel I; Reddy, Govardhan; Straub, John E; Thirumalai, D
2014-07-15
Protein aggregation, linked to many of diseases, is initiated when monomers access rogue conformations that are poised to form amyloid fibrils. We show, using simulations of src SH3 domain, that mechanical force enhances the population of the aggregation-prone (N(⁎)) states, which are rarely populated under force free native conditions but are encoded in the spectrum of native fluctuations. The folding phase diagrams of SH3 as a function of denaturant concentration ([C]), mechanical force (f), and temperature exhibit an apparent two-state behavior, without revealing the presence of the elusive N(⁎) states. Interestingly, the phase boundaries separating the folded and unfolded states at all [C] and f fall on a master curve, which can be quantitatively described using an analogy to superconductors in a magnetic field. The free energy profiles as a function of the molecular extension (R), which are accessible in pulling experiments, (R), reveal the presence of a native-like N(⁎) with a disordered solvent-exposed amino-terminal β-strand. The structure of the N(⁎) state is identical with that found in Fyn SH3 by NMR dispersion experiments. We show that the timescale for fibril formation can be estimated from the population of the N(⁎) state, determined by the free energy gap separating the native structure and the N(⁎) state, a finding that can be used to assess fibril forming tendencies of proteins. The structures of the N(⁎) state are used to show that oligomer formation and likely route to fibrils occur by a domain-swap mechanism in SH3 domain. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Lehmann, Andreas; Wixted, Josephine H F; Shapovalov, Maxim V; Roder, Heinrich; Dunbrack, Roland L; Robinson, Matthew K
2015-01-01
Phage-display technology facilitates rapid selection of antigen-specific single-chain variable fragment (scFv) antibodies from large recombinant libraries. ScFv antibodies, composed of a VH and VL domain, are readily engineered into multimeric formats for the development of diagnostics and targeted therapies. However, the recombinant nature of the selection strategy can result in VH and VL domains with sub-optimal biophysical properties, such as reduced thermodynamic stability and enhanced aggregation propensity, which lead to poor production and limited application. We found that the C10 anti-epidermal growth factor receptor (EGFR) scFv, and its affinity mutant, P2224, exhibit weak production from E. coli. Interestingly, these scFv contain a fusion of lambda3 and lambda1 V-region (LV3 and LV1) genes, most likely the result of a PCR aberration during library construction. To enhance the biophysical properties of these scFvs, we utilized a structure-based approach to replace and redesign the pre-existing framework of the VL domain to one that best pairs with the existing VH. We describe a method to exchange lambda sequences with a more stable kappa3 framework (KV3) within the VL domain that incorporates the original lambda DE-loop. The resulting scFvs, C10KV3_LV1DE and P2224KV3_LV1DE, are more thermodynamically stable and easier to produce from bacterial culture. Additionally, C10KV3_LV1DE and P2224KV3_LV1DE retain binding affinity to EGFR, suggesting that such a dramatic framework swap does not significantly affect scFv binding. We provide here a novel strategy for redesigning the light chain of problematic scFvs to enhance their stability and therapeutic applicability.
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Theoretical Modeling of Molecular Mechanisms, Time Scales and Strains in Prion Diseases
2008-01-01
transmembrane form of the prion protein is localized in the Golgi apparatus of neurons. J. Biol. Chem. 280: 15855-15864. 5 Baskakov, I.V., G. Legname, M.A...research on the prion problem, particularly on a promising new model for the in vitro mammalian prion fibril which involves a new suggestion for a C... new model for in vitro grown fibrils, new domain swapped oligomer models, and models of the influence of proline mutations on the kinetics of
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Simple Comb Generator Design for SWaP Constrained Applications
2016-01-26
symmetry in the time domain, all the even harmonics are zero. Following the oscillator is a series capacitor and shunt resistor that together form a...filter’s ideal frequency response is represented by H(j2πk) = 1 1 + 1j2πkRC , (2) where R and C are the resistor and capacitor values, respectively. In...Finally, the output capacitor was included to block the DC bias current from the output connector. III. RESULTS For the prototype measurements discussed
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-10-12
... terms including Cleared Swap, Cleared Swaps Customer, Cleared Swaps Customer Account and Cleared Swaps... segregated (futures) accounts, including CFTC Regulations 1.20, 1.25, 1.27 to 1.30, and 1.49. Derivatives... designed to protect investors. As such, the proposed changes are designed to promote the prompt and...
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17 CFR 1.9 - Regulation of mixed swaps.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 17 Commodity and Securities Exchanges 1 2014-04-01 2014-04-01 false Regulation of mixed swaps. 1.9... UNDER THE COMMODITY EXCHANGE ACT Definitions § 1.9 Regulation of mixed swaps. (a) In general. The term mixed swap has the meaning set forth in section 1a(47)(D) of the Commodity Exchange Act. (b) Regulation...
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17 CFR 1.9 - Regulation of mixed swaps.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 17 Commodity and Securities Exchanges 1 2013-04-01 2013-04-01 false Regulation of mixed swaps. 1.9... UNDER THE COMMODITY EXCHANGE ACT Definitions § 1.9 Regulation of mixed swaps. (a) In general. The term mixed swap has the meaning set forth in section 1a(47)(D) of the Commodity Exchange Act. (b) Regulation...
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75 FR 78892 - Reporting Certain Post-Enactment Swap Transactions
Federal Register 2010, 2011, 2012, 2013, 2014
2010-12-17
...)--to a registered swap data repository (``SDR'') or to the Commission. Each category of data is subject... expired by that date. \\5\\ The term ``swap data repository'' is defined in Section 1a(48) of the CEA to... date of the enactment of this subsection shall be reported to a registered swap data repository or the...
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-08-03
... SECURITIES AND EXCHANGE COMMISSION 17 CFR Part 240 [Release No. 34-64766; File No. S7-25-11] RIN 3235-AL10 Business Conduct Standards for Security-Based Swap Dealers and Major Security-Based Swap Participants Correction In proposed rule document number 2011-16758, appearing on pages 42396-42455 in the...
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-11-23
... COMMODITY FUTURES TRADING COMMISSION 17 CFR Part 23 RIN 3038-AC96 Implementation of Conflicts of... regulations establish conflicts of interest requirements for swap dealers (SDs) and major swap participants...-AC96 and SD-MSP Conflicts of Interest, by any of the following methods: Agency Web site, via its...
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-05-23
... context of the security-based swap dealer definition, for affiliated groups with a registered security... for Affiliated Groups with Registered Security-Based Swap Dealers); Rule 3a71-5 (Substituted... 13n-12 (Exemption from Requirements Governing Security-Based Swap Data Repositories for Certain Non-U...
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-09-04
... in automated system preparation and testing in preparation for swap data reporting beginning on the... Legal Entity Identifiers To Be Used in the Recordkeeping and Swap Data Reporting AGENCY: Commodity...) which will be used by registered entities and swap counterparties in complying with the CFTC's swap data...
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-12-14
..., 2011 at 9; Letter from Robert Pickel and Kenneth Bentsen, International Swaps and Derivatives..., dated Apr. 5, 2011 at 19; Letter from Robert Pickel and Kenneth Bentsen, International Swaps and... LLP, on behalf of certain dealers, dated Apr. 5, 2011 at 19; Letter from Robert Pickel and Kenneth...
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Patel, Raj B; Ho, Joseph; Ferreyrol, Franck; Ralph, Timothy C; Pryde, Geoff J
2016-03-01
Minimizing the resources required to build logic gates into useful processing circuits is key to realizing quantum computers. Although the salient features of a quantum computer have been shown in proof-of-principle experiments, difficulties in scaling quantum systems have made more complex operations intractable. This is exemplified in the classical Fredkin (controlled-SWAP) gate for which, despite theoretical proposals, no quantum analog has been realized. By adding control to the SWAP unitary, we use photonic qubit logic to demonstrate the first quantum Fredkin gate, which promises many applications in quantum information and measurement. We implement example algorithms and generate the highest-fidelity three-photon Greenberger-Horne-Zeilinger states to date. The technique we use allows one to add a control operation to a black-box unitary, something that is impossible in the standard circuit model. Our experiment represents the first use of this technique to control a two-qubit operation and paves the way for larger controlled circuits to be realized efficiently.
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Racette, Lyne; Chiou, Christine Y.; Hao, Jiucang; Bowd, Christopher; Goldbaum, Michael H.; Zangwill, Linda M.; Lee, Te-Won; Weinreb, Robert N.; Sample, Pamela A.
2009-01-01
Purpose To investigate whether combining optic disc topography and short-wavelength automated perimetry (SWAP) data improves the diagnostic accuracy of relevance vector machine (RVM) classifiers for detecting glaucomatous eyes compared to using each test alone. Methods One eye of 144 glaucoma patients and 68 healthy controls from the Diagnostic Innovations in Glaucoma Study were included. RVM were trained and tested with cross-validation on optimized (backward elimination) SWAP features (thresholds plus age; pattern deviation (PD); total deviation (TD)) and on Heidelberg Retina Tomograph II (HRT) optic disc topography features, independently and in combination. RVM performance was also compared to two HRT linear discriminant functions (LDF) and to SWAP mean deviation (MD) and pattern standard deviation (PSD). Classifier performance was measured by the area under the receiver operating characteristic curves (AUROCs) generated for each feature set and by the sensitivities at set specificities of 75%, 90% and 96%. Results RVM trained on combined HRT and SWAP thresholds plus age had significantly higher AUROC (0.93) than RVM trained on HRT (0.88) and SWAP (0.76) alone. AUROCs for the SWAP global indices (MD: 0.68; PSD: 0.72) offered no advantage over SWAP thresholds plus age, while the LDF AUROCs were significantly lower than RVM trained on the combined SWAP and HRT feature set and on HRT alone feature set. Conclusions Training RVM on combined optimized HRT and SWAP data improved diagnostic accuracy compared to training on SWAP and HRT parameters alone. Future research may identify other combinations of tests and classifiers that can also improve diagnostic accuracy. PMID:19528827
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The SWAP EUV Imaging Telescope Part I: Instrument Overview and Pre-Flight Testing
NASA Astrophysics Data System (ADS)
Seaton, D. B.; Berghmans, D.; Nicula, B.; Halain, J.-P.; De Groof, A.; Thibert, T.; Bloomfield, D. S.; Raftery, C. L.; Gallagher, P. T.; Auchère, F.; Defise, J.-M.; D'Huys, E.; Lecat, J.-H.; Mazy, E.; Rochus, P.; Rossi, L.; Schühle, U.; Slemzin, V.; Yalim, M. S.; Zender, J.
2013-08-01
The Sun Watcher with Active Pixels and Image Processing (SWAP) is an EUV solar telescope onboard ESA's Project for Onboard Autonomy 2 (PROBA2) mission launched on 2 November 2009. SWAP has a spectral bandpass centered on 17.4 nm and provides images of the low solar corona over a 54×54 arcmin field-of-view with 3.2 arcsec pixels and an imaging cadence of about two minutes. SWAP is designed to monitor all space-weather-relevant events and features in the low solar corona. Given the limited resources of the PROBA2 microsatellite, the SWAP telescope is designed with various innovative technologies, including an off-axis optical design and a CMOS-APS detector. This article provides reference documentation for users of the SWAP image data.
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Soler, Miguel A; de Marco, Ario; Fortuna, Sara
2016-10-10
Nanobodies (VHHs) have proved to be valuable substitutes of conventional antibodies for molecular recognition. Their small size represents a precious advantage for rational mutagenesis based on modelling. Here we address the problem of predicting how Camelidae nanobody sequences can tolerate mutations by developing a simulation protocol based on all-atom molecular dynamics and whole-molecule docking. The method was tested on two sets of nanobodies characterized experimentally for their biophysical features. One set contained point mutations introduced to humanize a wild type sequence, in the second the CDRs were swapped between single-domain frameworks with Camelidae and human hallmarks. The method resulted in accurate scoring approaches to predict experimental yields and enabled to identify the structural modifications induced by mutations. This work is a promising tool for the in silico development of single-domain antibodies and opens the opportunity to customize single functional domains of larger macromolecules.
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NASA Astrophysics Data System (ADS)
Soler, Miguel A.; De Marco, Ario; Fortuna, Sara
2016-10-01
Nanobodies (VHHs) have proved to be valuable substitutes of conventional antibodies for molecular recognition. Their small size represents a precious advantage for rational mutagenesis based on modelling. Here we address the problem of predicting how Camelidae nanobody sequences can tolerate mutations by developing a simulation protocol based on all-atom molecular dynamics and whole-molecule docking. The method was tested on two sets of nanobodies characterized experimentally for their biophysical features. One set contained point mutations introduced to humanize a wild type sequence, in the second the CDRs were swapped between single-domain frameworks with Camelidae and human hallmarks. The method resulted in accurate scoring approaches to predict experimental yields and enabled to identify the structural modifications induced by mutations. This work is a promising tool for the in silico development of single-domain antibodies and opens the opportunity to customize single functional domains of larger macromolecules.
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Green Team Hosts Plant Swap to Encourage Gardening | Poster
By Carolynne Keenan, Contributing Writer What started out as a way for Howard Young, Ph.D., to thin out his garden last fall turned into the NCI at Frederick Green Team’s Plant Swap. The group held its Fall Plant Swap on October 24, encouraging all members of the Fort Detrick community to pick up a free plant or swap a plant of theirs for another. “Those who love to garden introduce others to the joy of gardening,” said Dolores Winterstein, a member of the Green Team and the coordinator of the Fall Plant Swap.
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-06-17
...) pursuant to Section 4(c) of the Act, (a) to permit the clearing of coffee, sugar, and cocoa OTC swap..., ``a * * * commodity swap,'' which latter term includes swaps on agricultural products. While the...(c) of the Act, ICE Clear could not engage in the clearing of OTC swap contracts in cocoa, sugar and...
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Fifteen years of sector-wide approach (SWAp) in Bangladesh health sector: an assessment of progress
Ahsan, Karar Zunaid; Streatfield, Peter Kim; Ijdi, Rashida -E-; Escudero, Gabriela Maria; Khan, Abdul Waheed; Reza, M M
2016-01-01
The Ministry of Health and Family Welfare (MOHFW) of the Government of Bangladesh embarked on a sector-wide approach (SWAp) modality for the health, nutrition and population (HNP) sector in 1998. This programmatic shift initiated a different set of planning disciplines and practices along with institutional changes in the MOHFW. Over the years, the SWAp modality has evolved in Bangladesh as the MOHFW has learnt from its implementation and refined the program design. This article explores the progress made, both in terms of achievement of health outcomes and systems strengthening results, since the implementation of the SWAp for Bangladesh’s health sector. Secondary analyses of survey data from 1993 to 2011 as well as a literature review of published and grey literature on health SWAp in Bangladesh was conducted for this assessment. Results of the assessment indicate that the MOHFW made substantial progress in health outcomes and health systems strengthening. SWAps facilitated the alignment of funding and technical support around national priorities, and improved the government’s role in program design as well as in implementation and development partner coordination. Notable systemic improvements have taken place in the country systems with regards to monitoring and evaluation, procurement and service provision, which have improved functionality of health facilities to provide essential care. Implementation of the SWAp has, therefore, contributed to an accelerated improvement in key health outcomes in Bangladesh over the last 15 years. The health SWAp in Bangladesh offers an example of a successful adaptation of such an approach in a complex administrative structure. Based on the lessons learned from SWAp implementation in Bangladesh, the MOHFW needs to play a stronger stewardship and regulatory role to reap the full benefits of a SWAp in its subsequent programming. PMID:26582744
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-02-17
...The Commodity Futures Trading Commission (``Commission'' or ``CFTC'') is adopting final rules to implement Section 4s(h) of the Commodity Exchange Act (``CEA'') pursuant to Section 731 of Title VII of the Dodd-Frank Wall Street Reform and Consumer Protection Act of 2010 (the ``Dodd-Frank Act''). These rules prescribe external business conduct standards for swap dealers and major swap participants.
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Unfolding the HIV-1 reverse transcriptase RNase H domain – how to lose a molecular tug-of-war
Zheng, Xunhai; Pedersen, Lars C.; Gabel, Scott A.; ...
2016-01-14
Formation of the mature HIV-1 reverse transcriptase (RT) p66/p51 heterodimer requires subunit-specific processing of the p66/p66' homodimer precursor. Since the ribonuclease H (RH) domain contains an occult cleavage site located near its center, cleavage must occur either prior to folding or subsequent to unfolding. Recent NMR studies have identified a slow, subunit-specific RH domain unfolding process proposed to result from a residue tug-of-war between the polymerase and RH domains on the functionally inactive, p66' subunit. Here, we describe a structural comparison of the isolated RH domain with a domain swapped RH dimer that reveals several intrinsically destabilizing characteristics of themore » isolated domain that facilitate excursions of Tyr427 from its binding pocket and separation of helices B and D. These studies provide independent support for the subunit-selective RH domain unfolding pathway in which instability of the Tyr427 binding pocket facilitates its release followed by domain transfer, acting as a trigger for further RH domain destabilization and subsequent unfolding. As further support for this pathway, NMR studies demonstrate that addition of an RH active site-directed isoquinolone ligand retards the subunit-selective RH' domain unfolding behavior of the p66/p66' homodimer. As a result, this study demonstrates the feasibility of directly targeting RT maturation with therapeutics.« less
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Unfolding the HIV-1 reverse transcriptase RNase H domain – how to lose a molecular tug-of-war
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zheng, Xunhai; Pedersen, Lars C.; Gabel, Scott A.
Formation of the mature HIV-1 reverse transcriptase (RT) p66/p51 heterodimer requires subunit-specific processing of the p66/p66' homodimer precursor. Since the ribonuclease H (RH) domain contains an occult cleavage site located near its center, cleavage must occur either prior to folding or subsequent to unfolding. Recent NMR studies have identified a slow, subunit-specific RH domain unfolding process proposed to result from a residue tug-of-war between the polymerase and RH domains on the functionally inactive, p66' subunit. Here, we describe a structural comparison of the isolated RH domain with a domain swapped RH dimer that reveals several intrinsically destabilizing characteristics of themore » isolated domain that facilitate excursions of Tyr427 from its binding pocket and separation of helices B and D. These studies provide independent support for the subunit-selective RH domain unfolding pathway in which instability of the Tyr427 binding pocket facilitates its release followed by domain transfer, acting as a trigger for further RH domain destabilization and subsequent unfolding. As further support for this pathway, NMR studies demonstrate that addition of an RH active site-directed isoquinolone ligand retards the subunit-selective RH' domain unfolding behavior of the p66/p66' homodimer. As a result, this study demonstrates the feasibility of directly targeting RT maturation with therapeutics.« less
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Green Team Hosts Plant Swap to Encourage Gardening | Poster
By Carolynne Keenan, Contributing Writer What started out as a way for Howard Young, Ph.D., to thin out his garden last fall turned into the NCI at Frederick Green Team’s Plant Swap. The group held its Fall Plant Swap on October 24, encouraging all members of the Fort Detrick community to pick up a free plant or swap a plant of theirs for another. “Those who love to garden
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Three-dimensional unstructured grid refinement and optimization using edge-swapping
NASA Technical Reports Server (NTRS)
Gandhi, Amar; Barth, Timothy
1993-01-01
This paper presents a three-dimensional (3-D) 'edge-swapping method based on local transformations. This method extends Lawson's edge-swapping algorithm into 3-D. The 3-D edge-swapping algorithm is employed for the purpose of refining and optimizing unstructured meshes according to arbitrary mesh-quality measures. Several criteria including Delaunay triangulations are examined. Extensions from two to three dimensions of several known properties of Delaunay triangulations are also discussed.
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Design of low SWaP optical terminals for free space optical communications
NASA Astrophysics Data System (ADS)
Shubert, P.; Cline, A.; McNally, J.; Pierson, R.
2017-02-01
Along with advantages in higher data rates, spectrum contention, and security, free space optical communications can provide size, weight, and power (SWaP) advantages over radio frequency (RF) systems. SWaP is always an issue in space systems and can be critical in applying free space optical communications to small satellite platforms. The system design of small space-based free space optical terminals with Gbps data rates is addressed. System architectures and requirements are defined to ensure the terminals are capable of acquisition, establishment and maintenance of a free space optical communications link. Design trades, identification of blocking technologies, and performance analyses are used to evaluate the practical limitations to terminal SWaP. Small terminal design concepts are developed to establish their practicality and feasibility. Techniques, such as modulation formats and capacity approaching encoding, are considered to mitigate the disadvantages brought by SWaP limitations, and performance as a function of SWaP is evaluated.
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McLean, Michelle
2004-01-01
To canvas perceptions and experiences of students who had failed Year 2 of a traditional medical program and who chose to remain in the conventional program (n = 6) or had swapped to Curriculum 2001 (C2001), a problem-based learning (PBL) curriculum (n = 14). A year after their decision regarding curriculum choice, students were canvassed (largely open-ended survey) about this decision and about their perceptions of their curricular experiences. C2001 students were positive about their PBL experiences. Overwhelmingly, their decision to swap streams had been a good one. They identified PBL features as supporting their learning. Repeating traditional curriculum students were, however, more circumspect in their opinions. C2001 students had clearly embraced PBL. They were now medical students, largely because of PBL activities underpinned by a sound educational philosophy. This unique case study has provided additional evidence that PBL students are generally more content with their studies than their conventional curriculum counterparts.
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Code of Federal Regulations, 2013 CFR
2013-04-01
... control with a covered affiliate. (b) Clear and conspicuous. The term “clear and conspicuous” means... exchange dealer, commodity trading advisor, commodity pool operator, introducing broker, major swap..., commodity trading advisor, commodity pool operator, introducing broker, major swap participant or swap...
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Code of Federal Regulations, 2014 CFR
2014-04-01
... corporate control with a covered affiliate. (b) Clear and conspicuous. The term “clear and conspicuous... exchange dealer, commodity trading advisor, commodity pool operator, introducing broker, major swap..., commodity trading advisor, commodity pool operator, introducing broker, major swap participant or swap...
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Code of Federal Regulations, 2012 CFR
2012-04-01
... control with a covered affiliate. (b) Clear and conspicuous. The term “clear and conspicuous” means... exchange dealer, commodity trading advisor, commodity pool operator, introducing broker, major swap..., commodity trading advisor, commodity pool operator, introducing broker, major swap participant or swap...
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77 FR 41109 - Margin Requirements for Uncleared Swaps for Swap Dealers and Major Swap Participants
Federal Register 2010, 2011, 2012, 2013, 2014
2012-07-12
... and specifically requests quantitative data and analysis on the comparative costs and benefits of the... quantitative impact study (``QIS'') to assess the costs and benefits of margin requirements. The results of the...
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Accelerated sampling by infinite swapping of path integral molecular dynamics with surface hopping
NASA Astrophysics Data System (ADS)
Lu, Jianfeng; Zhou, Zhennan
2018-02-01
To accelerate the thermal equilibrium sampling of multi-level quantum systems, the infinite swapping limit of a recently proposed multi-level ring polymer representation is investigated. In the infinite swapping limit, the ring polymer evolves according to an averaged Hamiltonian with respect to all possible surface index configurations of the ring polymer and thus connects the surface hopping approach to the mean-field path-integral molecular dynamics. A multiscale integrator for the infinite swapping limit is also proposed to enable efficient sampling based on the limiting dynamics. Numerical results demonstrate the huge improvement of sampling efficiency of the infinite swapping compared with the direct simulation of path-integral molecular dynamics with surface hopping.
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More than 3,200 Books and DVDs Donated to Annual Book Swap | Poster
Robin Meckley, Contributing Writer The Scientific Library’s 14th Annual Book and Media Swap, held on April 16 in the lobby of Building 549, proved to be a popular event. When the swap was rescheduled from fall 2013 to spring 2014, the library staff was uncertain if the response would be equal to previous years, said Sue Wilson, principal manager of the Scientific Library. NCI at Frederick employees rose to the challenge, however, with 87 people donating more than 3,200 books and DVDs, according to Pam Noble, serials technician and book swap team leader. By the end of the first day of the swap, almost half of the materials had been claimed.
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Online Digital Archives Technology That Supports Rich, Student-Centered Learning Experiences
ERIC Educational Resources Information Center
Hofer, Mark
2004-01-01
Today's students watch the newest movie trailers on the Web, share music files, play video games with other players over the Internet, and swap digital pictures of the latest teen idols. Donald Tapscott points out in his book Growing Up Digital that as this rich multimedia experience becomes more a part of students' lives outside of school, they…
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17 CFR 45.2 - Swap recordkeeping.
Code of Federal Regulations, 2013 CFR
2013-04-01
... Section 45.2 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP DATA..., complete, and systematic records, together with all pertinent data and memoranda, of all activities..., complete, and systematic records, together with all pertinent data and memoranda, with respect to each swap...
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17 CFR 45.2 - Swap recordkeeping.
Code of Federal Regulations, 2012 CFR
2012-04-01
... Section 45.2 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP DATA..., complete, and systematic records, together with all pertinent data and memoranda, of all activities..., complete, and systematic records, together with all pertinent data and memoranda, with respect to each swap...
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-07-13
... Swaps g. Other Issues Related to Security-Based Swap Submissions h. Additional Comments 2. Prevention of... clearing and exchange trading due to individual business needs of certain users. Those users should retain...
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Functional Specialization and Evolution of Leader Proteinases in the Family Closteroviridae
Peng, Chih-Wen; Peremyslov, Valera V.; Mushegian, Arcady R.; Dawson, William O.; Dolja, Valerian V.
2001-01-01
Members of the Closteroviridae and Potyviridae families of the plant positive-strand RNA viruses encode one or two papain-like leader proteinases. In addition to a C-terminal proteolytic domain, each of these proteinases possesses a nonproteolytic N-terminal domain. We compared functions of the several leader proteinases using a gene swapping approach. The leader proteinase (L-Pro) of Beet yellows virus (BYV; a closterovirus) was replaced with L1 or L2 proteinases of Citrus tristeza virus (CTV; another closterovirus), P-Pro proteinase of Lettuce infectious yellows virus (LIYV; a crinivirus), and HC-Pro proteinase of Tobacco etch virus (a potyvirus). Each foreign proteinase efficiently processed the chimeric BYV polyprotein in vitro. However, only L1 and P-Pro, not L2 and HC-Pro, were able to rescue the amplification of the chimeric BYV variants. The combined expression of L1 and L2 resulted in an increased RNA accumulation compared to that of the parental BYV. Remarkably, this L1-L2 chimera exhibited reduced invasiveness and inability to move from cell to cell. Similar analyses of the BYV hybrids, in which only the papain-like domain of L-Pro was replaced with those derived from L1, L2, P-Pro, and HC-Pro, also revealed functional specialization of these domains. In subcellular-localization experiments, distinct patterns were observed for the leader proteinases of BYV, CTV, and LIYV. Taken together, these results demonstrated that, in addition to a common proteolytic activity, the leader proteinases of closteroviruses possess specialized functions in virus RNA amplification, virus invasion, and cell-to-cell movement. The phylogenetic analysis suggested that functionally distinct L1 and L2 of CTV originated by a gene duplication event. PMID:11711606
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Functional specialization and evolution of leader proteinases in the family Closteroviridae.
Peng, C W; Peremyslov, V V; Mushegian, A R; Dawson, W O; Dolja, V V
2001-12-01
Members of the Closteroviridae and Potyviridae families of the plant positive-strand RNA viruses encode one or two papain-like leader proteinases. In addition to a C-terminal proteolytic domain, each of these proteinases possesses a nonproteolytic N-terminal domain. We compared functions of the several leader proteinases using a gene swapping approach. The leader proteinase (L-Pro) of Beet yellows virus (BYV; a closterovirus) was replaced with L1 or L2 proteinases of Citrus tristeza virus (CTV; another closterovirus), P-Pro proteinase of Lettuce infectious yellows virus (LIYV; a crinivirus), and HC-Pro proteinase of Tobacco etch virus (a potyvirus). Each foreign proteinase efficiently processed the chimeric BYV polyprotein in vitro. However, only L1 and P-Pro, not L2 and HC-Pro, were able to rescue the amplification of the chimeric BYV variants. The combined expression of L1 and L2 resulted in an increased RNA accumulation compared to that of the parental BYV. Remarkably, this L1-L2 chimera exhibited reduced invasiveness and inability to move from cell to cell. Similar analyses of the BYV hybrids, in which only the papain-like domain of L-Pro was replaced with those derived from L1, L2, P-Pro, and HC-Pro, also revealed functional specialization of these domains. In subcellular-localization experiments, distinct patterns were observed for the leader proteinases of BYV, CTV, and LIYV. Taken together, these results demonstrated that, in addition to a common proteolytic activity, the leader proteinases of closteroviruses possess specialized functions in virus RNA amplification, virus invasion, and cell-to-cell movement. The phylogenetic analysis suggested that functionally distinct L1 and L2 of CTV originated by a gene duplication event.
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Fifteen years of sector-wide approach (SWAp) in Bangladesh health sector: an assessment of progress.
Ahsan, Karar Zunaid; Streatfield, Peter Kim; Ijdi, Rashida-E-; Escudero, Gabriela Maria; Khan, Abdul Waheed; Reza, M M
2016-06-01
The Ministry of Health and Family Welfare (MOHFW) of the Government of Bangladesh embarked on a sector-wide approach (SWAp) modality for the health, nutrition and population (HNP) sector in 1998. This programmatic shift initiated a different set of planning disciplines and practices along with institutional changes in the MOHFW. Over the years, the SWAp modality has evolved in Bangladesh as the MOHFW has learnt from its implementation and refined the program design. This article explores the progress made, both in terms of achievement of health outcomes and systems strengthening results, since the implementation of the SWAp for Bangladesh's health sector. Secondary analyses of survey data from 1993 to 2011 as well as a literature review of published and grey literature on health SWAp in Bangladesh was conducted for this assessment. Results of the assessment indicate that the MOHFW made substantial progress in health outcomes and health systems strengthening. SWAps facilitated the alignment of funding and technical support around national priorities, and improved the government's role in program design as well as in implementation and development partner coordination. Notable systemic improvements have taken place in the country systems with regards to monitoring and evaluation, procurement and service provision, which have improved functionality of health facilities to provide essential care. Implementation of the SWAp has, therefore, contributed to an accelerated improvement in key health outcomes in Bangladesh over the last 15 years. The health SWAp in Bangladesh offers an example of a successful adaptation of such an approach in a complex administrative structure. Based on the lessons learned from SWAp implementation in Bangladesh, the MOHFW needs to play a stronger stewardship and regulatory role to reap the full benefits of a SWAp in its subsequent programming. © The Author 2015. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.
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17 CFR 45.2 - Swap recordkeeping.
Code of Federal Regulations, 2014 CFR
2014-04-01
... Section 45.2 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION (CONTINUED) SWAP DATA..., complete, and systematic records, together with all pertinent data and memoranda, of all activities..., complete, and systematic records, together with all pertinent data and memoranda, with respect to each swap...
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75 FR 70310 - Sunshine Act Meeting
Federal Register 2010, 2011, 2012, 2013, 2014
2010-11-17
... Consumer Protection Act governing the security-based swap data repository registration process, the duties of such repositories, and the core principles applicable to such repositories. 4. The Commission will... security-based swap data repositories or the Commission and the public dissemination of security-based swap...
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Chansa, Collins; Sundewall, Jesper; McIntyre, Di; Tomson, Göran; Forsberg, Birger C
2008-07-01
Zambia introduced a sector-wide approach (SWAp) in the health sector in 1993. The goal was to improve efficiency in the use of domestic funds and externally sourced development assistance by integrating these into a joint sectoral framework. Over a decade into its existence, however, the SWAp remains largely unevaluated. This study explores whether the envisaged improvements have been achieved by studying developments in administrative, technical and allocative efficiency in the Zambian health sector from 1990-2006. A case study was conducted using interviews and analysis of secondary data. Respondents represented a cross-section of stakeholders in the Zambian health sector. Secondary data from 1990-2006 were collected for six indicators related to administrative, technical and allocative efficiency. The results showed small improvements in administrative efficiency. Transaction costs still appeared to be high despite the introduction of the SWAp. Indicators for technical efficiency showed a drop in hospital bed utilization rates and government share of funding for drugs. As for allocative efficiency, budget execution did not improve with the SWAp, although there were large variations between both donors and year. Funding levels had apparently improved at district level but declined for hospitals. Finally, the SWAp had not succeeded in bringing all external assistance together under a common framework. Despite strong commitment to implement the SWAp in Zambia, the envisaged efficiency improvements do not seem to have been attained. Possible explanations could be that the SWAp has not been fully developed or that not all parties have completely embraced it. SWAp is not ruled out as a coordination model, but the current setup in Zambia has not proved to be fully effective.
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-11-06
...The Commodity Futures Trading Commission (the ``Commission'') is issuing final rules implementing new statutory provisions enacted by Title VII of the Dodd-Frank Wall Street Reform and Consumer Protection Act (the ``Dodd-Frank Act''). Specifically, the final rule contained herein imposes requirements on swap dealers (``SDs'') and major swap participants (``MSPs'') with respect to the treatment of collateral posted by their counterparties to margin, guarantee, or secure uncleared swaps. Additionally, the final rule includes revisions to ensure that, for purposes of subchapter IV of chapter 7 of the Bankruptcy Code, securities held in a portfolio margining account that is a futures account or a Cleared Swaps Customer Account constitute ``customer property''; and owners of such account constitute ``customers.''
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Patel, Raj B.; Ho, Joseph; Ferreyrol, Franck; Ralph, Timothy C.; Pryde, Geoff J.
2016-01-01
Minimizing the resources required to build logic gates into useful processing circuits is key to realizing quantum computers. Although the salient features of a quantum computer have been shown in proof-of-principle experiments, difficulties in scaling quantum systems have made more complex operations intractable. This is exemplified in the classical Fredkin (controlled-SWAP) gate for which, despite theoretical proposals, no quantum analog has been realized. By adding control to the SWAP unitary, we use photonic qubit logic to demonstrate the first quantum Fredkin gate, which promises many applications in quantum information and measurement. We implement example algorithms and generate the highest-fidelity three-photon Greenberger-Horne-Zeilinger states to date. The technique we use allows one to add a control operation to a black-box unitary, something that is impossible in the standard circuit model. Our experiment represents the first use of this technique to control a two-qubit operation and paves the way for larger controlled circuits to be realized efficiently. PMID:27051868
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2004-01-01
The nucleotide pyrophosphatases/phosphodiesterases NPP1 and NPP2/autotaxin are structurally related eukaryotic ecto-enzymes, but display a very different substrate specificity. NPP1 releases nucleoside 5′-monophosphates from various nucleotides, whereas NPP2 mainly functions as a lysophospholipase D. We have used a domain-swapping approach to map substrate-specifying determinants of NPP1 and NPP2. The catalytic domain of NPP1 fused to the N- and C-terminal domains of NPP2 was hyperactive as a nucleotide phosphodiesterase, but did not show any lysophospholipase D activity. In contrast, chimaeras of the catalytic domain of NPP2 and the N- and/or C-terminal domains of NPP1 were completely inactive. These data indicate that the catalytic domain as well as both extremities of NPP2 contain lysophospholipid-specifying sequences. Within the catalytic domain of NPP1 and NPP2, we have mapped residues close to the catalytic site that determine the activities towards nucleotides and lysophospholipids. We also show that the conserved Gly/Phe-Xaa-Gly-Xaa-Xaa-Gly (G/FXGXXG) motif near the catalytic site is required for metal binding, but is not involved in substrate-specification. Our data suggest that the distinct activities of NPP1 and NPP2 stem from multiple differences throughout the polypeptide chain. PMID:15096095
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17 CFR 49.10 - Acceptance of data.
Code of Federal Regulations, 2012 CFR
2012-04-01
... protocols established by a swap data repository shall provide for the receipt of swap creation data, swap continuation data, real-time public reporting data, and all other data and information required to be reported... repository shall adopt policies and procedures, including technological protocols, which provide for...
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17 CFR 49.10 - Acceptance of data.
Code of Federal Regulations, 2013 CFR
2013-04-01
... protocols established by a swap data repository shall provide for the receipt of swap creation data, swap continuation data, real-time public reporting data, and all other data and information required to be reported... repository shall adopt policies and procedures, including technological protocols, which provide for...
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17 CFR 49.3 - Procedures for registration.
Code of Federal Regulations, 2012 CFR
2012-04-01
... that such swap data repository is appropriately organized, and has the capacity: to ensure the prompt.... 49.3 Section 49.3 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP DATA... desiring to be registered as a swap data repository shall file electronically an application for...
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17 CFR 49.3 - Procedures for registration.
Code of Federal Regulations, 2014 CFR
2014-04-01
... if the Commission finds that such swap data repository is appropriately organized, and has the...) SWAP DATA REPOSITORIES § 49.3 Procedures for registration. (a) Application procedures. (1) An applicant, person or entity desiring to be registered as a swap data repository shall file electronically an...
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17 CFR 49.3 - Procedures for registration.
Code of Federal Regulations, 2013 CFR
2013-04-01
... that such swap data repository is appropriately organized, and has the capacity: to ensure the prompt.... 49.3 Section 49.3 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP DATA... desiring to be registered as a swap data repository shall file electronically an application for...
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-16
... Agreement''; Mixed Swaps; Security- Based Swap Agreement Recordkeeping: Book-out Agreement Confirmation... Protection Act (``Dodd-Frank Act''), requiring that oral book- out agreements must be followed in a..., ``Product Definitions''); regarding ``mixed swaps;'' and governing books and records with respect to...
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A stochastic hybrid model for pricing forward-start variance swaps
NASA Astrophysics Data System (ADS)
Roslan, Teh Raihana Nazirah
2017-11-01
Recently, market players have been exposed to the astounding increase in the trading volume of variance swaps. In this paper, the forward-start nature of a variance swap is being inspected, where hybridizations of equity and interest rate models are used to evaluate the price of discretely-sampled forward-start variance swaps. The Heston stochastic volatility model is being extended to incorporate the dynamics of the Cox-Ingersoll-Ross (CIR) stochastic interest rate model. This is essential since previous studies on variance swaps were mainly focusing on instantaneous-start variance swaps without considering the interest rate effects. This hybrid model produces an efficient semi-closed form pricing formula through the development of forward characteristic functions. The performance of this formula is investigated via simulations to demonstrate how the formula performs for different sampling times and against the real market scenario. Comparison done with the Monte Carlo simulation which was set as our main reference point reveals that our pricing formula gains almost the same precision in a shorter execution time.
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-03-15
... Commission is of the view that the term swap category is a more descriptive term to convey the concept of a... inappropriate comparative measure for the swaps market.\\46\\ Some of these commenters, for example, argued that...
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17 CFR 45.6 - Legal entity identifiers
Code of Federal Regulations, 2013 CFR
2013-04-01
... applied to swap data repositories by part 49 of this chapter. (4) Open Source. The schema for the legal... Section 45.6 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP DATA... to the jurisdiction of the Commission shall be identified in all recordkeeping and all swap data...
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17 CFR 45.6 - Legal entity identifiers
Code of Federal Regulations, 2012 CFR
2012-04-01
... applied to swap data repositories by part 49 of this chapter. (4) Open Source. The schema for the legal... Section 45.6 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP DATA... to the jurisdiction of the Commission shall be identified in all recordkeeping and all swap data...
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17 CFR 49.22 - Chief compliance officer.
Code of Federal Regulations, 2013 CFR
2013-04-01
....22 Section 49.22 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP DATA... 49, the term “board of directors” means the board of directors of a registered swap data repository, or for those swap data repositories whose organizational structure does not include a board of...
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17 CFR 49.22 - Chief compliance officer.
Code of Federal Regulations, 2012 CFR
2012-04-01
....22 Section 49.22 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP DATA... 49, the term “board of directors” means the board of directors of a registered swap data repository, or for those swap data repositories whose organizational structure does not include a board of...
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78 FR 21045 - Adaptation of Regulations to Incorporate Swaps-Records of Transactions; Correction
Federal Register 2010, 2011, 2012, 2013, 2014
2013-04-09
... COMMODITY FUTURES TRADING COMMISSION 17 CFR Part 1 RIN 3038-AD53 Adaptation of Regulations to Incorporate Swaps--Records of Transactions; Correction AGENCY: Commodity Futures Trading Commission. ACTION...), regarding Adaptation of Regulations to Incorporate Swaps--Records of Transactions. DATES: This correction to...
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Sasaki, Takayuki; Tsuchiya, Yoshiyuki; Ariyoshi, Michiyo; Ryan, Peter R; Furuichi, Takuya; Yamamoto, Yoko
2014-12-01
Wheat and Arabidopsis plants respond to aluminum (Al) ions by releasing malate from their root apices via Al-activated malate transporter. Malate anions bind with the toxic Al ions and contribute to the Al tolerance of these species. The genes encoding the transporters in wheat and Arabidopsis, TaALMT1 and AtALMT1, respectively, were expressed in Xenopus laevis oocytes and characterized electrophysiologically using the two-electrode voltage clamp system. The Al-activated currents generated by malate efflux were detected for TaALMT1 but not for AtALMT1. Chimeric proteins were generated by swapping the N- and C-terminal halves of TaALMT1 and AtALMT1 (Ta::At and At::Ta). When these chimeras were characterized in oocytes, Al-activated malate efflux was detected for the Ta::At chimera but not for At::Ta, suggesting that the N-terminal half of TaALMT1 is necessary for function in oocytes. An additional chimera, Ta(48)::At, generated by swapping 17 residues from the N-terminus of AtALMT1 with the equivalent 48 residues from TaALMT1, was sufficient to support transport activity. This 48 residue region includes a helical region with a putative transmembrane domain which is absent in AtALMT1. The deletion of this domain from Ta(48)::At led to the complete loss of transport activity. Furthermore, truncations and a deletion at the C-terminal end of TaALMT1 indicated that a putative helical structure in this region was also required for transport function. This study provides insights into the structure-function relationships of Al-activated ALMT proteins by identifying specific domains on the N- and C-termini of TaALMT1 that are critical for basal transport function and Al responsiveness in oocytes. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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2014-01-01
The tyrosine kinase A (TrkA) receptor is a validated therapeutic intervention point for a wide range of conditions. TrkA activation by nerve growth factor (NGF) binding the second extracellular immunoglobulin (TrkAIg2) domain triggers intracellular signaling cascades. In the periphery, this promotes the pain phenotype and, in the brain, cell survival or differentiation. Reproducible structural information and detailed validation of protein–ligand interactions aid drug discovery. However, the isolated TrkAIg2 domain crystallizes as a β-strand-swapped dimer in the absence of NGF, occluding the binding surface. Here we report the design and structural validation by nuclear magnetic resonance spectroscopy of the first stable, biologically active construct of the TrkAIg2 domain for binding site confirmation. Our structure closely mimics the wild-type fold of TrkAIg2 in complex with NGF (1WWW.pdb), and the 1H–15N correlation spectra confirm that both NGF and a competing small molecule interact at the known binding interface in solution. PMID:25454499
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SPIDER: Next Generation Chip Scale Imaging Sensor Update
NASA Astrophysics Data System (ADS)
Duncan, A.; Kendrick, R.; Ogden, C.; Wuchenich, D.; Thurman, S.; Su, T.; Lai, W.; Chun, J.; Li, S.; Liu, G.; Yoo, S. J. B.
2016-09-01
The Lockheed Martin Advanced Technology Center (LM ATC) and the University of California at Davis (UC Davis) are developing an electro-optical (EO) imaging sensor called SPIDER (Segmented Planar Imaging Detector for Electro-optical Reconnaissance) that seeks to provide a 10x to 100x size, weight, and power (SWaP) reduction alternative to the traditional bulky optical telescope and focal-plane detector array. The substantial reductions in SWaP would reduce cost and/or provide higher resolution by enabling a larger-aperture imager in a constrained volume. Our SPIDER imager replaces the traditional optical telescope and digital focal plane detector array with a densely packed interferometer array based on emerging photonic integrated circuit (PIC) technologies that samples the object being imaged in the Fourier domain (i.e., spatial frequency domain), and then reconstructs an image. Our approach replaces the large optics and structures required by a conventional telescope with PICs that are accommodated by standard lithographic fabrication techniques (e.g., complementary metal-oxide-semiconductor (CMOS) fabrication). The standard EO payload integration and test process that involves precision alignment and test of optical components to form a diffraction limited telescope is, therefore, replaced by in-process integration and test as part of the PIC fabrication, which substantially reduces associated schedule and cost. This paper provides an overview of performance data on the second-generation PIC for SPIDER developed under the Defense Advanced Research Projects Agency (DARPA)'s SPIDER Zoom research funding. We also update the design description of the SPIDER Zoom imaging sensor and the second-generation PIC (high- and low resolution versions).
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17 CFR 49.22 - Chief compliance officer.
Code of Federal Regulations, 2014 CFR
2014-04-01
... that the registered swap data repository provide fair and open access as set forth in § 49.27 of this...) SWAP DATA REPOSITORIES § 49.22 Chief compliance officer. (a) Definition of Board of Directors. For... data repository, or for those swap data repositories whose organizational structure does not include a...
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-01-22
... 3235-AL12 Capital, Margin, and Segregation Requirements for Security-Based Swap Dealers and Major... public comment to establish capital, margin, and segregation requirements for security-based swap dealers... soliciting comment on proposed rules and rule amendments establishing capital, margin, and segregation...
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75 FR 76930 - Real-Time Public Reporting of Swap Transaction Data
Federal Register 2010, 2011, 2012, 2013, 2014
2010-12-10
... COMMODITY FUTURES TRADING COMMISSION 17 CFR Part 43 RIN 3038-AD08 Real-Time Public Reporting of Swap Transaction Data Correction In proposed rule document 2010-29994 beginning on page 76140 in the...--Additional Real-Time Public Reporting Data Fields for Options, Swaptions and Swaps with Embedded Options...
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Scientific Library Will Hold 16th Annual Book and Media Swap | Poster
The Scientific Library has begun collecting materials for the 16th Annual Book and Media Swap and will continue to do so through Tuesday, October 25. Opening day for the Swap is Wednesday, October 26, and the event will continue through Wednesday, November 30.
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NASA Astrophysics Data System (ADS)
Elkind, Edith; Faliszewski, Piotr; Slinko, Arkadii
In voting theory, bribery is a form of manipulative behavior in which an external actor (the briber) offers to pay the voters to change their votes in order to get her preferred candidate elected. We investigate a model of bribery where the price of each vote depends on the amount of change that the voter is asked to implement. Specifically, in our model the briber can change a voter’s preference list by paying for a sequence of swaps of consecutive candidates. Each swap may have a different price; the price of a bribery is the sum of the prices of all swaps that it involves. We prove complexity results for this model, which we call swap bribery, for a broad class of voting rules, including variants of approval and k-approval, Borda, Copeland, and maximin.
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Sweeney, Rohan; Mortimer, Duncan; Johnston, David W
2014-03-01
Sector Wide Approaches (SWAp) emerged during the 1990s as a new policy mechanism for aid delivery. Eschewing many features of traditional project-based aid, SWAps give greater control of aid allocation to recipient countries. Some critics have questioned whether reducing a donor's level of influence over aid allocation might lead to a decrease in donor contributions. While some qualitative evaluations have described the level of fund pooling and donor participation in SWAps, no previous study has empirically examined this potential 'donor-flight' response to health SWAp implementation. This paper utilises a uniquely compiled dataset of 46 low-income countries over 1990-2009 and a variety of panel data regression models to estimate the impact of health SWAp implementation on levels of health aid. Results suggest that amongst 16 especially poor low-income countries, SWAp implementation is associated with significant decreases in health aid levels compared with non-implementers. This suggests donors are not indifferent to how their contributions are allocated by recipients, and that low-income countries considering a SWAp may need to weigh the benefits of greater control of aid allocations against the possibility of reduced aid income. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Tanaka, Shiho; Miyamoto, Kazuhisa; Noda, Hiroaki; Endo, Haruka; Kikuta, Shingo; Sato, Ryoichi
2016-04-01
In a previous report, seven Cry1Ab-resistant strains were identified in the silkworm, Bombyx mori; these strains were shown to have a tyrosine insertion at position 234 in extracellular loop 2 of the ABC transporter C2 (BmABCC2). This insertion was confirmed to destroy the receptor function of BmABCC2 and confer the strains resistance against Cry1Ab and Cry1Ac. However, these strains were susceptible to Cry1Aa. In this report, we examined the mechanisms of the loss of receptor function of the transporter by expressing mutations in Sf9 cells. After replacement of one or two of the five amino acid residues in loop 2 of the susceptible BmABCC2 gene [BmABCC2_S] with alanine, cells still showed susceptibility, retaining the receptor function. Five mutants with single amino acid insertions at position 234 in BmABCC2 were also generated, resulting in loop 2 having six amino acids, which corresponds to replacing the tyrosine insertion in the resistant BmABCC2 gene [BmABCC2_R(+(234)Y)] with another amino acid. All five mutants exhibited loss of function against Cry1Ab and Cry1Ac. These results suggest that the amino acid sequence in loop 2 is less important than the loop size (five vs. six amino acids) or loop structure for Cry1Ab and Cry1Ac activity. Several domain-swapped mutant toxins were then generated among Cry1Aa, Cry1Ab, and Cry1Ac, which are composed of three domains. Swapped mutants containing domain II of Cry1Ab or Cry1Ac did not kill Sf9 cells expressing BmABCC2_R(+(234)Y), suggesting that domain II of the Cry toxin is related to the interaction with the receptor function of BmABCC2. This also suggests that different reactions against Bt-toxins in some B. mori strains, that is, Cry1Ab resistance or Cry1Aa susceptibility, are attributable to structural differences in domain II of Cry1A toxins. Copyright © 2016. Published by Elsevier Inc.
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Structure and activation of pro-activin A
Wang, Xuelu; Fischer, Gerhard; Hyvönen, Marko
2016-01-01
Activins are growth factors with multiple roles in the development and homeostasis. Like all TGF-β family of growth factors, activins are synthesized as large precursors from which mature dimeric growth factors are released proteolytically. Here we have studied the activation of activin A and determined crystal structures of the unprocessed precursor and of the cleaved pro-mature complex. Replacing the natural furin cleavage site with a HRV 3C protease site, we show how the protein gains its bioactivity after proteolysis and is as active as the isolated mature domain. The complex remains associated in conditions used for biochemical analysis with a dissociation constant of 5 nM, but the pro-domain can be actively displaced from the complex by follistatin. Our high-resolution structures of pro-activin A share features seen in the pro-TGF-β1 and pro-BMP-9 structures, but reveal a new oligomeric arrangement, with a domain-swapped, cross-armed conformation for the protomers in the dimeric protein. PMID:27373274
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17 CFR 23.205 - Real-time public reporting.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 17 Commodity and Securities Exchanges 1 2013-04-01 2013-04-01 false Real-time public reporting. 23... Swap Dealers and Major Swap Participants § 23.205 Real-time public reporting. (a) Real-time public... information and swap transaction and pricing data required to be reported in accordance with the real-time...
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17 CFR 23.205 - Real-time public reporting.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 17 Commodity and Securities Exchanges 1 2014-04-01 2014-04-01 false Real-time public reporting. 23... Swap Dealers and Major Swap Participants § 23.205 Real-time public reporting. (a) Real-time public... information and swap transaction and pricing data required to be reported in accordance with the real-time...
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-06-09
...-defaulting cleared swaps customers for risk management reasons. If the DCO makes such a choice, it would... risk management standpoint. Id. 4. Benefits a. Fellow-Customer Risk and Investment Risk In general... 22 and 190 Protection of Cleared Swaps Customer Contracts and Collateral; Conforming Amendments to...
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76 FR 27621 - Margin Requirements for Uncleared Swaps for Swap Dealers and Major Swap Participants
Federal Register 2010, 2011, 2012, 2013, 2014
2011-05-12
...). Elsewhere today in the Federal Register, the Commission is proposing to adopt capital, financial reporting... requirements, and supplemental financial reporting requirements for these FCMs. The Commission now is extending... proposing to adopt capital, financial reporting, and recordkeeping requirements for SDs and MSPs, as well as...
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Code of Federal Regulations, 2014 CFR
2014-04-01
... Section 22.17 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION CLEARED SWAPS § 22... of Cleared Swaps Customer Collateral with the funds of a futures commission merchant, shall not be construed to prevent a futures commission merchant from having a residual financial interest in the funds...
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76 FR 23732 - Margin Requirements for Uncleared Swaps for Swap Dealers and Major Swap Participants
Federal Register 2010, 2011, 2012, 2013, 2014
2011-04-28
... these statutory bounds the Commission has endeavored to limit costs appropriately. For example, as... Commission anticipates that the prudential regulators will publicly post their proposed rules on their Web... containing a threshold below which the CSE was not required to post initial margin, i.e., zero thresholds...
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17 CFR 230.239 - Exemption for offers and sales of certain security-based swaps.
Code of Federal Regulations, 2013 CFR
2013-04-01
... specified Internet address or includes in its agreement covering the security-based swap that the eligible... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false Exemption for offers and sales of certain security-based swaps. 230.239 Section 230.239 Commodity and Securities Exchanges...
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17 CFR 230.239 - Exemption for offers and sales of certain security-based swaps.
Code of Federal Regulations, 2014 CFR
2014-04-01
... specified Internet address or includes in its agreement covering the security-based swap that the eligible... 17 Commodity and Securities Exchanges 3 2014-04-01 2014-04-01 false Exemption for offers and sales of certain security-based swaps. 230.239 Section 230.239 Commodity and Securities Exchanges...
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78 FR 33475 - Core Principles and Other Requirements for Swap Execution Facilities
Federal Register 2010, 2011, 2012, 2013, 2014
2013-06-04
... Core Principles and Other Requirements for Swap Execution Facilities; Final Rule #0;#0;Federal Register... FUTURES TRADING COMMISSION 17 CFR Part 37 RIN 3038-AD18 Core Principles and Other Requirements for Swap... Core Principles 1. Subpart B--Core Principle 1 (Compliance With Core Principles) 2. Subpart C--Core...
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-07-26
... Section 2(i) A. Comments B. Statutory Analysis C. Principles of International Comity IV. Guidance A... Reporting ii. Swap Data Recordkeeping Relating to Complaints and Marketing and Sales Materials iii. Physical... Reporting 2. Swap Data Recordkeeping Relating to Complaints and Marketing and Sales Materials 3. Physical...
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77 FR 26709 - Swap Data Repositories: Interpretative Statement Regarding the Confidentiality and...
Federal Register 2010, 2011, 2012, 2013, 2014
2012-05-07
... COMMODITY FUTURES TRADING COMMISSION 17 CFR Part 49 RIN 3038-AD83 Swap Data Repositories... data repositories (``SDRs'').SDRs are new registered entities created by section 728 of the Dodd-Frank... Act amends section 1a of the CEA to add a definition of the term ``swap data repository.'' Pursuant to...
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-04-15
... governing security-based swap data repositories and security-based swap reporting. See, e.g., Pub. L. No... Depository Trust & Clearing Corporation (``DTCC''), in conjunction with DTCC Data Repository (U.S.) LLC.\\40... 75208 (Dec. 2, 2010); Security-Based Swap Data Repository Registration, Duties, and Core Principles...
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77 FR 48060 - Real-Time Public Reporting of Swap Transaction Data; Correction
Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-13
... COMMODITY FUTURES TRADING COMMISSION 17 CFR Part 43 RIN 3038-AD08 Real-Time Public Reporting of...'') published the Real-Time Public Reporting of Swap Transaction Data (``Real-Time Public Reporting'') rule and.... Background The Commission published the final rule entitled Real-Time Public Reporting of Swap Transaction...
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17 CFR 50.4 - Classes of swaps required to be cleared.
Code of Federal Regulations, 2014 CFR
2014-04-01
... Fixed-to-floating swap class Currency U.S. dollar (USD) Euro (EUR) Sterling (GBP) Yen (JPY). Floating.... Conditional Notional Amounts No No No No. Specification Basis swap class Currency U.S. dollar (USD) Euro (EUR... agreement class Currency U.S. dollar (USD) Euro (EUR) Sterling (GBP) Yen (JPY). Floating Rate Indexes LIBOR...
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Crystal structure of YHI9, the yeast member of the phenazine biosynthesis PhzF enzyme superfamily.
Liger, Dominique; Quevillon-Cheruel, Sophie; Sorel, Isabelle; Bremang, Michael; Blondeau, Karine; Aboulfath, Ilham; Janin, Joël; van Tilbeurgh, Herman; Leulliot, Nicolas
2005-09-01
In the Pseudomonas bacterial genomes, the PhzF proteins are involved in the production of phenazine derivative antibiotic and antifungal compounds. The PhzF superfamily however also encompasses proteins in all genomes from bacteria to eukaryotes, for which no function has been assigned. We have determined the three dimensional crystal structure at 2.05 A resolution of YHI9, the yeast member of the PhzF family. YHI9 has a fold similar to bacterial diaminopimelate epimerase, revealing a bimodular structure with an internal symmetry. Residue conservation identifies a putative active site at the interface between the two domains. Evolution of this protein by gene duplication, gene fusion and domain swapping from an ancestral gene containing the "hot dog" fold, identifies the protein as a "kinked double hot dog" fold. Copyright 2005 Wiley-Liss, Inc.
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Fast ion swapping for quantum-information processing
NASA Astrophysics Data System (ADS)
Kaufmann, H.; Ruster, T.; Schmiegelow, C. T.; Luda, M. A.; Kaushal, V.; Schulz, J.; von Lindenfels, D.; Schmidt-Kaler, F.; Poschinger, U. G.
2017-05-01
We demonstrate a swap gate between laser-cooled ions in a segmented microtrap via fast physical swapping of the ion positions. This operation is used in conjunction with qubit initialization, manipulation, and readout and with other types of shuttling operations such as linear transport and crystal separation and merging. Combining these operations, we perform quantum process tomography of the swap gate, obtaining a mean process fidelity of 99.5(5)%. The swap operation is demonstrated with motional excitations below 0.05(1) quantum for all six collective modes of a two-ion crystal for a process duration of 42 μ s . Extending these techniques to three ions, we reverse the order of a three-ion crystal and reconstruct the truth table for this operation, resulting in a mean process fidelity of 99.96(13)% in the logical basis.
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A Cellular Automaton model for pedestrian counterflow with swapping
NASA Astrophysics Data System (ADS)
Tao, Y. Z.; Dong, L. Y.
2017-06-01
In this paper, we propose a new floor field Cellular Automaton (CA) model with considering the swapping behaviors of pedestrians. The neighboring pedestrians in opposite directions take swapping in a probability decided by the linear density of pedestrian flow. The swapping which happens simultaneously with the normal movement is introduced to eliminate the gridlock in low density region. Numerical results show that the fundamental diagram is in good agreement with the measured data. Then the model is applied to investigate the counterflow and four typical states such as free flow, lane, intermediate and congestion states are found. More attention is paid on the intermediate state which lane-formation and local congestions switch in an irregular manner. The swapping plays a vital role in reducing the gridlock. Furthermore, the influence of the corridor size and individual's eyesight on counterflow are discussed in detail.
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NASA Astrophysics Data System (ADS)
Nagarkar, Radhika P.
2009-12-01
The objective of this dissertation is to apply rational peptide design to fabricate nanomaterials via self-assembly. This has been demonstrated in structurally diverse systems with an aim of deciphering the underlying principles governing how sequence affects the peptide's ability to adopt a specific secondary structure and ultimate material properties that are realized from the association of these secondary structural elements. Several amyloidogenic proteins have been shown to self-assemble into fibrils using a mechanism known as domain swapping. Here, discreet units of secondary structure are exchanged among discreet proteins during self-assembly to form extended networks with precise three dimensional organization. The possibility of using these mechanisms to design peptides capable of controlled assembly and fibril formation leading to materials with targeted properties is explored. By altering the placement of a beta-turn sequence that varies the size and location of the exchanged strand, twisting, non-twisting and laminated fibrillar nanostructures are obtained. Hydrogels prepared from these strand swapping beta-hairpins have varied rheological properties due to differences in their fibrillar nanostructures. In a second distinct design, alpha/beta-proteins are used to prepare environmentally sensitive hydrogels. Here, multiple distinct motifs for structural integrity and dynamic response within a single self-assembling peptide allow the amyloid-like fibrils formed to controllably alter their nano-topography in response to an external stimulus such as temperature. The development of these self-assembling alpha/beta-protein motifs also necessitated the design of pH sensitive antiparallel coiled coils. Exploring the basic principles responsible for pH dependent conformational changes in coiled coils can lead to new insights in the control of protein structure and function. Lastly, this dissertation discusses the interface between biomolecules and inorganic materials. Here, a new methodology of functionalizing titania nanoparticles with peptides is developed. In all of these different material forming systems, extensive biophysical characterization by circular dichroism spectroscopy, fourier transform infrared spectroscopy, X-ray diffraction and analytical ultracentrifugation is performed to understand peptide folding and self-assembly. Careful nanostructural characterization by electron and force microscopies is performed to elucidate self-assembly mechanisms and has proved to be vital in applying the iterative design process to develop responsive nanomaterials.
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-07-16
... Change Regarding a Change to Interest Rate Swap Margin Calculation Parameters July 10, 2013. Pursuant to... Interest Rate Swap Margin Parameters Please be advised that beginning 7/15/2013, CME Clearing will utilize a revised set of parameters for the margining of CME cleared Interest Rate Swap Products. The...
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-07-18
... received. Table of Contents I. Introduction A. Statutory Framework B. Consultations C. Approach to Drafting.... Generally B. Consistency With CFTC Approach IV. Paperwork Reduction Act A. Summary of Collections of... that may rely on security-based swaps to manage risk and reduce volatility. C. Approach to Drafting the...
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-12-21
.... The Commission will post all comments on the Commission's Internet Web site ( http://www.sec.gov/rules..., which are the subject of separate rulemakings. For example, whether the definition of a major... Regarding Dealing Activities Commenters provided numerous examples of conduct they viewed as dealing...
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17 CFR 43.3 - Method and timing for real-time public reporting.
Code of Federal Regulations, 2012 CFR
2012-04-01
... § 43.5. (3) Prohibitions on disclosure of data. (i) If there is a registered swap data repository for... disclosure is made no earlier than the transmittal of such data to a registered swap data repository for... such data by a registered swap data repository unless: (A) Such disclosure is made no earlier than the...
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76 FR 22833 - Swap Data Recordkeeping and Reporting Requirements: Pre-Enactment and Transition Swaps
Federal Register 2010, 2011, 2012, 2013, 2014
2011-04-25
... the IFRs. Comments generally fell into one or more of several broad categories and in a number of instances were common to both IFRs. Some commenters observed that issuance of IFRs in advance of regulations... required to keep records as provided in the Commission's IFRs concerning pre-enactment and transition swaps...
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-02-08
... VII of the Dodd-Frank Wall Street Reform and Consumer Protection Act (Dodd-Frank Act). Section 731 of... registered entities and intermediaries subject to the Commission's oversight. \\1\\ See Dodd-Frank Wall Street... section 701 of the Dodd-Frank Act, Title VII may be cited as the ``Wall Street Transparency and...
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-11-30
... SECURITIES AND EXCHANGE COMMISSION 17 CFR Part 240 [Release No. 34-68071; File No. S7-08-12] RIN 3235-AL12 Capital, Margin, and Segregation Requirements for Security-Based Swap Dealers and Major Security-Based Swap Participants and Capital Requirements for Broker-Dealers Correction In proposed rule...
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Code of Federal Regulations, 2013 CFR
2013-04-01
.... (c) Delegation of authority to the Chief Information Officer: The Commission hereby delegates to its Chief Information Officer, until the Commission orders otherwise, the authority set forth in paragraph (c) of this section, to be exercised by the Chief Information Officer or by such other employee or...
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Code of Federal Regulations, 2012 CFR
2012-04-01
... to the Commission. (c) Delegation of authority to the Chief Information Officer: The Commission hereby delegates to its Chief Information Officer, until the Commission orders otherwise, the authority set forth in paragraph (c) of this section, to be exercised by the Chief Information Officer or by...
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Code of Federal Regulations, 2014 CFR
2014-04-01
.... (c) Delegation of authority to the Chief Information Officer: The Commission hereby delegates to its Chief Information Officer, until the Commission orders otherwise, the authority set forth in paragraph (c) of this section, to be exercised by the Chief Information Officer or by such other employee or...
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Code of Federal Regulations, 2013 CFR
2013-04-01
... to the Commission. (c) Delegation of authority to the Chief Information Officer: The Commission hereby delegates to its Chief Information Officer, until the Commission orders otherwise, the authority set forth in paragraph (c) of this section, to be exercised by the Chief Information Officer or by...
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76 FR 10947 - Registration and Regulation of Security-Based Swap Execution Facilities
Federal Register 2010, 2011, 2012, 2013, 2014
2011-02-28
... electronic media to execute transactions in SB swaps varies greatly across trading venues, with some venues... telephone. The reasons for use of, or lack of use of, electronic media vary from such factors as user... communications to contact directly a potential counterparty to negotiate a SB swap. Once the terms are agreed...
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Hu, Rongrong; Wang, Chenkun; Gu, Yangshun; Racette, Lyne
2016-01-01
Abstract Detection of progression is paramount to the clinical management of glaucoma. Our goal is to compare the performance of standard automated perimetry (SAP), short-wavelength automated perimetry (SWAP), and frequency-doubling technology (FDT) perimetry in monitoring glaucoma progression. Longitudinal data of paired SAP, SWAP, and FDT from 113 eyes with primary open-angle glaucoma enrolled in the Diagnostic Innovations in Glaucoma Study or the African Descent and Glaucoma Evaluation Study were included. Data from all tests were expressed in comparable units by converting the sensitivity from decibels to unitless contrast sensitivity and by expressing sensitivity values in percent of mean normal based on an independent dataset of 207 healthy eyes with aging deterioration taken into consideration. Pointwise linear regression analysis was performed and 3 criteria (conservative, moderate, and liberal) were used to define progression and improvement. Global mean sensitivity (MS) was fitted with linear mixed models. No statistically significant difference in the proportion of progressing and improving eyes was observed across tests using the conservative criterion. Fewer eyes showed improvement on SAP compared to SWAP and FDT using the moderate criterion; and FDT detected less progressing eyes than SAP and SWAP using the liberal criterion. The agreement between these test types was poor. The linear mixed model showed a progressing trend of global MS overtime for SAP and SWAP, but not for FDT. The baseline estimate of SWAP MS was significantly lower than SAP MS by 21.59% of mean normal. FDT showed comparable estimation of baseline MS with SAP. SWAP and FDT do not appear to have significant benefits over SAP in monitoring glaucoma progression. SAP, SWAP, and FDT may, however, detect progression in different glaucoma eyes. PMID:26886602
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Mentoring console improves collaboration and teaching in surgical robotics.
Hanly, Eric J; Miller, Brian E; Kumar, Rajesh; Hasser, Christopher J; Coste-Maniere, Eve; Talamini, Mark A; Aurora, Alexander A; Schenkman, Noah S; Marohn, Michael R
2006-10-01
One of the most significant limitations of surgical robots has been their inability to allow multiple surgeons and surgeons-in-training to engage in collaborative control of robotic surgical instruments. We report the initial experience with a novel two-headed da Vinci surgical robot that has two collaborative modes: the "swap" mode allows two surgeons to simultaneously operate and actively swap control of the robot's four arms, and the "nudge" mode allows them to share control of two of the robot's arms. The utility of the mentoring console operating in its two collaborative modes was evaluated through a combination of dry laboratory exercises and animal laboratory surgery. The results from surgeon-resident collaborative performance of complex three-handed surgical tasks were compared to results from single-surgeon and single-resident performance. Statistical significance was determined using Student's t-test. Collaborative surgeon-resident swap control reduced the time to completion of complex three-handed surgical tasks by 25% compared to single-surgeon operation of a four-armed da Vinci (P < 0.01) and by 34% compared to single-resident operation (P < 0.001). While swap mode was found to be most helpful during parts of surgical procedures that require multiple hands (such as isolation and division of vessels), nudge mode was particularly useful for guiding a resident's hands during crucially precise steps of an operation (such as proper placement of stitches). The da Vinci mentoring console greatly facilitates surgeon collaboration during robotic surgery and improves the performance of complex surgical tasks. The mentoring console has the potential to improve resident participation in surgical robotics cases, enhance resident education in surgical training programs engaged in surgical robotics, and improve patient safety during robotic surgery.
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Pan, Ankita; Saw, Wuan Geok; Subramanian Manimekalai, Malathy Sony; Grüber, Ardina; Joon, Shin; Matsui, Tsutomu; Weiss, Thomas M; Grüber, Gerhard
2017-05-01
Dengue virus (DENV), which has four serotypes (DENV-1 to DENV-4), is the causative agent of the viral infection dengue. DENV nonstructural protein 3 (NS3) comprises a serine protease domain and an RNA helicase domain which has nucleotide triphosphatase activities that are essential for RNA replication and viral assembly. Here, solution X-ray scattering was used to provide insight into the overall structure and flexibility of the entire NS3 and its recombinant helicase and protease domains for Dengue virus serotypes 2 and 4 in solution. The DENV-2 and DENV-4 NS3 forms are elongated and flexible in solution. The importance of the linker residues in flexibility and domain-domain arrangement was shown by the compactness of the individual protease and helicase domains. Swapping of the 174 PPAVP 179 linker stretch of the related Hepatitis C virus (HCV) NS3 into DENV-2 NS3 did not alter the elongated shape of the engineered mutant. Conformational alterations owing to RNA binding are described in the protease domain, which undergoes substantial conformational alterations that are required for the optimal catalysis of bound RNA. Finally, the effects of ATPase inhibitors on the enzymatically active DENV-2 and DENV-4 NS3 and the individual helicases are presented, and insight into the allosteric effect of the inhibitor quercetin is provided.
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Recognition of Acyl Carrier Proteins by Ketoreductases in Assembly Line Polyketide Synthases
Ostrowski, Matthew P.; Cane, David E.; Khosla, Chaitan
2016-01-01
Ketoreductases (KRs) are the most widespread tailoring domains found in individual modules of assembly line polyketide synthases (PKSs), and are responsible for controlling the configurations of both the α-methyl and β-hydroxyl stereogenic centers in the growing polyketide chain. Because they recognize substrates that are covalently bound to acyl carrier proteins (ACPs) within the same PKS module, we sought to quantify the extent to which protein-protein recognition contributes to the turnover of these oxidoreductive enzymes using stand-alone domains from the 6-deoxyerythronolide B synthase (DEBS). Reduced 2-methyl-3-hydroxyacyl-ACP substrates derived from two enantiomeric acyl chains and four distinct ACP domains were synthesized and presented to four distinct KR domains. Two KRs, from DEBS modules 2 and 5, displayed little preference for oxidation of substrates tethered to their cognate ACP domains over those attached to the other ACP domains tested. In contrast, the KR from DEBS module 1 showed a ca. 10-50-fold preference for substrate attached to its native ACP domain, whereas the KR from DEBS module 6 actually displayed a ca. 10-fold preference for the ACP from DEBS module 5. Our findings suggest that recognition of the ACP by a KR domain is unlikely to affect the rate of native assembly line polyketide biosynthesis. In some cases, however, unfavorable KR-ACP interactions may suppress the rate of substrate processing when KR domains are swapped to construct hybrid PKS modules. PMID:27118242
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31 CFR 560.603 - Reports on oil transactions engaged in by foreign affiliates.
Code of Federal Regulations, 2010 CFR
2010-07-01
... transaction means any purchase, sale, or swap of Iranian-origin crude oil or natural gas. For purposes of this paragraph (b), a purchase, sale, or swap is deemed to have occurred as of the date of the bill of lading... each reportable transaction): (i) The nature of the transaction, e.g., purchase, sale, swap; (ii) A...
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-07-05
... chapter. * * * * * 0 3. On page 30747, in the third column, correct paragraph (hhh)(6)(iii)(B)(2) to read as follows: Sec. 1.3 Definitions. * * * * * (hhh) * * * (6) * * * (iii) * * * (B) * * * (2) The sum of the amount calculated under paragraph (hhh)(6)(iii)(B)(1) of this section and the product of the...
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Code of Federal Regulations, 2014 CFR
2014-04-01
... 17 Commodity and Securities Exchanges 1 2014-04-01 2014-04-01 false Publication of market data on... MARKETS AND SWAP EXECUTION FACILITIES § 16.01 Publication of market data on futures, swaps and options.... (1) Each reporting market, as defined in part 15 of this chapter, must separately record for each...
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Code of Federal Regulations, 2013 CFR
2013-04-01
... 17 Commodity and Securities Exchanges 1 2013-04-01 2013-04-01 false Publication of market data on... MARKETS AND SWAP EXECUTION FACILITIES § 16.01 Publication of market data on futures, swaps and options.... (1) Each reporting market, as defined in part 15 of this chapter, must separately record for each...
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Dynamic Quantum Allocation and Swap-Time Variability in Time-Sharing Operating Systems.
ERIC Educational Resources Information Center
Bhat, U. Narayan; Nance, Richard E.
The effects of dynamic quantum allocation and swap-time variability on central processing unit (CPU) behavior are investigated using a model that allows both quantum length and swap-time to be state-dependent random variables. Effective CPU utilization is defined to be the proportion of a CPU busy period that is devoted to program processing, i.e.…
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Book Swap Now Open to All Employees | Poster
Not only did the year 2000 mark the start of a new millennium, the beginning of the Human Genome Project, and the opening of the International Space Station, but it was also the first year that the Scientific Library held its annual Book & Media Swap. Starting Nov. 12, the 15th annual Book Swap is open to all NCI at Frederick employees.
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Code of Federal Regulations, 2014 CFR
2014-04-01
... format acceptable to the Commission. (c) Delegation of authority to the Chief Information Officer: The Commission hereby delegates to its Chief Information Officer, until the Commission orders otherwise, the authority set forth in paragraph (c) of this section, to be exercised by the Chief Information Officer or by...
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-06-21
... Act, Permitting the Kansas City Board of Trade Clearing Corporation To Clear Over-the-Counter Wheat...-the-counter (OTC) swap agreements (swaps) in wheat. Authority for granting this request is found in... grant KCBTCC approval to clear OTC wheat calendar swaps, and it would permit KCBT to list those products...
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-05-23
... present their views more generally on implementation of the Dodd-Frank Act through their Web sites... . The views expressed in the comments in response to the ANPR, in response to the Commissions' informal solicitations, and at such meetings are collectively referred to as the views of ``commenters.'' Based on this...
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-04-08
... Commission registrants (i.e., FCMs, retail foreign exchange dealers (RFEDs), IBs, CTAs, CPOs, and LTMs), and... FCMs, IBs, CPOs and CTAs and their APs that engage in swaps activity that is subject to Commission...\\ Therefore, the requirements of the RFA do not apply to SDs and MSPs. With respect to CTAs and IBs, the...
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Interest rate swaps: financial tool of the '90s.
Woodard, M A
1993-11-01
The implementation of prospective payment for capital costs makes it more necessary than ever for healthcare financial managers to be able to creatively balance capital costs with risk. A new financial management tool--the interest rate swap (a contractual agreement in which one party with a fixed interest rate payment liability and another party with a variable interest payment liability agree to trade those obligations)--is proving to be a solution for a growing number of hospital managers. This article describes the uses of interest rate swaps and discusses the variables to be considered when evaluating whether the benefits of an interest rate swap offset the additional risk.
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Are reproductive health NGOs in Uganda able to engage in the health SWAp?
Mugisha, Frank; Birungi, Harriet; Askew, Ian
2005-01-01
This paper explores the ability for reproductive health (RH) non-governmental organizations (NGO) in Uganda to survive in the context of SWAp and decentralization. The authors argue that, contrary to the perceptions that this context may increase NGO's financial vulnerability, a SWAp and a decentralized system may provide an opportunity that should be embraced by NGOs to enhance their sustainability and effectiveness by reducing their current dependency on donor funding. The paper discusses the systemic weaknesses of many NGOs that currently make them vulnerable, and observes that unless these weaknesses are addressed, such NGOs will lose their space in the SWAp and decentralization arena. The authors suggest that NGOs need to recognize the opportunities that participating in public-private partnerships through a SWAp can offer them for long-term and significant funding. They need also to develop their capacity to pro-actively participate in a SWAp and decentralized context by becoming more entrepreneurial in nature, through re-orienting their organizational philosophies and strategic planning and budgeting so as to be able to partner effectively with the public sector in accessing funds made available through health sector reform.
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Simultaneous entanglement swapping of multiple orbital angular momentum states of light.
Zhang, Yingwen; Agnew, Megan; Roger, Thomas; Roux, Filippus S; Konrad, Thomas; Faccio, Daniele; Leach, Jonathan; Forbes, Andrew
2017-09-21
High-bit-rate long-distance quantum communication is a proposed technology for future communication networks and relies on high-dimensional quantum entanglement as a core resource. While it is known that spatial modes of light provide an avenue for high-dimensional entanglement, the ability to transport such quantum states robustly over long distances remains challenging. To overcome this, entanglement swapping may be used to generate remote quantum correlations between particles that have not interacted; this is the core ingredient of a quantum repeater, akin to repeaters in optical fibre networks. Here we demonstrate entanglement swapping of multiple orbital angular momentum states of light. Our approach does not distinguish between different anti-symmetric states, and thus entanglement swapping occurs for several thousand pairs of spatial light modes simultaneously. This work represents the first step towards a quantum network for high-dimensional entangled states and provides a test bed for fundamental tests of quantum science.Entanglement swapping in high dimensions requires large numbers of entangled photons and consequently suffers from low photon flux. Here the authors demonstrate entanglement swapping of multiple spatial modes of light simultaneously, without the need for increasing the photon numbers with dimension.
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Doll, J.; Dupuis, P.; Nyquist, P.
2017-02-08
Parallel tempering, or replica exchange, is a popular method for simulating complex systems. The idea is to run parallel simulations at different temperatures, and at a given swap rate exchange configurations between the parallel simulations. From the perspective of large deviations it is optimal to let the swap rate tend to infinity and it is possible to construct a corresponding simulation scheme, known as infinite swapping. In this paper we propose a novel use of large deviations for empirical measures for a more detailed analysis of the infinite swapping limit in the setting of continuous time jump Markov processes. Usingmore » the large deviations rate function and associated stochastic control problems we consider a diagnostic based on temperature assignments, which can be easily computed during a simulation. We show that the convergence of this diagnostic to its a priori known limit is a necessary condition for the convergence of infinite swapping. The rate function is also used to investigate the impact of asymmetries in the underlying potential landscape, and where in the state space poor sampling is most likely to occur.« less
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NASA Astrophysics Data System (ADS)
Otranto, Sebastian
2014-10-01
During the last few years, several experimental and theoretical studies have focused on state selective charge exchange processes between charged ions and alkali metals. These data are of particular importance for the tokamak nuclear fusion reactor program, since diagnostics on the plasma usually rely on charge-exchange spectroscopy. In this sense, alkali metals, have been proposed as potential alternatives to excited hydrogen/deuterium for which laboratory experiments are not feasible at present. In this talk, we present our recent work involving ion collisions with alkali metals. Oscillatory structures in the angular differential charge-exchange cross sections obtained using the MOTRIMS technique are correctly described by classical trajectory Monte Carlo simulations. These oscillations are found to originate from the number of swaps the electron undergoes around the projectile-target potential saddle before capture takes place and are very prominent at impact energies below 10 keV/amu. Moreover, cross sections of higher order of differentiability also indicate that the swaps leave distinctive signatures in the (n,l)-state selective cross sections and in the photon line emission cross sections. Oscillatory structures for the x-ray hardness ratio parameter are also predicted. In collaboration with Ronnie Hoekstra, Zernike Institute for Advanced Materials, University of Groningen and Ronald Olson, Department of Physics, Missouri University of Science and Technology.
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Domain architecture conservation in orthologs
2011-01-01
Background As orthologous proteins are expected to retain function more often than other homologs, they are often used for functional annotation transfer between species. However, ortholog identification methods do not take into account changes in domain architecture, which are likely to modify a protein's function. By domain architecture we refer to the sequential arrangement of domains along a protein sequence. To assess the level of domain architecture conservation among orthologs, we carried out a large-scale study of such events between human and 40 other species spanning the entire evolutionary range. We designed a score to measure domain architecture similarity and used it to analyze differences in domain architecture conservation between orthologs and paralogs relative to the conservation of primary sequence. We also statistically characterized the extents of different types of domain swapping events across pairs of orthologs and paralogs. Results The analysis shows that orthologs exhibit greater domain architecture conservation than paralogous homologs, even when differences in average sequence divergence are compensated for, for homologs that have diverged beyond a certain threshold. We interpret this as an indication of a stronger selective pressure on orthologs than paralogs to retain the domain architecture required for the proteins to perform a specific function. In general, orthologs as well as the closest paralogous homologs have very similar domain architectures, even at large evolutionary separation. The most common domain architecture changes observed in both ortholog and paralog pairs involved insertion/deletion of new domains, while domain shuffling and segment duplication/deletion were very infrequent. Conclusions On the whole, our results support the hypothesis that function conservation between orthologs demands higher domain architecture conservation than other types of homologs, relative to primary sequence conservation. This supports the notion that orthologs are functionally more similar than other types of homologs at the same evolutionary distance. PMID:21819573
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Sub-Project 7 of Wisconsin 553, Part F, EPDA--Industry/Exchange Program: Final Report.
ERIC Educational Resources Information Center
Wisconsin Univ. - Stout, Menomonie. Center for Vocational, Technical and Adult Education.
The final report describes a study to develop a statewide teacher/industry exchange program in Wisconsin that would provide vocational-technical instructors with occupational experience opportunities. Three plans for implementing the program were developed: (A) swapping the positions of a business or industrial person with that of a vocational…
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CIR fuel reservoir swap closeout
2014-08-11
ISS040-E-090493 (11 Aug. 2014) --- NASA astronaut Reid Wiseman, Expedition 40 flight engineer, performs routine in-flight maintenance on the Multi-user Drop Combustion Apparatus (MDCA) inside the Combustion Integrated Rack (CIR) in the Destiny laboratory of the International Space Station. The MDCA contains hardware and software to conduct unique droplet combustion experiments in space.
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CIR fuel reservoir swap closeout
2014-08-11
ISS040-E-090497 (11 Aug. 2014) --- NASA astronaut Reid Wiseman, Expedition 40 flight engineer, performs routine in-flight maintenance on the Multi-user Drop Combustion Apparatus (MDCA) inside the Combustion Integrated Rack (CIR) in the Destiny laboratory of the International Space Station. The MDCA contains hardware and software to conduct unique droplet combustion experiments in space.
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CIR fuel reservoir swap closeout
2014-08-11
ISS040-E-090482 (11 Aug. 2014) --- NASA astronaut Reid Wiseman, Expedition 40 flight engineer, performs routine in-flight maintenance on the Multi-user Drop Combustion Apparatus (MDCA) inside the Combustion Integrated Rack (CIR) in the Destiny laboratory of the International Space Station. The MDCA contains hardware and software to conduct unique droplet combustion experiments in space.
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CIR fuel reservoir swap closeout
2014-08-11
ISS040-E-090484 (11 Aug. 2014) --- NASA astronaut Reid Wiseman, Expedition 40 flight engineer, performs routine in-flight maintenance on the Multi-user Drop Combustion Apparatus (MDCA) inside the Combustion Integrated Rack (CIR) in the Destiny laboratory of the International Space Station. The MDCA contains hardware and software to conduct unique droplet combustion experiments in space.
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The impact of solubility and electrostatics on fibril formation by the H3 and H4 histones
Topping, Traci B; Gloss, Lisa M
2011-01-01
The goal of this study was to examine fibril formation by the heterodimeric eukaryotic histones (H2A-H2B and H3-H4) and homodimeric archaeal histones (hMfB and hPyA1). The histone fold dimerization motif is an obligatorily domain-swapped structure comprised of two fused helix:β-loop:helix motifs. Domain swapping has been proposed as a mechanism for the evolution of protein oligomers as well as a means to form precursors in the formation of amyloid-like fibrils. Despite sharing a common fold, the eukaryotic histones of the core nucleosome and archaeal histones fold by kinetic mechanisms of differing complexity with transient population of partially folded monomeric and/or dimeric species. No relationship was apparent between fibrillation propensity and equilibrium stability or population of kinetic intermediates. Only H3 and H4, as isolated monomers and as a heterodimer, readily formed fibrils at room temperature, and this propensity correlates with the significantly lower solubility of these polypeptides. The fibrils were characterized by ThT fluorescence, FTIR, and far-UV CD spectroscopies and electron microscopy. The helical histone fold comprises the protease-resistant core of the fibrils, with little or no protease protection of the poorly structured N-terminal tails. The highly charged tails inhibit fibrillation through electrostatic repulsion. Kinetic studies indicate that H3 and H4 form a co-fibril, with simultaneous incorporation of both histones. The potential impact of H3 and H4 fibrillation on the cytotoxicity of extracellular histones and α-synuclein-mediated neurotoxicity and fibrillation is considered. PMID:21953551
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Evolution of the nuclear receptor gene superfamily.
Laudet, V; Hänni, C; Coll, J; Catzeflis, F; Stéhelin, D
1992-01-01
Nuclear receptor genes represent a large family of genes encoding receptors for various hydrophobic ligands such as steroids, vitamin D, retinoic acid and thyroid hormones. This family also contains genes encoding putative receptors for unknown ligands. Nuclear receptor gene products are composed of several domains important for transcriptional activation, DNA binding (C domain), hormone binding and dimerization (E domain). It is not known whether these genes have evolved through gene duplication from a common ancestor or if their different domains came from different independent sources. To test these possibilities we have constructed and compared the phylogenetic trees derived from two different domains of 30 nuclear receptor genes. The tree built from the DNA binding C domain clearly shows a common progeny of all nuclear receptors, which can be grouped into three subfamilies: (i) thyroid hormone and retinoic acid receptors, (ii) orphan receptors and (iii) steroid hormone receptors. The tree constructed from the central part of the E domain which is implicated in transcriptional regulation and dimerization shows the same distribution in three subfamilies but two groups of receptors are in a different position from that in the C domain tree: (i) the Drosophila knirps family genes have acquired very different E domains during evolution, and (ii) the vitamin D and ecdysone receptors, as well as the FTZ-F1 and the NGF1B genes, seem to have DNA binding and hormone binding domains belonging to different classes. These data suggest a complex evolutionary history for nuclear receptor genes in which gene duplication events and swapping between domains of different origins took place. PMID:1312460
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75 FR 80747 - End-User Exception to Mandatory Clearing of Swaps
Federal Register 2010, 2011, 2012, 2013, 2014
2010-12-23
...The Commodity Futures Trading Commission (``CFTC'' or ``Commission'') is proposing new requirements governing the elective exception to mandatory clearing of swaps available for swap counterparties meeting certain conditions under Section 2(h)(7) of the Commodity Exchange Act, as amended by the Dodd-Frank Wall Street Reform and Consumer Protection Act. The Commission is requesting comments on the proposed rule and related matters.
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Multivariate Complexity Analysis of Swap Bribery
NASA Astrophysics Data System (ADS)
Dorn, Britta; Schlotter, Ildikó
We consider the computational complexity of a problem modeling bribery in the context of voting systems. In the scenario of Swap Bribery, each voter assigns a certain price for swapping the positions of two consecutive candidates in his preference ranking. The question is whether it is possible, without exceeding a given budget, to bribe the voters in a way that the preferred candidate wins in the election.
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17 CFR 43.4 - Swap transaction and pricing data to be publicly disseminated in real-time.
Code of Federal Regulations, 2014 CFR
2014-04-01
... the nearest one million; (6) If the notional or principal amount is less than 500 million but equal to... greater than zero up to and including two years; (B) USD 100 million for swaps with a tenor greater than two years up to and including ten years; and (C) USD 75 million for swaps with a tenor greater than...
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Monomer/Dimer Transition of the Caspase-Recruitment Domain of Human Nod1
DOE Office of Scientific and Technical Information (OSTI.GOV)
Srimathi,T.; Robbins, S.; Dubas, R.
2008-01-01
Nod1 is an essential cytoplasmic sensor for bacterial peptidoglycans in the innate immune system. The caspase-recruitment domain of Nod1 (Nod1{_}CARD) is indispensable for recruiting a downstream kinase, receptor-interacting protein 2 (RIP2), that activates nuclear factor-?B (NF-?B). The crystal structure of human Nod1{_}CARD at 1.9 Angstroms resolution reveals a novel homodimeric conformation. Our structural and biochemical analysis shows that the homodimerization of Nod1{_}CARD is achieved by swapping the H6 helices at the carboxy termini and stabilized by forming an interchain disulfide bond between the Cys39 residues of the two monomers in solution and in the crystal. In addition, we present experimentalmore » evidence for a pH-sensitive conformational change of Nod1{_}CARD. Our results suggest that the pH-sensitive monomer/dimer transition is a unique molecular property of Nod1{_}CARD.« less
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Structured Post-IQ Domain Governs Selectivity of Myosin X for Fascin-Actin Bundles*
Nagy, Stanislav; Rock, Ronald S.
2010-01-01
Without guidance cues, cytoskeletal motors would traffic components to the wrong destination with disastrous consequences for the cell. Recently, we identified a motor protein, myosin X, that identifies bundled actin filaments for transport. These bundles direct myosin X to a unique destination, the tips of cellular filopodia. Because the structural and kinetic features that drive bundle selection are unknown, we employed a domain-swapping approach with the nonselective myosin V to identify the selectivity module of myosin X. We found a surprising role of the myosin X tail region (post-IQ) in supporting long runs on bundles. Moreover, the myosin X head is adapted for initiating processive runs on bundles. We found that the tail is structured and biases the orientation of the two myosin X heads because a targeted insertion that introduces flexibility in the tail abolishes selectivity. Together, these results suggest how myosin motors may manage to read cellular addresses. PMID:20538587
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A Facile Two-Step Method to Implement N√ {iSWAP} and N√ {SWAP} Gates in a Circuit QED
NASA Astrophysics Data System (ADS)
Said, T.; Chouikh, A.; Bennai, M.
2018-05-01
We propose a way for implementing a two-step N√ {iSWAP} and N √ {SWAP} gates based on the qubit-qubit interaction with N superconducting qubits, by coupling them to a resonator driven by a strong microwave field. The operation times do not increase with the growth of the qubit number. Due to the virtual excitations of the resonator, the scheme is insensitive to the decay of the resonator. Numerical analysis shows that the scheme can be implemented with high fidelity. Moreover, we propose a detailed procedure and analyze the experimental feasibility. So, our proposal can be experimentally realized in the range of current circuit QED techniques.
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Crystal Structure of the Eukaryotic Origin Recognition Complex
Bleichert, Franziska; Botchan, Michael R.; Berger, James M.
2015-01-01
Initiation of cellular DNA replication is tightly controlled to sustain genomic integrity. In eukaryotes, the heterohexameric origin recognition complex (ORC) is essential for coordinating replication onset. The 3.5 Å resolution crystal structure of Drosophila ORC reveals that the 270 kDa initiator core complex comprises a two-layered notched ring in which a collar of winged-helix domains from the Orc1-5 subunits sits atop a layer of AAA+ ATPase folds. Although canonical inter-AAA+ domain interactions exist between four of the six ORC subunits, unanticipated features are also evident, including highly interdigitated domain-swapping interactions between the winged-helix folds and AAA+ modules of neighboring protomers, and a quasi-spiral arrangement of DNA binding elements that circumnavigate a ~20 Å wide channel in the center of the complex. Comparative analyses indicate that ORC encircles DNA, using its winged-helix domain face to engage the MCM2-7 complex during replicative helicase loading; however, an observed >90° out-of-plane rotation for the Orc1 AAA+ domain disrupts interactions with catalytic amino acids in Orc4, narrowing and sealing off entry into the central channel. Prima facie, our data indicate that Drosophila ORC can switch between active and autoinhibited conformations, suggesting a novel means for cell cycle and/or developmental control of ORC functions. PMID:25762138
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More than 3,200 Books and DVDs Donated to Annual Book Swap | Poster
Robin Meckley, Contributing Writer The Scientific Library’s 14th Annual Book and Media Swap, held on April 16 in the lobby of Building 549, proved to be a popular event. When the swap was rescheduled from fall 2013 to spring 2014, the library staff was uncertain if the response would be equal to previous years, said Sue Wilson, principal manager of the Scientific Library. NCI
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Cao, Yongqiang; Grossberg, Stephen; Markowitz, Jeffrey
2011-12-01
All primates depend for their survival on being able to rapidly learn about and recognize objects. Objects may be visually detected at multiple positions, sizes, and viewpoints. How does the brain rapidly learn and recognize objects while scanning a scene with eye movements, without causing a combinatorial explosion in the number of cells that are needed? How does the brain avoid the problem of erroneously classifying parts of different objects together at the same or different positions in a visual scene? In monkeys and humans, a key area for such invariant object category learning and recognition is the inferotemporal cortex (IT). A neural model is proposed to explain how spatial and object attention coordinate the ability of IT to learn invariant category representations of objects that are seen at multiple positions, sizes, and viewpoints. The model clarifies how interactions within a hierarchy of processing stages in the visual brain accomplish this. These stages include the retina, lateral geniculate nucleus, and cortical areas V1, V2, V4, and IT in the brain's What cortical stream, as they interact with spatial attention processes within the parietal cortex of the Where cortical stream. The model builds upon the ARTSCAN model, which proposed how view-invariant object representations are generated. The positional ARTSCAN (pARTSCAN) model proposes how the following additional processes in the What cortical processing stream also enable position-invariant object representations to be learned: IT cells with persistent activity, and a combination of normalizing object category competition and a view-to-object learning law which together ensure that unambiguous views have a larger effect on object recognition than ambiguous views. The model explains how such invariant learning can be fooled when monkeys, or other primates, are presented with an object that is swapped with another object during eye movements to foveate the original object. The swapping procedure is predicted to prevent the reset of spatial attention, which would otherwise keep the representations of multiple objects from being combined by learning. Li and DiCarlo (2008) have presented neurophysiological data from monkeys showing how unsupervised natural experience in a target swapping experiment can rapidly alter object representations in IT. The model quantitatively simulates the swapping data by showing how the swapping procedure fools the spatial attention mechanism. More generally, the model provides a unifying framework, and testable predictions in both monkeys and humans, for understanding object learning data using neurophysiological methods in monkeys, and spatial attention, episodic learning, and memory retrieval data using functional imaging methods in humans. Copyright © 2011 Elsevier Ltd. All rights reserved.
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O'Hara, Blythe J; Grunseit, Anne; Phongsavan, Philayrath; Bellew, William; Briggs, Megan; Bauman, Adrian E
2016-12-01
Mass media campaigns aimed at influencing lifestyle risk factors are one way that governments are attempting to address chronic disease risk. In Australia, a national campaign aimed at encouraging Australians to make changes in lifestyle-related behaviors was implemented from 2008 to 2011. The first phase, Measure Up (2008-2009), focused on why lifestyle changes are needed by increasing awareness of the link between waist circumference and chronic disease risk. The second phase, Swap It, Don't Stop It (2011), emphasized how adults can change their behaviors. Cross-sectional telephone surveys (after the campaign) were undertaken in July and November 2011 to evaluate the Swap It, Don't Stop It campaign and included measures of campaign awareness and lifestyle-related behavior change. Survey participants (N = 5,097) were similar across the two survey periods. Prompted campaign awareness was 62% (16% for unprompted awareness); females, younger respondents (18-44 years), those in paid employment, and those who spoke English at home were more likely to report prompted/unprompted campaign awareness. Moreover, 16% of survey respondents reported any swapping behavior in the previous 6 months, with the majority (14%) reporting only one swap; younger respondents and those in paid employment were significantly more likely to report having implemented a swapping behavior. The campaign achieved modest population awareness but demonstrated limited effect in terms of nudging behaviors. This evaluation indicates that encouraging swapping behaviors as a prelude to lifestyle change may not result from a mass media campaign alone; a comprehensive multicomponent population approach may be required.
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Stewart, Louis J; Trussel, John
2006-01-01
Although the use of derivatives, particularly interest rate swaps, has grown explosively over the past decade, derivative financial instrument use by nonprofits has received only limited attention in the research literature. Because little is known about the risk management activities of nonprofits, the impact of these instruments on the ability of nonprofits to raise capital may have significant public policy implications. The primary motivation of this study is to determine the types of derivatives used by nonprofits and estimate the frequency of their use among these organizations. Our study also extends contemporary finance theory by an empirical examination of the motivation for interest rate swap usage among nonprofits. Our empirical data came from 193 large nonprofit health care providers that issued debt to the public between 2000 and 2003. We used a univariate analysis and a multivariate analysis relying on logistic regression models to test alternative explanations of interest rate swaps usage by nonprofits, finding that more than 45 percent of our sample, 88 organizations, used interest rate swaps with an aggregate notional value in excess of $8.3 billion. Our empirical tests indicate the primary motive for nonprofits to use interest rate derivatives is to hedge their exposure to interest rate risk. Although these derivatives are a useful risk management tool, under conditions of falling bond market interest rates these derivatives may also expose a nonprofit swap user to the risk of a material unscheduled termination payment. Finally, we found considerable diversity in the informativeness of footnote disclosure among sample organizations that used interest rate swaps. Many nonprofits did not disclose these risks in their financial statements. In conclusion, we find financial managers in large nonprofits commonly use derivative financial instruments as risk management tools, but the use of interest rate swaps by nonprofits may expose them to other risks that are not adequately disclosed in their financial statements.
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Verma, Apoorva; Jing-Song, Fan; Finch-Edmondson, Megan L.; Velazquez-Campoy, Adrian; Balasegaran, Shanker; Sudol, Marius; Sivaraman, Jayaraman
2018-01-01
YES-associated protein (YAP) is a major effector protein of the Hippo tumor suppressor pathway, and is phosphorylated by the serine/threonine kinase LATS. Their binding is mediated by the interaction between WW domains of YAP and PPxY motifs of LATS. Their isoforms, YAP2 and LATS1 contain two WW domains and two PPxY motifs respectively. Here, we report the study of the interaction of these domains both in vitro and in human cell lines, to better understand the mechanism of their binding. We show that there is a reciprocal binding preference of YAP2-WW1 with LATS1-PPxY2, and YAP2-WW2 with LATS1-PPxY1. We solved the NMR structures of these complexes and identified several conserved residues that play a critical role in binding. We further created a YAP2 mutant by swapping the WW domains, and found that YAP2 phosphorylation at S127 by LATS1 is not affected by the spatial configuration of its WW domains. This is likely because the region between the PPxY motifs of LATS1 is unstructured, even upon binding with its partner. Based on our observations, we propose possible models for the interaction between YAP2 and LATS1. PMID:29487715
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Verma, Apoorva; Jing-Song, Fan; Finch-Edmondson, Megan L; Velazquez-Campoy, Adrian; Balasegaran, Shanker; Sudol, Marius; Sivaraman, Jayaraman
2018-01-30
YES-associated protein (YAP) is a major effector protein of the Hippo tumor suppressor pathway, and is phosphorylated by the serine/threonine kinase LATS. Their binding is mediated by the interaction between WW domains of YAP and PPxY motifs of LATS. Their isoforms, YAP2 and LATS1 contain two WW domains and two PPxY motifs respectively. Here, we report the study of the interaction of these domains both in vitro and in human cell lines, to better understand the mechanism of their binding. We show that there is a reciprocal binding preference of YAP2-WW1 with LATS1-PPxY2, and YAP2-WW2 with LATS1-PPxY1. We solved the NMR structures of these complexes and identified several conserved residues that play a critical role in binding. We further created a YAP2 mutant by swapping the WW domains, and found that YAP2 phosphorylation at S127 by LATS1 is not affected by the spatial configuration of its WW domains. This is likely because the region between the PPxY motifs of LATS1 is unstructured, even upon binding with its partner. Based on our observations, we propose possible models for the interaction between YAP2 and LATS1.
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Demand Economics: What Happens Before the Swap.
ERIC Educational Resources Information Center
Smith, H. Doyle
Although this book is about how things work, it is also about flaws in the U.S. economic system. It is difficult to realize that every economic activity gravitates toward monopoly or rebellion against monopoly. This is the subject of the book, which is the result of 50 years of actual experience, informed observations, and trained readings. The…
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ERIC Educational Resources Information Center
Ji, Qing; El-Hamdi, Nadia S.; Miljanic´, Ognjen S?.
2014-01-01
Esters are volatile and pleasantly smelling compounds, commonly used as food additives. Using Ti(OBu)[subscript 4]-catalyzed acyl exchange, we demonstrate a scent transmutation experiment, in which two fragrant esters swap their acyl and alkoxy substituents and are, during the course of a reactive distillation, quantitatively converted into two…
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Zhan, Xuanzhi; Gimenez, Luis E.; Gurevich, Vsevolod V.; Spiller, Benjamin W.
2011-01-01
Arrestins are multi-functional proteins that regulate signaling and trafficking of the majority of G protein-coupled receptors (GPCRs), as well as sub-cellular localization and activity of many other signaling proteins. Here we report the first crystal structure of arrestin-3, solved at 3.0Å. Arrestin-3 is an elongated two-domain molecule with the overall fold and key inter-domain interactions that hold free protein in the basal conformation similar to the other subtypes. Arrestin-3 is the least selective member of the family, binding wide variety of GPCRs with high affinity and demonstrating lower preference for active phosphorylated forms of the receptors. In contrast to the other three arrestins, part of the receptor-binding surface in the arrestin-3 C-domain does not form a contiguous β-sheet, consistent with increased flexibility. By swapping the corresponding elements between arrestin-2 and -3 we show that the presence of this loose structure correlates with reduced arrestin selectivity for activated receptor, consistent with a conformational change in this β-sheet upon receptor binding. PMID:21215759
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Directed evolution can rapidly improve the activity of chimeric assembly-line enzymes
Fischbach, Michael A.; Lai, Jonathan R.; Roche, Eric D.; Walsh, Christopher T.; Liu, David R.
2007-01-01
Nonribosomal peptides (NRPs) are produced by NRP synthetase (NRPS) enzymes that function as molecular assembly lines. The modular architecture of NRPSs suggests that a domain responsible for activating a building block could be replaced with a domain from a foreign NRPS to create a chimeric assembly line that produces a new variant of a natural NRP. However, such chimeric NRPS modules are often heavily impaired, impeding efforts to create novel NRP variants by swapping domains from different modules or organisms. Here we show that impaired chimeric NRPSs can be functionally restored by directed evolution. Using rounds of mutagenesis coupled with in vivo screens for NRP production, we rapidly isolated variants of two different chimeric NRPSs with ≈10-fold improvements in enzyme activity and product yield, including one that produces new derivatives of the potent NRP/polyketide antibiotic andrimid. Because functional restoration in these examples required only modest library sizes (103 to 104 clones) and three or fewer rounds of screening, our approach may be widely applicable even for NRPSs from genetically challenging hosts. PMID:17620609
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-06-04
... 37.10(c) and 38.12(c)--Applicability D. Sections 37.10(d) and 38.12(d)--Removal E. Annual Review F... 17 CFR 40.5(e), 40.6(c)(3). Upon the Commission approving a SEF's or DCM's available-to-trade... adequate pricing data'' of a subject swap. \\18\\ WMBAA Comment Letter at 2; MarketAxess Comment Letter at 9...
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Scientific Library’s Book and Media Swap Coming April 16 | Poster
By Robin Meckley, Contributing Writer The 14th annual Book and Media Swap will be held on Wednesday, April 16, from 10 a.m. to 2 p.m., in the lobby of the Conference Center in Building 549. The staff is holding the swap to coincide with National Library Week, an annual celebration of libraries that occurs in April. As of April 10, the library had collected nearly 2,000 books,
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Saw, Wuan Geok; Tria, Giancarlo; Grüber, Ardina; Subramanian Manimekalai, Malathy Sony; Zhao, Yongqian; Chandramohan, Arun; Srinivasan Anand, Ganesh; Matsui, Tsutomu; Weiss, Thomas M.; Vasudevan, Subhash G.; Grüber, Gerhard
2015-01-01
Infection by the four serotypes of Dengue virus (DENV-1 to DENV-4) causes an important arthropod-borne viral disease in humans. The multifunctional DENV nonstructural protein 5 (NS5) is essential for capping and replication of the viral RNA and harbours a methyltransferase (MTase) domain and an RNA-dependent RNA polymerase (RdRp) domain. In this study, insights into the overall structure and flexibility of the entire NS5 of all four Dengue virus serotypes in solution are presented for the first time. The solution models derived revealed an arrangement of the full-length NS5 (NS5FL) proteins with the MTase domain positioned at the top of the RdRP domain. The DENV-1 to DENV-4 NS5 forms are elongated and flexible in solution, with DENV-4 NS5 being more compact relative to NS5 from DENV-1, DENV-2 and DENV-3. Solution studies of the individual MTase and RdRp domains show the compactness of the RdRp domain as well as the contribution of the MTase domain and the ten-residue linker region to the flexibility of the entire NS5. Swapping the ten-residue linker between DENV-4 NS5FL and DENV-3 NS5FL demonstrated its importance in MTase–RdRp communication and in concerted interaction with viral and host proteins, as probed by amide hydrogen/deuterium mass spectrometry. Conformational alterations owing to RNA binding are presented. PMID:26527147
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Saw, Wuan Geok; Tria, Giancarlo; Grüber, Ardina
Infection by the four serotypes ofDengue virus(DENV-1 to DENV-4) causes an important arthropod-borne viral disease in humans. The multifunctional DENV nonstructural protein 5 (NS5) is essential for capping and replication of the viral RNA and harbours a methyltransferase (MTase) domain and an RNA-dependent RNA polymerase (RdRp) domain. In this study, insights into the overall structure and flexibility of the entire NS5 of all fourDengue virusserotypes in solution are presented for the first time. The solution models derived revealed an arrangement of the full-length NS5 (NS5FL) proteins with the MTase domain positioned at the top of the RdRP domain. The DENV-1more » to DENV-4 NS5 forms are elongated and flexible in solution, with DENV-4 NS5 being more compact relative to NS5 from DENV-1, DENV-2 and DENV-3. Solution studies of the individual MTase and RdRp domains show the compactness of the RdRp domain as well as the contribution of the MTase domain and the ten-residue linker region to the flexibility of the entire NS5. Swapping the ten-residue linker between DENV-4 NS5FL and DENV-3 NS5FL demonstrated its importance in MTase–RdRp communication and in concerted interaction with viral and host proteins, as probed by amide hydrogen/deuterium mass spectrometry. Conformational alterations owing to RNA binding are presented.« less
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Teleportation of entanglement over 143 km
Herbst, Thomas; Scheidl, Thomas; Fink, Matthias; Handsteiner, Johannes; Wittmann, Bernhard; Ursin, Rupert; Zeilinger, Anton
2015-01-01
As a direct consequence of the no-cloning theorem, the deterministic amplification as in classical communication is impossible for unknown quantum states. This calls for more advanced techniques in a future global quantum network, e.g., for cloud quantum computing. A unique solution is the teleportation of an entangled state, i.e., entanglement swapping, representing the central resource to relay entanglement between distant nodes. Together with entanglement purification and a quantum memory it constitutes a so-called quantum repeater. Since the aforementioned building blocks have been individually demonstrated in laboratory setups only, the applicability of the required technology in real-world scenarios remained to be proven. Here we present a free-space entanglement-swapping experiment between the Canary Islands of La Palma and Tenerife, verifying the presence of quantum entanglement between two previously independent photons separated by 143 km. We obtained an expectation value for the entanglement-witness operator, more than 6 SDs beyond the classical limit. By consecutive generation of the two required photon pairs and space-like separation of the relevant measurement events, we also showed the feasibility of the swapping protocol in a long-distance scenario, where the independence of the nodes is highly demanded. Because our results already allow for efficient implementation of entanglement purification, we anticipate our research to lay the ground for a fully fledged quantum repeater over a realistic high-loss and even turbulent quantum channel. PMID:26578764
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Fat water decomposition using globally optimal surface estimation (GOOSE) algorithm.
Cui, Chen; Wu, Xiaodong; Newell, John D; Jacob, Mathews
2015-03-01
This article focuses on developing a novel noniterative fat water decomposition algorithm more robust to fat water swaps and related ambiguities. Field map estimation is reformulated as a constrained surface estimation problem to exploit the spatial smoothness of the field, thus minimizing the ambiguities in the recovery. Specifically, the differences in the field map-induced frequency shift between adjacent voxels are constrained to be in a finite range. The discretization of the above problem yields a graph optimization scheme, where each node of the graph is only connected with few other nodes. Thanks to the low graph connectivity, the problem is solved efficiently using a noniterative graph cut algorithm. The global minimum of the constrained optimization problem is guaranteed. The performance of the algorithm is compared with that of state-of-the-art schemes. Quantitative comparisons are also made against reference data. The proposed algorithm is observed to yield more robust fat water estimates with fewer fat water swaps and better quantitative results than other state-of-the-art algorithms in a range of challenging applications. The proposed algorithm is capable of considerably reducing the swaps in challenging fat water decomposition problems. The experiments demonstrate the benefit of using explicit smoothness constraints in field map estimation and solving the problem using a globally convergent graph-cut optimization algorithm. © 2014 Wiley Periodicals, Inc.
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Teleportation of entanglement over 143 km.
Herbst, Thomas; Scheidl, Thomas; Fink, Matthias; Handsteiner, Johannes; Wittmann, Bernhard; Ursin, Rupert; Zeilinger, Anton
2015-11-17
As a direct consequence of the no-cloning theorem, the deterministic amplification as in classical communication is impossible for unknown quantum states. This calls for more advanced techniques in a future global quantum network, e.g., for cloud quantum computing. A unique solution is the teleportation of an entangled state, i.e., entanglement swapping, representing the central resource to relay entanglement between distant nodes. Together with entanglement purification and a quantum memory it constitutes a so-called quantum repeater. Since the aforementioned building blocks have been individually demonstrated in laboratory setups only, the applicability of the required technology in real-world scenarios remained to be proven. Here we present a free-space entanglement-swapping experiment between the Canary Islands of La Palma and Tenerife, verifying the presence of quantum entanglement between two previously independent photons separated by 143 km. We obtained an expectation value for the entanglement-witness operator, more than 6 SDs beyond the classical limit. By consecutive generation of the two required photon pairs and space-like separation of the relevant measurement events, we also showed the feasibility of the swapping protocol in a long-distance scenario, where the independence of the nodes is highly demanded. Because our results already allow for efficient implementation of entanglement purification, we anticipate our research to lay the ground for a fully fledged quantum repeater over a realistic high-loss and even turbulent quantum channel.
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2014-07-01
corrosion studies (16). A schematic of the SWAP process and example of the powder produced is included in figure 4. This alloy contains amounts of Al ...advanced powder -based alloy and ZAXE1711 (both from Japan) were produced using a Spinning Water Atomization Process (SWAP) to yield powder particles with...and ZAXE1711 Mg alloy powders and (b) morphology of coarse Mg alloy powder prepared by SWAP
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Green Team Readies for Spring with Plant Swap | Poster
By Carolynne Keenan, Contributing Writer Those looking for a cost-effective way to spruce up their yards this spring can stop by the National Cancer Institute at Frederick Green Team’s booth during the Spring Research Festival (SRF) on May 7 and 8. Pick up a free plant, donate overgrown plants from your yard, or swap for a new plant. Everyone is invited to participate in the swap, whether you have plants to donate or not.
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The Annual Fall Book Swap Is On! | Poster
The Scientific Library staff is happy to announce that our 17th Annual Book and Media Swap will be held again this year beginning on Wednesday, November 1 from 10:00 a.m. to 2:00 p.m. in Building 549. If you need to make room for new books, are looking for new homes for your old books, or are tired of viewing those same old DVDs over and over, then the Swap is for you.
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Preliminary Results on Irradiance Measurements from Lyra and Swap
NASA Astrophysics Data System (ADS)
Kumara, S. T.; Kariyappa, R.; Dominique, M.; Berghmans, D.; Damé, L.; Hochedez, J. F.; Doddamani, V. H.; Chitta, Lakshmi Pradeep
The first and preliminary results of the photometry of Large Yield Radiometer (LYRA) and Sun Watcher using Active Pixel system detector and Image Processing (SWAP) onboard PROBA2 are presented in this paper. To study the day-to-day variations of LYRA irradiance, we have compared the LYRA irradiance values (observed Sun as a star) measured in Aluminum filter channel (171Å-500Å) with spatially resolved full-disk integrated intensity values measured with SWAP (174Å) and Ca II K 1 Å index values (ground-based observations from NSO/Sac Peak) for the period from 01 April 2010 to 15 Mar 2011. We found that there is a good correlation between these parameters. This indicates that the spatial resolution of SWAP complements the high temporal resolution of LYRA. Hence SWAP can be considered as an additional radiometric channel. Also the K emission index is the integrated intensity (or flux) over a 1 Å band centered on the K line and is proportional to the total emission from the chromosphere; this comparison clearly explains that the LYRA irradiance variations are due to the various magnetic features, which are contributing significantly. In addition to this we have made an attempt to segregate coronal features from full-disk SWAP images. This will help to understand and determine the actual contribution of the individual coronal feature to LYRA irradiance variations.
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Multiscale implementation of infinite-swap replica exchange molecular dynamics.
Yu, Tang-Qing; Lu, Jianfeng; Abrams, Cameron F; Vanden-Eijnden, Eric
2016-10-18
Replica exchange molecular dynamics (REMD) is a popular method to accelerate conformational sampling of complex molecular systems. The idea is to run several replicas of the system in parallel at different temperatures that are swapped periodically. These swaps are typically attempted every few MD steps and accepted or rejected according to a Metropolis-Hastings criterion. This guarantees that the joint distribution of the composite system of replicas is the normalized sum of the symmetrized product of the canonical distributions of these replicas at the different temperatures. Here we propose a different implementation of REMD in which (i) the swaps obey a continuous-time Markov jump process implemented via Gillespie's stochastic simulation algorithm (SSA), which also samples exactly the aforementioned joint distribution and has the advantage of being rejection free, and (ii) this REMD-SSA is combined with the heterogeneous multiscale method to accelerate the rate of the swaps and reach the so-called infinite-swap limit that is known to optimize sampling efficiency. The method is easy to implement and can be trivially parallelized. Here we illustrate its accuracy and efficiency on the examples of alanine dipeptide in vacuum and C-terminal β-hairpin of protein G in explicit solvent. In this latter example, our results indicate that the landscape of the protein is a triple funnel with two folded structures and one misfolded structure that are stabilized by H-bonds.
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Debt-for-nature swaps: A new strategy for protecting environmental interests in developing nations
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hamlin, T.B.
1989-01-01
Nature swaps are a generally well-conceived approach to mitigating the destruction of environmentally sensitive areas in developing nations while remaining sensitive to the economic needs of developing countries. They allow developing countries to dedicate some of their debt repayment to local projects, thus benefiting both their economies and the environment. Swaps also help them obtain assistance from environmental organizations in developed nations to manage their own natural resources. Environmentalists, through the purchase of steeply discounted debt, maximize their investment in tropical forest preservation. In addition they can strengthen environmental organizations in developing nations by including local environmentalists in both policymore » decisionmaking and the implementation of conservation projects. Debt-for-nature swaps also keep the subject of tropical deforestation on the agenda of the international community and offer small international lending institutions a socially redeeming means of removing bad loans from their ledgers. Finally, each government's authority to choose its own development objectives is only slightly encumbered by sharing decisionmaking authority with the environmentalists. Essentially, the swapping governments have agreed to cooperate. consequently, tropical forests only have as much protection as the tropical states desire. This does not mean that swaps are of little moment. Hopefully, collaboration between conservationists in the developed world and leaders of the developing nations will contribute to a constructive framework for future efforts to preserve the earth's tropical forests.« less
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Exploring the Influence of Domain Architecture on the Catalytic Function of Diterpene Synthases.
Pemberton, Travis A; Chen, Mengbin; Harris, Golda G; Chou, Wayne K W; Duan, Lian; Köksal, Mustafa; Genshaft, Alex S; Cane, David E; Christianson, David W
2017-04-11
Terpenoid synthases catalyze isoprenoid cyclization reactions underlying the generation of more than 80,000 natural products. Such dramatic chemodiversity belies the fact that these enzymes generally consist of only three domain folds designated as α, β, and γ. Catalysis by class I terpenoid synthases occurs exclusively in the α domain, which is found with α, αα, αβ, and αβγ domain architectures. Here, we explore the influence of domain architecture on catalysis by taxadiene synthase from Taxus brevifolia (TbTS, αβγ), fusicoccadiene synthase from Phomopsis amygdali (PaFS, (αα) 6 ), and ophiobolin F synthase from Aspergillus clavatus (AcOS, αα). We show that the cyclization fidelity and catalytic efficiency of the α domain of TbTS are severely compromised by deletion of the βγ domains; however, retention of the β domain preserves significant cyclization fidelity. In PaFS, we previously demonstrated that one α domain similarly influences catalysis by the other α domain [ Chen , M. , Chou , W. K. W. , Toyomasu , T. , Cane , D. E. , and Christianson , D. W. ( 2016 ) ACS Chem. Biol. 11 , 889 - 899 ]. Here, we show that the hexameric quaternary structure of PaFS enables cluster channeling. We also show that the α domains of PaFS and AcOS can be swapped so as to make functional chimeric αα synthases. Notably, both cyclization fidelity and catalytic efficiency are altered in all chimeric synthases. Twelve newly formed and uncharacterized C 20 diterpene products and three C 25 sesterterpene products are generated by these chimeras. Thus, engineered αβγ and αα terpenoid cyclases promise to generate chemodiversity in the greater family of terpenoid natural products.
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Study of quantum correlation swapping with relative entropy methods
NASA Astrophysics Data System (ADS)
Xie, Chuanmei; Liu, Yimin; Chen, Jianlan; Zhang, Zhanjun
2016-02-01
To generate long-distance shared quantum correlations (QCs) for information processing in future quantum networks, recently we proposed the concept of QC repeater and its kernel technique named QC swapping. Besides, we extensively studied the QC swapping between two simple QC resources (i.e., a pair of Werner states) with four different methods to quantify QCs (Xie et al. in Quantum Inf Process 14:653-679, 2015). In this paper, we continue to treat the same issue by employing other three different methods associated with relative entropies, i.e., the MPSVW method (Modi et al. in Phys Rev Lett 104:080501, 2010), the Zhang method (arXiv:1011.4333 [quant-ph]) and the RS method (Rulli and Sarandy in Phys Rev A 84:042109, 2011). We first derive analytic expressions of all QCs which occur during the swapping process and then reveal their properties about monotonicity and threshold. Importantly, we find that a long-distance shared QC can be generated from two short-distance ones via QC swapping indeed. In addition, we simply compare our present results with our previous ones.
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Einstein-Podolsky-Rosen-steering swapping between two Gaussian multipartite entangled states
NASA Astrophysics Data System (ADS)
Wang, Meihong; Qin, Zhongzhong; Wang, Yu; Su, Xiaolong
2017-08-01
Multipartite Einstein-Podolsky-Rosen (EPR) steering is a useful quantum resource for quantum communication in quantum networks. It has potential applications in secure quantum communication, such as one-sided device-independent quantum key distribution and quantum secret sharing. By distributing optical modes of a multipartite entangled state to space-separated quantum nodes, a local quantum network can be established. Based on the existing multipartite EPR steering in a local quantum network, secure quantum communication protocol can be accomplished. In this manuscript, we present swapping schemes for EPR steering between two space-separated Gaussian multipartite entangled states, which can be used to connect two space-separated quantum networks. Two swapping schemes, including the swapping between a tripartite Greenberger-Horne-Zeilinger (GHZ) entangled state and an EPR entangled state and that between two tripartite GHZ entangled states, are analyzed. Various types of EPR steering are presented after the swapping of two space-separated independent multipartite entanglement states without direct interaction, which can be used to implement quantum communication between two quantum networks. The presented schemes provide technical reference for more complicated quantum networks with EPR steering.
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Replacement of tritiated water from irradiated fuel storage bay
DOE Office of Scientific and Technical Information (OSTI.GOV)
Castillo, I.; Boniface, H.; Suppiah, S.
2015-03-15
Recently, AECL developed a novel method to reduce tritium emissions (to groundwater) and personnel doses at the NRU (National Research Universal) reactor irradiated fuel storage bay (also known as rod or spent fuel bay) through a water swap process. The light water in the fuel bay had built up tritium that had been transferred from the heavy water moderator through normal fuel transfers. The major advantage of the thermal stratification method was that a very effective tritium reduction could be achieved by swapping a minimal volume of bay water and warm tritiated water would be skimmed off the bay surface.more » A demonstration of the method was done that involved Computational Fluid Dynamics (CFD) modeling of the swap process and a test program that showed excellent agreement with model prediction for the effective removal of almost all the tritium with a minimal water volume. Building on the successful demonstration, AECL fabricated, installed, commissioned and operated a full-scale system to perform a water swap. This full-scale water swap operation achieved a tritium removal efficiency of about 96%.« less
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Improved IR detectors to swap heavy systems for SWaP
NASA Astrophysics Data System (ADS)
Manissadjian, Alain; Rubaldo, Laurent; Rebeil, Yann; Kerlain, Alexandre; Brellier, Delphine; Mollard, Laurent
2012-06-01
Cooled IR technologies are challenged for answering new system needs like the compactness and the reduction of cryopower which is a key feature for the SWaP (Size, Weight and Power) requirements. Over the last years, SOFRADIR has improved its HgCdTe technology, with effect on dark current reduction, opening the way for High Operating Temperature (HOT) systems that can get rid of the 80K temperature constraint, and therefore releases the Stirling cooler engine power consumption. Performances of the 640×512 15μm pitch LW detector working above 100K will be presented. A compact 640×512 15μm pitch MW detector presenting high EO performance above 130K with cut-off wavelength above 5.0μm has been developed. Its different performances with respect to the market requirements for SWaP will be discussed. High performance compact systems will make no compromise on detector resolution. The pixel pitch reduction is the answer for resolution enhancement with size reduction. We will therefore also discuss the ongoing developments and market needs for SWaP systems.
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Efficient quantum circuits for one-way quantum computing.
Tanamoto, Tetsufumi; Liu, Yu-Xi; Hu, Xuedong; Nori, Franco
2009-03-13
While Ising-type interactions are ideal for implementing controlled phase flip gates in one-way quantum computing, natural interactions between solid-state qubits are most often described by either the XY or the Heisenberg models. We show an efficient way of generating cluster states directly using either the imaginary SWAP (iSWAP) gate for the XY model, or the sqrt[SWAP] gate for the Heisenberg model. Our approach thus makes one-way quantum computing more feasible for solid-state devices.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Bubanja, Vladimir, E-mail: vladimir.bubanja@callaghaninnovation.govt.nz
2015-06-15
We present schemes for quantum teleportation and entanglement swapping of electronic spin states in hybrid superconductor–normal-metal systems. The proposed schemes employ subgap transport whereby the lowest order processes involve Cooper pair-electron and double Cooper-pair cotunneling in quantum teleportation and entanglement swapping protocols, respectively. The competition between elastic cotunneling and Cooper-pair splitting results in the success probability of 25% in both cases. Described implementations of these protocols are within reach of present-day experimental techniques.
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17 CFR 240.3a68-4 - Regulation of mixed swaps.
Code of Federal Regulations, 2013 CFR
2013-04-01
....S.C. 78c(a)(68)(D)). (b) Regulation of bilateral uncleared mixed swaps entered into by dually...(f) and 12; (B) Enforcement: 7 U.S.C. 2(a)(1)(B), 6(b), 6b, 6c, 6s(h)(1)(A), 6s(h)(4)(A), 9, 13b, 13a-1, 13a-2, 13, 13c(a), 13c(b), 15 and 26; (C) Reporting to a swap data repository: 7 U.S.C. 6r; (D...
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Ahn, J-E; Lovingshimer, M R; Salzman, R A; Presnail, J K; Lu, A L; Koiwa, H; Zhu-Salzman, K
2007-06-01
Cowpea bruchids, when challenged by consumption of the soybean cysteine protease inhibitor scN, reconfigure expression of their major CmCP digestive proteases and resume normal feeding and development. Previous evidence indicated that insects selectively induced CmCPs from subfamily B, that were more efficient in autoprocessing and possessed not only higher proteolytic, but also scN-degrading activities. In contrast, dietary scN only marginally up-regulated genes from the more predominant CmCP subfamily A that were inferior to subfamily B. To gain further molecular insight into this adaptive adjustment, we performed domain swapping between the two respective subfamily members B1 and A16, the latter unable to autoprocess or degrade scN even after intermolecular processing. Swapping the propeptides did not qualitatively alter autoprocessing in either protease isoform. Incorporation of either the N- (pAmBA) or C-terminal (pAmAB) mature B1 segment into A16, however, was sufficient to prime autoprocessing of A16 to its mature form. Further, the swap at the N-terminal mature A16 protein region (pAmBA) resulted in four amino acid changes. Replacement of these amino acid residues by the corresponding B1 residues, singly and pair-wise, revealed that autoprocessing activation in pAmBA resulted from cumulative and/or coordinated individual effects. Bacterially expressed isolated propeptides (pA16 and pB1) differed in their ability to inhibit mature B1 enzyme. Lower inhibitory activity in pB1 is likely attributable to its lack of protein stability. This instability in the cleaved propeptide is necessary, although insufficient by itself, for scN-degradation by the mature B1 enzyme. Taken together, cowpea bruchids modulate proteolysis of their digestive enzymes by controlling proCmCP cleavage and propeptide stability, which explains at least in part the plasticity cowpea bruchids demonstrate in response to protease inhibitors.
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75 FR 57740 - Sunshine Act Meetings
Federal Register 2010, 2011, 2012, 2013, 2014
2010-09-22
... the time frame for reporting pre-enactment unexpired swaps to a swap data repository or to the... governance arrangements and mitigation of conflicts of interest. CONTACT PERSON FOR MORE INFORMATION: David A...
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Structural Determinants of DNA Binding by a P. falciparum ApiAP2 Transcriptional Regulator
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lindner, Scott E.; De Silva, Erandi K.; Keck, James L.
2010-11-05
Putative transcription factors have only recently been identified in the Plasmodium spp., with the major family of regulators comprising the Apicomplexan Apetala2 (AP2) proteins. To better understand the DNA-binding mechanisms of these transcriptional regulators, we characterized the structure and in vitro function of an AP2 DNA-binding domain from a prototypical Apicomplexan AP2 protein, PF14{_}0633 from Plasmodium falciparum. The X-ray crystal structure of the PF14{_}0633 AP2 domain bound to DNA reveals a {beta}-sheet fold that binds the DNA major groove through base-specific and backbone contacts; a prominent {alpha}-helix supports the {beta}-sheet structure. Substitution of predicted DNA-binding residues with alanine weakened ormore » eliminated DNA binding in solution. In contrast to plant AP2 domains, the PF14{_}0633 AP2 domain dimerizes upon binding to DNA through a domain-swapping mechanism in which the {alpha}-helices of the AP2 domains pack against the {beta}-sheets of the dimer mates. DNA-induced dimerization of PF14{_}0633 may be important for tethering two distal DNA loci together in the nucleus and/or for inducing functional rearrangements of its domains to facilitate transcriptional regulation. Consistent with a multisite binding mode, at least two copies of the consensus sequence recognized by PF14{_}0633 are present upstream of a previously identified group of sporozoite-stage genes. Taken together, these findings illustrate how Plasmodium has adapted the AP2 DNA-binding domain for genome-wide transcriptional regulation.« less
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17 CFR 1.4 - Electronic signatures, acknowledgments and verifications.
Code of Federal Regulations, 2014 CFR
2014-04-01
... commission merchant or introducing broker, a retail forex customer of a retail foreign exchange dealer or..., retail forex customer, participant, client, counterparty, swap dealer, or major swap participant will be...
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17 CFR 1.4 - Electronic signatures, acknowledgments and verifications.
Code of Federal Regulations, 2013 CFR
2013-04-01
... commission merchant or introducing broker, a retail forex customer of a retail foreign exchange dealer or..., retail forex customer, participant, client, counterparty, swap dealer, or major swap participant will be...
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17 CFR 23.603 - Business continuity and disaster recovery.
Code of Federal Regulations, 2013 CFR
2013-04-01
..., facilities, infrastructure, personnel and competencies essential to the continued operations of the swap.... The individuals identified shall be authorized to make key decisions on behalf of the swap dealer or...
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17 CFR 23.603 - Business continuity and disaster recovery.
Code of Federal Regulations, 2014 CFR
2014-04-01
..., facilities, infrastructure, personnel and competencies essential to the continued operations of the swap.... The individuals identified shall be authorized to make key decisions on behalf of the swap dealer or...
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Predictive energy landscapes for folding membrane protein assemblies
NASA Astrophysics Data System (ADS)
Truong, Ha H.; Kim, Bobby L.; Schafer, Nicholas P.; Wolynes, Peter G.
2015-12-01
We study the energy landscapes for membrane protein oligomerization using the Associative memory, Water mediated, Structure and Energy Model with an implicit membrane potential (AWSEM-membrane), a coarse-grained molecular dynamics model previously optimized under the assumption that the energy landscapes for folding α-helical membrane protein monomers are funneled once their native topology within the membrane is established. In this study we show that the AWSEM-membrane force field is able to sample near native binding interfaces of several oligomeric systems. By predicting candidate structures using simulated annealing, we further show that degeneracies in predicting structures of membrane protein monomers are generally resolved in the folding of the higher order assemblies as is the case in the assemblies of both nicotinic acetylcholine receptor and V-type Na+-ATPase dimers. The physics of the phenomenon resembles domain swapping, which is consistent with the landscape following the principle of minimal frustration. We revisit also the classic Khorana study of the reconstitution of bacteriorhodopsin from its fragments, which is the close analogue of the early Anfinsen experiment on globular proteins. Here, we show the retinal cofactor likely plays a major role in selecting the final functional assembly.
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Narayanan, Pratibha; Hütte, Meike; Kudryasheva, Galina; Taberner, Francisco J; Lechner, Stefan G; Rehfeldt, Florian; Gomez-Varela, David
2018-01-01
Piezo2 ion channels are critical determinants of the sense of light touch in vertebrates. Yet, their regulation is only incompletely understood. We recently identified myotubularin related protein-2 (Mtmr2), a phosphoinositide (PI) phosphatase, in the native Piezo2 interactome of murine dorsal root ganglia (DRG). Here, we demonstrate that Mtmr2 attenuates Piezo2-mediated rapidly adapting mechanically activated (RA-MA) currents. Interestingly, heterologous Piezo1 and other known MA current subtypes in DRG appeared largely unaffected by Mtmr2. Experiments with catalytically inactive Mtmr2, pharmacological blockers of PI(3,5)P2 synthesis, and osmotic stress suggest that Mtmr2-dependent Piezo2 inhibition involves depletion of PI(3,5)P2. Further, we identified a PI(3,5)P2 binding region in Piezo2, but not Piezo1, that confers sensitivity to Mtmr2 as indicated by functional analysis of a domain-swapped Piezo2 mutant. Altogether, our results propose local PI(3,5)P2 modulation via Mtmr2 in the vicinity of Piezo2 as a novel mechanism to dynamically control Piezo2-dependent mechanotransduction in peripheral sensory neurons. PMID:29521261
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de Diego, Iñaki; Ksiazek, Miroslaw; Mizgalska, Danuta; Koneru, Lahari; Golik, Przemyslaw; Szmigielski, Borys; Nowak, Magdalena; Nowakowska, Zuzanna; Potempa, Barbara; Houston, John A.; Enghild, Jan J.; Thøgersen, Ida B.; Gao, Jinlong; Kwan, Ann H.; Trewhella, Jill; Dubin, Grzegorz; Gomis-Rüth, F. Xavier; Nguyen, Ky-Anh; Potempa, Jan
2016-01-01
In the recently characterized Type IX Secretion System (T9SS), the conserved C-terminal domain (CTD) in secreted proteins functions as an outer membrane translocation signal for export of virulence factors to the cell surface in the Gram-negative Bacteroidetes phylum. In the periodontal pathogen Porphyromonas gingivalis, the CTD is cleaved off by PorU sortase in a sequence-independent manner, and anionic lipopolysaccharide (A-LPS) is attached to many translocated proteins, thus anchoring them to the bacterial surface. Here, we solved the atomic structure of the CTD of gingipain B (RgpB) from P. gingivalis, alone and together with a preceding immunoglobulin-superfamily domain (IgSF). The CTD was found to possess a typical Ig-like fold encompassing seven antiparallel β-strands organized in two β-sheets, packed into a β-sandwich structure that can spontaneously dimerise through C-terminal strand swapping. Small angle X-ray scattering (SAXS) revealed no fixed orientation of the CTD with respect to the IgSF. By introducing insertion or substitution of residues within the inter-domain linker in the native protein, we were able to show that despite the region being unstructured, it nevertheless is resistant to general proteolysis. These data suggest structural motifs located in the two adjacent Ig-like domains dictate the processing of CTDs by the T9SS secretion pathway. PMID:27005013
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Bulfer, Stacie L.; Scott, Erin M.; Couture, Jean-François
2010-01-12
Homocitrate synthase (HCS) catalyzes the first and committed step in lysine biosynthesis in many fungi and certain Archaea and is a potential target for antifungal drugs. Here we report the crystal structure of the HCS apoenzyme from Schizosaccharomyces pombe and two distinct structures of the enzyme in complex with the substrate 2-oxoglutarate (2-OG). The structures reveal that HCS forms an intertwined homodimer stabilized by domain-swapping between the N- and C-terminal domains of each monomer. The N-terminal catalytic domain is composed of a TIM barrel fold in which 2-OG binds via hydrogen bonds and coordination to the active site divalent metalmore » ion, whereas the C-terminal domain is composed of mixed {alpha}/{beta} topology. In the structures of the HCS apoenzyme and one of the 2-OG binary complexes, a lid motif from the C-terminal domain occludes the entrance to the active site of the neighboring monomer, whereas in the second 2-OG complex the lid is disordered, suggesting that it regulates substrate access to the active site through its apparent flexibility. Mutations of the active site residues involved in 2-OG binding or implicated in acid-base catalysis impair or abolish activity in vitro and in vivo. Together, these results yield new insights into the structure and catalytic mechanism of HCSs and furnish a platform for developing HCS-selective inhibitors.« less
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Distinct Functional Domains of Ubc9 Dictate Cell Survival and Resistance to Genotoxic Stress
van Waardenburg, Robert C. A. M.; Duda, David M.; Lancaster, Cynthia S.; Schulman, Brenda A.; Bjornsti, Mary-Ann
2006-01-01
Covalent modification with SUMO alters protein function, intracellular localization, or protein-protein interactions. Target recognition is determined, in part, by the SUMO E2 enzyme, Ubc9, while Siz/Pias E3 ligases may facilitate select interactions by acting as substrate adaptors. A yeast conditional Ubc9P123L mutant was viable at 36°C yet exhibited enhanced sensitivity to DNA damage. To define functional domains in Ubc9 that dictate cellular responses to genotoxic stress versus those necessary for cell viability, a 1.75-Å structure of yeast Ubc9 that demonstrated considerable conservation of backbone architecture with human Ubc9 was solved. Nevertheless, differences in side chain geometry/charge guided the design of human/yeast chimeras, where swapping domains implicated in (i) binding residues within substrates that flank canonical SUMOylation sites, (ii) interactions with the RanBP2 E3 ligase, and (iii) binding of the heterodimeric E1 and SUMO had distinct effects on cell growth and resistance to DNA-damaging agents. Our findings establish a functional interaction between N-terminal and substrate-binding domains of Ubc9 and distinguish the activities of E3 ligases Siz1 and Siz2 in regulating cellular responses to genotoxic stress. PMID:16782883
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CryoEM structure of a prokaryotic cyclic nucleotide-gated ion channel
James, Zachary M.; Borst, Andrew J.; Haitin, Yoni; Frenz, Brandon; DiMaio, Frank; Zagotta, William N.; Veesler, David
2017-01-01
Cyclic nucleotide-gated (CNG) and hyperpolarization-activated cyclic nucleotide-regulated (HCN) ion channels play crucial physiological roles in phototransduction, olfaction, and cardiac pace making. These channels are characterized by the presence of a carboxyl-terminal cyclic nucleotide-binding domain (CNBD) that connects to the channel pore via a C-linker domain. Although cyclic nucleotide binding has been shown to promote CNG and HCN channel opening, the precise mechanism underlying gating remains poorly understood. Here we used cryoEM to determine the structure of the intact LliK CNG channel isolated from Leptospira licerasiae—which shares sequence similarity to eukaryotic CNG and HCN channels—in the presence of a saturating concentration of cAMP. A short S4–S5 linker connects nearby voltage-sensing and pore domains to produce a non–domain-swapped transmembrane architecture, which appears to be a hallmark of this channel family. We also observe major conformational changes of the LliK C-linkers and CNBDs relative to the crystal structures of isolated C-linker/CNBD fragments and the cryoEM structures of related CNG, HCN, and KCNH channels. The conformation of our LliK structure may represent a functional state of this channel family not captured in previous studies. PMID:28396445
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76 FR 27801 - Capital Requirements of Swap Dealers and Major Swap Participants
Federal Register 2010, 2011, 2012, 2013, 2014
2011-05-12
...The Commodity Futures Trading Commission (Commission or CFTC) is proposing regulations that would implement the new statutory framework in the Commodity Exchange Act (CEA), added by the Wall Street Reform and Consumer Protection Act (Dodd-Frank Act). These new provisions of the CEA require, among other things, the Commission to adopt capital requirements for certain swap dealers (SDs) and major swap participants (MSPs). The proposed rules also provide for related financial condition reporting and recordkeeping by SDs and MSPs. The Commission further proposes to amend existing capital and financial reporting regulations for futures commission merchants (FCMs) that also register as SDs or MSPs. The proposed regulations also include requirements for supplemental FCM financial reporting to reflect section 724 of the Dodd-Frank Act. In order to align the comment periods for this proposed rule and the Commission's earlier proposed rulemaking on margin requirements for uncleared swaps,\\1\\ the comment period for the proposed margin rulemaking is being extended elsewhere in the Federal Register today, so that commenters will have the opportunity to review the proposed capital and margin rules together before the expiration of the comment periods for either proposed rule. ---------------------------------------------------------------------------
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Rapid formin-mediated actin-filament elongation is essential for polarized plant cell growth.
Vidali, Luis; van Gisbergen, Peter A C; Guérin, Christophe; Franco, Paula; Li, Ming; Burkart, Graham M; Augustine, Robert C; Blanchoin, Laurent; Bezanilla, Magdalena
2009-08-11
Formins are present in all eukaryotes and are essential for the creation of actin-based structures responsible for diverse cellular processes. Because multicellular organisms contain large formin gene families, establishing the physiological functions of formin isoforms has been difficult. Using RNAi, we analyzed the function of all 9 formin genes within the moss Physcomitrella patens. We show that plants lacking class II formins (For2) are severely stunted and composed of spherical cells with disrupted actin organization. In contrast, silencing of all other formins results in normal elongated cell morphology and actin organization. Consistent with a role in polarized growth, For2 are apically localized in growing cells. We show that an N-terminal phosphatase tensin (PTEN)-like domain mediates apical localization. The PTEN-like domain is followed by a conserved formin homology (FH)1-FH2 domain, known to promote actin polymerization. To determine whether apical localization of any FH1-FH2 domain mediates polarized growth, we performed domain swapping. We found that only the class II FH1-FH2, in combination with the PTEN-like domain, rescues polarized growth, because it cannot be replaced with a similar domain from a For1. We used in vitro polymerization assays to dissect the functional differences between these FH1-FH2 domains. We found that both the FH1 and the FH2 domains from For2 are required to mediate exceptionally rapid rates of actin filament elongation, much faster than any other known formin. Thus, our data demonstrate that rapid rates of actin elongation are critical for driving the formation of apical filamentous actin necessary for polarized growth.
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The Annual Fall Book Swap Is On! | Poster
The Scientific Library staff is happy to announce that our 17th Annual Book and Media Swap will be held again this year beginning on Wednesday, November 1 from 10:00 a.m. to 2:00 p.m. in Building 549. If you need to make room for new books, are looking for new homes for your old books, or are tired of viewing those same old DVDs over and over, then the Swap is for you. Collection for materials has already begun, but donations will continue to be accepted through Tuesday, October 31.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Balakrishnan, S.; Sankaranarayanan, R.
Nonlocal two-qubit gates are geometrically represented by tetrahedron known as Weyl chamber within which perfect entanglers form a polyhedron. We identify that all edges of the Weyl chamber and polyhedron are formed by single parametric gates. Nonlocal attributes of these edges are characterized using entangling power and local invariants. In particular, SWAP{sup -{alpha}} family of gates with 0{<=}{alpha}{<=}1 constitutes one edge of the Weyl chamber with SWAP{sup -1/2} being the only perfect entangler. Finally, optimal constructions of controlled-NOT using SWAP{sup -1/2} gate and gates belong to three edges of the polyhedron are presented.
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Software Acquisition Process (SWAP) Model FY81
1982-12-01
experience. In addition, the manpower accounting techniques and the effects of resource limitation are described below. a. Contractor Personnel. Five job...developed are each oriented to a specific type of developmental activity. Between them, they account for all types of activities in the acquisition...manning levels and duration; Decision Box probability; and project staffing levels. They take into account the overall size of the project and the
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-04-03
... between research and trading and between clearing and trading. Finally, these regulations also require... compared to the costs involved. ISDA & SIFMA provided the Commission with no quantitative data regarding...
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Venkataramani, Prakash; Johnson, Tricia; O'Neil, Patricia; Poindexter, Victoria; Rooney, Jeffrey
2006-01-01
The utilization of interest rate derivative instruments in US for-profit companies has grown exponentially since the early 1980s. International Swaps and Derivatives Association, Inc. (ISDA), reported that the amount of outstanding standard swaps grew by 25 percent during the first six months of 2003. The growth rate of all interest rate derivatives, which includes single-currency interest rate swaps, cross-currency interest rate swaps, and interest rate options, grew by 24 percent during the same period. The total outstanding amount of interest rate derivatives now totals $123.9 trillion compared to $99.9 trillion at the end of 2002 (Dodd, 2003). This explosion in usage is a testament to the efficacy and flexibility of the instruments and the increased appreciation by financial managers of the importance of financial risk management in a volatile interest rate environment.
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Deterministically Entangling Two Remote Atomic Ensembles via Light-Atom Mixed Entanglement Swapping
Liu, Yanhong; Yan, Zhihui; Jia, Xiaojun; Xie, Changde
2016-01-01
Entanglement of two distant macroscopic objects is a key element for implementing large-scale quantum networks consisting of quantum channels and quantum nodes. Entanglement swapping can entangle two spatially separated quantum systems without direct interaction. Here we propose a scheme of deterministically entangling two remote atomic ensembles via continuous-variable entanglement swapping between two independent quantum systems involving light and atoms. Each of two stationary atomic ensembles placed at two remote nodes in a quantum network is prepared to a mixed entangled state of light and atoms respectively. Then, the entanglement swapping is unconditionally implemented between the two prepared quantum systems by means of the balanced homodyne detection of light and the feedback of the measured results. Finally, the established entanglement between two macroscopic atomic ensembles is verified by the inseparability criterion of correlation variances between two anti-Stokes optical beams respectively coming from the two atomic ensembles. PMID:27165122
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Structure of the voltage-gated K⁺ channel Eag1 reveals an alternative voltage sensing mechanism.
Whicher, Jonathan R; MacKinnon, Roderick
2016-08-12
Voltage-gated potassium (K(v)) channels are gated by the movement of the transmembrane voltage sensor, which is coupled, through the helical S4-S5 linker, to the potassium pore. We determined the single-particle cryo-electron microscopy structure of mammalian K(v)10.1, or Eag1, bound to the channel inhibitor calmodulin, at 3.78 angstrom resolution. Unlike previous K(v) structures, the S4-S5 linker of Eag1 is a five-residue loop and the transmembrane segments are not domain swapped, which suggest an alternative mechanism of voltage-dependent gating. Additionally, the structure and position of the S4-S5 linker allow calmodulin to bind to the intracellular domains and to close the potassium pore, independent of voltage-sensor position. The structure reveals an alternative gating mechanism for K(v) channels and provides a template to further understand the gating properties of Eag1 and related channels. Copyright © 2016, American Association for the Advancement of Science.
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Bie, Yiming; Wang, Yinhai
2017-01-01
To deal with the conflicts between left-turn and through traffic streams and increase the discharge capacity, this paper addresses the pre-signal which is implemented at a signalized intersection. Such an intersection with pre-signal is termed as a tandem intersection. For the tandem intersection, phase swap sorting strategy is deemed as the most effective phasing scheme in view of some exclusive merits, such as easier compliance of drivers, and shorter sorting area. However, a major limitation of the phase swap sorting strategy is not considered in previous studies: if one or more vehicle is left at the sorting area after the signal light turns to red, the capacity of the approach would be dramatically dropped. Besides, previous signal control studies deal with a fixed timing plan that is not adaptive with the fluctuation of traffic flows. Therefore, to cope with these two gaps, this paper firstly takes an in-depth analysis of the traffic flow operations at the tandem intersection. Secondly, three groups of loop detectors are placed to obtain the real-time vehicle information for adaptive signalization. The lane selection behavior in the sorting area is considered to set the green time for intersection signals. With the objective of minimizing the vehicle delay, the signal control parameters are then optimized based on a dynamic programming method. Finally, numerical experiments show that average vehicle delay and maximum queue length can be reduced under all scenarios. PMID:28531198
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Bie, Yiming; Liu, Zhiyuan; Wang, Yinhai
2017-01-01
To deal with the conflicts between left-turn and through traffic streams and increase the discharge capacity, this paper addresses the pre-signal which is implemented at a signalized intersection. Such an intersection with pre-signal is termed as a tandem intersection. For the tandem intersection, phase swap sorting strategy is deemed as the most effective phasing scheme in view of some exclusive merits, such as easier compliance of drivers, and shorter sorting area. However, a major limitation of the phase swap sorting strategy is not considered in previous studies: if one or more vehicle is left at the sorting area after the signal light turns to red, the capacity of the approach would be dramatically dropped. Besides, previous signal control studies deal with a fixed timing plan that is not adaptive with the fluctuation of traffic flows. Therefore, to cope with these two gaps, this paper firstly takes an in-depth analysis of the traffic flow operations at the tandem intersection. Secondly, three groups of loop detectors are placed to obtain the real-time vehicle information for adaptive signalization. The lane selection behavior in the sorting area is considered to set the green time for intersection signals. With the objective of minimizing the vehicle delay, the signal control parameters are then optimized based on a dynamic programming method. Finally, numerical experiments show that average vehicle delay and maximum queue length can be reduced under all scenarios.
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Greene, Nathaniel T; Anbuhl, Kelsey L; Ferber, Alexander T; DeGuzman, Marisa; Allen, Paul D; Tollin, Daniel J
2018-08-01
Despite the common use of guinea pigs in investigations of the neural mechanisms of binaural and spatial hearing, their behavioral capabilities in spatial hearing tasks have surprisingly not been thoroughly investigated. To begin to fill this void, we tested the spatial hearing of adult male guinea pigs in several experiments using a paradigm based on the prepulse inhibition (PPI) of the acoustic startle response. In the first experiment, we presented continuous broadband noise from one speaker location and switched to a second speaker location (the "prepulse") along the azimuth prior to presenting a brief, ∼110 dB SPL startle-eliciting stimulus. We found that the startle response amplitude was systematically reduced for larger changes in speaker swap angle (i.e., greater PPI), indicating that using the speaker "swap" paradigm is sufficient to assess stimulus detection of spatially separated sounds. In a second set of experiments, we swapped low- and high-pass noise across the midline to estimate their ability to utilize interaural time- and level-difference cues, respectively. The results reveal that guinea pigs can utilize both binaural cues to discriminate azimuthal sound sources. A third set of experiments examined spatial release from masking using a continuous broadband noise masker and a broadband chirp signal, both presented concurrently at various speaker locations. In general, animals displayed an increase in startle amplitude (i.e., lower PPI) when the masker was presented at speaker locations near that of the chirp signal, and reduced startle amplitudes (increased PPI) indicating lower detection thresholds when the noise was presented from more distant speaker locations. In summary, these results indicate that guinea pigs can: 1) discriminate changes in source location within a hemifield as well as across the midline, 2) discriminate sources of low- and high-pass sounds, demonstrating that they can effectively utilize both low-frequency interaural time and high-frequency level difference sound localization cues, and 3) utilize spatial release from masking to discriminate sound sources. This report confirms the guinea pig as a suitable spatial hearing model and reinforces prior estimates of guinea pig hearing ability from acoustical and physiological measurements. Copyright © 2018 Elsevier B.V. All rights reserved.
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2015-01-01
Iterative, nonreducing polyketide synthases (NR-PKSs) are multidomain enzymes responsible for the construction of the core architecture of aromatic polyketide natural products in fungi. Engineering these enzymes for the production of non-native metabolites has been a long-standing goal. We conducted a systematic survey of in vitro “domain swapped” NR-PKSs using an enzyme deconstruction approach. The NR-PKSs were dissected into mono- to multidomain fragments and recombined as noncognate pairs in vitro, reconstituting enzymatic activity. The enzymes used in this study produce aromatic polyketides that are representative of the four main chemical features set by the individual NR-PKS: starter unit selection, chain-length control, cyclization register control, and product release mechanism. We found that boundary conditions limit successful chemistry, which are dependent on a set of underlying enzymatic mechanisms. Crucial for successful redirection of catalysis, the rate of productive chemistry must outpace the rate of spontaneous derailment and thioesterase-mediated editing. Additionally, all of the domains in a noncognate system must interact efficiently if chemical redirection is to proceed. These observations refine and further substantiate current understanding of the mechanisms governing NR-PKS catalysis. PMID:24815013
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-04-17
... Proposed Rule Change Regarding Acceptance of Additional Interest Rate Swaps and Related Interbank Rates for... organization offering interest rate swap (``IRS'') clearing services. More specifically, the proposed rule... Dollar (``AUD'') [[Page 22826
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Impacts and Future of the California Fuel Tax Swap of 2010.
DOT National Transportation Integrated Search
2016-05-01
California's Gas Tax Swap remains controversial, and the issue is compounded by the States current need to finance some $59 billion worth of backlogged highway maintenance projects. Even before the Governor Schwarzenegger made his proposal, there ...
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-09-24
...; Overnight Index Swaps (``OIS'') denominated in USD, EUR, GBP and Japanese Yen (``JPY'') with Termination... Termination Dates up to 50 years; Overnight Index Swaps (``OIS'') denominated in USD, EUR, GBP and Japanese...
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NASA Astrophysics Data System (ADS)
Rosenblum, Serge; Borne, Adrien; Dayan, Barak
2017-03-01
The long-standing goal of deterministic quantum interactions between single photons and single atoms was recently realized in various experiments. Among these, an appealing demonstration relied on single-photon Raman interaction (SPRINT) in a three-level atom coupled to a single-mode waveguide. In essence, the interference-based process of SPRINT deterministically swaps the qubits encoded in a single photon and a single atom, without the need for additional control pulses. It can also be harnessed to construct passive entangling quantum gates, and can therefore form the basis for scalable quantum networks in which communication between the nodes is carried out only by single-photon pulses. Here we present an analytical and numerical study of SPRINT, characterizing its limitations and defining parameters for its optimal operation. Specifically, we study the effect of losses, imperfect polarization, and the presence of multiple excited states. In all cases we discuss strategies for restoring the operation of SPRINT.
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Rovenich, Hanna; Song, Yin; Liebrand, Thomas W. H.; Masini, Laura; van den Berg, Grardy C. M.; Joosten, Matthieu H. A. J.; Thomma, Bart P. H. J.
2014-01-01
Resistance in tomato against race 1 strains of the fungal vascular wilt pathogens Verticillium dahliae and V. albo-atrum is mediated by the Ve locus. This locus comprises two closely linked inversely oriented genes, Ve1 and Ve2, which encode cell surface receptors of the extracellular leucine-rich repeat receptor-like protein (eLRR-RLP) type. While Ve1 mediates Verticillium resistance through monitoring the presence of the recently identified V. dahliae Ave1 effector, no functionality for Ve2 has been demonstrated in tomato. Ve1 and Ve2 contain 37 eLRRs and share 84% amino acid identity, facilitating investigation of Ve protein functionality through domain swapping. In this study it is shown that Ve chimeras in which the first thirty eLRRs of Ve1 were replaced by those of Ve2 remain able to induce HR and activate Verticillium resistance, and that deletion of these thirty eLRRs from Ve1 resulted in loss of functionality. Also the region between eLRR30 and eLRR35 is required for Ve1-mediated resistance, and cannot be replaced by the region between eLRR30 and eLRR35 of Ve2. We furthermore show that the cytoplasmic tail of Ve1 is required for functionality, as truncation of this tail results in loss of functionality. Moreover, the C-terminus of Ve2 fails to activate immune signaling as chimeras containing the C-terminus of Ve2 do not provide Verticillium resistance. Furthermore, Ve1 was found to interact through its C-terminus with the eLRR-containing receptor-like kinase (eLRR-RLK) interactor SOBIR1 that was recently identified as an interactor of eLRR-RLP (immune) receptors. Intriguingly, also Ve2 was found to interact with SOBIR1. PMID:24505431
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78 FR 43785 - Exemptive Order Regarding Compliance With Certain Swap Regulations
Federal Register 2010, 2011, 2012, 2013, 2014
2013-07-22
... the MSP definition in Commission regulation 1.3(hhh). When a person holds swap positions above those...(ggg)(4) or in its calculation of whether it is an MSP for purposes of Commission regulation 1.3(hhh...
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17 CFR 37.203 - Rule enforcement program.
Code of Federal Regulations, 2014 CFR
2014-04-01
... shall establish and enforce trading, trade processing, and participation rules that will deter abuses... practices prohibited. A swap execution facility shall prohibit abusive trading practices on its markets by members and market participants. Swap execution facilities that permit intermediation shall prohibit...
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Understanding your capital options.
Payne, Christopher T
2012-05-01
When planning capital expenditures, hospitals and health systems should understand the following financing considerations: Traditional fixed-rate tax-exempt bonds; Variable-rate financing alternatives; Basel III Accord requirements; Direct tax-exempt bank loans; Total return swaps Taxable financings; Interest-rate swaps and collateral requirements
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-03-29
... Circular Related to Swap Data Repository Reporting March 21, 2013. Pursuant to Section 19(b)(1) of the... (``CFTC'') Part 43 and Part 45 regulations (Swap Data Repository Reporting) (``ICC Circular 2013/005...
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Can we scan the supernova model space for collective oscillations?
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pehlivan, Y., E-mail: yamac.pehlivan@msgsu.edu.tr; National Astronomical Observatory of Japan 2-21-1 Osawa, Mitaka, Tokyo, 181-8588; Subaşı, A. L.
Collective neutrino oscillations in a core collapse supernova is a many-body phenomenon which can transform the neutrino energy spectra through emergent effects. One example of this behavior is the neutrino spectral swaps in which neutrinos of different flavors partially or completely exchange their spectra. In this talk, we address the question of how model dependent this behavior is. In particular, we demonstrate that these swaps may be independent of the mean field approximation that is typically employed in numerical treatments by showing an example of a spectral swap in the exact many-body picture.
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Theoretical Bounds of Direct Binary Search Halftoning.
Liao, Jan-Ray
2015-11-01
Direct binary search (DBS) produces the images of the best quality among half-toning algorithms. The reason is that it minimizes the total squared perceived error instead of using heuristic approaches. The search for the optimal solution involves two operations: (1) toggle and (2) swap. Both operations try to find the binary states for each pixel to minimize the total squared perceived error. This error energy minimization leads to a conjecture that the absolute value of the filtered error after DBS converges is bounded by half of the peak value of the autocorrelation filter. However, a proof of the bound's existence has not yet been found. In this paper, we present a proof that shows the bound existed as conjectured under the condition that at least one swap occurs after toggle converges. The theoretical analysis also indicates that a swap with a pixel further away from the center of the autocorrelation filter results in a tighter bound. Therefore, we propose a new DBS algorithm which considers toggle and swap separately, and the swap operations are considered in the order from the edge to the center of the filter. Experimental results show that the new algorithm is more efficient than the previous algorithm and can produce half-toned images of the same quality as the previous algorithm.
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Dude Looks like a Lady: Gender Swapping in an Online Game
NASA Astrophysics Data System (ADS)
Huh, Searle; Williams, Dmitri
After reviewing the literature on online identity construction and developing a set of theory-based hypotheses, this chapter employs a novel combination of survey data and game-generated behavioral logs to examine gender swapping in EverQuest II. Gender swapping is defined as a difference between the gender reported by the player in the survey from the gender of the player's main character in the game. Motivations for play were measured using Yee's condensed MMO motivations scale, and behavioral logs supplied four main measures of gender-stereotypical in-game behaviors. Contrary to expectations, gender swapping was less common among female players, and swapping was rather rare in general. Homosexual players were more likely to change their online gender than straight players. Performance and socialization motivations for play did not differ significantly between swappers and nonswappers. Men who play female characters were not more likely to engage in stereotypically female acts than men who play male characters; however, women who played male characters did display a degree of hyper-masculine behavior. Some of these findings suggest that there may be less of the identity exploration or challenging of gender norms than some had expected, but the female population of players may be bimodal, composed of stereotypically female and male-leaning subgroups.
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Straccamore, Francesca; Ruggi, Simona; Lingiardi, Vittorio; Zanardi, Raffaella; Vecchi, Sara; Oasi, Osmano
2017-01-01
Introduction: This study focuses on the relationship between personality configurations and depressive experiences. More specifically, the aim of this study is to investigate the relationship between self-criticism and dependency and personality styles or disorders, exploring the association between personality features and depressive symptoms. The two-configurations model of personality developed by Blatt (2004, 2008) is adopted as a reference point in sharing a valid framework and in understanding the results. Methods: Five instruments are administered to 51 participants with a diagnosis of depressive disorder, in accordance with DSM-IV-TR (American Psychiatric Association, 2000): Self-criticism and dependency dimensions of depression are measured with the Depressive Experiences Questionnaire (DEQ); self-reported depression is assessed with the Beck Depression Inventory-II (BDI-II); observer-rated depression is assessed with the Hamilton Depression Rating Scale (HDRS); personality is assessed with the Clinical Diagnostic Interview (CDI) and the Shedler Westen Assessment Procedure-200 (SWAP-200). Results: Only self-criticism, and not dependency, is associated with depressive symptoms. In addition, the SWAP Borderline PD Scale and the Dysphoric: Emotionally dysregulated Q-factor emerge as significant in predicting depression. Conclusions: Findings support the assumption that depressive personality configurations can enhance the vulnerability to developing depression. Theoretical and clinical implications of these results are discussed. PMID:28316575
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17 CFR 37.406 - Trade reconstruction.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 17 Commodity and Securities Exchanges 1 2014-04-01 2014-04-01 false Trade reconstruction. 37.406 Section 37.406 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP EXECUTION FACILITIES Monitoring of Trading and Trade Processing § 37.406 Trade reconstruction. The swap execution...
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Code of Federal Regulations, 2014 CFR
2014-04-01
... data repository. (10) Position. The term “position” means the gross and net notional amounts of open... Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION (CONTINUED) SWAP DATA REPOSITORIES... directly, or indirectly, controls, is controlled by, or is under common control with, the swap data...
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75 FR 59666 - Agricultural Swaps
Federal Register 2010, 2011, 2012, 2013, 2014
2010-09-28
..., grain sorghums, mill feeds, butter, eggs, Solanum tuberosum (Irish potatoes), wool, wool tops, fats and oils (including lard, tallow, cottonseed oil, peanut oil, soybean oil, and all other fats and oils... the Commodity Exchange Act (a) Permitting Eligible Swap Participants To Submit for Clearing and ICE...
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77 FR 41110 - Exemptive Order Regarding Compliance With Certain Swap Regulations
Federal Register 2010, 2011, 2012, 2013, 2014
2012-07-12
... delay compliance with certain entity-level requirements of the CEA (and Commission regulations promulgated thereunder), subject to specified conditions. Additionally, with respect to transaction-level.... major swap participants may delay compliance with certain entity-level requirements of the CEA (and...
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-12-30
... Part IV Securities and Exchange Commission 17 CFR Parts 240 and 249 Process for Submissions for Review of Security-Based Swaps for Mandatory Clearing and Notice Filing Requirements for Clearing...;#0; [[Page 82490
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17 CFR 39.5 - Review of swaps for Commission determination on clearing requirement.
Code of Federal Regulations, 2013 CFR
2013-04-01
... publicly; (vi) Risk management procedures, including measurement and monitoring of credit exposures... derivative clearing organization's ability to manage the risks associated with clearing the swap, especially... of rule framework, capacity, operational expertise and resources, and credit support infrastructure...
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17 CFR 39.5 - Review of swaps for Commission determination on clearing requirement.
Code of Federal Regulations, 2014 CFR
2014-04-01
... publicly; (vi) Risk management procedures, including measurement and monitoring of credit exposures... derivative clearing organization's ability to manage the risks associated with clearing the swap, especially... of rule framework, capacity, operational expertise and resources, and credit support infrastructure...
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Marinov, Dimitar; Querner, Erik; Roelsma, Jan
2005-04-01
Unsaturated zone models are useful tools in predicting effects of measures and can be used to optimise agricultural practice aiming to minimise the impact on the environment. However, current soil models have a varying degree of abstraction level referring to simulated processes in time and space. In the framework of an EU funded project the SWAP (Soil-Water-Atmosphere-Plant) and ANIMO (Agricultural-Nutrient-Model) models were tested for an experimental arable plot in Bulgaria. SWAP was used to simulate water flow in the soil while ANIMO describes nitrogen movement and transformations. The objectives of this study are: (i) to show results of the combined application of water and nitrogen dynamics of originally Dutch models SWAP and ANIMO for specific Bulgarian soil and hydrological conditions; (ii) to calibrate and evaluate SWAP and ANIMO models by comparing numerical results with field measurements collected for an arable field in western Bulgaria and (iii) to analyse possible contamination of groundwater due to agricultural practice in the considered region. Further a short description of the experimental plot, as well as information about parameters of the investigated soil profiles, is provided. The obtained SWAP results evidenced that the model gives sufficient adaptation for soil water dynamics. The simulations of ANIMO for nitrogen cycle show greater divergence with observations but are satisfactory precise for the purposes of assessing land use impact on groundwater quality. In general, differences between model results and field measurements do not exceed 10-15%. For the experimental plot predictions indicate nitrate-N concentrations less then 5 mg/l in deeper soil compartments and low downward annual flux containing 0.133 kg N/ha. These results indicate that there is no serious pollution of the shallow groundwater table by nitrogen resulting from land use and agricultural activities.
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76 FR 43851 - Large Trader Reporting for Physical Commodity Swaps
Federal Register 2010, 2011, 2012, 2013, 2014
2011-07-22
... position, or gross long and gross short futures equivalent positions on a non-delta-adjusted basis if the... from clearing organizations, clearing members and swap dealers and apply non-routine reporting... implementing and conducting effective surveillance of economically equivalent physical commodity futures...
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17 CFR 23.23-23.40 - [Reserved
Code of Federal Regulations, 2012 CFR
2012-04-01
... 17 Commodity and Securities Exchanges 1 2012-04-01 2012-04-01 false [Reserved] 23.23-23.40 Section 23.23-23.40 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP DEALERS AND MAJOR SWAP PARTICIPANTS Registration §§ 23.23-23.40 [Reserved] ...
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Code of Federal Regulations, 2012 CFR
2012-04-01
... 17 Commodity and Securities Exchanges 1 2012-04-01 2012-04-01 false [Reserved] 23.1-23.20 Section 23.1-23.20 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP DEALERS AND MAJOR SWAP PARTICIPANTS Reserved §§ 23.1-23.20 [Reserved] ...
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17 CFR 23.23-23.40 - [Reserved
Code of Federal Regulations, 2013 CFR
2013-04-01
... 17 Commodity and Securities Exchanges 1 2013-04-01 2013-04-01 false [Reserved] 23.23-23.40 Section 23.23-23.40 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP DEALERS AND MAJOR SWAP PARTICIPANTS Registration §§ 23.23-23.40 [Reserved] ...
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17 CFR 23.23-23.40 - [Reserved
Code of Federal Regulations, 2014 CFR
2014-04-01
... 17 Commodity and Securities Exchanges 1 2014-04-01 2014-04-01 false [Reserved] 23.23-23.40 Section 23.23-23.40 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP DEALERS AND MAJOR SWAP PARTICIPANTS Registration §§ 23.23-23.40 [Reserved] ...
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17 CFR 37.12 - Trade execution compliance schedule.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 17 Commodity and Securities Exchanges 1 2014-04-01 2014-04-01 false Trade execution compliance... EXECUTION FACILITIES General Provisions § 37.12 Trade execution compliance schedule. (a) A swap transaction... days after the available-to-trade determination submission or certification for that swap is...
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17 CFR 37.1000 - Core Principle 10-Recordkeeping and reporting.
Code of Federal Regulations, 2014 CFR
2014-04-01
... records relating to swaps defined in section 1a(47)(A)(v) of the Act open to inspection and examination by the Securities and Exchange Commission. (b) Requirements. The Commission shall adopt data collection... requirements for derivatives clearing organizations and swap data repositories. ...
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75 FR 67277 - Process for Review of Swaps for Mandatory Clearing
Federal Register 2010, 2011, 2012, 2013, 2014
2010-11-02
... enacted to reduce risk, increase transparency, and promote market integrity within the financial system by... ability to manage the risks associated with clearing the swap, especially if the Commission determines... relating to product specifications; participant eligibility standards; pricing sources, models, and...
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76 FR 4751 - Position Limits for Derivatives
Federal Register 2010, 2011, 2012, 2013, 2014
2011-01-26
... designated contract markets (``DCM'') and physical commodity swaps that are economically equivalent to such... non-spot-month limits based on open interest levels as well as establishing Commission-determined spot...''), swaps that are economically equivalent to DCM futures and option contracts with position limits, and...
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76 FR 65999 - Effective Date for Swap Regulation
Federal Register 2010, 2011, 2012, 2013, 2014
2011-10-25
... COMMODITY FUTURES TRADING COMMISSION 17 CFR Chapter 1 Effective Date for Swap Regulation AGENCY: Commodity Futures Trading Commission. ACTION: Notice of proposed amendment. SUMMARY: On July 14, 2011, the Commodity Futures Trading Commission (``CFTC'' or the ``Commission'') issued a final order (``July 14 Order...
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Ravi, Maruthachalam; Kwong, Pak N; Menorca, Ron M G; Valencia, Joel T; Ramahi, Joseph S; Stewart, Jodi L; Tran, Robert K; Sundaresan, Venkatesan; Comai, Luca; Chan, Simon W-L
2010-10-01
Centromeres control chromosome inheritance in eukaryotes, yet their DNA structure and primary sequence are hypervariable. Most animals and plants have megabases of tandem repeats at their centromeres, unlike yeast with unique centromere sequences. Centromere function requires the centromere-specific histone CENH3 (CENP-A in human), which replaces histone H3 in centromeric nucleosomes. CENH3 evolves rapidly, particularly in its N-terminal tail domain. A portion of the CENH3 histone-fold domain, the CENP-A targeting domain (CATD), has been previously shown to confer kinetochore localization and centromere function when swapped into human H3. Furthermore, CENP-A in human cells can be functionally replaced by CENH3 from distantly related organisms including Saccharomyces cerevisiae. We have used cenh3-1 (a null mutant in Arabidopsis thaliana) to replace endogenous CENH3 with GFP-tagged variants. A H3.3 tail domain-CENH3 histone-fold domain chimera rescued viability of cenh3-1, but CENH3's lacking a tail domain were nonfunctional. In contrast to human results, H3 containing the A. thaliana CATD cannot complement cenh3-1. GFP-CENH3 from the sister species A. arenosa functionally replaces A. thaliana CENH3. GFP-CENH3 from the close relative Brassica rapa was targeted to centromeres, but did not complement cenh3-1, indicating that kinetochore localization and centromere function can be uncoupled. We conclude that CENH3 function in A. thaliana, an organism with large tandem repeat centromeres, has stringent requirements for functional complementation in mitosis.
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Dynamical emergence of the Universe into the false vacuum
NASA Astrophysics Data System (ADS)
Rafelski, Johann; Birrell, Jeremiah
2015-11-01
We study how the hot Universe evolves and acquires the prevailing vacuum state, demonstrating that in specific conditions which are believed to apply, the Universe becomes frozen into the state with the smallest value of Higgs vacuum field v=langle hrangle, even if this is not the state of lowest energy. This supports the false vacuum dark energy Λ-model. Under several likely hypotheses we determine the temperature in the evolution of the Universe at which two vacuua v1, v2 can swap between being true and false. We evaluate the dynamical surface pressure on domain walls between low and high mass vaccua due to the presence of matter and show that the low mass state remains the preferred vacuum of the Universe.
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-11-23
...In accordance with the Dodd-Frank Wall Street Reform and Consumer Protection Act of 2010 (``Dodd-Frank Act''), the Securities and Exchange Commission (``Commission''), pursuant to the Securities Exchange Act of 1934 (``Exchange Act''), is proposing capital and margin requirements for security-based swap dealers (``SBSDs'') and major security-based swap participants (``MSBSPs''), segregation requirements for SBSDs, and notification requirements with respect to segregation for SBSDs and MSBSPs. The Commission also is proposing to increase the minimum net capital requirements for broker-dealers permitted to use the alternative internal model-based method for computing net capital (``ANC broker-dealers'').
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Analytical pricing formulas for hybrid variance swaps with regime-switching
NASA Astrophysics Data System (ADS)
Roslan, Teh Raihana Nazirah; Cao, Jiling; Zhang, Wenjun
2017-11-01
The problem of pricing discretely-sampled variance swaps under stochastic volatility, stochastic interest rate and regime-switching is being considered in this paper. An extension of the Heston stochastic volatility model structure is done by adding the Cox-Ingersoll-Ross (CIR) stochastic interest rate model. In addition, the parameters of the model are permitted to have transitions following a Markov chain process which is continuous and discoverable. This hybrid model can be used to illustrate certain macroeconomic conditions, for example the changing phases of business stages. The outcome of our regime-switching hybrid model is presented in terms of analytical pricing formulas for variance swaps.
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Monniot, Céline; Boisramé, Anita; Da Costa, Grégory; Chauvel, Muriel; Sautour, Marc; Bougnoux, Marie-Elisabeth; Bellon-Fontaine, Marie-Noëlle; Dalle, Frédéric; d'Enfert, Christophe; Richard, Mathias L
2013-01-01
Cell wall proteins are central to the virulence of Candida albicans. Hwp1, Hwp2 and Rbt1 form a family of hypha-associated cell surface proteins. Hwp1 and Hwp2 have been involved in adhesion and other virulence traits but Rbt1 is still poorly characterized. To assess the role of Rbt1 in the interaction of C. albicans with biotic and abiotic surfaces independently of its morphological state, heterologous expression and promoter swap strategies were applied. The N-terminal domain with features typical of the Flo11 superfamily was found to be essential for adhesiveness to polystyrene through an increase in cell surface hydrophobicity. A 42 amino acid-long domain localized in the central part of the protein was shown to enhance the aggregation function. We demonstrated that a VTTGVVVVT motif within the 42 amino acid domain displayed a high β-aggregation potential and was responsible for cell-to-cell interactions by promoting the aggregation of hyphae. Finally, we showed through constitutive expression that while Rbt1 was directly accessible to antibodies in hyphae, it was not so in yeast. Similar results were obtained for another cell wall protein, namely Iff8, and suggested that modification of the cell wall structure between yeast and hyphae can regulate the extracellular accessibility of cell wall proteins independently of gene regulation.
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Sanchez-Sandoval, Ana Laura; Herrera Carrillo, Zazil; Díaz Velásquez, Clara Estela; Delgadillo, Dulce María; Rivera, Heriberto Manuel; Gomora, Juan Carlos
2018-01-01
Voltage-gated calcium channels contain four highly conserved transmembrane helices known as S4 segments that exhibit a positively charged residue every third position, and play the role of voltage sensing. Nonetheless, the activation range between high-voltage (HVA) and low-voltage (LVA) activated calcium channels is around 30-40 mV apart, despite the high level of amino acid similarity within their S4 segments. To investigate the contribution of S4 voltage sensors for the low-voltage activation characteristics of CaV3.3 channels we constructed chimeras by swapping S4 segments between this LVA channel and the HVA CaV1.2 channel. The substitution of S4 segment of Domain II in CaV3.3 by that of CaV1.2 (chimera IIS4C) induced a ~35 mV shift in the voltage-dependence of activation towards positive potentials, showing an I-V curve that almost overlaps with that of CaV1.2 channel. This HVA behavior induced by IIS4C chimera was accompanied by a 2-fold decrease in the voltage-dependence of channel gating. The IVS4 segment had also a strong effect in the voltage sensing of activation, while substitution of segments IS4 and IIIS4 moved the activation curve of CaV3.3 to more negative potentials. Swapping of IIS4 voltage sensor influenced additional properties of this channel such as steady-state inactivation, current decay, and deactivation. Notably, Domain I voltage sensor played a major role in preventing CaV3.3 channels to inactivate from closed states at extreme hyperpolarized potentials. Finally, site-directed mutagenesis in the CaV3.3 channel revealed a partial contribution of the S4-S5 linker of Domain II to LVA behavior, with synergic effects observed in double and triple mutations. These findings indicate that IIS4 and, to a lesser degree IVS4, voltage sensors are crucial in determining the LVA properties of CaV3.3 channels, although the accomplishment of this function involves the participation of other structural elements like S4-S5 linkers.
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Sanchez-Sandoval, Ana Laura; Herrera Carrillo, Zazil; Díaz Velásquez, Clara Estela; Delgadillo, Dulce María; Rivera, Heriberto Manuel
2018-01-01
Voltage-gated calcium channels contain four highly conserved transmembrane helices known as S4 segments that exhibit a positively charged residue every third position, and play the role of voltage sensing. Nonetheless, the activation range between high-voltage (HVA) and low-voltage (LVA) activated calcium channels is around 30–40 mV apart, despite the high level of amino acid similarity within their S4 segments. To investigate the contribution of S4 voltage sensors for the low-voltage activation characteristics of CaV3.3 channels we constructed chimeras by swapping S4 segments between this LVA channel and the HVA CaV1.2 channel. The substitution of S4 segment of Domain II in CaV3.3 by that of CaV1.2 (chimera IIS4C) induced a ~35 mV shift in the voltage-dependence of activation towards positive potentials, showing an I-V curve that almost overlaps with that of CaV1.2 channel. This HVA behavior induced by IIS4C chimera was accompanied by a 2-fold decrease in the voltage-dependence of channel gating. The IVS4 segment had also a strong effect in the voltage sensing of activation, while substitution of segments IS4 and IIIS4 moved the activation curve of CaV3.3 to more negative potentials. Swapping of IIS4 voltage sensor influenced additional properties of this channel such as steady-state inactivation, current decay, and deactivation. Notably, Domain I voltage sensor played a major role in preventing CaV3.3 channels to inactivate from closed states at extreme hyperpolarized potentials. Finally, site-directed mutagenesis in the CaV3.3 channel revealed a partial contribution of the S4-S5 linker of Domain II to LVA behavior, with synergic effects observed in double and triple mutations. These findings indicate that IIS4 and, to a lesser degree IVS4, voltage sensors are crucial in determining the LVA properties of CaV3.3 channels, although the accomplishment of this function involves the participation of other structural elements like S4-S5 linkers. PMID:29474447
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-12-22
... Acting as Counterparties to Special Entities 1. Qualifications of the Independent Representative 2. Statutory Disqualification 3. Independent 4. Best Interests 5. Makes Appropriate and Timely Disclosures 6... Contributions by Independent Representative of a Municipal Entity 9. Unqualified Independent Representative 10...
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17 CFR 4.34 - General disclosures required.
Code of Federal Regulations, 2013 CFR
2013-04-01
... the commodity trading advisor may engage in retail forex transactions pursuant to the offered trading... pursuant to such program (including retail forex and swap transactions, if any). (h) Trading program. A... difference between bid and asked prices on retail forex or swap transactions, the trading advisor must...
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17 CFR 4.34 - General disclosures required.
Code of Federal Regulations, 2014 CFR
2014-04-01
... the commodity trading advisor may engage in retail forex transactions pursuant to the offered trading... pursuant to such program (including retail forex and swap transactions, if any). (h) Trading program. A... difference between bid and asked prices on retail forex or swap transactions, the trading advisor must...
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17 CFR 38.11 - Trade execution compliance schedule.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 17 Commodity and Securities Exchanges 1 2014-04-01 2014-04-01 false Trade execution compliance... DESIGNATED CONTRACT MARKETS General Provisions § 38.11 Trade execution compliance schedule. (a) A swap... (2) Thirty days after the available-to-trade determination submission or certification for that swap...
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12 CFR 237.22 - Transition period for insured depository institutions.
Code of Federal Regulations, 2014 CFR
2014-01-01
... quantitative and qualitative impacts of divestiture or cessation of swap or security-based swaps activities on the insured depository institution, including information that addresses the factors in paragraph (d... consideration of the factors in paragraph (c) of this section. (c) Factors governing Board determinations. In...
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78 FR 909 - Further Proposed Guidance Regarding Compliance With Certain Swap Regulations
Federal Register 2010, 2011, 2012, 2013, 2014
2013-01-07
... establish a new regulatory framework for swaps. The legislation was enacted to reduce systemic risk... increase understanding of each other's regulatory approaches and to harmonize the cross-border approaches... may lead to divergent approaches to cross-border activities. The Commission also recognizes the...
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Code of Federal Regulations, 2014 CFR
2014-04-01
... market value or net present value of a swap. [77 FR 55960, Sept. 11, 2012] ... notional value of some or all of the swaps submitted by the counterparties for inclusion in the portfolio... whose combined notional value (or some other measure of risk) is less than the combined notional value...
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Code of Federal Regulations, 2013 CFR
2013-04-01
... market value or net present value of a swap. [77 FR 55960, Sept. 11, 2012] ... notional value of some or all of the swaps submitted by the counterparties for inclusion in the portfolio... whose combined notional value (or some other measure of risk) is less than the combined notional value...
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76 FR 44464 - Process for Review of Swaps for Mandatory Clearing
Federal Register 2010, 2011, 2012, 2013, 2014
2011-07-26
... COMMODITY FUTURES TRADING COMMISSION 17 CFR Parts 39 and 140 RIN 3038-AD00 Process for Review of Swaps for Mandatory Clearing AGENCY: Commodity Futures Trading Commission. ACTION: Final rule. SUMMARY: The Commodity Futures Trading Commission (Commission or CFTC) is adopting regulations to implement...
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Smith, Heidi K.; Luo, Linjiao; O’Halloran, Damien; Guo, Dagang; Huang, Xin-Yun; Samuel, Aravinthan D. T.; Hobert, Oliver
2013-01-01
Cyclic guanosine monophosphate (cGMP) is a key secondary messenger used in signal transduction in various types of sensory neurons. The importance of cGMP in the ASE gustatory receptor neurons of the nematode Caenorhabditis elegans was deduced by the observation that multiple receptor-type guanylyl cyclases (rGCs), encoded by the gcy genes, and two presently known cyclic nucleotide-gated ion channel subunits, encoded by the tax-2 and tax-4 genes, are essential for ASE-mediated gustatory behavior. We describe here specific mechanistic features of cGMP-mediated signal transduction in the ASE neurons. First, we assess the specificity of the sensory functions of individual rGC proteins. We have previously shown that multiple rGC proteins are expressed in a left/right asymmetric manner in the functionally lateralized ASE neurons and are required to sense distinct salt cues. Through domain swap experiments among three different rGC proteins, we show here that the specificity of individual rGC proteins lies in their extracellular domains and not in their intracellular, signal-transducing domains. Furthermore, we find that rGC proteins are also sufficient to confer salt sensory responses to other neurons. Both findings support the hypothesis that rGC proteins are salt receptor proteins. Second, we identify a novel, likely downstream effector of the rGC proteins in gustatory signal transduction, a previously uncharacterized cyclic nucleotide-gated (CNG) ion channel, encoded by the che-6 locus. che-6 mutants show defects in gustatory sensory transduction that are similar to defects observed in animals lacking the tax-2 and tax-4 CNG channels. In contrast, thermosensory signal transduction, which also requires tax-2 and tax-4, does not require che-6, but requires another CNG, cng-3. We propose that CHE-6 may form together with two other CNG subunits, TAX-2 and TAX-4, a gustatory neuron-specific heteromeric CNG channel complex. PMID:23695300
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Narayan, Sreenath; Kalhan, Satish C.; Wilson, David L.
2012-01-01
I.Abstract Purpose To reduce swaps in fat-water separation methods, a particular issue on 7T small animal scanners due to field inhomogeneity, using image postprocessing innovations that detect and correct errors in the B0 field map. Materials and Methods Fat-water decompositions and B0 field maps were computed for images of mice acquired on a 7T Bruker BioSpec scanner, using a computationally efficient method for solving the Markov Random Field formulation of the multi-point Dixon model. The B0 field maps were processed with a novel hole-filling method, based on edge strength between regions, and a novel k-means method, based on field-map intensities, which were iteratively applied to automatically detect and reinitialize error regions in the B0 field maps. Errors were manually assessed in the B0 field maps and chemical parameter maps both before and after error correction. Results Partial swaps were found in 6% of images when processed with FLAWLESS. After REFINED correction, only 0.7% of images contained partial swaps, resulting in an 88% decrease in error rate. Complete swaps were not problematic. Conclusion Ex post facto error correction is a viable supplement to a priori techniques for producing globally smooth B0 field maps, without partial swaps. With our processing pipeline, it is possible to process image volumes rapidly, robustly, and almost automatically. PMID:23023815
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Narayan, Sreenath; Kalhan, Satish C; Wilson, David L
2013-05-01
To reduce swaps in fat-water separation methods, a particular issue on 7 Tesla (T) small animal scanners due to field inhomogeneity, using image postprocessing innovations that detect and correct errors in the B0 field map. Fat-water decompositions and B0 field maps were computed for images of mice acquired on a 7T Bruker BioSpec scanner, using a computationally efficient method for solving the Markov Random Field formulation of the multi-point Dixon model. The B0 field maps were processed with a novel hole-filling method, based on edge strength between regions, and a novel k-means method, based on field-map intensities, which were iteratively applied to automatically detect and reinitialize error regions in the B0 field maps. Errors were manually assessed in the B0 field maps and chemical parameter maps both before and after error correction. Partial swaps were found in 6% of images when processed with FLAWLESS. After REFINED correction, only 0.7% of images contained partial swaps, resulting in an 88% decrease in error rate. Complete swaps were not problematic. Ex post facto error correction is a viable supplement to a priori techniques for producing globally smooth B0 field maps, without partial swaps. With our processing pipeline, it is possible to process image volumes rapidly, robustly, and almost automatically. Copyright © 2012 Wiley Periodicals, Inc.
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Roodveldt, Cintia; Andersson, August; De Genst, Erwin J; Labrador-Garrido, Adahir; Buell, Alexander K; Dobson, Christopher M; Tartaglia, Gian Gaetano; Vendruscolo, Michele
2012-11-06
The aggregation process of α-synuclein, a protein closely associated with Parkinson's disease, is highly sensitive to sequence variations. It is therefore of great importance to understand the factors that define the aggregation propensity of specific mutational variants as well as their toxic behavior in the cellular environment. In this context, we investigated the extent to which the aggregation behavior of α-synuclein can be altered to resemble that of β-synuclein, an aggregation-resistant homologue of α-synuclein not associated with disease, by swapping residues between the two proteins. Because of the vast number of possible swaps, we have applied a rational design procedure to single out a mutational variant, called α2β, in which two short stretches of the sequence in the NAC region have been replaced in α-synuclein from β-synuclein. We find not only that the aggregation rate of α2β is close to that of β-synuclein, being much lower than that of α-synuclein, but also that α2β effectively changes the cellular toxicity of α-synuclein to a value similar to that of β-synuclein upon exposure of SH-SY5Y cells to preformed oligomers. Remarkably, control experiments on the corresponding mutational variant of β-synuclein, called β2α, confirmed that the mutations that we have identified also shift the aggregation behavior of this protein toward that of α-synuclein. These results demonstrate that it is becoming possible to control in quantitative detail the sequence code that defines the aggregation behavior and toxicity of α-synuclein.
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NASA Astrophysics Data System (ADS)
Holasek, Rick; Nakanishi, Keith; Ziph-Schatzberg, Leah; Santman, Jeff; Woodman, Patrick; Zacaroli, Richard; Wiggins, Richard
2017-04-01
Hyperspectral imaging (HSI) has been used for over two decades in laboratory research, academic, environmental and defense applications. In more recent time, HSI has started to be adopted for commercial applications in machine vision, conservation, resource exploration, and precision agriculture, to name just a few of the economically viable uses for the technology. Corning Incorporated (Corning) has been developing and manufacturing HSI sensors, sensor systems, and sensor optical engines, as well as HSI sensor components such as gratings and slits for over a decade and a half. This depth of experience and technological breadth has allowed Corning to design and develop unique HSI spectrometers with an unprecedented combination of high performance, low cost and low Size, Weight, and Power (SWaP). These sensors and sensor systems are offered with wavelength coverage ranges from the visible to the Long Wave Infrared (LWIR). The extremely low SWaP of Corning's HSI sensors and sensor systems enables their deployment using limited payload platforms such as small unmanned aerial vehicles (UAVs). This paper discusses use of the Corning patented monolithic design Offner spectrometer, the microHSI™, to build a highly compact 400-1000 nm HSI sensor in combination with a small Inertial Navigation System (INS) and micro-computer to make a complete turn-key airborne remote sensing payload. This Selectable Hyperspectral Airborne Remote sensing Kit (SHARK) has industry leading SWaP (1.5 lbs) at a disruptively low price due, in large part, to Corning's ability to manufacture the monolithic spectrometer out of polymers (i.e. plastic) and therefore reduce manufacturing costs considerably. The other factor in lowering costs is Corning's well established in house manufacturing capability in optical components and sensors that further enable cost-effective fabrication. The competitive SWaP and low cost of the microHSI™ sensor is approaching, and in some cases less than the price point of Multi Spectral Imaging (MSI) sensors. Specific designs of the Corning microHSI™ SHARK visNIR turn-key system are presented along with salient performance characteristics. Initial focus market areas include precision agriculture and historic and recent microHSI™ SHARK prototype test results are presented.
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-07-16
... Change Regarding Interest Rate Swap Clearing Changes July 10, 2013. Pursuant to Section 19(b)(1) of the... a derivatives clearing organization offering interest rate swap (``IRS'') clearing services. More... the Commodity Futures Trading Commission and currently offers clearing services for interest rate...
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-11-02
... audited by independent public accountants to all CDS Clearing Members engaged in security-based swap... clearing security-based swaps a report by independent public accountants regarding CME Group's system of... CME Group Inc. by independent public accountant regarding its system of internal accounting control...
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-01-28
... accommodate customer clearing of credit default swaps that reference government securities. Treasury is also... regulations impose obligations concerning financial responsibility, protection of customer securities and... clearance of credit default swaps (CDS)\\8\\ transactions on behalf of customers of ICE Trust clearing members...
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77 FR 65177 - Swap Data Repositories: Interpretative Statement Regarding the Confidentiality and...
Federal Register 2010, 2011, 2012, 2013, 2014
2012-10-25
... participation in standard-setting bodies to develop international standards relevant to the swap markets. Cloud Strategix, LLC (``Cloud Strategix''), representing the data hosting and cloud computing industry, in... Roundtable, June 6, 2012; (iii) Cloud Strategix, LLC, June 5, 2012; and (iv) the Depository Trust & Clearing...
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Lessons Learned from a Collaborative Sensor Web Prototype
NASA Technical Reports Server (NTRS)
Ames, Troy; Case, Lynne; Krahe, Chris; Hess, Melissa; Hennessy, Joseph F. (Technical Monitor)
2002-01-01
This paper describes the Sensor Web Application Prototype (SWAP) system that was developed for the Earth Science Technology Office (ESTO). The SWAP is aimed at providing an initial engineering proof-of-concept prototype highlighting sensor collaboration, dynamic cause-effect relationship between sensors, dynamic reconfiguration, and remote monitoring of sensor webs.
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78 FR 21046 - Amendment to Rule Filing Requirements for Dually-Registered Clearing Agencies
Federal Register 2010, 2011, 2012, 2013, 2014
2013-04-09
... relating to foreign currency, or, in general, any instrument commonly known as a `security'; or any..., potentially, energy and foreign exchange swaps.\\35\\ CME raised concerns that, by omitting swaps and certain... substantial potential delays'' when implementing rule changes that deal with products over which the...
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17 CFR 1.35 - Records of commodity interest and related cash or forward transactions.
Code of Federal Regulations, 2014 CFR
2014-04-01
... merchants, retail foreign exchange dealers, introducing brokers, and members of designated contract markets..., introducing broker, and member of a designated contract market or swap execution facility shall keep full... member of a designated contract market or swap execution facility must retain and produce for inspection...
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17 CFR 1.35 - Records of commodity interest and related cash or forward transactions.
Code of Federal Regulations, 2013 CFR
2013-04-01
... merchants, retail foreign exchange dealers, introducing brokers, and members of designated contract markets..., introducing broker, and member of a designated contract market or swap execution facility shall keep full... member of a designated contract market or swap execution facility must retain and produce for inspection...
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-09-20
...(h) of the CEA, by any of the following methods: Agency Web site, via its Comments Online process at... promote market integrity within the financial system by, among other things: (1) Providing for the... existing and potential market infrastructures, including clearinghouses, trading platforms, and swap data...
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76 FR 1213 - Core Principles and Other Requirements for Swap Execution Facilities
Federal Register 2010, 2011, 2012, 2013, 2014
2011-01-07
... Part II Commodity Futures Trading Commission 17 CFR Part 37 Core Principles and Other Requirements... RIN Number 3038-AD18 Core Principles and Other Requirements for Swap Execution Facilities AGENCY... Compliance With the Core Principles III. Effective Date and Transition Period IV. Related Matters A...
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Green Team News and Upcoming Events | Poster
By Melissa Porter, Staff Writer Spring Plant Swap 2013 This past October, you may have seen several members of the Green Team standing in front of Building 549 giving out free plants or offering to take extra plants off your hands—this was the first Green Team Fall Plant Swap.
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17 CFR 50.25 - Clearing requirement compliance schedule.
Code of Federal Regulations, 2014 CFR
2014-04-01
... major security-based swap participant; or an active fund. Category 2Entity means a commodity pool; a... beneficial owner to clear swaps. (b) Upon issuing a clearing requirement determination under section 2(h)(2... Entity, or any other entity that desires to clear the transaction, must comply with the requirements of...
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17 CFR 50.50 - Exceptions to the clearing requirement.
Code of Federal Regulations, 2014 CFR
2014-04-01
... the reduction of risks in the conduct and management of a commercial enterprise, where the risks arise... causes to be provided, the information specified in paragraph (b) of this section to a registered swap data repository or, if no registered swap data repository is available to receive the information from...
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17 CFR 50.50 - Exceptions to the clearing requirement.
Code of Federal Regulations, 2013 CFR
2013-04-01
... management of a commercial enterprise, where the risks arise from: (A) The potential change in the value of... information specified in paragraph (b) of this section to a registered swap data repository or, if no registered swap data repository is available to receive the information from the reporting counterparty, to...
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76 FR 49291 - Agricultural Swaps
Federal Register 2010, 2011, 2012, 2013, 2014
2011-08-10
...) Pursuant to Section 4(c) of the Commodity Exchange Act, Permitting the Kansas City Board of Trade Clearing Corporation To Clear Over-the-Counter Wheat Calendar Swaps and (2) Pursuant to Section 4d of the Commodity... businesses that produce, process, and merchandize energy commodities at retail and wholesale levels; National...
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17 CFR 37.1400 - Core Principle 14-System safeguards.
Code of Federal Regulations, 2014 CFR
2014-04-01
... procedures, and automated systems, that: (1) Are reliable and secure; and (2) Have adequate scalable capacity... 17 Commodity and Securities Exchanges 1 2014-04-01 2014-04-01 false Core Principle 14-System... SWAP EXECUTION FACILITIES System Safeguards § 37.1400 Core Principle 14—System safeguards. The swap...
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17 CFR 23.451 - Political contributions by certain swap dealers.
Code of Federal Regulations, 2013 CFR
2013-04-01
... any person who supervises, directly or indirectly, such employee; and (iii) Any political action... Special Entity for the swap dealer and any person who supervises, directly or indirectly, such employee...) After learning of the contribution: (A) Has taken all available steps to cause the contributor involved...
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17 CFR 23.451 - Political contributions by certain swap dealers.
Code of Federal Regulations, 2012 CFR
2012-04-01
... any person who supervises, directly or indirectly, such employee; and (iii) Any political action... Special Entity for the swap dealer and any person who supervises, directly or indirectly, such employee...) After learning of the contribution: (A) Has taken all available steps to cause the contributor involved...
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17 CFR 23.451 - Political contributions by certain swap dealers.
Code of Federal Regulations, 2014 CFR
2014-04-01
... any person who supervises, directly or indirectly, such employee; and (iii) Any political action... Special Entity for the swap dealer and any person who supervises, directly or indirectly, such employee...) After learning of the contribution: (A) Has taken all available steps to cause the contributor involved...
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17 CFR 39.15 - Treatment of funds.
Code of Federal Regulations, 2013 CFR
2013-04-01
... members and customers; (J) An analysis of the ability of the derivatives clearing organization to manage a... the criteria that would be used to define eligible futures, options, and swaps; (B) Analysis of the...) Analysis of the liquidity of the respective markets for the futures, options, and swaps that would be...
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17 CFR 39.15 - Treatment of funds.
Code of Federal Regulations, 2014 CFR
2014-04-01
... members and customers; (J) An analysis of the ability of the derivatives clearing organization to manage a... the criteria that would be used to define eligible futures, options, and swaps; (B) Analysis of the...) Analysis of the liquidity of the respective markets for the futures, options, and swaps that would be...
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17 CFR 39.15 - Treatment of funds.
Code of Federal Regulations, 2012 CFR
2012-04-01
... members and customers; (J) An analysis of the ability of the derivatives clearing organization to manage a... the criteria that would be used to define eligible futures, options, and swaps; (B) Analysis of the...) Analysis of the liquidity of the respective markets for the futures, options, and swaps that would be...
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17 CFR 39.12 - Participant and product eligibility.
Code of Federal Regulations, 2014 CFR
2014-04-01
... a customer that: (A) Discloses to the futures commission merchant or any swap dealer or major swap participant the identity of a customer's original executing counterparty; (B) Limits the number of counterparties with whom a customer may enter into trades; (C) Restricts the size of the position a customer may...
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77 FR 42559 - End-User Exception to the Clearing Requirement for Swaps
Federal Register 2010, 2011, 2012, 2013, 2014
2012-07-19
...-owners to support their general business activities, rather than to finance purchases from its member... using non-cleared swaps to hedge risks associated with their underlying business, such as manufacturing... (IPM&CSA) stated that the end-user exception should be narrowly tailored to businesses that produce...
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Geospatial Video Monitoring of Benthic Habitats Using the Shallow-Water Positioning System (SWaPS)
2007-01-01
established from the video frames collected using SWaPS. C) Cover contours for the seagrass Thalassia testudinum. A B C surveyed using a spatial grid...distributions of seagrass species within this area are clearly influenced by their tolerance to salinity patterns. Thalassia testudinum, a species
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17 CFR 39.12 - Participant and product eligibility.
Code of Federal Regulations, 2013 CFR
2013-04-01
... a customer that: (A) Discloses to the futures commission merchant or any swap dealer or major swap participant the identity of a customer's original executing counterparty; (B) Limits the number of counterparties with whom a customer may enter into trades; (C) Restricts the size of the position a customer may...
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17 CFR 37.405 - Risk controls for trading.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 17 Commodity and Securities Exchanges 1 2014-04-01 2014-04-01 false Risk controls for trading. 37.405 Section 37.405 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP EXECUTION FACILITIES Monitoring of Trading and Trade Processing § 37.405 Risk controls for trading. The swap...
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17 CFR 37.900 - Core Principle 9-Timely publication of trading information.
Code of Federal Regulations, 2014 CFR
2014-04-01
... publication of trading information. 37.900 Section 37.900 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP EXECUTION FACILITIES Timely Publication of Trading Information § 37.900 Core Principle 9—Timely publication of trading information. (a) In general. The swap execution facility shall...
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75 FR 71379 - Registration of Swap Dealers and Major Swap Participants
Federal Register 2010, 2011, 2012, 2013, 2014
2010-11-23
.... Presently, all registered futures commission merchants (``FCMs''), introducing brokers (``IBs''), retail...., FCMs, IBs, RFEDs, CPOs and CTAs. The information called for includes the firm's full legal name and... Commission registrants (e.g., FCMs, IBs, RFEDs, CPOs or CTAs) are required to be registered. The term...
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Luo, Huifeng; Dai, Cheng; Li, Yongping; Feng, Jia; Liu, Zhongchi; Kang, Chunying
2018-04-27
The red color of the foliage and fruit in strawberry comes from anthocyanins stored in the vacuole; however, how this anthocyanin accumulation is regulated remains unclear. A reduced anthocyanin in petioles (rap) mutant was identified in an N-ethyl-N-nitrosourea (ENU) mutagenized population of YW5AF7, a white-fruited variety of the wild strawberry Fragaria vesca. The causative mutation was identified to be a premature stop codon in a glutathione S-transferase (GST) gene. In addition to the foliage coloration, RAP also mediates fruit pigmentation and acts downstream of the fruit-specific transcription factor FvMYB10. Among all eight GST genes in the same subfamily, RAP is most abundantly expressed in the ripening fruit. Expression analysis and transient expression assays demonstrated that RAP is the principal transporter of anthocyanins among the paralogs. Moreover, domain-swap experiments showed that both the N- and C-terminals of RAP are essential for the binding capability of anthocyanins. In addition, transient knock-down of RAP resulted in reduced fruit coloration in cultivated strawberry. Collectively, our results demonstrate that RAP encodes the principal GST transporter of anthocyanins in the strawberry foliage and fruit, and it could be modified to alter the fruit color in strawberry.
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75 FR 76573 - Swap Data Recordkeeping and Reporting Requirements
Federal Register 2010, 2011, 2012, 2013, 2014
2010-12-08
..., counterparties verify the primary or essential economic terms of their swap with each other in some fashion... Omissions in Previously Reported Data Appendix 1 to Part 45--Tables of Minimum Primary Economic Terms Data..., as a response to the global economic crisis, the G-20 met in Washington. In September 2009, G-20...
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-10-26
... or make available for trading security-based swaps: Nancy Burke-Sanow, Assistant Director, at (202... Cong. (2008) (Statement of Erik Sirri, Director of the Division of Trading and Markets, Commission..., 2009, and letter from Ann K. Shuman, Managing Director and Deputy General Counsel, CME, to Elizabeth...
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-11-26
...-traded futures contracts, options on futures contracts and swap agreements. Generally, derivatives are... to invest in derivative instruments, such as options contracts, futures contracts and swap agreements... derivatives will allow the Fund to selectively add diversifying sources of return from selling options. Option...
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-05-23
..., among other things: (1) The registration and comprehensive oversight of security-based swap dealers and... SECURITIES AND EXCHANGE COMMISSION 17 CFR Parts 240, 242, and 249 [Release No. 34-69491; File Nos... Releases and Policy Statements Applicable to Security-Based Swaps AGENCY: Securities and Exchange...
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-03-07
... Proposed Rule Change Regarding Acceptance of Additional Interest Rate Swaps for Clearing March 1, 2013... amend rules related to its business as a derivatives clearing organization offering interest rate swap... this notice to solicit comments on the proposed rule change from interested persons and to approve the...
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Code of Federal Regulations, 2012 CFR
2012-04-01
... Designated contract market and swap execution facility position limits and accountability rules. (a) Spot... rules and procedures for monitoring and enforcing spot-month position limits set at levels no greater... monitoring and enforcing spot-month position limits set at levels no greater than 25 percent of estimated...
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Code of Federal Regulations, 2013 CFR
2013-04-01
... Designated contract market and swap execution facility position limits and accountability rules. (a) Spot... rules and procedures for monitoring and enforcing spot-month position limits set at levels no greater... monitoring and enforcing spot-month position limits set at levels no greater than 25 percent of estimated...
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76 FR 65783 - Registration of Security-Based Swap Dealers and Major Security-Based Swap Participants
Federal Register 2010, 2011, 2012, 2013, 2014
2011-10-24
... Act Rules and Forms A. Registration Application and Amendment 1. Proposed Rule 15Fb2-1 i. Form of Application ii. Senior Officer Certification iii. Electronic Filing iv. Standards for Granting or Denying Applications v. Request for Comment on Additional Registration Considerations 2. Amendments to Application...
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-06-22
... Econ. Dep't, Bank for Int'l Settlements, Triennial and Semiannual Surveys--Positions in Global Over-the...-Based Swap Data Repository Registration, Duties, and Core Principles, 75 FR 77305 (Dec. 10, 2010..., duties, and core principles for SB SEFs. See Registration and Regulation of Security-Based Swap Execution...
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76 FR 80233 - Amendment to July 14, 2011 Order for Swap Regulation
Federal Register 2010, 2011, 2012, 2013, 2014
2011-12-23
... amendment to agricultural swaps; and, (3) the expiry date applicable to exempt commercial markets (``ECMs... on exempt and excluded commodities, may trade on either a DCM, ECM or exempt board of trade (``EBOT... agricultural commodities on ECMs or EBOTs.\\35\\ Nothing in the Notice or the Commission's recently promulgated...
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17 CFR 23.600 - Risk Management Program for swap dealers and major swap participants.
Code of Federal Regulations, 2013 CFR
2013-04-01
... at the consolidated entity level. (iii) The Risk Management Program shall include policies and...; and whether the product requires a novel pricing methodology or presents novel legal and regulatory... management unit, as to whether the new product would materially alter the overall entity-wide risk profile of...
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17 CFR 23.600 - Risk Management Program for swap dealers and major swap participants.
Code of Federal Regulations, 2014 CFR
2014-04-01
... at the consolidated entity level. (iii) The Risk Management Program shall include policies and...; and whether the product requires a novel pricing methodology or presents novel legal and regulatory... management unit, as to whether the new product would materially alter the overall entity-wide risk profile of...
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Code of Federal Regulations, 2014 CFR
2014-04-01
..., registered futures association or self-regulatory organization. 140.72 Section 140.72 Commodity and... or self-regulatory organization. (a) Pursuant to the authority granted under sections 2(a)(11), 8a(5... execution facility, swap data repository, registered futures association, or self-regulatory organization as...
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76 FR 34920 - Exemptions for Security-Based Swaps Issued by Certain Clearing Agencies
Federal Register 2010, 2011, 2012, 2013, 2014
2011-06-15
... SECURITIES AND EXCHANGE COMMISSION 17 CFR Parts 230, 240 and 260 [Release Nos. 33-9222; 34-64639; 39-2474; File No. S7-22-11] RIN 3235-AL16 Exemptions for Security-Based Swaps Issued by Certain Clearing Agencies AGENCY: Securities and Exchange Commission. ACTION: Proposed rules. SUMMARY: We are...
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-12-03
... other things, that transactions in security-based swaps be cleared through a clearing agency that is... Reserve System, shall, among other things, jointly further define the terms ``swap'' and ``security- based... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63389; File No. S7-16-09] Order Extending...
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-11-20
... trading and clearing of foreign exchange swaps and foreign exchange forwards would create systemic risk... clearing and exchange trading requirements on the foreign exchange market would increase systemic risk by... argue that the exemption would create a large regulatory loophole that could exacerbate systemic risk...
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17 CFR 240.3a67-3 - Definition of “substantial position.”
Code of Federal Regulations, 2014 CFR
2014-04-01
... at the net present value of the unpaid premiums. (ii) Adjustment for netting agreements... value in a major security-based swap category, less the value of the collateral the person has posted in... given major security-based swap category: (i) Determine the dollar value of the aggregate current...
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17 CFR 240.3a67-3 - Definition of “substantial position.”
Code of Federal Regulations, 2013 CFR
2013-04-01
... at the net present value of the unpaid premiums. (ii) Adjustment for netting agreements... value in a major security-based swap category, less the value of the collateral the person has posted in... given major security-based swap category: (i) Determine the dollar value of the aggregate current...
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17 CFR 50.4 - Classes of swaps required to be cleared.
Code of Federal Regulations, 2013 CFR
2013-04-01
... class Currency U.S. dollar (USD) Euro (EUR) Sterling (GBP) Yen (JPY). Floating Rate Indexes LIBOR... Amounts No No No No. Specification Basis swap class Currency U.S. dollar (USD) Euro (EUR) Sterling (GBP... Currency U.S. dollar (USD) Euro (EUR) Sterling (GBP) Yen (JPY). Floating Rate Indexes LIBOR EURIBOR LIBOR...
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17 CFR 37.400 - Core Principle 4-Monitoring of trading and trade processing.
Code of Federal Regulations, 2014 CFR
2014-04-01
... trading and trade processing. 37.400 Section 37.400 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION SWAP EXECUTION FACILITIES Monitoring of Trading and Trade Processing § 37.400 Core Principle 4—Monitoring of trading and trade processing. The swap execution facility shall: (a) Establish and...
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17 CFR 1.7 - Books and records requirements for security-based swap agreements.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 17 Commodity and Securities Exchanges 1 2013-04-01 2013-04-01 false Books and records requirements... FUTURES TRADING COMMISSION GENERAL REGULATIONS UNDER THE COMMODITY EXCHANGE ACT Definitions § 1.7 Books... not be required to keep and maintain additional books and records regarding security-based swap...
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17 CFR 1.7 - Books and records requirements for security-based swap agreements.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 17 Commodity and Securities Exchanges 1 2014-04-01 2014-04-01 false Books and records requirements... FUTURES TRADING COMMISSION GENERAL REGULATIONS UNDER THE COMMODITY EXCHANGE ACT Definitions § 1.7 Books... not be required to keep and maintain additional books and records regarding security-based swap...
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75 FR 75162 - Protection of Cleared Swaps Customers Before and After Commodity Broker Bankruptcies
Federal Register 2010, 2011, 2012, 2013, 2014
2010-12-02
... are different from the current model for protecting futures customer collateral would bring... 10-11. (4) Baseline Model--The current approach to futures. The rights and obligations arising out of... COMMODITY FUTURES TRADING COMMISSION 17 CFR Part 190 RIN 3038-AD99 Protection of Cleared Swaps...
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17 CFR 43.6 - Block trades and large notional off-facility swaps.
Code of Federal Regulations, 2014 CFR
2014-04-01
..., Poland, Russia, and Turkey; or (ii) By unique currency combinations not included in paragraph (b)(4)(i... the date of publication. (g) Required notification. (1) Block trade election. (i) The parties to a... election to have the publicly reportable swap transaction treated as a block trade. (ii) The registered...
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NASA Astrophysics Data System (ADS)
Rizk, Charbel G.; Lin, Joseph H.; Kennerly, Stephen W.; Pouliquen, Philippe; Goldberg, Arnold C.; Andreou, Andreas G.
2012-06-01
The advanced imagers team at JHU APL and ECE has been advocating and developing a new class of sensor systems that address key system level performance bottlenecks but are sufficiently flexible to allow optimization of associated cost and size, weight, and power (SWaP) for different applications and missions. A primary component of this approach is the innovative system-on-chip architecture: Flexible Readout and Integration Sensors (FRIS). This paper reports on the development and testing of a prototype based on the FRIS concept. It will include the architecture, a summary of test results to date relevant to the hostile fire detection challenge. For this application, this prototype demonstrates the potential for this concept to yield the smallest SWaP and lowest cost imaging solution with a low false alarm rate. In addition, a specific solution based on the visible band is proposed. Similar performance and SWaP gains are expected for other wavebands such as SWIR, MWIR, and LWIR and/or other applications like persistent surveillance for critical infrastructure and border control in addition to unattended sensors.
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Strand swapping regulates the iron-sulfur cluster in the diabetes drug target mitoNEET
Baxter, Elizabeth Leigh; Jennings, Patricia A.; Onuchic, José N.
2012-01-01
MitoNEET is a recently identified diabetes drug target that coordinates a transferable 2Fe-2S cluster, and additionally contains an unusual strand swap. In this manuscript, we use a dual basin structure-based model to predict and characterize the folding and functionality of strand swapping in mitoNEET. We demonstrate that a strand unswapped conformation is kinetically accessible and that multiple levels of control are employed to regulate the conformational dynamics of the system. Environmental factors such as temperature can shift route preference toward the unswapped pathway. Additionally we see that a region recently identified as contributing to frustration in folding acts as a regulatory hinge loop that modulates conformational balance. Interestingly, strand unswapping transfers strain specifically to cluster-coordinating residues, opening the cluster-coordinating pocket. Strengthening contacts within the cluster-coordinating pocket opens a new pathway between the swapped and unswapped conformation that utilizes cracking to bypass the unfolded basin. These results suggest that local control within distinct regions affect motions important in regulating mitoNEET’s 2Fe-2S clusters. PMID:22308404
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NASA Astrophysics Data System (ADS)
Qamar, Muhammad Uzair; Azmat, Muhammad; Cheema, Muhammad Jehanzeb Masud; Shahid, Muhammad Adnan; Khushnood, Rao Arsalan; Ahmad, Sajjad
2016-10-01
The issue of lack of donor basins for prediction of flow duration curves (FDCs) in ungauged basins (PUB) is an important area of research that is not resolved in the literature. We present a distance based approach to predict FDCs at ungauged basins by quantifying the dissimilarity between FDCs and characteristics data of basins. This enables us to bracket hydrologically similar basins and thus allowing us to estimate FDCs at ungauged basins. Generally, a single regression model is selected to make hydrological estimates at an ungauged basin. Based on established laws and theories of hydrology, we work to devise a method to improve the output of selected model for an ungauged basin by swapping it with another model in case the latter gives better coverage and statistical estimates of the nearest neighbors of an ungauged basin. We report two examples to demonstrate the effectiveness of model swapping. Out of 124 basins used in analysis, 34 basins in example 1 and 41 basins in example 2 fulfill the set criteria of model swapping and subsequently their estimates are improved significantly.
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Low-SWAP Lidar Instrument for Arctic Ice Sheet Mass Balance Monitoring Final Report
DOE Office of Scientific and Technical Information (OSTI.GOV)
Williams, George; Barsic, David
To meet the need to obtain statistically significant data in the North Slope of Alaska (NSA) in support of climate models, Voxtel is developing an nmanned-aircraft-system (UAS)-optimized lidar focal plane array (FPA) and lidar instrument design that integrates the most recent developments in optics, electronics, and computing. Bound by the size, weight, and power (SWAP) budget of low altitude/long endurance (LALE) small UAS (SUAS) platforms—a design tradeoff study was conducted. The class of SUAS considered typically: operates at altitudes between 150 meters and 2,000 meters; accommodates payloads weighing less than 5 kg; encompasses no more than 4,000 cm3 of space;more » and consumes no more than 50 watts of power. To address the SWAP constraints, a lowpower standalone strap-down (gimbal-less) lidar was developed based on single-photon-counting silicon avalanche photodiodes. To reduce SWAP, a lidar FPA design capable of simultaneous imaging and lidar was developed. The 532-nm-optimized FPA modular design was developed for easy integration, as a lidar payload, in any of a variety of SUAS platforms.« less
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Wang, Yan; Li, Xi; Zhang, Wenyan; Zhou, Xiuwen; Li, Yue-zhong
2014-03-01
Myxococcus xanthus DK1622 possesses two copies of the groEL gene: groEL1, which participates in development, and groEL2, which is involved in the predatory ability of cells. In this study, we determined that the groEL2 gene is required for the biosynthesis of the secondary metabolite myxovirescin (TA), which plays essential roles in predation. The groEL2-knockout mutant strain was defective in producing a zone of inhibition and displayed decreased killing ability against Escherichia coli, while the groEL1-knockout mutant strain exhibited little difference from the wild-type strain DK1622. HPLC revealed that deletion of the groEL2 gene blocked the production of TA, which was present in the groEL1-knockout mutant. The addition of exogenous TA rescued the inhibition and killing abilities of the groEL2-knockout mutant against E. coli. Analysis of GroEL domain-swapping mutants indicated that the C-terminal equatorial domain of GroEL2 was essential for TA production, while the N-terminal equatorial or apical domains of GroEL2 were not sufficient to rescue TA production of the groEL2 knockout.
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Hori, Motohide; Shibato, Junko; Nakamachi, Tomoya; Rakwal, Randeep; Ogawa, Tetsuo; Shioda, Seiji; Numazawa, Satoshi
2015-01-01
Toward twin goals of identifying molecular factors in brain injured by ischemic stroke, and the effects of neuropeptide pituitary adenylate-cyclase activating polypeptide (PACAP) on the ischemic brain, we have established the permanent middle cerebral artery occlusion (PMCAO) mouse model and utilized the Agilent mouse whole genome 4 × 44 K DNA chip. PACAP38 (1 pmol) injection was given intracerebroventrically in comparison to a control saline (0.9% NaCl) injection, to screen genes responsive to PACAP38. Two sets of tissues were prepared, whole hemispheres (ischemic and non-ischemic) and infract core and penumbra regions at 6 and 24 h. In this study, we have detailed the experimental design and protocol used therein and explained the quality controls for the use of total RNA in the downstream DNA microarray experiment utilizing a two-color dye-swap approach for stringent and confident gene identification published in a series of papers by Hori and coworkers (Hori et al., 2012–2015). PMID:26484166
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The pricing of credit default swaps under a generalized mixed fractional Brownian motion
NASA Astrophysics Data System (ADS)
He, Xinjiang; Chen, Wenting
2014-06-01
In this paper, we consider the pricing of the CDS (credit default swap) under a GMFBM (generalized mixed fractional Brownian motion) model. As the name suggests, the GMFBM model is indeed a generalization of all the FBM (fractional Brownian motion) models used in the literature, and is proved to be able to effectively capture the long-range dependence of the stock returns. To develop the pricing mechanics of the CDS, we firstly derive a sufficient condition for the market modeled under the GMFBM to be arbitrage free. Then under the risk-neutral assumption, the CDS is fairly priced by investigating the two legs of the cash flow involved. The price we obtained involves elementary functions only, and can be easily implemented for practical purpose. Finally, based on numerical experiments, we analyze quantitatively the impacts of different parameters on the prices of the CDS. Interestingly, in comparison with all the other FBM models documented in the literature, the results produced from the GMFBM model are in a better agreement with those calculated from the classical Black-Scholes model.
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Satisfaction With Appearance Scale-SWAP: Adaptation and validation for Brazilian burn victims.
Caltran, Marina P; Freitas, Noélle O; Dantas, Rosana A S; Farina, Jayme Adriano; Rossi, Lidia A
2016-09-01
Methodological study that aimed to adapt the Satisfaction with Appearance Scale (SWAP) into Brazilian Portuguese language and to assess the validity, the reliability and the dimensionality of the adapted version in a sample of Brazilian burn victims. We carried out the adaptation process according to the international literature. Construct validity was assessed by correlating the adapted version of SWAP scores with depression (Beck Depression Index), self-esteem (Rosenberg Self-Esteem Scale), health-related quality of Life (Short Form Health Survey-36) and health status of burn victims (Burn Specific Health Scale-Revised), and with gender, total body surface area burned, and visibility of the scars. We tested dimensionality using Exploratory Factor Analysis (EFA) and the reliability by means of Cronbach's alpha. Participants were 106 adult burned patients. The correlations between the Brazilian version of the SWAP scores and the correlated construct measures varied from moderate to strong (r=.30-.77). The participants who perceived their burn sequelae was visible reported being more dissatisfied with their body image than the participants who answered that their scars would not be visible (p<.001). Cronbach's alpha for the adapted version was 0.88 and the item-total correlation varied from moderate to strong (r=.35-.73). The EFA resulted in three factors with a total explained variance percentage of 63.2%. The Brazilian version of the SWAP was valid and reliable for use with Brazilian burn victims. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.
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Staufen1 dimerizes via a conserved motif and a degenerate dsRNA-binding domain to promote mRNA decay
Gleghorn, Michael L.; Gong, Chenguang; Kielkopf, Clara L.; Maquat, Lynne E.
2014-01-01
Staufen (STAU)1-mediated mRNA decay (SMD) degrades mammalian-cell mRNAs that bind the double-stranded (ds)RNA-binding protein STAU1 in their 3′-untranslated region. We report a new motif, which typifies STAU homologs from all vertebrate classes, that is responsible for human (h)STAU1 homodimerization. Our crystal structure and mutagenesis analyses reveal that this motif, now named the Staufen-swapping motif (SSM), and dsRNA-binding domain 5 (‘RBD’5) mediate protein dimerization: the two SSM α-helices of one molecule interact primarily through a hydrophobic patch with the two ‘RBD’5 α-helices of a second molecule. ‘RBD’5 adopts the canonical α-β-β-β-α fold of a functional RBD, but it lacks residues and features needed to bind duplex RNA. In cells, SSM-mediated hSTAU1 dimerization increases the efficiency of SMD by augmenting hSTAU1 binding to the ATP-dependent RNA helicase hUPF1. Dimerization regulates keratinocyte-mediated wound-healing and, undoubtedly, many other cellular processes. PMID:23524536
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Structure of Bombyx mori Densovirus 1, a Silkworm Pathogen▿‡
Kaufmann, Bärbel; El-Far, Mohamed; Plevka, Pavel; Bowman, Valorie D.; Li, Yi; Tijssen, Peter; Rossmann, Michael G.
2011-01-01
Bombyx mori densovirus 1 (BmDNV-1), a major pathogen of silkworms, causes significant losses to the silk industry. The structure of the recombinant BmDNV-1 virus-like particle has been determined at 3.1-Å resolution using X-ray crystallography. It is the first near-atomic-resolution structure of a virus-like particle within the genus Iteravirus. The particles consist of 60 copies of the 55-kDa VP3 coat protein. The capsid protein has a β-barrel “jelly roll” fold similar to that found in many diverse icosahedral viruses, including archaeal, bacterial, plant, and animal viruses, as well as other parvoviruses. Most of the surface loops have little structural resemblance to other known parvovirus capsid proteins. In contrast to vertebrate parvoviruses, the N-terminal β-strand of BmDNV-1 VP3 is positioned relative to the neighboring 2-fold related subunit in a “domain-swapped” conformation, similar to findings for other invertebrate parvoviruses, suggesting domain swapping is an evolutionarily conserved structural feature of the Densovirinae. PMID:21367906
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Engineering enhanced cellobiohydrolase activity
DOE Office of Scientific and Technical Information (OSTI.GOV)
Taylor, Larry E.; Knott, Brandon C.; Baker, John O.
Glycoside Hydrolase Family 7 cellobiohydrolases (GH7 CBHs) catalyze cellulose depolymerization in cellulolytic eukaryotes, making them key discovery and engineering targets. However, there remains a lack of robust structure–activity relationships for these industrially important cellulases. Here, we compare CBHs from Trichoderma reesei (TrCel7A) and Penicillium funiculosum (PfCel7A), which exhibit a multi-modular architecture consisting of catalytic domain (CD), carbohydrate-binding module, and linker. We show that PfCel7A exhibits 60% greater performance on biomass than TrCel7A. To understand the contribution of each domain to this improvement, we measure enzymatic activity for a library of CBH chimeras with swapped subdomains, demonstrating that the enhancement ismore » mainly caused by PfCel7A CD. We solve the crystal structure of PfCel7A CD and use this information to create a second library of TrCel7A CD mutants, identifying a TrCel7A double mutant with near-equivalent activity to wild-type PfCel7A. Overall, these results reveal CBH regions that enable targeted activity improvements.« less
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Engineering enhanced cellobiohydrolase activity
Taylor, Larry E.; Knott, Brandon C.; Baker, John O.; ...
2018-03-22
Glycoside Hydrolase Family 7 cellobiohydrolases (GH7 CBHs) catalyze cellulose depolymerization in cellulolytic eukaryotes, making them key discovery and engineering targets. However, there remains a lack of robust structure–activity relationships for these industrially important cellulases. Here, we compare CBHs from Trichoderma reesei (TrCel7A) and Penicillium funiculosum (PfCel7A), which exhibit a multi-modular architecture consisting of catalytic domain (CD), carbohydrate-binding module, and linker. We show that PfCel7A exhibits 60% greater performance on biomass than TrCel7A. To understand the contribution of each domain to this improvement, we measure enzymatic activity for a library of CBH chimeras with swapped subdomains, demonstrating that the enhancement ismore » mainly caused by PfCel7A CD. We solve the crystal structure of PfCel7A CD and use this information to create a second library of TrCel7A CD mutants, identifying a TrCel7A double mutant with near-equivalent activity to wild-type PfCel7A. Overall, these results reveal CBH regions that enable targeted activity improvements.« less
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Hansen, Michael Riis; Harris, Richard; Barr, Eric W; Cheng, Hong; Girvin, Mark E; Grubmeyer, Charles
2014-04-01
The type I phosphoribosyltransferase OMP synthase (EC 2.4.2.10) is involved in de novo synthesis of pyrimidine nucleotides forming the UMP precursor orotidine 5'-monophosphate (OMP). The homodimeric enzyme has a Rossman α/β core topped by a base-enclosing "hood" domain and a flexible domain-swapped catalytic loop. High-resolution X-ray structures of the homologous Salmonella typhimurium and yeast enzymes show that a general compacting of the core as well as movement of the hood and a major disorder-to-order transition of the loop occur upon binding of ligands MgPRPP and orotate. Here we present backbone NMR assignments for the unliganded yeast enzyme (49 kDa) and its complex with product OMP. We were able to assign 212-213 of the 225 non-proline backbone (15)N and amide proton resonances. Significant difference in chemical shifts of the amide cross peaks occur in regions of the structure that undergo movement upon ligand occupancy in the S. typhimurium enzyme.
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Molecular Basis of ADP Inhibition of Vacuolar (V)-type ATPase/Synthase*
Kishikawa, Jun-ichi; Nakanishi, Atsuko; Furuike, Shou; Tamakoshi, Masatada; Yokoyama, Ken
2014-01-01
Reduction of ATP hydrolysis activity of vacuolar-type ATPase/synthase (V0V1) as a result of ADP inhibition occurs as part of the normal mechanism of V0V1 of Thermus thermophilus but not V0V1 of Enterococcus hirae or eukaryotes. To investigate the molecular basis for this difference, domain-swapped chimeric V1 consisting of both T. thermophilus and E. hirae enzymes were generated, and their function was analyzed. The data showed that the interaction between the nucleotide binding and C-terminal domains of the catalytic A subunit from E. hirae V1 is central to increasing binding affinity of the chimeric V1 for phosphate, resulting in reduction of the ADP inhibition. These findings together with a comparison of the crystal structures of T. thermophilus V1 with E. hirae V1 strongly suggest that the A subunit adopts a conformation in T. thermophilus V1 different from that in E. hirae V1. This key difference results in ADP inhibition of T. thermophilus V1 by abolishing the binding affinity for phosphate during ATP hydrolysis. PMID:24247239
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A new role for Hedgehogs in juxtacrine signaling.
Pettigrew, Christopher A; Asp, Eva; Emerson, Charles P
2014-02-01
The Hedgehog pathway plays important roles in embryonic development, adult stem cell maintenance and tumorigenesis. In mammals these effects are mediated by Sonic, Desert and Indian Hedgehog (Shh, Dhh and Ihh). Shh undergoes autocatalytic cleavage and dual lipidation prior to secretion and forming a response gradient. Post-translational processing and secretion of Dhh and Ihh ligands has not previously been investigated. This study reports on the synthesis, processing, secretion and signaling activities of SHH, IHH and DHH preproteins expressed in cultured cells, providing unexpected evidence that DHH does not undergo substantial autoprocessing or secretion, and does not function in paracrine signaling. Rather, DHH functions as a juxtacrine signaling ligand to activate a cell contact-mediated HH signaling response, consistent with its localised signaling in vivo. Further, the LnCAP prostate cancer cell, when induced to express endogenous DHH and SHH, is active only in juxtacrine signaling. Domain swap studies reveal that the C-terminal domain of HH regulates its processing and secretion. These findings establish a new regulatory role for HHs in cell-mediated juxtacrine signaling in development and cancer. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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NASA Astrophysics Data System (ADS)
Pakniat, R.; Soltani, M.; Tavassoly, M. K.
2018-03-01
Recently we studied the effect of photon addition in the initial coherent field on the entanglement swapping which causes some improvements in the process [Soltani et al., Int. J. Mod. Phys. B 31, 1750198 (2017)]. In this paper, we investigate the influence of multiphoton transitions in the atom-field interaction based on the cavity quantum electrodynamics on the entanglement swapping and show its considerable constructive effect on this process. The presented model consists of two two-level atoms namely A1 and A2 and two distinct cavity fields F1 and F2. Initially, the atoms are prepared in a maximally entangled state and the fields in the cavities are prepared in hybrid entangled state of number and coherent states, separately. Making the atom A2 to interact with the field F1 (via the generalized Jaynes-Cummings model which allows m-photon transitions between atomic levels in the emission and absorption processes) followed by their detection allows us to arrive at the entanglement swapping from the two atoms A1, A2 and the two fields F1, F2 to the atom-field A1-F2 system. Then, we pay our attention to the time evolution of success probability of detecting processes and fidelity. Also, to determine the amount of entanglement of the generated entangled state in the swapping process, the linear entropy is evaluated and the effect of parameter m concerning the multiphoton transitions on these quantities is investigated, numerically. It is observed that, by increasing the number of photons in the transition process, one may obtain considerable improvement in the relevant quantities of the entanglement swapping. In detail, the satisfactorily acceptable values 1 and 0.5 corresponding to success probability and fidelity are obtained for most of the times during observing of the above-mentioned procedure. We concluded that the presented formalism in this paper is much more advantageous than our presentation model in our earlier work mentioned above.
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Reducing Size, Weight, and Power (SWaP) of Perception Systems in Small Autonomous Aerial Systems
NASA Technical Reports Server (NTRS)
Jones, Kennie H.; Gross, Jason
2014-01-01
The objectives are to examine recent trends in the reduction of size, weight, and power (SWaP) requirements of sensor systems for environmental perception and to explore new technology that may overcome limitations in current systems. Improving perception systems to facilitate situation awareness is critical in the move to introduce increasing autonomy in aerial systems. Whether the autonomy is in the current state-of-the-art of increasing automation or is enabling cognitive decisions that facilitate adaptive behavior, collection of environmental information and fusion of that information into knowledge that can direct actuation is imperative to decisions resulting in appropriate behavior. Artificial sensory systems such as cameras, radar, LIDAR, and acoustic sensors have been in use on aircraft for many years but, due to the large size and weight of the airplane and electrical power made available through powerful engines, the SWaP requirements of these sensors was inconsequential. With the proliferation of Remote Piloted Vehicles (RPV), the trend is in significant reduction in SWaP of the vehicles. This requires at least an equivalent reduction in SWaP for the sensory systems. A survey of some currently available sensor systems and changing technology will reveal the trend toward reduction of SWaP of these systems and will predict future reductions. A new technology will be introduced that provides an example of a desirable new trend. A new device replaces multiple conventional sensory devices facilitating synchronization, localization, altimetry, collision avoidance, terrain mapping, and data communication in a single integrated, small form-factor, extremely lightweight, and low power device that it is practical for integration into small autonomous vehicles and can facilitate cooperative behavior. The technology is based on Ultra WideBand (UWB) radio using short pulses of energy rather than continuous sine waves. The characteristics of UWB yield several desirable characteristics to facilitate integration of perception for autonomous activities. The capabilities of this device and its limitations will be assessed.
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Im, Young Jun; Kim, Jeong-Il; Shen, Yu; Na, Young; Han, Yun-Jeong; Kim, Seong-Hee; Song, Pill-Soon; Eom, Soo Hyun
2004-10-22
In plants, nucleoside diphosphate kinases (NDPKs) play a key role in the signaling of both stress and light. However, little is known about the structural elements involved in their function. Of the three NDPKs (NDPK1-NDPK3) expressed in Arabidopsis thaliana, NDPK2 is involved in phytochrome-mediated signal transduction. In this study, we found that the binding of dNDP or NTP to NDPK2 strengthens the interaction significantly between activated phytochrome and NDPK2. To better understand the structural basis of the phytochrome-NDPK2 interaction, we determined the X-ray structures of NDPK1, NDPK2, and dGTP-bound NDPK2 from A.thaliana at 1.8A, 2.6A, and 2.4A, respectively. The structures showed that nucleotide binding caused a slight conformational change in NDPK2 that was confined to helices alphaA and alpha2. This suggests that the presence of nucleotide in the active site and/or the evoked conformational change contributes to the recognition of NDPK2 by activated phytochrome. In vitro binding assays showed that only NDPK2 interacted specifically with the phytochrome and the C-terminal regulatory domain of phytochrome is involved in the interaction. A domain swap experiment between NDPK1 and NDPK2 showed that the variable C-terminal region of NDPK2 is important for the activation by phytochrome. The structure of Arabidopsis NDPK1 and NDPK2 showed that the isoforms share common electrostatic surfaces at the nucleotide-binding site, but the variable C-terminal regions have distinct electrostatic charge distributions. These findings suggest that the binding of nucleotide to NDPK2 plays a regulatory role in phytochrome signaling and that the C-terminal extension of NDPK2 provides a potential binding surface for the specific interaction with phytochromes.
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Gupta, Anjali Bansal; Wee, Liang En; Zhou, Yi Ting; Hortsch, Michael; Low, Boon Chuan
2012-01-01
The CRAL_TRIO protein domain, which is unique to the Sec14 protein superfamily, binds to a diverse set of small lipophilic ligands. Similar domains are found in a range of different proteins including neurofibromatosis type-1, a Ras GTPase-activating Protein (RasGAP) and Rho guanine nucleotide exchange factors (RhoGEFs). Proteins containing this structural protein domain exhibit a low sequence similarity and ligand specificity while maintaining an overall characteristic three-dimensional structure. We have previously demonstrated that the BNIP-2 and Cdc42GAP Homology (BCH) protein domain, which shares a low sequence homology with the CRAL_TRIO domain, can serve as a regulatory scaffold that binds to Rho, RhoGEFs and RhoGAPs to control various cell signalling processes. In this work, we investigate 175 BCH domain-containing proteins from a wide range of different organisms. A phylogenetic analysis with ∼100 CRAL_TRIO and similar domains from eight representative species indicates a clear distinction of BCH-containing proteins as a novel subclass within the CRAL_TRIO/Sec14 superfamily. BCH-containing proteins contain a hallmark sequence motif R(R/K)h(R/K)(R/K)NL(R/K)xhhhhHPs (‘h’ is large and hydrophobic residue and ‘s’ is small and weekly polar residue) and can be further subdivided into three unique subtypes associated with BNIP-2-N, macro- and RhoGAP-type protein domains. A previously unknown group of genes encoding ‘BCH-only’ domains is also identified in plants and arthropod species. Based on an analysis of their gene-structure and their protein domain context we hypothesize that BCH domain-containing genes evolved through gene duplication, intron insertions and domain swapping events. Furthermore, we explore the point of divergence between BCH and CRAL-TRIO proteins in relation to their ability to bind small GTPases, GAPs and GEFs and lipid ligands. Our study suggests a need for a more extensive analysis of previously uncharacterized BCH, ‘BCH-like’ and CRAL_TRIO-containing proteins and their significance in regulating signaling events involving small GTPases. PMID:22479462
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Women as Symbols and Swords in Boko Haram’s Terror
2016-03-01
kid - napped women and telling them that, “these are your teachers from Chibok.” During raids “people were tied and laid down and the girls took it...discourages premarital sex and extols vir- tue. The women’s experiences have justifiably instilled a fear and loathing of Boko Haram among a diverse...boko-haram-offers-to-swap-detainees-for- kid - napped-girls/312497711/>. 48 “Shekau Denies Ceasefire, Says Chibok Girls have Converted to Islam
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Molecular Characterization of Human MUC16 (CA125) in Breast Cancer
2015-04-01
and O-linked glycosylation takes place as it progresses through the cis-medial-trans Golgi apparatus . In addition, the juxta-membrane ectodomain...swapping experiment. Further, the cleavage of MUC16 was found to take place in the Golgi /post- Golgi compartments and is dependent on the acidic pH in the...therapeutic interventions based on MUC16. 15. SUBJECT TERMS Mucin 16 (MUC16), MUC16-Cter, Golgi /post- Golgi , nuclear localization 16. SECURITY
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Kearfott, Kimberlee J; West, W Geoffrey
2015-10-01
A lower-cost optically stimulated luminescence (OSL) reader with increased flexibility for pursuing laboratory research into OSL theory and application was designed and constructed. This was achieved by using off-the-shelf optical components and higher-power light emitting diodes. The resulting reader includes more wavelengths of excitation light than current commercial readers, as well as the ability to swap out filters and other components during an experiment. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Lee, Yie Chia; Boehm, Mark K; Chester, Kerry A; Begent, Richard H J; Perkins, Stephen J
2002-06-28
MFE-23 is a single chain Fv (scFv) antibody molecule used to target colorectal cancer through its high affinity for the tumour marker carcinoembryonic antigen (CEA). ScFv molecules are formed from peptide-linked antibody V(H) and V(L) domains, and many of these form dimers. Our recent crystal structure for MFE-23 showed that this formed an unusual symmetric back-to-back association of two monomers that is consistent with a domain-swapped diabody structure. Neutron scattering and modelling fits showed that MFE-23 existed as compact V(H)-V(L)-linked monomers at therapeutically relevant concentrations below 1 mg/ml. Size-exclusion gel chromatography showed that the monomeric and dimeric forms of MFE-23 could be separated, and that the proportions of these two forms depended on the starting MFE-23 concentration. Sedimentation equilibrium experiments by analytical ultracentrifugation at nine concentrations of MFE-23 indicated a reversible monomer-dimer self-association equilibrium with an association constant of 1.9x10(3)-2.2x10(3) M(-1). Sedimentation velocity experiments using the time derivative g(s(*)) method showed that MFE-23-His has a concentration-dependent weight average sedimentation coefficient that increased from 1.8 S for the monomer to about 3-6 S for the dimer. Both values agreed with those calculated from the MFE-23 crystal structure. In relation to the thermal stability of MFE-23, denaturation experiments by (1)H NMR and FT-IR spectroscopy showed that the molecule is stable up to 47 degrees C, after which denaturation was irreversible. MFE-23 dimerisation is discussed in terms of a new model for diabody structures, in which the V(H) and V(L) domains in the monomer are able to dissociate and reassociate to form a dimer, or diabody, but in which symmetric back-to-back contacts between the two monomers are formed. This dimerisation in solution is attributed to the complementary nature of the C-terminal surface of the MFE-23 monomer. Crystal structures for seven other scFv molecules have shown that, while the contact residues for symmetric back-to-back dimer formation in MFE-23 are not fully conserved, in principle, back-to-back contacts can be formed in these too. This offers possibilities for the creation of other forms of scFv molecules. (c) 2002 Elsevier Science Ltd.
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Proton assisted recoupling and protein structure determination
NASA Astrophysics Data System (ADS)
de Paëpe, Gaël; Lewandowski, Józef R.; Loquet, Antoine; Böckmann, Anja; Griffin, Robert G.
2008-12-01
We introduce a homonuclear version of third spin assisted recoupling, a second-order mechanism that can be used for polarization transfer between 13C or 15N spins in magic angle spinning (MAS) NMR experiments, particularly at high spinning frequencies employed in contemporary high field MAS experiments. The resulting sequence, which we refer to as proton assisted recoupling (PAR), relies on a cross-term between 1H-13C (or 1H-15N) couplings to mediate zero quantum 13C-13C (or 15N-15N recoupling). In particular, using average Hamiltonian theory we derive an effective Hamiltonian for PAR and show that the transfer is mediated by trilinear terms of the form C1+/-C2-/+HZ for 13C-13C recoupling experiments (or N1+/-N2-/+HZ for 15N-15N). We use analytical and numerical simulations to explain the structure of the PAR optimization maps and to delineate the PAR matching conditions. We also detail the PAR polarization transfer dependence with respect to the local molecular geometry and explain the observed reduction in dipolar truncation. Finally, we demonstrate the utility of PAR in structural studies of proteins with 13C-13C spectra of uniformly 13C, 15N labeled microcrystalline Crh, a 85 amino acid model protein that forms a domain swapped dimer (MW=2×10.4 kDa). The spectra, which were acquired at high MAS frequencies (ωr2π>20 kHz) and magnetic fields (750-900 MHz 1H frequencies) using moderate rf fields, exhibit numerous cross peaks corresponding to long (up to 6-7 A˚) 13C-13C distances which are particularly useful in protein structure determination. Using results from PAR spectra we calculate the structure of the Crh protein.
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Dynamical emergence of the Universe into the false vacuum
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rafelski, Johann; Birrell, Jeremiah, E-mail: rafelski@physics.arizona.edu, E-mail: jbirrell@email.arizona.edu
We study how the hot Universe evolves and acquires the prevailing vacuum state, demonstrating that in specific conditions which are believed to apply, the Universe becomes frozen into the state with the smallest value of Higgs vacuum field v=( h), even if this is not the state of lowest energy. This supports the false vacuum dark energy Λ-model. Under several likely hypotheses we determine the temperature in the evolution of the Universe at which two vacuua v{sub 1}, v{sub 2} can swap between being true and false. We evaluate the dynamical surface pressure on domain walls between low and high mass vaccuamore » due to the presence of matter and show that the low mass state remains the preferred vacuum of the Universe.« less
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76 FR 8919 - Airworthiness Directives; DASSAULT AVIATION Model MYSTERE-FALCON 50 Airplanes
Federal Register 2010, 2011, 2012, 2013, 2014
2011-02-16
... of the emergency brake system 2 located near the nose landing gear bearing were swapped. The swapping of these two pipes implies that when the Left Hand (LH) brake pedal is depressed, the Right Hand (RH) brake unit is activated, and conversely, when the RH brake pedal is depressed, the LH brake unit is...
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76 FR 27880 - Airworthiness Directives; DASSAULT AVIATION Model MYSTERE-FALCON 50 Airplanes
Federal Register 2010, 2011, 2012, 2013, 2014
2011-05-13
... pipes of the emergency brake system 2 located near the nose landing gear bearing were swapped. The swapping of these two pipes implies that when the Left Hand (LH) brake pedal is depressed, the Right Hand (RH) brake unit is activated, and conversely, when the RH brake pedal is depressed, the LH brake unit...
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17 CFR 151.5 - Bona fide hedging and other exemptions for Referenced Contracts.
Code of Federal Regulations, 2013 CFR
2013-04-01
... or anticipated unfilled storage capacity owned or leased by the same person during the period of... representation shall be retained by the parties to the swap for a period of at least two years following the... representation for a period of at least two years following the expiration of the swap. (j) Financial distress...
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17 CFR 151.5 - Bona fide hedging and other exemptions for Referenced Contracts.
Code of Federal Regulations, 2012 CFR
2012-04-01
... or anticipated unfilled storage capacity owned or leased by the same person during the period of... representation shall be retained by the parties to the swap for a period of at least two years following the... representation for a period of at least two years following the expiration of the swap. (j) Financial distress...
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17 CFR 151.5 - Bona fide hedging and other exemptions for Referenced Contracts.
Code of Federal Regulations, 2014 CFR
2014-04-01
... or anticipated unfilled storage capacity owned or leased by the same person during the period of... representation shall be retained by the parties to the swap for a period of at least two years following the... representation for a period of at least two years following the expiration of the swap. (j) Financial distress...
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-11-08
... Change Related to the Reference Rate for Singapore Dollar Denominated Interest Rate Swaps November 4... reference rate for Singapore Dollar (``SGD'') denominated interest rate swaps (``IRS''). II. Self-Regulatory... this notice to solicit comments on the proposed rule change from interested persons. \\1\\ 15 U.S.C. 78s...
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Code of Federal Regulations, 2014 CFR
2014-04-01
.... (a) Spot-month limits. (1) For all Referenced Contracts executed pursuant to their rules, swap..., establish rules and procedures for monitoring and enforcing spot-month position limits set at levels no... monitoring and enforcing spot-month position limits set at levels no greater than 25 percent of estimated...