Phytochrome regulates GTP-binding protein activity in the envelope of pea nuclei

NASA Technical Reports Server (NTRS)

Clark, G. B.; Memon, A. R.; Thompson, G. A. Jr; Roux, S. J.

1993-01-01

Three GTP-binding proteins with apparent molecular masses of 27, 28 and 30 kDa have been detected in isolated nuclei of etiolated pea plumules. After LDS-PAGE and transfer to nitrocellulose these proteins bind [32P]GTP in the presence of excess ATP, suggesting that they are monomeric G proteins. When nuclei are disrupted, three proteins co-purify with the nuclear envelope fraction and are highly enriched in this fraction. The level of [32P]GTP-binding for all three protein bands is significantly increased when harvested pea plumules are irradiated by red light, and this effect is reversed by far-red light. The results indicate that GTP-binding activity associated with the nuclear envelope of plant cells is photoreversibly regulated by the pigment phytochrome.

NDK Interacts with FtsZ and Converts GDP to GTP to Trigger FtsZ Polymerisation--A Novel Role for NDK.

PubMed

Mishra, Saurabh; Jakkala, Kishor; Srinivasan, Ramanujam; Arumugam, Muthu; Ranjeri, Raghavendra; Gupta, Prabuddha; Rajeswari, Haryadi; Ajitkumar, Parthasarathi

2015-01-01

phosphorylation of FtsZ-bound GDP by NDK. Irrespective of the bacterial species, NDK interacts with FtsZ in vitro and ex vivo and, through the synthesis of GTP from FtsZ-bound GDP and/or free GDP, and ATP (CTP/TTP/UTP), triggers FtsZ polymerisation. The possible biological context of this novel activity of NDK is presented.

NDK Interacts with FtsZ and Converts GDP to GTP to Trigger FtsZ Polymerisation - A Novel Role for NDK

PubMed Central

Mishra, Saurabh; Jakkala, Kishor; Srinivasan, Ramanujam; Arumugam, Muthu; Ranjeri, Raghavendra; Gupta, Prabuddha; Rajeswari, Haryadi; Ajitkumar, Parthasarathi

2015-01-01

to the possibility of direct phosphorylation of FtsZ-bound GDP by NDK. Conclusion Irrespective of the bacterial species, NDK interacts with FtsZ in vitro and ex vivo and, through the synthesis of GTP from FtsZ-bound GDP and/or free GDP, and ATP (CTP/TTP/UTP), triggers FtsZ polymerisation. The possible biological context of this novel activity of NDK is presented. PMID:26630542

Thermodynamics of the GTP-GDP-operated Conformational Switch of Selenocysteine-specific Translation Factor SelB*

PubMed Central

Paleskava, Alena; Konevega, Andrey L.; Rodnina, Marina V.

2012-01-01

SelB is a specialized translation factor that binds GTP and GDP and delivers selenocysteyl-tRNA (Sec-tRNASec) to the ribosome. By analogy to elongation factor Tu (EF-Tu), SelB is expected to control the delivery and release of Sec-tRNASec to the ribosome by the structural switch between GTP- and GDP-bound conformations. However, crystal structures of SelB suggested a similar domain arrangement in the apo form and GDP- and GTP-bound forms of the factor, raising the question of how SelB can fulfill its delivery function. Here, we studied the thermodynamics of guanine nucleotide binding to SelB by isothermal titration calorimetry in the temperature range between 10 and 25 °C using GTP, GDP, and two nonhydrolyzable GTP analogs, guanosine 5′-O-(γ-thio)triphosphate (GTPγS) and guanosine 5′-(β,γ-imido)-triphosphate (GDPNP). The binding of SelB to either guanine nucleotide is characterized by a large heat capacity change (−621, −467, −235, and −275 cal × mol−1 × K−1, with GTP, GTPγS, GDPNP, and GDP, respectively), associated with compensatory changes in binding entropy and enthalpy. Changes in heat capacity indicate a large decrease of the solvent-accessible surface area in SelB, amounting to 43 or 32 amino acids buried upon binding of GTP or GTPγS, respectively, and 15–19 amino acids upon binding GDP or GDPNP. The similarity of the GTP and GDP forms in the crystal structures can be attributed to the use of GDPNP, which appears to induce a structure of SelB that is more similar to the GDP than to the GTP-bound form. PMID:22740700

GDP-to-GTP exchange on the microtubule end can contribute to the frequency of catastrophe

PubMed Central

Piedra, Felipe-Andrés; Kim, Tae; Garza, Emily S.; Geyer, Elisabeth A.; Burns, Alexander; Ye, Xuecheng; Rice, Luke M.

2016-01-01

Microtubules are dynamic polymers of αβ-tubulin that have essential roles in chromosome segregation and organization of the cytoplasm. Catastrophe—the switch from growing to shrinking—occurs when a microtubule loses its stabilizing GTP cap. Recent evidence indicates that the nucleotide on the microtubule end controls how tightly an incoming subunit will be bound (trans-acting GTP), but most current models do not incorporate this information. We implemented trans-acting GTP into a computational model for microtubule dynamics. In simulations, growing microtubules often exposed terminal GDP-bound subunits without undergoing catastrophe. Transient GDP exposure on the growing plus end slowed elongation by reducing the number of favorable binding sites on the microtubule end. Slower elongation led to erosion of the GTP cap and an increase in the frequency of catastrophe. Allowing GDP-to-GTP exchange on terminal subunits in simulations mitigated these effects. Using mutant αβ-tubulin or modified GTP, we showed experimentally that a more readily exchangeable nucleotide led to less frequent catastrophe. Current models for microtubule dynamics do not account for GDP-to-GTP exchange on the growing microtubule end, so our findings provide a new way of thinking about the molecular events that initiate catastrophe. PMID:27146111

Cex1p facilitates Rna1p-mediated dissociation of the Los1p-tRNA-Gsp1p-GTP export complex.

PubMed

McGuire, Andrew T; Mangroo, Dev

2012-02-01

Nuclear tRNA export plays an essential role in key cellular processes such as regulation of protein synthesis, cell cycle progression, response to nutrient availability and DNA damage and development. Like other nuclear export processes, assembly of the nuclear tRNA export complex in the nucleus is dependent on Ran-GTP/Gsp1p-GTP, and dissociation of the export receptor-tRNA-Ran-GTP/Gsp1p-GTP complex in the cytoplasm requires RanBP1/Yrb1p and RanGAP/Rna1p to activate the GTPase activity of Ran-GTP/Gsp1p-GTP. The Saccharomyces cerevisiae Cex1p and Human Scyl1 have also been proposed to participate in unloading of the tRNA export receptors at the cytoplasmic face of the nuclear pore complex (NPC). Here, we provide evidence suggesting that Cex1p is required for activation of the GTPase activity of Gsp1p and dissociation of the receptor-tRNA-Gsp1p export complex in S. cerevisiae. The data suggest that Cex1p recruits Rna1p from the cytoplasm to the NPC and facilitates Rna1p activation of the GTPase activity of Gsp1p by enabling Rna1p to gain access to Gsp1p-GTP bound to the export receptor tRNA complex. It is possible that this tRNA unloading mechanism is conserved in evolutionarily diverse organisms and that other Gsp1p-GTP-dependent export processes use a pathway-specific component to recruit Rna1p to the NPC. © 2011 John Wiley & Sons A/S.

GDP-to-GTP exchange on the microtubule end can contribute to the frequency of catastrophe.

PubMed

Piedra, Felipe-Andrés; Kim, Tae; Garza, Emily S; Geyer, Elisabeth A; Burns, Alexander; Ye, Xuecheng; Rice, Luke M

2016-11-07

Microtubules are dynamic polymers of αβ-tubulin that have essential roles in chromosome segregation and organization of the cytoplasm. Catastrophe-the switch from growing to shrinking-occurs when a microtubule loses its stabilizing GTP cap. Recent evidence indicates that the nucleotide on the microtubule end controls how tightly an incoming subunit will be bound (trans-acting GTP), but most current models do not incorporate this information. We implemented trans-acting GTP into a computational model for microtubule dynamics. In simulations, growing microtubules often exposed terminal GDP-bound subunits without undergoing catastrophe. Transient GDP exposure on the growing plus end slowed elongation by reducing the number of favorable binding sites on the microtubule end. Slower elongation led to erosion of the GTP cap and an increase in the frequency of catastrophe. Allowing GDP-to-GTP exchange on terminal subunits in simulations mitigated these effects. Using mutant αβ-tubulin or modified GTP, we showed experimentally that a more readily exchangeable nucleotide led to less frequent catastrophe. Current models for microtubule dynamics do not account for GDP-to-GTP exchange on the growing microtubule end, so our findings provide a new way of thinking about the molecular events that initiate catastrophe. © 2016 Piedra et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Characterization of mouse and human GTP cyclohydrolase I genes. Mutations in patients with GTP cyclohydrolase I deficiency.

PubMed

Ichinose, H; Ohye, T; Matsuda, Y; Hori, T; Blau, N; Burlina, A; Rouse, B; Matalon, R; Fujita, K; Nagatsu, T

1995-04-28

GTP cyclohydrolase I is the first and rate-limiting enzyme for the biosynthesis of tetrahydrobiopterin in mammals. Previously, we reported three species of human GTP cyclohydrolase I cDNA in a human liver cDNA library (Togari, A., Ichinose, H., Matsumoto, S., Fujita, K., and Nagatsu, T. (1992) Biochem. Biophys. Res. Commun. 187, 359-365). Furthermore, very recently, we found that the GTP cyclohydrolase I gene is causative for hereditary progressive dystonia with marked diurnal fluctuation, also known as DOPA-responsive dystonia (Ichinose, H., Ohye, T., Takahashi, E., Seki, N., Hori, T., Segawa, M., Nomura, Y., Endo, K., Tanaka, H., Tsuji, S., Fujita, K., and Nagatsu, T. (1994) Nature Genetics 8, 236-242). To clarify the mechanisms that regulate transcription of the GTP cyclohydrolase I gene and to generate multiple species of mRNA, we isolated genomic DNA clones for the human and mouse GTP cyclohydrolase I genes. Structural analysis of the isolated clones revealed that the GTP cyclohydrolase I gene is encoded by a single copy gene and is composed of six exons spanning approximately 30 kilobases. We sequenced all exon/intron boundaries of the human and mouse genes. Structural analysis also demonstrated that the heterogeneity of GTP cyclohydrolase I mRNA is caused by an alternative usage of the splicing acceptor site at the sixth exon. The transcription start site of the mouse GTP cyclohydrolase I gene and the 5'-flanking sequences of the mouse and human genes were determined. We performed regional mapping of the mouse gene by fluorescence in situ hybridization, and the mouse GTP cyclohydrolase I gene was assigned to region C2-3 of mouse chromosome 14. We identified missense mutations in patients with GTP cyclohydrolase I deficiency and expressed mutated enzymes in Escherichia coli to confirm alterations in the enzyme activity.

Blue News Update: BODIPY-GTP Binds to the Blue-Light Receptor YtvA While GTP Does Not

PubMed Central

Schmieder, Peter

2012-01-01

Light is an important environmental factor for almost all organisms. It is mainly used as an energy source but it is also a key factor for the regulation of multiple cellular functions. Light as the extracellular stimulus is thereby converted into an intracellular signal by photoreceptors that act as signal transducers. The blue-light receptor YtvA, a bacterial counterpart of plant phototropins, is involved in the stress response of Bacillus subtilis. The mechanism behind its activation, however, remains unknown. It was suggested based on fluorescence spectroscopic studies that YtvA function involves GTP binding and that this interaction is altered by absorption of light. We have investigated this interaction by several biophysical methods and show here using fluorescence spectroscopy, ITC titrations, and three NMR spectroscopic assays that while YtvA interacts with BODIPY-GTP as a fluorescent GTP analogue originally used for the detection of GTP binding, it does not bind GTP. PMID:22247770

The nucleotide-free state of heterotrimeric G proteins α-subunit adopts a highly stable conformation.

PubMed

Andhirka, Sai Krishna; Vignesh, Ravichandran; Aradhyam, Gopala Krishna

2017-08-01

Deciphering the mechanism of activation of heterotrimeric G proteins by their cognate receptors continues to be an intriguing area of research. The recently solved crystal structure of the ternary complex captured the receptor-bound α-subunit in an open conformation, without bound nucleotide has improved our understanding of the activation process. Despite these advancements, the mechanism by which the receptor causes GDP release from the α-subunit remains elusive. To elucidate the mechanism of activation, we studied guanine nucleotide-induced structural stability of the α-subunit (in response to thermal/chaotrope-mediated stress). Inherent stabilities of the inactive (GDP-bound) and active (GTP-bound) forms contribute antagonistically to the difference in conformational stability whereas the GDP-bound protein is able to switch to a stable intermediate state, GTP-bound protein loses this ability. Partial perturbation of the protein fold reveals the underlying influence of the bound nucleotide providing an insight into the mechanism of activation. An extra stable, pretransition intermediate, 'empty pocket' state (conformationally active-state like) in the unfolding pathway of GDP-bound protein mimics a gating system - the activation process having to overcome this stable intermediate state. We demonstrate that a relatively more complex conformational fold of the GDP-bound protein is at the core of the gating system. We report capturing this threshold, 'metastable empty pocket' conformation (the gate) of α-subunit of G protein and hypothesize that the receptor activates the G protein by enabling it to achieve this structure through mild structural perturbation. © 2017 Federation of European Biochemical Societies.

In vitro guanine nucleotide exchange activity of DHR-2/DOCKER/CZH2 domains.

PubMed

Côté, Jean-François; Vuori, Kristiina

2006-01-01

Rho family GTPases regulate a large variety of biological processes, including the reorganization of the actin cytoskeleton. Like other members of the Ras superfamily of small GTP-binding proteins, Rho GTPases cycle between a GDP-bound (inactive) and a GTP-bound (active) state, and, when active, the GTPases relay extracellular signals to a large number of downstream effectors. Guanine nucleotide exchange factors (GEFs) promote the exchange of GDP for GTP on Rho GTPases, thereby activating them. Most Rho-GEFs mediate their effects through their signature domain known as the Dbl Homology-Pleckstrin Homology (DH-PH) module. Recently, we and others identified a family of evolutionarily conserved, DOCK180-related proteins that also display GEF activity toward Rho GTPases. The DOCK180-family of proteins lacks the canonical DH-PH module. Instead, they rely on a novel domain, termed DHR-2, DOCKER, or CZH2, to exchange GDP for GTP on Rho targets. In this chapter, the experimental approach that we used to uncover the exchange activity of the DHR-2 domain of DOCK180-related proteins will be described.

Neutron Crystal Structure of RAS GTPase Puts in Question the Protonation State of the GTP γ-Phosphate*

PubMed Central

Knihtila, Ryan; Holzapfel, Genevieve; Weiss, Kevin; Meilleur, Flora; Mattos, Carla

2015-01-01

RAS GTPase is a prototype for nucleotide-binding proteins that function by cycling between GTP and GDP, with hydrogen atoms playing an important role in the GTP hydrolysis mechanism. It is one of the most well studied proteins in the superfamily of small GTPases, which has representatives in a wide range of cellular functions. These proteins share a GTP-binding pocket with highly conserved motifs that promote hydrolysis to GDP. The neutron crystal structure of RAS presented here strongly supports a protonated γ-phosphate at physiological pH. This counters the notion that the phosphate groups of GTP are fully deprotonated at the start of the hydrolysis reaction, which has colored the interpretation of experimental and computational data in studies of the hydrolysis mechanism. The neutron crystal structure presented here puts in question our understanding of the pre-catalytic state associated with the hydrolysis reaction central to the function of RAS and other GTPases. PMID:26515069

Neutron crystal structure of RAS GTPase puts in question the protonation state of the GTP γ-phosphate

DOE PAGES

Knihtila, Ryan; Holzapfel, Genevieve; Weiss, Kevin; ...

2015-10-29

RAS GTPase is a prototype for nucleotide-binding proteins that function by cycling between GTP and GDP, with hydrogen atoms playing an important role in the GTP hydrolysis mechanism. It is one of the most well studied proteins in the superfamily of small GTPases, which has representatives in a wide range of cellular functions. These proteins share a GTP-binding pocket with highly conserved motifs that promote hydrolysis to GDP. The neutron crystal structure of RAS presented here strongly supports a protonated gamma-phosphate at physiological pH. This counters the notion that the phosphate groups of GTP are fully deprotonated at the startmore » of the hydrolysis reaction, which has colored the interpretation of experimental and computational data in studies of the hydrolysis mechanism. As a result, the neutron crystal structure presented here puts in question our understanding of the pre-catalytic state associated with the hydrolysis reaction central to the function of RAS and other GTPases.« less

GDP beta S enhances the activation of phospholipase C caused by thrombin in human platelets: evidence for involvement of an inhibitory GTP-binding protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oberdisse, E.; Lapetina, E.G.

1987-05-14

Guanosine 5'-O-thiotriphosphate (GTP gamma S) and thrombin stimulate the activity of phospholipase C in platelets that have been permeabilized with saponin and whose inositol phospholipids have been prelabeled with (/sup 3/H)inositol. Ca/sup 2 +/ has opposite effects on the formation of (/sup 3/H)inositol phosphates induced by thrombin or GTP gamma S. While the action of GTP gamma S on the formation of (/sup 3/H)inositol phosphates is inhibited by Ca/sup 2 +/, action of thrombin is stimulated by Ca/sup 2 +/. Guanosine 5'-O-(2-thiodiphosphate) (GDP beta S), which inhibits the function of GTP-binding proteins, also inhibits the effect of GTP gamma Smore » on phospholipase C stimulation but, surprisingly, increases the effect of thrombin. Ca/sup 2 +/ increases the inhibitory effect of GDP beta S on GTP gamma S activation of phospholipase C, but Ca/sup 2 +/ further enhances the stimulatory effect of GDP beta S on the thrombin activation of phospholipase C. This indicates that two mechanisms are responsible for the activation of phospholipase C in platelets. A GTP-binding protein is responsible for regulation of phospholipase C induced by GTP gamma S, while the effect of thrombin on the stimulation of phospholipase C is independent of GTP-binding proteins. However, the effect of thrombin may be modulated by the action of an inhibitory GTP-binding protein.« less

Cloning and molecular characterization of the salt-regulated jojoba ScRab cDNA encoding a small GTP-binding protein.

PubMed

Mizrahi-Aviv, Ela; Mills, David; Benzioni, Aliza; Bar-Zvi, Dudy

2002-10-01

Salt stress results in a massive change in gene expression. An 837 bp cDNA designated ScRab was cloned from shoot cultures of the salt tolerant jojoba (Simmondsia chinesis). The cloned cDNA encodes a full length 200 amino acid long polypeptide that bears high homology to the Rab subfamily of small GTP binding proteins, particularly, the Rab5 subfamily. ScRab expression is reduced in shoots grown in the presence of salt compared to shoots from non-stressed cultures. His6-tagged ScRAB protein was expressed in E. coli, and purified to homogeneity. The purified protein bound radiolabelled GTP. The unlabelled guanine nucleotides GTP, GTP gamma S and GDP but not ATP, CTP or UTP competed with GTP binding.

The mechanism of GTP hydrolysis by dynamin II: a transient kinetic study.

PubMed

Binns, D D; Helms, M K; Barylko, B; Davis, C T; Jameson, D M; Albanesi, J P; Eccleston, J F

2000-06-20

Dynamin II is a 98 kDa protein (870 amino acids) required for the late stages of clathrin-mediated endocytosis. The GTPase activity of dynamin is required for its function in the budding stages of receptor-mediated endocytosis and synaptic vesicle recycling. This activity is stimulated when dynamin self-associates on multivalent binding surfaces, such as microtubules and anionic liposomes. We first investigated the oligomeric state of dynamin II by analytical ultracentrifuge sedimentation equilibrium measurements at high ionic strength and found that it was best described by a monomer-tetramer equilibrium. We then studied the intrinsic dynamin GTPase mechanism by using a combination of fluorescence stopped-flow and HPLC methods using the fluorescent analogue of GTP, mantdGTP (2'-deoxy-3'-O-(N-methylanthraniloyl) guanosine-5'-triphosphate), under the same ionic strength conditions. The results are interpreted as showing that mantdGTP binds to dynamin in a two-step mechanism. The dissociation constant of mantdGTP binding to dynamin, calculated from the ratio of the off-rate to the on-rate (k(off)/k(on)), was 0.5 microM. Cleavage of mantdGTP then occurs to mantdGDP and P(i) followed by the rapid release of mantdGDP and P(i). No evidence of reversibility of hydrolysis was observed. The cleavage step itself is the rate-limiting step in the mechanism. This mechanism more closely resembles that of the Ras family of proteins involved in cell signaling than the myosin ATPase involved in cellular motility.

Structural basis for nuclear import complex dissociation by RanGTP.

PubMed

Lee, Soo Jae; Matsuura, Yoshiyuki; Liu, Sai Man; Stewart, Murray

2005-06-02

Nuclear protein import is mediated mainly by the transport factor importin-beta that binds cytoplasmic cargo, most often via the importin-alpha adaptor, and then transports it through nuclear pore complexes. This active transport is driven by disassembly of the import complex by nuclear RanGTP. The switch I and II loops of Ran change conformation with nucleotide state, and regulate its interactions with nuclear trafficking components. Importin-beta consists of 19 HEAT repeats that are based on a pair of antiparallel alpha-helices (referred to as the A- and B-helices). The HEAT repeats stack to yield two C-shaped arches, linked together to form a helicoidal molecule that has considerable conformational flexibility. Here we present the structure of full-length yeast importin-beta (Kap95p or karyopherin-beta) complexed with RanGTP, which provides a basis for understanding the crucial cargo-release step of nuclear import. We identify a key interaction site where the RanGTP switch I loop binds to the carboxy-terminal arch of Kap95p. This interaction produces a change in helicoidal pitch that locks Kap95p in a conformation that cannot bind importin-alpha or cargo. We suggest an allosteric mechanism for nuclear import complex disassembly by RanGTP.

Role of a ribosomal RNA phosphate oxygen during the EF-G–triggered GTP hydrolysis

PubMed Central

Koch, Miriam; Flür, Sara; Kreutz, Christoph; Ennifar, Eric; Micura, Ronald; Polacek, Norbert

2015-01-01

Elongation factor-catalyzed GTP hydrolysis is a key reaction during the ribosomal elongation cycle. Recent crystal structures of G proteins, such as elongation factor G (EF-G) bound to the ribosome, as well as many biochemical studies, provide evidence that the direct interaction of translational GTPases (trGTPases) with the sarcin-ricin loop (SRL) of ribosomal RNA (rRNA) is pivotal for hydrolysis. However, the precise mechanism remains elusive and is intensively debated. Based on the close proximity of the phosphate oxygen of A2662 of the SRL to the supposedly catalytic histidine of EF-G (His87), we probed this interaction by an atomic mutagenesis approach. We individually replaced either of the two nonbridging phosphate oxygens at A2662 with a methyl group by the introduction of a methylphosphonate instead of the natural phosphate in fully functional, reconstituted bacterial ribosomes. Our major finding was that only one of the two resulting diastereomers, the SP methylphosphonate, was compatible with efficient GTPase activation on EF-G. The same trend was observed for a second trGTPase, namely EF4 (LepA). In addition, we provide evidence that the negative charge of the A2662 phosphate group must be retained for uncompromised activity in GTP hydrolysis. In summary, our data strongly corroborate that the nonbridging proSP phosphate oxygen at the A2662 of the SRL is critically involved in the activation of GTP hydrolysis. A mechanistic scenario is supported in which positioning of the catalytically active, protonated His87 through electrostatic interactions with the A2662 phosphate group and H-bond networks are key features of ribosome-triggered activation of trGTPases. PMID:25941362

Hormonal control of GTP cyclohydrolase I gene expression and enzyme activity during color pattern development in wings of Precis coenia.

PubMed

Sawada, H; Nakagoshi, M; Reinhardt, R K; Ziegler, I; Koch, P B

2002-06-01

Color patterns of butterfly wings are composed of single color points represented by each scale. In the case of Precis coenia, at the end of pupal development, different types of pigments are synthesized sequentially in the differently colored scales beginning with white (pterins) followed by red (ommatins) and then black (melanin). In order to explain how formation of these different colors is regulated, we examined the expression of an mRNA-encoding guanosine triphosphate-cyclohydrolase I (GTP-CH I; EC 3.5.4.16), the first key enzyme in the biosynthesis of pteridines, during pigment formation in the wings of P. coenia. The strongest positive signal was recognized around pigment formation one day before butterfly emergence. This GTP-CH I gene expression is paralleled by GTP-CH I enzyme activity measured in wing extracts. We also investigated the effect of 20-hydroxyecdysone on the expression of GTP-CH I mRNA and the enzyme activity during color formation. The results strongly suggest that the onset and duration of the expression of a GTP-CH I mRNA is triggered by a declining ecdysteroid hormone titer during late pupal development.

Different effects of guanine nucleotides (GDP and GTP) on protein-mediated mitochondrial proton leak.

PubMed

Woyda-Ploszczyca, Andrzej M; Jarmuszkiewicz, Wieslawa

2014-01-01

In this study, we compared the influence of GDP and GTP on isolated mitochondria respiring under conditions favoring oxidative phosphorylation (OXPHOS) and under conditions excluding this process, i.e., in the presence of carboxyatractyloside, an adenine nucleotide translocase inhibitor, and/or oligomycin, an FOF1-ATP synthase inhibitor. Using mitochondria isolated from rat kidney and human endothelial cells, we found that the action of GDP and GTP can differ diametrically depending on the conditions. Namely, under conditions favoring OXPHOS, both in the absence and presence of linoleic acid, an activator of uncoupling proteins (UCPs), the addition of 1 mM GDP resulted in the state 4 (non-phosphorylating respiration)-state 3 (phosphorylating respiration) transition, which is characteristic of ADP oxidative phosphorylation. In contrast, the addition of 1 mM GTP resulted in a decrease in the respiratory rate and an increase in the membrane potential, which is characteristic of UCP inhibition. The stimulatory effect of GDP, but not GTP, was also observed in inside-out submitochondrial particles prepared from rat kidney mitochondria. However, the effects of GDP and GTP were more similar in the presence of OXPHOS inhibitors. The importance of these observations in connection with the action of UCPs, adenine nucleotide translocase (or other carboxyatractyloside-sensitive carriers), carboxyatractyloside- and purine nucleotide-insensitive carriers, as well as nucleoside-diphosphate kinase (NDPK) are considered. Because the measurements favoring oxidative phosphorylation better reflect in vivo conditions, our study strongly supports the idea that GDP cannot be considered a significant physiological inhibitor of UCP. Moreover, it appears that, under native conditions, GTP functions as a more efficient UCP inhibitor than GDP and ATP.

Different Effects of Guanine Nucleotides (GDP and GTP) on Protein-Mediated Mitochondrial Proton Leak

PubMed Central

Woyda-Ploszczyca, Andrzej M.; Jarmuszkiewicz, Wieslawa

2014-01-01

In this study, we compared the influence of GDP and GTP on isolated mitochondria respiring under conditions favoring oxidative phosphorylation (OXPHOS) and under conditions excluding this process, i.e., in the presence of carboxyatractyloside, an adenine nucleotide translocase inhibitor, and/or oligomycin, an FOF1-ATP synthase inhibitor. Using mitochondria isolated from rat kidney and human endothelial cells, we found that the action of GDP and GTP can differ diametrically depending on the conditions. Namely, under conditions favoring OXPHOS, both in the absence and presence of linoleic acid, an activator of uncoupling proteins (UCPs), the addition of 1 mM GDP resulted in the state 4 (non-phosphorylating respiration)-state 3 (phosphorylating respiration) transition, which is characteristic of ADP oxidative phosphorylation. In contrast, the addition of 1 mM GTP resulted in a decrease in the respiratory rate and an increase in the membrane potential, which is characteristic of UCP inhibition. The stimulatory effect of GDP, but not GTP, was also observed in inside-out submitochondrial particles prepared from rat kidney mitochondria. However, the effects of GDP and GTP were more similar in the presence of OXPHOS inhibitors. The importance of these observations in connection with the action of UCPs, adenine nucleotide translocase (or other carboxyatractyloside-sensitive carriers), carboxyatractyloside- and purine nucleotide-insensitive carriers, as well as nucleoside-diphosphate kinase (NDPK) are considered. Because the measurements favoring oxidative phosphorylation better reflect in vivo conditions, our study strongly supports the idea that GDP cannot be considered a significant physiological inhibitor of UCP. Moreover, it appears that, under native conditions, GTP functions as a more efficient UCP inhibitor than GDP and ATP. PMID:24904988

Activating distillation with an infinitesimal amount of bound entanglement.

PubMed

Vollbrecht, Karl Gerd H; Wolf, Michael M

2002-06-17

We show that bipartite quantum states of any dimension, which do not have a positive partial transpose (NPPT), become 1-distillable when one adds an infinitesimal amount of bound entanglement. To this end we investigate the activation properties of a new class of symmetric bound entangled states of full rank. It is shown that in this set there exist universal activator states capable of activating the distillation of any NPPT state. The result shows that even a small amount of bound entanglement can be useful for quantum information purposes.

Mammalian translation elongation factor eEF1A2: X-ray structure and new features of GDP/GTP exchange mechanism in higher eukaryotes.

PubMed

Crepin, Thibaut; Shalak, Vyacheslav F; Yaremchuk, Anna D; Vlasenko, Dmytro O; McCarthy, Andrew; Negrutskii, Boris S; Tukalo, Michail A; El'skaya, Anna V

2014-11-10

Eukaryotic elongation factor eEF1A transits between the GTP- and GDP-bound conformations during the ribosomal polypeptide chain elongation. eEF1A*GTP establishes a complex with the aminoacyl-tRNA in the A site of the 80S ribosome. Correct codon-anticodon recognition triggers GTP hydrolysis, with subsequent dissociation of eEF1A*GDP from the ribosome. The structures of both the 'GTP'- and 'GDP'-bound conformations of eEF1A are unknown. Thus, the eEF1A-related ribosomal mechanisms were anticipated only by analogy with the bacterial homolog EF-Tu. Here, we report the first crystal structure of the mammalian eEF1A2*GDP complex which indicates major differences in the organization of the nucleotide-binding domain and intramolecular movements of eEF1A compared to EF-Tu. Our results explain the nucleotide exchange mechanism in the mammalian eEF1A and suggest that the first step of eEF1A*GDP dissociation from the 80S ribosome is the rotation of the nucleotide-binding domain observed after GTP hydrolysis. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Shift in the equilibrium between on and off states of the allosteric switch in Ras-GppNHp affected by small molecules and bulk solvent composition.

PubMed

Holzapfel, Genevieve; Buhrman, Greg; Mattos, Carla

2012-08-07

Ras GTPase cycles between its active GTP-bound form promoted by GEFs and its inactive GDP-bound form promoted by GAPs to affect the control of various cellular functions. It is becoming increasingly apparent that subtle regulation of the GTP-bound active state may occur through promotion of substates mediated by an allosteric switch mechanism that induces a disorder to order transition in switch II upon ligand binding at an allosteric site. We show with high-resolution structures that calcium acetate and either dithioerythritol (DTE) or dithiothreitol (DTT) soaked into H-Ras-GppNHp crystals in the presence of a moderate amount of poly(ethylene glycol) (PEG) can selectively shift the equilibrium to the "on" state, where the active site appears to be poised for catalysis (calcium acetate), or to what we call the "ordered off" state, which is associated with an anticatalytic conformation (DTE or DTT). We also show that the equilibrium is reversible in our crystals and dependent on the nature of the small molecule present. Calcium acetate binding in the allosteric site stabilizes the conformation observed in the H-Ras-GppNHp/NOR1A complex, and PEG, DTE, and DTT stabilize the anticatalytic conformation observed in the complex between the Ras homologue Ran and Importin-β. The small molecules are therefore selecting biologically relevant conformations in the crystal that are sampled by the disordered switch II in the uncomplexed GTP-bound form of H-Ras. In the presence of a large amount of PEG, the ordered off conformation predominates, whereas in solution, in the absence of PEG, switch regions appear to remain disordered in what we call the off state, unable to bind DTE.

Distinguishing Majorana bound states and Andreev bound states with microwave spectra

NASA Astrophysics Data System (ADS)

Zhang, Zhen-Tao

2018-04-01

Majorana fermions are a fascinating and not yet confirmed quasiparticles in condensed matter physics. Here we propose using microwave spectra to distinguish Majorana bound states (MBSs) from topological trivial Andreev bound states. By numerically calculating the transmission and Zeeman field dependence of the many-body excitation spectrum of a 1D Josephson junction, we find that the two kinds of bound states have distinct responses to variations in the related parameters. Furthermore, the singular behaviors of the MBSs spectrum could be attributed to the robust fractional Josephson coupling and nonlocality of MBSs. Our results provide a feasible method to verify the existence of MBSs and could accelerate its application to topological quantum computation.

Determination of Rab5 activity in the cell by effector pull-down assay.

PubMed

Qi, Yaoyao; Liang, Zhimin; Wang, Zonghua; Lu, Guodong; Li, Guangpu

2015-01-01

Rab5 targets to early endosomes and is a master regulator of early endosome fusion and endocytosis in all eukaryotic cells. Like other GTPases, Rab5 functions as a molecular switch by alternating between GTP-bound and GDP-bound forms, with the former being biologically active via interactions with multiple effector proteins. Thus the Rab5-GTP level in the cell reflects Rab5 activity in promoting endosome fusion and endocytosis and is indicative of cellular endocytic activity. In this chapter, we describe a Rab5 activity assay by using GST fusion proteins with the Rab5 effectors such as Rabaptin-5, Rabenosyn-5, and EEA1 that specifically bind to GTP-bound Rab5. We compare the efficiencies of the three GST fusion proteins in the pull-down of mammalian and fungal Rab5 proteins.

The Role of Magnesium for Geometry and Charge in GTP Hydrolysis, Revealed by Quantum Mechanics/Molecular Mechanics Simulations

PubMed Central

Rudack, Till; Xia, Fei; Schlitter, Jürgen; Kötting, Carsten; Gerwert, Klaus

2012-01-01

The coordination of the magnesium ion in proteins by triphosphates plays an important role in catalytic hydrolysis of GTP or ATP, either in signal transduction or energy conversion. For example, in Ras the magnesium ion contributes to the catalysis of GTP hydrolysis. The cleavage of GTP to GDP and Pi in Ras switches off cellular signaling. We analyzed GTP hydrolysis in water, Ras, and Ras·Ras-GTPase-activating protein using quantum mechanics/molecular mechanics simulations. By comparison of the theoretical IR-difference spectra for magnesium ion coordinated triphosphate to experimental ones, the simulations are validated. We elucidated thereby how the magnesium ion contributes to catalysis. It provides a temporary storage for the electrons taken from the triphosphate and it returns them after bond cleavage and Pi release back to the diphosphate. Furthermore, the Ras·Mg2+ complex forces the triphosphate into a stretched conformation in which the β- and γ-phosphates are coordinated in a bidentate manner. In this conformation, the triphosphate elongates the bond, which has to be cleaved during hydrolysis. Furthermore, the γ-phosphate adopts a more planar structure, driving the conformation of the molecule closer to the hydrolysis transition state. GTPase-activating protein enhances these changes in GTP conformation and charge distribution via the intruding arginine finger. PMID:22853907

Mammalian translation elongation factor eEF1A2: X-ray structure and new features of GDP/GTP exchange mechanism in higher eukaryotes

PubMed Central

Crepin, Thibaut; Shalak, Vyacheslav F.; Yaremchuk, Anna D.; Vlasenko, Dmytro O.; McCarthy, Andrew; Negrutskii, Boris S.; Tukalo, Michail A.; El'skaya, Anna V.

2014-01-01

Eukaryotic elongation factor eEF1A transits between the GTP- and GDP-bound conformations during the ribosomal polypeptide chain elongation. eEF1A*GTP establishes a complex with the aminoacyl-tRNA in the A site of the 80S ribosome. Correct codon–anticodon recognition triggers GTP hydrolysis, with subsequent dissociation of eEF1A*GDP from the ribosome. The structures of both the ‘GTP’- and ‘GDP’-bound conformations of eEF1A are unknown. Thus, the eEF1A-related ribosomal mechanisms were anticipated only by analogy with the bacterial homolog EF-Tu. Here, we report the first crystal structure of the mammalian eEF1A2*GDP complex which indicates major differences in the organization of the nucleotide-binding domain and intramolecular movements of eEF1A compared to EF-Tu. Our results explain the nucleotide exchange mechanism in the mammalian eEF1A and suggest that the first step of eEF1A*GDP dissociation from the 80S ribosome is the rotation of the nucleotide-binding domain observed after GTP hydrolysis. PMID:25326326

Shift in the Equilibrium between On and Off States of the Allosteric Switch in Ras-GppNHp Affected by Small Molecules and Bulk Solvent Composition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holzapfel, Genevieve; Buhrman, Greg; Mattos, Carla

2012-08-31

Ras GTPase cycles between its active GTP-bound form promoted by GEFs and its inactive GDP-bound form promoted by GAPs to affect the control of various cellular functions. It is becoming increasingly apparent that subtle regulation of the GTP-bound active state may occur through promotion of substates mediated by an allosteric switch mechanism that induces a disorder to order transition in switch II upon ligand binding at an allosteric site. We show with high-resolution structures that calcium acetate and either dithioerythritol (DTE) or dithiothreitol (DTT) soaked into H-Ras-GppNHp crystals in the presence of a moderate amount of poly(ethylene glycol) (PEG) canmore » selectively shift the equilibrium to the 'on' state, where the active site appears to be poised for catalysis (calcium acetate), or to what we call the 'ordered off' state, which is associated with an anticatalytic conformation (DTE or DTT). We also show that the equilibrium is reversible in our crystals and dependent on the nature of the small molecule present. Calcium acetate binding in the allosteric site stabilizes the conformation observed in the H-Ras-GppNHp/NOR1A complex, and PEG, DTE, and DTT stabilize the anticatalytic conformation observed in the complex between the Ras homologue Ran and Importin-{beta}. The small molecules are therefore selecting biologically relevant conformations in the crystal that are sampled by the disordered switch II in the uncomplexed GTP-bound form of H-Ras. In the presence of a large amount of PEG, the ordered off conformation predominates, whereas in solution, in the absence of PEG, switch regions appear to remain disordered in what we call the off state, unable to bind DTE.« less

Identification of a Novel, Putative Rho-specific GDP/GTP Exchange Factor and a RhoA-binding Protein: Control of Neuronal Morphology

PubMed Central

Gebbink, Martijn F.B.G.; Kranenburg, Onno; Poland, Mieke; van Horck, Francis P.G.; Houssa, Brahim; Moolenaar, Wouter H.

1997-01-01

The small GTP-binding protein Rho has been implicated in the control of neuronal morphology. In N1E-115 neuronal cells, the Rho-inactivating C3 toxin stimulates neurite outgrowth and prevents actomyosin-based neurite retraction and cell rounding induced by lysophosphatidic acid (LPA), sphingosine-1-phosphate, or thrombin acting on their cognate G protein–coupled receptors. We have identified a novel putative GDP/GTP exchange factor, RhoGEF (190 kD), that interacts with both wild-type and activated RhoA, but not with Rac or Cdc42. RhoGEF, like activated RhoA, mimics receptor stimulation in inducing cell rounding and in preventing neurite outgrowth. Furthermore, we have identified a 116-kD protein, p116Rip, that interacts with both the GDP- and GTP-bound forms of RhoA in N1E-115 cells. Overexpression of p116Rip stimulates cell flattening and neurite outgrowth in a similar way to dominant-negative RhoA and C3 toxin. Cells overexpressing p116Rip fail to change their shape in response to LPA, as is observed after Rho inactivation. Our results indicate that (a) RhoGEF may link G protein–coupled receptors to RhoA activation and ensuing neurite retraction and cell rounding; and (b) p116Rip inhibits RhoA-stimulated contractility and promotes neurite outgrowth. PMID:9199174

Bound states in string nets

NASA Astrophysics Data System (ADS)

Schulz, Marc Daniel; Dusuel, Sébastien; Vidal, Julien

2016-11-01

We discuss the emergence of bound states in the low-energy spectrum of the string-net Hamiltonian in the presence of a string tension. In the ladder geometry, we show that a single bound state arises either for a finite tension or in the zero-tension limit depending on the theory considered. In the latter case, we perturbatively compute the binding energy as a function of the total quantum dimension. We also address this issue in the honeycomb lattice where the number of bound states in the topological phase depends on the total quantum dimension. Finally, the internal structure of these bound states is analyzed in the zero-tension limit.

Mitochondrial NUDIX hydrolases: A metabolic link between NAD catabolism, GTP and mitochondrial dynamics.

PubMed

Long, Aaron; Klimova, Nina; Kristian, Tibor

2017-10-01

NAD + catabolism and mitochondrial dynamics are important parts of normal mitochondrial function and are both reported to be disrupted in aging, neurodegenerative diseases, and acute brain injury. While both processes have been extensively studied there has been little reported on how the mechanisms of these two processes are linked. This review focuses on how downstream NAD + catabolism via NUDIX hydrolases affects mitochondrial dynamics under pathologic conditions. Additionally, several potential targets in mitochondrial dysfunction and fragmentation are discussed, including the roles of mitochondrial poly(ADP-ribose) polymerase 1(mtPARP1), AMPK, AMP, and intra-mitochondrial GTP metabolism. Mitochondrial and cytosolic NUDIX hydrolases (NUDT9α and NUDT9β) can affect mitochondrial and cellular AMP levels by hydrolyzing ADP- ribose (ADPr) and subsequently altering the levels of GTP and ATP. Poly (ADP-ribose) polymerase 1 (PARP1) is activated after DNA damage, which depletes NAD + pools and results in the PARylation of nuclear and mitochondrial proteins. In the mitochondria, ADP-ribosyl hydrolase-3 (ARH3) hydrolyzes PAR to ADPr, while NUDT9α metabolizes ADPr to AMP. Elevated AMP levels have been reported to reduce mitochondrial ATP production by inhibiting the adenine nucleotide translocase (ANT), allosterically activating AMPK by altering the cellular AMP: ATP ratio, and by depleting mitochondrial GTP pools by being phosphorylated by adenylate kinase 3 (AK3), which uses GTP as a phosphate donor. Recently, activated AMPK was reported to phosphorylate mitochondria fission factor (MFF), which increases Drp1 localization to the mitochondria and promotes mitochondrial fission. Moreover, the increased AK3 activity could deplete mitochondrial GTP pools and possibly inhibit normal activity of GTP-dependent fusion enzymes, thus altering mitochondrial dynamics. Published by Elsevier Ltd.

The GTP-bound and Sumoylated Form of the rab17 Small Molecular Weight GTPase Selectively Binds Syntaxin 2 in Polarized Hepatic WIF-B Cells*

PubMed Central

Striz, Anneliese C.; Tuma, Pamela L.

2016-01-01

A major focus for our laboratory is identifying the molecules and mechanisms that regulate polarized apical protein sorting in hepatocytes, the major epithelial cells of the liver. These trafficking pathways are regulated, in part, by small molecular weight rab GTPases. We chose to investigate rab17, whose expression is restricted to polarized epithelial cells, is enriched in liver, and has been implicated in regulating basolateral to apical transcytosis. To initiate our studies, we generated three recombinant adenoviruses expressing wild type, constitutively active (GTP bound), or dominant-negative (GDP bound) rab17. Immunoblotting revealed rab17 immunoreactive species at 25 kDa (the predicted rab17 molecular mass) and 40 kDa. We determined that mono-sumoylation of the 25-kDa rab17 is responsible for the shift in molecular mass, and that rab17 prenylation is required for sumoylation. We further determined that sumoylation selectively promotes interactions with syntaxin 2 (but not syntaxins 3 or 4) and that these interactions are nucleotide dependent. Furthermore, a K68R-mutated rab17 led to the redistribution of syntaxin 2 and 5′ nucleotidase from the apical membrane to subapical puncta, whereas multidrug resistance protein 2 distributions were not changed. Together these data are consistent with the proposed role of rab17 in vesicle fusion with the apical plasma membrane and further implicate sumoylation as an important mediator of protein-protein interactions. The selectivity in syntaxin binding and apical protein redistribution further suggests that rab17 and syntaxin 2 mediate fusion of transcytotic vesicles at the apical surface. PMID:26957544

Effective GTP-replacing FtsZ inhibitors and antibacterial mechanism of action.

PubMed

Artola, Marta; Ruiz-Avila, Laura B; Vergoñós, Albert; Huecas, Sonia; Araujo-Bazán, Lidia; Martín-Fontecha, Mar; Vázquez-Villa, Henar; Turrado, Carlos; Ramírez-Aportela, Erney; Hoegl, Annabelle; Nodwell, Matthew; Barasoain, Isabel; Chacón, Pablo; Sieber, Stephan A; Andreu, Jose M; López-Rodríguez, María L

2015-03-20

Essential cell division protein FtsZ is considered an attractive target in the search for antibacterials with novel mechanisms of action to overcome the resistance problem. FtsZ undergoes GTP-dependent assembly at midcell to form the Z-ring, a dynamic structure that evolves until final constriction of the cell. Therefore, molecules able to inhibit its activity will eventually disrupt bacterial viability. In this work, we report a new series of small molecules able to replace GTP and to specifically inhibit FtsZ, blocking the bacterial division process. These new synthesized inhibitors interact with the GTP-binding site of FtsZ (Kd = 0.4-0.8 μM), display antibacterial activity against Gram-positive pathogenic bacteria, and show selectivity against tubulin. Biphenyl derivative 28 stands out as a potent FtsZ inhibitor (Kd = 0.5 μM) with high antibacterial activity [MIC (MRSA) = 7 μM]. In-depth analysis of the mechanism of action of compounds 22, 28, 33, and 36 has revealed that they act as effective inhibitors of correct FtsZ assembly, blocking bacterial division and thus leading to filamentous undivided cells. These findings provide a compelling rationale for the development of compounds targeting the GTP-binding site as antibacterial agents and open the door to antibiotics with novel mechanisms of action.

Recurrent De Novo Mutations Disturbing the GTP/GDP Binding Pocket of RAB11B Cause Intellectual Disability and a Distinctive Brain Phenotype.

PubMed

Lamers, Ideke J C; Reijnders, Margot R F; Venselaar, Hanka; Kraus, Alison; Jansen, Sandra; de Vries, Bert B A; Houge, Gunnar; Gradek, Gyri Aasland; Seo, Jieun; Choi, Murim; Chae, Jong-Hee; van der Burgt, Ineke; Pfundt, Rolph; Letteboer, Stef J F; van Beersum, Sylvia E C; Dusseljee, Simone; Brunner, Han G; Doherty, Dan; Kleefstra, Tjitske; Roepman, Ronald

2017-11-02

The Rab GTPase family comprises ∼70 GTP-binding proteins, functioning in vesicle formation, transport and fusion. They are activated by a conformational change induced by GTP-binding, allowing interactions with downstream effectors. Here, we report five individuals with two recurrent de novo missense mutations in RAB11B; c.64G>A; p.Val22Met in three individuals and c.202G>A; p.Ala68Thr in two individuals. An overlapping neurodevelopmental phenotype, including severe intellectual disability with absent speech, epilepsy, and hypotonia was observed in all affected individuals. Additionally, visual problems, musculoskeletal abnormalities, and microcephaly were present in the majority of cases. Re-evaluation of brain MRI images of four individuals showed a shared distinct brain phenotype, consisting of abnormal white matter (severely decreased volume and abnormal signal), thin corpus callosum, cerebellar vermis hypoplasia, optic nerve hypoplasia and mild ventriculomegaly. To compare the effects of both variants with known inactive GDP- and active GTP-bound RAB11B mutants, we modeled the variants on the three-dimensional protein structure and performed subcellular localization studies. We predicted that both variants alter the GTP/GDP binding pocket and show that they both have localization patterns similar to inactive RAB11B. Evaluation of their influence on the affinity of RAB11B to a series of binary interactors, both effectors and guanine nucleotide exchange factors (GEFs), showed induction of RAB11B binding to the GEF SH3BP5, again similar to inactive RAB11B. In conclusion, we report two recurrent dominant mutations in RAB11B leading to a neurodevelopmental syndrome, likely caused by altered GDP/GTP binding that inactivate the protein and induce GEF binding and protein mislocalization. Copyright © 2017 American Society of Human Genetics. All rights reserved.

ELMOD1 Stimulates ARF6-GTP Hydrolysis to Stabilize Apical Structures in Developing Vestibular Hair Cells.

PubMed

Krey, Jocelyn F; Dumont, Rachel A; Wilmarth, Philip A; David, Larry L; Johnson, Kenneth R; Barr-Gillespie, Peter G

2018-01-24

Sensory hair cells require control of physical properties of their apical plasma membranes for normal development and function. Members of the ADP-ribosylation factor (ARF) small GTPase family regulate membrane trafficking and cytoskeletal assembly in many cells. We identified ELMO domain-containing protein 1 (ELMOD1), a guanine nucleoside triphosphatase activating protein (GAP) for ARF6, as the most highly enriched ARF regulator in hair cells. To characterize ELMOD1 control of trafficking, we analyzed mice of both sexes from a strain lacking functional ELMOD1 [roundabout ( rda )]. In rda/rda mice, cuticular plates of utricle hair cells initially formed normally, then degenerated after postnatal day 5; large numbers of vesicles invaded the compromised cuticular plate. Hair bundles initially developed normally, but the cell's apical membrane lifted away from the cuticular plate, and stereocilia elongated and fused. Membrane trafficking in type I hair cells, measured by FM1-43 dye labeling, was altered in rda/rda mice. Consistent with the proposed GAP role for ELMOD1, the ARF6 GTP/GDP ratio was significantly elevated in rda/rda utricles compared with controls, and the level of ARF6-GTP was correlated with the severity of the rda/rda phenotype. These results suggest that conversion of ARF6 to its GDP-bound form is necessary for final stabilization of the hair bundle. SIGNIFICANCE STATEMENT Assembly of the mechanically sensitive hair bundle of sensory hair cells requires growth and reorganization of apical actin and membrane structures. Hair bundles and apical membranes in mice with mutations in the Elmod1 gene degenerate after formation, suggesting that the ELMOD1 protein stabilizes these structures. We show that ELMOD1 is a GTPase-activating protein in hair cells for the small GTP-binding protein ARF6, known to participate in actin assembly and membrane trafficking. We propose that conversion of ARF6 into the GDP-bound form in the apical domain of hair cells is

Distinguishing Majorana bound states from localized Andreev bound states by interferometry

NASA Astrophysics Data System (ADS)

Hell, Michael; Flensberg, Karsten; Leijnse, Martin

2018-04-01

Experimental evidence for Majorana bound states (MBSs) is so far mainly based on the robustness of a zero-bias conductance peak. However, similar features can also arise due to Andreev bound states (ABSs) localized at the end of an island. We show that these two scenarios can be distinguished by an interferometry experiment based on embedding a Coulomb-blockaded island into an Aharonov-Bohm ring. For two ABSs, when the ground state is nearly degenerate, cotunneling can change the state of the island, and interference is suppressed. By contrast, for two MBSs the ground state is nondegenerate, and cotunneling has to preserve the island state, which leads to h /e -periodic conductance oscillations with magnetic flux. Such interference setups can be realized with semiconducting nanowires or two-dimensional electron gases with proximity-induced superconductivity and may also be a useful spectroscopic tool for parity-flip mechanisms.

Disease Mutations in Rab7 Result in Unregulated Nucleotide Exchange and Inappropriate Activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

B McCray; E Skordalakes; J Taylor

2011-12-31

Rab GTPases are molecular switches that orchestrate vesicular trafficking, maturation and fusion by cycling between an active, GTP-bound form, and an inactive, GDP-bound form. The activity cycle is coupled to GTP hydrolysis and is tightly controlled by regulatory proteins. Missense mutations of the GTPase Rab7 cause a dominantly inherited axonal degeneration known as Charcot-Marie-Tooth type 2B through an unknown mechanism. We present the 2.8 A crystal structure of GTP-bound L129F mutant Rab7 which reveals normal conformations of the effector binding regions and catalytic site, but an alteration to the nucleotide binding pocket that is predicted to alter GTP binding. Throughmore » extensive biochemical analysis, we demonstrate that disease-associated mutations in Rab7 do not lead to an intrinsic GTPase defect, but permit unregulated nucleotide exchange leading to both excessive activation and hydrolysis-independent inactivation. Consistent with augmented activity, mutant Rab7 shows significantly enhanced interaction with a subset of effector proteins. In addition, dynamic imaging demonstrates that mutant Rab7 is abnormally retained on target membranes. However, we show that the increased activation of mutant Rab7 is counterbalanced by unregulated, GTP hydrolysis-independent membrane cycling. Notably, disease mutations are able to rescue the membrane cycling of a GTPase-deficient mutant. Thus, we demonstrate that disease mutations uncouple Rab7 from the spatial and temporal control normally imposed by regulatory proteins and cause disease not by a gain of novel toxic function, but by misregulation of native Rab7 activity.« less

Coulomb bound states of strongly interacting photons

DOE PAGES

Maghrebi, M. F.; Gullans, Michael J.; Bienias, P.; ...

2015-09-16

We show that two photons coupled to Rydberg states via electromagnetically induced transparency (EIT) can interact via an effective Coulomb potential. The interaction then gives rise to a continuum of two-body bound states. Within the continuum, metastable bound states are distinguished in analogy with quasi-bound states tunneling through a potential barrier. We find multiple branches of metastable bound states whose energy spectrum is governed by the Coulomb problem, thus obtaining a photonic analogue of the hydrogen atom. These states propagate with a negative group velocity in the medium, which allows for a simple preparation and detection scheme, before they slowlymore » decay to pairs of bound Rydberg atoms. As a result, we verify the metastability and backward propagation of these Coulomb bound states with exact numerical simulations.« less

NMR 1H,13C, 15N backbone and 13C side chain resonance assignment of the G12C mutant of human K-Ras bound to GDP.

PubMed

Sharma, Alok K; Lee, Seung-Joo; Rigby, Alan C; Townson, Sharon A

2018-05-02

K-Ras is a key driver of oncogenesis, accounting for approximately 80% of Ras-driven human cancers. The small GTPase cycles between an inactive, GDP-bound and an active, GTP-bound state, regulated by guanine nucleotide exchange factors and GTPase activating proteins, respectively. Activated K-Ras regulates cell proliferation, differentiation and survival by signaling through several effector pathways, including Raf-MAPK. Oncogenic mutations that impair the GTPase activity of K-Ras result in a hyperactivated state, leading to uncontrolled cellular proliferation and tumorogenesis. A cysteine mutation at glycine 12 is commonly found in K-Ras associated cancers, and has become a recent focus for therapeutic intervention. We report here 1 H N, 15 N, and 13 C resonance assignments for the 19.3 kDa (aa 1-169) human K-Ras protein harboring an oncogenic G12C mutation in the GDP-bound form (K-RAS G12C-GDP ), using heteronuclear, multidimensional NMR spectroscopy. Backbone 1 H- 15 N correlations have been assigned for all non-proline residues, except for the first methionine residue.

Exquisite Modulation of the Active Site of Methanocaldococcus jannaschii Adenylosuccinate Synthetase in Forward Reaction Complexes.

PubMed

Karnawat, Vishakha; Mehrotra, Sonali; Balaram, Hemalatha; Puranik, Mrinalini

2016-05-03

In enzymes that conduct complex reactions involving several substrates and chemical transformations, the active site must reorganize at each step to complement the transition state of that chemical step. Adenylosuccinate synthetase (ADSS) utilizes a molecule each of guanosine 5'-monophosphate (GTP) and aspartate to convert inosine 5'-monophosphate (IMP) into succinyl adenosine 5'-monophosphate (sAMP) through several kinetic intermediates. Here we followed catalysis by ADSS through high-resolution vibrational spectral fingerprints of each substrate and intermediate involved in the forward reaction. Vibrational spectra show differential ligand distortion at each step of catalysis, and band positions of substrates are influenced by binding of cosubstrates. We found that the bound IMP is distorted toward its N1-deprotonated form even in the absence of any other ligands. Several specific interactions between GTP and active-site amino acid residues result in large Raman shifts and contribute substantially to intrinsic binding energy. When both IMP and GTP are simultaneously bound to ADSS, IMP is converted into an intermediate 6-phosphoryl inosine 5'-monophosphate (6-pIMP). The 6-pIMP·ADSS complex was found to be stable upon binding of the third ligand, hadacidin (HDA), an analogue of l-aspartate. We find that in the absence of HDA, 6-pIMP is quickly released from ADSS, is unstable in solution, and converts back into IMP. HDA allosterically stabilizes ADSS through local conformational rearrangements. We captured this complex and determined the spectra and structure of 6-pIMP in its enzyme-bound state. These results provide important insights into the exquisite tuning of active-site interactions with changing substrate at each kinetic step of catalysis.

Characterization of GTP binding and hydrolysis in plasma membranes of zucchini

NASA Technical Reports Server (NTRS)

Perdue, D. O.; Lomax, T. L.

1992-01-01

We have investigated the possibility that G-protein-like entities may be present in the plasma membrane (PM) of zucchini (Cucurbita pepo L.) hypocotyls by examining a number of criteria common to animal and yeast G-proteins. The GTP binding and hydrolysis characteristics of purified zucchini PM are similar to the characteristics of a number of known G-proteins. Our results demonstrate GTP binding to a single PM site having a Kd value between 16-31 nM. This binding has a high specificity for guanine nucleotides, and is stimulated by Mg2+, detergents, and fluoride or aluminium ions. The GTPase activity (Km = 0.49 micromole) of zucchini PM shows a sensitivity to NaF similar to that seen for other G-proteins. Localization of GTP mu 35S binding to nitrocellulose blots of proteins separated by SDS-PAGE indicates a 30-kDa protein as the predominant GTP-binding species in zucchini PM. Taken together, these data indicate that plant PM contains proteins which are biochemically similar to previously characterized G-proteins.

Characterization of GTP binding and hydrolysis in plasma membranes of zucchini.

PubMed

Perdue, D O; Lomax, T L

1992-01-01

We have investigated the possibility that G-protein-like entities may be present in the plasma membrane (PM) of zucchini (Cucurbita pepo L.) hypocotyls by examining a number of criteria common to animal and yeast G-proteins. The GTP binding and hydrolysis characteristics of purified zucchini PM are similar to the characteristics of a number of known G-proteins. Our results demonstrate GTP binding to a single PM site having a Kd value between 16-31 nM. This binding has a high specificity for guanine nucleotides, and is stimulated by Mg2+, detergents, and fluoride or aluminium ions. The GTPase activity (Km = 0.49 micromole) of zucchini PM shows a sensitivity to NaF similar to that seen for other G-proteins. Localization of GTP mu 35S binding to nitrocellulose blots of proteins separated by SDS-PAGE indicates a 30-kDa protein as the predominant GTP-binding species in zucchini PM. Taken together, these data indicate that plant PM contains proteins which are biochemically similar to previously characterized G-proteins.

Human γ-Glutamyl Transpeptidase 1: STRUCTURES OF THE FREE ENZYME, INHIBITOR-BOUND TETRAHEDRAL TRANSITION STATES, AND GLUTAMATE-BOUND ENZYME REVEAL NOVEL MOVEMENT WITHIN THE ACTIVE SITE DURING CATALYSIS.

PubMed

Terzyan, Simon S; Burgett, Anthony W G; Heroux, Annie; Smith, Clyde A; Mooers, Blaine H M; Hanigan, Marie H

2015-07-10

γ-Glutamyl transpeptidase 1 (GGT1) is a cell surface, N-terminal nucleophile hydrolase that cleaves glutathione and other γ-glutamyl compounds. GGT1 expression is essential in cysteine homeostasis, and its induction has been implicated in the pathology of asthma, reperfusion injury, and cancer. In this study, we report four new crystal structures of human GGT1 (hGGT1) that show conformational changes within the active site as the enzyme progresses from the free enzyme to inhibitor-bound tetrahedral transition states and finally to the glutamate-bound structure prior to the release of this final product of the reaction. The structure of the apoenzyme shows flexibility within the active site. The serine-borate-bound hGGT1 crystal structure demonstrates that serine-borate occupies the active site of the enzyme, resulting in an enzyme-inhibitor complex that replicates the enzyme's tetrahedral intermediate/transition state. The structure of GGsTop-bound hGGT1 reveals its interactions with the enzyme and why neutral phosphonate diesters are more potent inhibitors than monoanionic phosphonates. These structures are the first structures for any eukaryotic GGT that include a molecule in the active site covalently bound to the catalytic Thr-381. The glutamate-bound structure shows the conformation of the enzyme prior to release of the final product and reveals novel information regarding the displacement of the main chain atoms that form the oxyanion hole and movement of the lid loop region when the active site is occupied. These data provide new insights into the mechanism of hGGT1-catalyzed reactions and will be invaluable in the development of new classes of hGGT1 inhibitors for therapeutic use. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Distinguishing topological Majorana bound states from trivial Andreev bound states: Proposed tests through differential tunneling conductance spectroscopy

NASA Astrophysics Data System (ADS)

Liu, Chun-Xiao; Sau, Jay D.; Das Sarma, S.

2018-06-01

Trivial Andreev bound states arising from chemical-potential variations could lead to zero-bias tunneling conductance peaks at finite magnetic field in class-D nanowires, precisely mimicking the predicted zero-bias conductance peaks arising from the topological Majorana bound states. This finding raises a serious question on the efficacy of using zero-bias tunneling conductance peaks, by themselves, as evidence supporting the existence of topological Majorana bound states in nanowires. In the current work, we provide specific experimental protocols for tunneling spectroscopy measurements to distinguish between Andreev and Majorana bound states without invoking more demanding nonlocal measurements which have not yet been successfully performed in nanowire systems. In particular, we discuss three distinct experimental schemes involving the response of the zero-bias peak to local perturbations of the tunnel barrier, the overlap of bound states from the wire ends, and, most compellingly, introducing a sharp localized potential in the wire itself to perturb the zero-bias tunneling peaks. We provide extensive numerical simulations clarifying and supporting our theoretical predictions.

Molecular cloning of a cDNA coding for GTP cyclohydrolase I from Dictyostelium discoideum.

PubMed Central

Witter, K; Cahill, D J; Werner, T; Ziegler, I; Rödl, W; Bacher, A; Gütlich, M

1996-01-01

The GTP cyclohydrolase I (GTP-CH) gene of the cellular slime mould Dictyostelium discoideum has been cloned and sequenced. The 855 bp cDNA of this gene contains the open reading frame (ORF) encoding 232 amino acids with a predicted molecular mass of approx. 26 kDa. Southern blot analysis indicated the presence of a single gene for GTP-CH in Dictyostelium. PCR amplification of the ORF from chromosomal DNA and sequencing showed the existence of a 101 bp intron in the GTP-CH gene of Dictyostelium discoideum. The amino acid sequence has 47% and 49% positional identity to those of the human and yeast enzymes respectively. Most of the sequence variation between species is located in the N-terminal part of the protein. The overall identity with the E. coli protein is markedly lower. The enzyme was expressed in E. coli and purified as a 68 kDa fusion protein with the maltose-binding protein of E. coli. GTP-CH of Dictyostelium is heat-stable and showed maximal activity at 60 degrees C. The Km value for GTP is 50 microM. PMID:8870645

Antiproton--neutron bound state

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ju, I.; Tomozawa, Y.

1972-08-01

The possibility of an antiproton-neutron bound state for explaining a narrow peak which was found recently in the experiment p + n yields 4 pi and 6 pi is discussed. It is pointed out that the state is likely to be a /sup 1/P/ sub 1/ state or a higher angular momentum state. (auth)

Activation of Elongation Factor G by Phosphate Analogues

PubMed Central

Salsi, Enea; Farah, Elie

2016-01-01

EF-G is a universally conserved translational GTPase that promotes the translocation of tRNA and mRNA through the ribosome. EF-G binds to the ribosome in a GTP-bound form and subsequently catalyzes GTP hydrolysis. The contribution of the ribosome-stimulated GTP hydrolysis by EF-G to tRNA/mRNA translocation remains debated. Here, we show that while EF-G•GDP does not stably bind to the ribosome and induce translocation, EFG• GDP in complex with phosphate group analogues BeF3− and AlF4− promotes the translocation of tRNA and mRNA. Furthermore, the rates of mRNA translocation induced by EF-G in the presence of GTP and a non-hydrolysable analogue of GTP, GDP•BeF3−are similar. Our results are consistent with the model suggesting that GTP hydrolysis is not directly coupled to mRNA/tRNA translocation. Hence, GTP binding is required to induce the activated, translocation-competent conformation of EF-G while GTP hydrolysis triggers EF-G release from the ribosome. PMID:27063503

Regulation of follitropin-sensitive adenylate cyclase by stimulatory and inhibitory forms of the guanine nucleotide regulatory protein in immature rat Sertoli cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, G.P.

1987-01-01

Studies have been designed to examine the role of guanine nucleotides in mediating FSH-sensitive adenylate cyclase activity in Sertoli cell plasma membranes. Analysis of ({sup 3}H)GDP binding to plasma membranes suggested a single high affinity site with a K{sub d} = 0.24 uM. Competition studies indicated that GTP{sub {gamma}}S was 7-fold more potent than GDP{sub {beta}}S. Bound GDP could be released by FSH in the presence of GTP{sub {gamma}}S, but not by FSH alone. Adenylate cyclase activity was enhanced 5-fold by FSH in the presence of GTP. Addition of GDP{sub {beta}}S to the activated enzyme (FSH plus GTP) resulted inmore » a time-dependent decay to basal activity within 20 sec. GDP{sub {beta}}S competitively inhibited GTP{sub {gamma}}S-stimulated adenylate cyclase activity with a K{sub i} = 0.18 uM. Adenylate cyclase activity was also demonstrated to be sensitive to the nucleotide bound state. In the presence of FSH, only the GTP{sub {gamma}}S-bound form persisted even if GDP{sub {beta}}S previously occupied all available binding sites. Two membrane proteins, M{sub r} = 43,000 and 48,000, were ADP{centered dot}ribosylated using cholera toxin and labeling was enhanced 2 to 4-fold by GTP{sub {gamma}}S but not by GDP{sub {beta}}S. The M{sub r} = 43,000 and 48,000 proteins represented variant forms of G{sub S}. A single protein of M{sub r} = 40,000 (G{sub i}) was ADP-ribosylated by pertussis toxin in vitro. GTP inhibited forskolin-stimulated adenylate cyclase activity with an IC{sub 50} = 0.1 uM. The adenosine analog, N{sup 6}{centered dot}phenylisopropyl adenosine enhanced GTP inhibition of forskolin-stimulated adenylate cyclase activity by an additional 15%. GTP-dependent inhibition of forskolin-sensitive adenylate cyclase activity was abolished in membranes prepared from Sertoli cells treated in culture with pertussis toxin.« less

Deletion mutants of Harvey ras p21 protein reveal the absolute requirement of at least two distant regions for GTP-binding and transforming activities.

PubMed Central

Lacal, J C; Anderson, P S; Aaronson, S A

1986-01-01

Deletions of small sequences from the viral Harvey ras gene have been generated, and resulting ras p21 mutants have been expressed in Escherichia coli. Purification of each deleted protein allowed the in vitro characterization of GTP-binding, GTPase and autokinase activity of the proteins. Microinjection of the highly purified proteins into quiescent NIH/3T3 cells, as well as transfection experiments utilizing a long terminal repeat (LTR)-containing vector, were utilized to analyze the biological activity of the deleted proteins. Two small regions located at 6-23 and 152-165 residues are shown to be absolutely required for in vitro and in vivo activities of the ras product. By contrast, the variable region comprising amino acids 165-184 was shown not to be necessary for either in vitro or in vivo activities. Thus, we demonstrate that: (i) amino acid sequences at positions 5-23 and 152-165 of ras p21 protein are probably directly involved in the GTP-binding activity; (ii) GTP-binding is required for the transforming activity of ras p21 and by extension for the normal function of the proto-oncogene product; and (iii) the variable region at the C-terminal end of the ras p21 molecule from amino acids 165 to 184 is not required for transformation. Images Fig.2. Fig.4. PMID:3011420

The specific GTP requirement for inositol 1,4,5-trisphosphate-induced Ca2+ release from skinned vascular smooth muscle.

PubMed

Saida, K; Twort, C; van Breemen, C

1988-01-01

Exogenous GTP was required for the induction of Ca2+ release from smooth muscle SR by IP3 if endogenous GTP was depleted. NaN3 could function as a partial substitute for GTP as a cofactor for the IP3-induced Ca2+ release from the SR. In contrast to the IP3-induced Ca2+ release, caffeine-induced Ca2+ release from the SR did not require GTP. Pertussis toxin inhibited the IP3-induced Ca2+ release from the SR, whereas it had no effect on caffeine-induced Ca2+ release. These results indicate that in smooth muscle two different Ca2+ release-channels exist in the SR: (a) activated by IP3, and (b) activated by caffeine or Ca2+.

Family of nonlocal bound entangled states

NASA Astrophysics Data System (ADS)

Yu, Sixia; Oh, C. H.

2017-03-01

Bound entanglement, being entangled yet not distillable, is essential to our understanding of the relations between nonlocality and entanglement besides its applications in certain quantum information tasks. Recently, bound entangled states that violate a Bell inequality have been constructed for a two-qutrit system, disproving a conjecture by Peres that bound entanglement is local. Here we construct this kind of nonlocal bound entangled state for all finite dimensions larger than two, making possible their experimental demonstration in most general systems. We propose a Bell inequality, based on a Hardy-type argument for nonlocality, and a steering inequality to identify their nonlocality. We also provide a family of entanglement witnesses to detect their entanglement beyond the Bell inequality and the steering inequality.

The Bound to Bound State Contribution to the Electric Polarizability of a Relativbistic Particle

NASA Astrophysics Data System (ADS)

Vidnovic, Theodore, III; Anis Maize, Mohamed

1998-04-01

We calculate, in our study, the contribution of the transition between bound energy states to the electric polarizability of a relativistic particle. The particle is moving under the influence of a one-dimensional delta potential. Our work is done in the case of the scalar potential. The solution of Dirac's equation and the calculation of the particles total electric polarizability has been done in references (1-3). The transitions contributing to the electric polarizability are: Continuum to continuum, bound to bound, negative energy bound states to continuum, and positive energy bound states to continuum. Our task is to study the bound to bound state contribution to the electric polarizability. We will also investigate the effect of the strength of the potential on the contribution. 1. T.H. Solomon and S. Fallieros, "Relativistic One Dimensional Binding and Two Dimensional Motion." J. Franklin Inst. 320, 323-344 (1985) 2. M.A. Maize and C.A. Burkholder, "Electric Polarizability and the Solution of an Inhomogenous Differential Equation." Am.J.Phys. 63, 244-247 (1995) 3. M.A. Maize, S. Paulson, and A. D'Avanti, "Electric Polarizability of a Relativistic Particle." Am.J.Phys. 65, 888-892 (1997)

Suppressors of dGTP Starvation in Escherichia coli

PubMed Central

Itsko, Mark

2017-01-01

ABSTRACT dGTP starvation, a newly discovered phenomenon in which Escherichia coli cells are starved specifically for the DNA precursor dGTP, leads to impaired growth and, ultimately, cell death. Phenomenologically, it represents an example of nutritionally induced unbalanced growth: cell mass amplifies normally as dictated by the nutritional status of the medium, but DNA content growth is specifically impaired. The other known example of such a condition, thymineless death (TLD), involves starvation for the DNA precursor dTTP, which has been found to have important chemotherapeutic applications. Experimentally, dGTP starvation is induced by depriving an E. coli gpt optA1 strain of its required purine source, hypoxanthine. In our studies of this phenomenon, we noted the emergence of a relatively high frequency of suppressor mutants that proved resistant to the treatment. To study such suppressors, we used next-generation sequencing on a collection of independently obtained mutants. A significant fraction was found to carry a defect in the PurR transcriptional repressor, controlling de novo purine biosynthesis, or in its downstream purEK operon. Thus, upregulation of de novo purine biosynthesis appears to be a major mode of overcoming the lethal effects of dGTP starvation. In addition, another large fraction of the suppressors contained a large tandem duplication of a 250- to 300-kb genomic region that included the purEK operon as well as the acrAB-encoded multidrug efflux system. Thus, the suppressive effects of the duplications could potentially involve beneficial effects of a number of genes/operons within the amplified regions. IMPORTANCE Concentrations of the four precursors for DNA synthesis (2′-deoxynucleoside-5′-triphosphates [dNTPs]) are critical for both the speed of DNA replication and its accuracy. Previously, we investigated consequences of dGTP starvation, where the DNA precursor dGTP was specifically reduced to a low level. Under this condition, E

GTP regeneration influences interactions of microtubules, neurofilaments, and microtubule-associated proteins in vitro.

PubMed

Flynn, G; Purich, D L

1987-11-15

Interactions of microtubules, neurofilaments, and microtubule-associated proteins were investigated by turbidity and falling-ball viscometry measurements. We found evidence of endogenous GTPase activity in neurofilaments and microtubule-associated proteins (MAPs) in preparations that do not include urea or heat treatment, respectively. The absence or presence of either adenyl-5'-yl imidodiphosphonic acid or a GTP-regenerating system markedly influenced observed polymerization and gelation characteristics. Most significantly, the apparent viscosity of neurofilament and microtubule samples did not display a biphasic optimal MAP concentration profile when a GTP-regenerating system was operant. Likewise, GTP regeneration promoted the recovery of gelation following mechanical disruption of neurofilament/MAP/microtubule mixtures. These and other observations require some reassessment of proposed roles for microtubule-associated proteins in modulating neurofilament-microtubule interactions in vitro.

Adenylylation of Tyr77 stabilizes Rab1b GTPase in an active state: A molecular dynamics simulation analysis

PubMed Central

Luitz, Manuel P.; Bomblies, Rainer; Ramcke, Evelyn; Itzen, Aymelt; Zacharias, Martin

2016-01-01

The pathogenic pathway of Legionella pneumophila exploits the intercellular vesicle transport system via the posttranslational attachment of adenosine monophosphate (AMP) to the Tyr77 sidechain of human Ras like GTPase Rab1b. The modification, termed adenylylation, is performed by the bacterial enzyme DrrA/SidM, however the effect on conformational properties of the molecular switch mechanism of Rab1b remained unresolved. In this study we find that the adenylylation of Tyr77 stabilizes the active Rab1b state by locking the switch in the active signaling conformation independent of bound GTP or GDP and that electrostatic interactions due to the additional negative charge in the switch region make significant contributions. The stacking interaction between adenine and Phe45 however, seems to have only minor influence on this stabilisation. The results may also have implications for the mechanistic understanding of conformational switching in other signaling proteins. PMID:26818796

The R-Ras/RIN2/Rab5 complex controls endothelial cell adhesion and morphogenesis via active integrin endocytosis and Rac signaling

PubMed Central

Sandri, Chiara; Caccavari, Francesca; Valdembri, Donatella; Camillo, Chiara; Veltel, Stefan; Santambrogio, Martina; Lanzetti, Letizia; Bussolino, Federico; Ivaska, Johanna; Serini, Guido

2012-01-01

During developmental and tumor angiogenesis, semaphorins regulate blood vessel navigation by signaling through plexin receptors that inhibit the R-Ras subfamily of small GTPases. R-Ras is mainly expressed in vascular cells, where it induces adhesion to the extracellular matrix (ECM) through unknown mechanisms. We identify the Ras and Rab5 interacting protein RIN2 as a key effector that in endothelial cells interacts with and mediates the pro-adhesive and -angiogenic activity of R-Ras. Both R-Ras-GTP and RIN2 localize at nascent ECM adhesion sites associated with lamellipodia. Upon binding, GTP-loaded R-Ras converts RIN2 from a Rab5 guanine nucleotide exchange factor (GEF) to an adaptor that first interacts at high affinity with Rab5-GTP to promote the selective endocytosis of ligand-bound/active β1 integrins and then causes the translocation of R-Ras to early endosomes. Here, the R-Ras/RIN2/Rab5 signaling module activates Rac1-dependent cell adhesion via TIAM1, a Rac GEF that localizes on early endosomes and is stimulated by the interaction with both Ras proteins and the vesicular lipid phosphatidylinositol 3-monophosphate. In conclusion, the ability of R-Ras-GTP to convert RIN2 from a GEF to an adaptor that preferentially binds Rab5-GTP allows the triggering of the endocytosis of ECM-bound/active β1 integrins and the ensuing funneling of R-Ras-GTP toward early endosomes to elicit the pro-adhesive and TIAM1-mediated activation of Rac1. PMID:22825554

Nucleotide Dependent Switching in Rho GTPase: Conformational Heterogeneity and Competing Molecular Interactions

PubMed Central

Kumawat, Amit; Chakrabarty, Suman; Kulkarni, Kiran

2017-01-01

Ras superfamily of GTPases regulate myriad cellular processes through a conserved nucleotide (GTP/GDP) dependent switching mechanism. Unlike Ras family of GTPases, for the Rho GTPases, there is no clear evidence for the existence of “sub-states” such as state 1 & state 2 in the GTP bound form. To explore the nucleotide dependent conformational space of the Switch I loop and also to look for existence of state 1 like conformations in Rho GTPases, atomistic molecular dynamics and metadynamics simulations on RhoA were performed. These studies demonstrate that both the nucleotide-free state and the GDP bound “OFF” state have very similar conformations, whereas the GTP bound “ON” state has unique conformations with signatures of two intermediate states. The conformational free energy landscape for these systems suggests the presence of multiple intermediate states. Interestingly, the energetic penalty of exposing the non-polar residues in the GTP bound form is counter balanced by the favourable hydrogen bonded interactions between the γ-phosphate group of GTP with the highly conserved Tyr34 and Thr37 residues. These competing molecular interactions lead to a tuneable energy landscape of the Switch I conformation, which can undergo significant changes based on the local environment including changes upon binding to effectors. PMID:28374773

Nucleotide Dependent Switching in Rho GTPase: Conformational Heterogeneity and Competing Molecular Interactions

NASA Astrophysics Data System (ADS)

Kumawat, Amit; Chakrabarty, Suman; Kulkarni, Kiran

2017-04-01

Ras superfamily of GTPases regulate myriad cellular processes through a conserved nucleotide (GTP/GDP) dependent switching mechanism. Unlike Ras family of GTPases, for the Rho GTPases, there is no clear evidence for the existence of “sub-states” such as state 1 & state 2 in the GTP bound form. To explore the nucleotide dependent conformational space of the Switch I loop and also to look for existence of state 1 like conformations in Rho GTPases, atomistic molecular dynamics and metadynamics simulations on RhoA were performed. These studies demonstrate that both the nucleotide-free state and the GDP bound “OFF” state have very similar conformations, whereas the GTP bound “ON” state has unique conformations with signatures of two intermediate states. The conformational free energy landscape for these systems suggests the presence of multiple intermediate states. Interestingly, the energetic penalty of exposing the non-polar residues in the GTP bound form is counter balanced by the favourable hydrogen bonded interactions between the γ-phosphate group of GTP with the highly conserved Tyr34 and Thr37 residues. These competing molecular interactions lead to a tuneable energy landscape of the Switch I conformation, which can undergo significant changes based on the local environment including changes upon binding to effectors.

Domain structure, GTP-hydrolyzing activity and 7S RNA binding of Acidianus ambivalens ffh-homologous protein suggest an SRP-like complex in archaea.

PubMed

Moll, R; Schmidtke, S; Schäfer, G

1999-01-01

In this study we provide, for the first time, experimental evidence that a protein homologous to bacterial Ffh is part of an SRP-like ribonucleoprotein complex in hyperthermophilic archaea. The gene encoding the Ffh homologue in the hyperthermophilic archaeote Acidianus ambivalens has been cloned and sequenced. Recombinant Ffh protein was expressed in E. coli and subjected to biochemical and functional studies. A. ambivalens Ffh encodes a 50.4-kDa protein that is structured by three distinct regions: the N-terminal hydrophilic N-region (N), the GTP/GDP-binding domain (G) and a C-terminal located C-domain (C). The A. ambivalens Ffh sequence shares 44-46% sequence similarity with Ffh of methanogenic archaea, 34-36% similarity with eukaryal SRP54 and 30-34% similarity with bacterial Ffh. A polyclonal antiserum raised against the first two domains of A. ambivalens Ffh reacts specifically with a single protein (apparent molecular mass: 46 kDa, termed p46) present in cytosolic and in plasmamembrane cell fractions of A. ambivalens. Recombinant Ffh has a melting point of tm = 89 degreesC. Its intrinsic GTPase activity obviously depends on neutral pH and low ionic strength with a preference for chloride and acetate salts. Highest rates of GTP hydrolysis have been achieved at 81 degreesC in presence of 0.1-1 mm Mg2+. GTP hydrolysis is significantly inhibited by high glycerol concentrations, and the GTP hydrolysis rate also markedly decreases by addition of detergents. The Km for GTP is 13.7 microm at 70 degreesC and GTP hydrolysis is strongly inhibited by GDP (Ki = 8 microm). A. ambivalens Ffh, which includes an RNA-binding motif in the C-terminal domain, is shown to bind specifically to 7S RNA of the related crenarchaeote Sulfolobus solfataricus. Comparative sequence analysis reveals the presence of typical signal sequences in plasma membrane as well as extracellular proteins of hyperthermophilic crenarchaea which strongly supposes recognition events by an Ffh containing

A homogeneous quenching resonance energy transfer assay for the kinetic analysis of the GTPase nucleotide exchange reaction.

PubMed

Kopra, Kari; Ligabue, Alessio; Wang, Qi; Syrjänpää, Markku; Blaževitš, Olga; Veltel, Stefan; van Adrichem, Arjan J; Hänninen, Pekka; Abankwa, Daniel; Härmä, Harri

2014-07-01

A quenching resonance energy transfer (QRET) assay for small GTPase nucleotide exchange kinetic monitoring is demonstrated using nanomolar protein concentrations. Small GTPases are central signaling proteins in all eukaryotic cells acting as a "molecular switches" that are active in the GTP-state and inactive in the GDP-state. GTP-loading is highly regulated by guanine nucleotide exchange factors (GEFs). In several diseases, most prominently cancer, this process in misregulated. The kinetics of the nucleotide exchange reaction reports on the enzymatic activity of the GEF reaction system and is, therefore, of special interest. We determined the nucleotide exchange kinetics using europium-labeled GTP (Eu-GTP) in the QRET assay for small GTPases. After GEF catalyzed GTP-loading of a GTPase, a high time-resolved luminescence signal was found to be associated with GTPase bound Eu-GTP, whereas the non-bound Eu-GTP fraction was quenched by soluble quencher. The association kinetics of the Eu-GTP was measured after GEF addition, whereas the dissociation kinetics could be determined after addition of unlabeled GTP. The resulting association and dissociation rates were in agreement with previously published values for H-Ras(Wt), H-Ras(Q61G), and K-Ras(Wt), respectively. The broader applicability of the QRET assay for small GTPases was demonstrated by determining the kinetics of the Ect2 catalyzed RhoA(Wt) GTP-loading. The QRET assay allows the use of nanomolar protein concentrations, as more than 3-fold signal-to-background ratio was achieved with 50 nM GTPase and GEF proteins. Thus, small GTPase exchange kinetics can be efficiently determined in a HTS compatible 384-well plate format.

An Arabidopsis Ran-binding protein, AtRanBP1c, is a co-activator of Ran GTPase-activating protein and requires the C-terminus for its cytoplasmic localization

NASA Technical Reports Server (NTRS)

Kim, Soo-Hwan; Roux, Stanley J.

2003-01-01

Ran-binding proteins (RanBPs) are a group of proteins that bind to Ran (Ras-related nuclear small GTP-binding protein), and thus either control the GTP/GDP-bound states of Ran or help couple the Ran GTPase cycle to a cellular process. AtRanBP1c is a Ran-binding protein from Arabidopsis thaliana (L.) Heynh. that was recently shown to be critically involved in the regulation of auxin-induced mitotic progression [S.-H. Kim et al. (2001) Plant Cell 13:2619-2630]. Here we report that AtRanBP1c inhibits the EDTA-induced release of GTP from Ran and serves as a co-activator of Ran-GTPase-activating protein (RanGAP) in vitro. Transient expression of AtRanBP1c fused to a beta-glucuronidase (GUS) reporter reveals that the protein localizes primarily to the cytosol. Neither the N- nor C-terminus of AtRanBP1c, which flank the Ran-binding domain (RanBD), is necessary for the binding of PsRan1-GTP to the protein, but both are needed for the cytosolic localization of GUS-fused AtRanBP1c. These findings, together with a previous report that AtRanBP1c is critically involved in root growth and development, imply that the promotion of GTP hydrolysis by the Ran/RanGAP/AtRanBP1c complex in the cytoplasm, and the resulting concentration gradient of Ran-GDP to Ran-GTP across the nuclear membrane could be important in the regulation of auxin-induced mitotic progression in root tips of A. thaliana.

Physical and functional connection between auxilin and dynamin during endocytosis

PubMed Central

Sever, Sanja; Skoch, Jesse; Newmyer, Sherri; Ramachandran, Rajesh; Ko, David; McKee, Mary; Bouley, Richard; Ausiello, Dennis; Hyman, Bradley T; Bacskai, Brian J

2006-01-01

During clathrin-mediated endocytosis, the GTPase dynamin promotes formation of clathrin-coated vesicles, but its mode of action is unresolved. We provide evidence that a switch in three functional states of dynamin (dimers, tetramers, rings/spirals) coordinates its GTPase cycle. Dimers exhibit negative cooperativity whereas tetramers exhibit positive cooperativity with respect to GTP. Our study identifies tetramers as the kinetically most stable GTP-bound conformation of dynamin, which is required to promote further assembly into higher order structures such as rings or spirals. In addition, using fluorescence lifetime imaging microscopy, we show that interactions between dynamin and auxilin in cells are GTP-, endocytosis- and tetramer-dependent. Furthermore, we show that the cochaperone activity of auxilin is required for constriction of clathrin-coated pits, the same early step in endocytosis known to be regulated by the lifetime of dynamin:GTP. Together, our findings support the model that the GTP-bound conformation of dynamin tetramers stimulates formation of constricted coated pits at the plasma membrane by regulating the chaperone activity of hsc70/auxilin. PMID:16946707

Human γ-glutamyl transpeptidase 1: Structures of the free enzyme, inhibitor-bound tetrahedral transition states, and glutamate-bound enzyme reveal novel movement within the active site during catalysis [Human gamma-glutamyl transpeptidase: Inhibitor binding and movement within the active site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Terzyan, Simon S.; Burgett, Anthony W. G.; Heroux, Annie

γ-Glutamyl transpeptidase 1 (GGT1) is a cell surface, N-terminal nucleophile hydrolase that cleaves glutathione and other γ-glutamyl compounds. GGT1 expression is essential in cysteine homeostasis, and its induction has been implicated in the pathology of asthma, reperfusion injury, and cancer. In this study, we report four new crystal structures of human GGT1 (hGGT1) that show conformational changes within the active site as the enzyme progresses from the free enzyme to inhibitor-bound tetrahedral transition states and finally to the glutamate-bound structure prior to the release of this final product of the reaction. The structure of the apoenzyme shows flexibility within themore » active site. The serine-borate-bound hGGT1 crystal structure demonstrates that serine-borate occupies the active site of the enzyme, resulting in an enzyme-inhibitor complex that replicates the enzyme's tetrahedral intermediate/transition state. The structure of GGsTop-bound hGGT1 reveals its interactions with the enzyme and why neutral phosphonate diesters are more potent inhibitors than monoanionic phosphonates. These structures are the first structures for any eukaryotic GGT that include a molecule in the active site covalently bound to the catalytic Thr-381. The glutamate-bound structure shows the conformation of the enzyme prior to release of the final product and reveals novel information regarding the displacement of the main chain atoms that form the oxyanion hole and movement of the lid loop region when the active site is occupied. Lastly,tThese data provide new insights into the mechanism of hGGT1-catalyzed reactions and will be invaluable in the development of new classes of hGGT1 inhibitors for therapeutic use.« less

Human γ-glutamyl transpeptidase 1: Structures of the free enzyme, inhibitor-bound tetrahedral transition states, and glutamate-bound enzyme reveal novel movement within the active site during catalysis [Human gamma-glutamyl transpeptidase: Inhibitor binding and movement within the active site

DOE PAGES

Terzyan, Simon S.; Burgett, Anthony W. G.; Heroux, Annie; ...

2015-05-26

γ-Glutamyl transpeptidase 1 (GGT1) is a cell surface, N-terminal nucleophile hydrolase that cleaves glutathione and other γ-glutamyl compounds. GGT1 expression is essential in cysteine homeostasis, and its induction has been implicated in the pathology of asthma, reperfusion injury, and cancer. In this study, we report four new crystal structures of human GGT1 (hGGT1) that show conformational changes within the active site as the enzyme progresses from the free enzyme to inhibitor-bound tetrahedral transition states and finally to the glutamate-bound structure prior to the release of this final product of the reaction. The structure of the apoenzyme shows flexibility within themore » active site. The serine-borate-bound hGGT1 crystal structure demonstrates that serine-borate occupies the active site of the enzyme, resulting in an enzyme-inhibitor complex that replicates the enzyme's tetrahedral intermediate/transition state. The structure of GGsTop-bound hGGT1 reveals its interactions with the enzyme and why neutral phosphonate diesters are more potent inhibitors than monoanionic phosphonates. These structures are the first structures for any eukaryotic GGT that include a molecule in the active site covalently bound to the catalytic Thr-381. The glutamate-bound structure shows the conformation of the enzyme prior to release of the final product and reveals novel information regarding the displacement of the main chain atoms that form the oxyanion hole and movement of the lid loop region when the active site is occupied. Lastly,tThese data provide new insights into the mechanism of hGGT1-catalyzed reactions and will be invaluable in the development of new classes of hGGT1 inhibitors for therapeutic use.« less

A naturally occurring, noncanonical GTP aptamer made of simple tandem repeats

PubMed Central

Curtis, Edward A; Liu, David R

2014-01-01

Recently, we used in vitro selection to identify a new class of naturally occurring GTP aptamer called the G motif. Here we report the discovery and characterization of a second class of naturally occurring GTP aptamer, the “CA motif.” The primary sequence of this aptamer is unusual in that it consists entirely of tandem repeats of CA-rich motifs as short as three nucleotides. Several active variants of the CA motif aptamer lack the ability to form consecutive Watson-Crick base pairs in any register, while others consist of repeats containing only cytidine and adenosine residues, indicating that noncanonical interactions play important roles in its structure. The circular dichroism spectrum of the CA motif aptamer is distinct from that of A-form RNA and other major classes of nucleic acid structures. Bioinformatic searches indicate that the CA motif is absent from most archaeal and bacterial genomes, but occurs in at least 70 percent of approximately 400 eukaryotic genomes examined. These searches also uncovered several phylogenetically conserved examples of the CA motif in rodent (mouse and rat) genomes. Together, these results reveal the existence of a second class of naturally occurring GTP aptamer whose sequence requirements, like that of the G motif, are not consistent with those of a canonical secondary structure. They also indicate a new and unexpected potential biochemical activity of certain naturally occurring tandem repeats. PMID:24824832

Cosmological implications of Dark Matter bound states

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitridate, Andrea; Redi, Michele; Smirnov, Juri

2017-05-01

We present generic formulæ for computing how Sommerfeld corrections together with bound-state formation affects the thermal abundance of Dark Matter with non-abelian gauge interactions. We consider DM as a fermion 3plet (wino) or 5plet under SU(2) {sub L} . In the latter case bound states raise to 11.5 TeV the DM mass required to reproduce the cosmological DM abundance and give indirect detection signals such as (for this mass) a dominant γ-line around 70 GeV. Furthermore, we consider DM co-annihilating with a colored particle, such as a squark or a gluino, finding that bound state effects are especially relevant inmore » the latter case.« less

Pertussis toxin modifies the characteristics of both the inhibitory GTP binding proteins and the somatostatin receptor in anterior pituitary tumor cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahy, N.; Woolkalis, M.; Thermos, K.

1988-08-01

The effects of pertussis toxin treatment on the characteristics of somatostatin receptors in the anterior pituitary tumor cell line AtT-20 were examined. Pertussis toxin selectively catalyzed the ADP ribosylation of the alpha subunits of the inhibitory GTP binding proteins in AtT-20 cells. Toxin treatment abolished somatostatin inhibition of forskolin-stimulated adenylyl cyclase activity and somatostatin stimulation of GTPase activity. To examine the effects of pertussis toxin treatment on the characteristics of the somatostatin receptor, the receptor was labeled by the somatostatin analog (125I)CGP 23996. (125I)CGP 23996 binding to AtT-20 cell membranes was saturable and within a limited concentration range was tomore » a single high affinity site. Pertussis toxin treatment reduced the apparent density of the high affinity (125I)CGP 23996 binding sites in AtT-20 cell membranes. Inhibition of (125I)CGP 23996 binding by a wide concentration range of CGP 23996 revealed the presence of two binding sites. GTP predominantly reduced the level of high affinity sites in control membranes. Pertussis toxin treatment also diminished the amount of high affinity sites. GTP did not affect (125I)CGP 23996 binding in the pertussis toxin-treated membranes. The high affinity somatostatin receptors were covalently labeled with (125I) CGP 23996 and the photoactivated crosslinking agent n-hydroxysuccinimidyl-4-azidobenzoate. No high affinity somatostatin receptors, covalently bound to (125I)CGP 23996, were detected in the pertussis toxin-treated membranes. These results are most consistent with pertussis toxin uncoupling the inhibitory G proteins from the somatostatin receptor thereby converting the receptor from a mixed population of high and low affinity sites to only low affinity receptors.« less

EPI64B Acts as a GTPase-activating Protein for Rab27B in Pancreatic Acinar Cells*

PubMed Central

Hou, Yanan; Chen, Xuequn; Tolmachova, Tatyana; Ernst, Stephen A.; Williams, John A.

2013-01-01

The small GTPase Rab27B localizes to the zymogen granule membranes and plays an important role in regulating protein secretion by pancreatic acinar cells, as does Rab3D. A common guanine nucleotide exchange factor (GEF) for Rab3 and Rab27 has been reported; however, the GTPase-activating protein (GAP) specific for Rab27B has not been identified. In this study, the expression in mouse pancreatic acini of two candidate Tre-2/Bub2/Cdc16 (TBC) domain-containing proteins, EPI64 (TBC1D10A) and EPI64B (TBC1D10B), was first demonstrated. Their GAP activity on digestive enzyme secretion was examined by adenovirus-mediated overexpression of EPI64 and EPI64B in isolated pancreatic acini. EPI64B almost completely abolished the GTP-bound form of Rab27B, without affecting GTP-Rab3D. Overexpression of EPI64B also enhanced amylase release. This enhanced release was independent of Rab27A, but dependent on Rab27B, as shown using acini from genetically modified mice. EPI64 had a mild effect on both GTP-Rab27B and amylase release. Co-overexpression of EPI64B with Rab27B can reverse the inhibitory effect of Rab27B on amylase release. Mutations that block the GAP activity decreased the inhibitory effect of EPI64B on the GTP-bound state of Rab27B and abolished the enhancing effect of EPI64B on the amylase release. These data suggest that EPI64B can serve as a potential physiological GAP for Rab27B and thereby participate in the regulation of exocytosis in pancreatic acinar cells. PMID:23671284

Bounded state variables and the calculus of variations

NASA Technical Reports Server (NTRS)

Hanafy, L. M.

1972-01-01

An optimal control problem with bounded state variables is transformed into a Lagrange problem by means of differentiable mappings which take some Euclidean space onto the control and state regions. Whereas all such mappings lead to a Lagrange problem, it is shown that only those which are defined as acceptable pairs of transformations are suitable in the sense that solutions to the transformed Lagrange problem will lead to solutions to the original bounded state problem and vice versa. In particular, an acceptable pair of transformations is exhibited for the case when the control and state regions are right parallelepipeds. Finally, a description of the necessary conditions for the bounded state problem which were obtained by this method is given.

Microscopic observation of magnon bound states and their dynamics.

PubMed

Fukuhara, Takeshi; Schauß, Peter; Endres, Manuel; Hild, Sebastian; Cheneau, Marc; Bloch, Immanuel; Gross, Christian

2013-10-03

The existence of bound states of elementary spin waves (magnons) in one-dimensional quantum magnets was predicted almost 80 years ago. Identifying signatures of magnon bound states has so far remained the subject of intense theoretical research, and their detection has proved challenging for experiments. Ultracold atoms offer an ideal setting in which to find such bound states by tracking the spin dynamics with single-spin and single-site resolution following a local excitation. Here we use in situ correlation measurements to observe two-magnon bound states directly in a one-dimensional Heisenberg spin chain comprising ultracold bosonic atoms in an optical lattice. We observe the quantum dynamics of free and bound magnon states through time-resolved measurements of two spin impurities. The increased effective mass of the compound magnon state results in slower spin dynamics as compared to single-magnon excitations. We also determine the decay time of bound magnons, which is probably limited by scattering on thermal fluctuations in the system. Our results provide a new way of studying fundamental properties of quantum magnets and, more generally, properties of interacting impurities in quantum many-body systems.

Bound states for magic state distillation in fault-tolerant quantum computation.

PubMed

Campbell, Earl T; Browne, Dan E

2010-01-22

Magic state distillation is an important primitive in fault-tolerant quantum computation. The magic states are pure nonstabilizer states which can be distilled from certain mixed nonstabilizer states via Clifford group operations alone. Because of the Gottesman-Knill theorem, mixtures of Pauli eigenstates are not expected to be magic state distillable, but it has been an open question whether all mixed states outside this set may be distilled. In this Letter we show that, when resources are finitely limited, nondistillable states exist outside the stabilizer octahedron. In analogy with the bound entangled states, which arise in entanglement theory, we call such states bound states for magic state distillation.

The bound states of ultracold KRb molecules

NASA Astrophysics Data System (ADS)

Julienne, Paul; Hanna, Thomas

2009-03-01

Recently ultracold vibrational ground state ^40K^87Rb polar molecules have been made using magnetoassociation of two cold atoms to a weakly bound Feshbach molecule, followed by a two-color optical STIRAP process to transfer molecules to the molecular ground state [1]. We have used accurate potential energy curves for the singlet and triplet states of the KRb molecule [2] with coupled channels calculations to calculate all of the bound states of the ^40K^87Rb molecule as a function of magnetic field from the cold atom collision threshold to the v=0 ground state. We have also developed approximate models for understanding the changing properties of the molecular bound states as binding energy increases. Some overall conclusions from these calculations will be presented. [1] K.-K. Ni, S. Ospelkaus, M. H. G. de Miranda, A. Peer, B. Neyenhuis, J. J. Zirbel, S. Kotochigova, P. S. Julienne, D. S. Jin, and J. Ye, Science, 2008, 322, 231--235. [2] A. Pashov, O. Docenko, M. Tamanis, R. Ferber, H. Kn"ockel, and E. Tiemann, Phys. Rev. A, 2007, 76, 022511.

A wheat embryo cell-free protein synthesis system not requiring an exogenous supply of GTP.

PubMed

Koga, Hirohisa; Misawa, Satoru; Shibui, Tatsuro

2009-01-01

Most in vitro protein synthesis systems require a supply of GTP for the formation of translation initiation complexes, with two GTP molecules per amino acid needed as an energy source for a peptide elongation reaction. In order to optimize protein synthesis reactions in a continuous-flow wheat embryo cell-free system, we have examined the influence of adding GTP and found that the system does not require any supply of GTP. We report here the preparation of a wheat embryo extract from which endogenous GTP was removed by gel filtration, and the influence of adding GTP to the system on protein synthesis reactions. Using Green Fluorescent Protein (GFP) as a reporter, higher levels of production were observed at lower concentrations of GTP, with the optimal level of production obtained with no supply of GTP. A HPLC-based analysis of the extract and the translation mixture containing only ATP as an energy source revealed that GTP was not detectable in the extract, however, 35 microM of GTP was found in the translation mixture. This result suggests that GTP could be generated from other compounds, such as GDP and GMP, using ATP. A similar experiment with a C-terminally truncated form of human protein tyrosine phosphatase 1B (hPTP1B(1-320)) gave almost the same result. The wheat embryo cell-free translation system worked most efficiently without exogenous GTP, producing 3.5 mg/mL of translation mixture over a 48-h period at 26 degrees C. 2009 American Institute of Chemical Engineers Biotechnol.

Photoregeneration of bovine rhodopsin from its signaling state.

PubMed

Arnis, S; Hofmann, K P

1995-07-25

In rhodopsin, 11-cis-retinal is bound by a protonated Schiff base and acts as a strong antagonist, which holds the receptor in its inactive ground state conformation. Light induces cis-/trans-retinal isomerization and a sequence of thermal transitions through intermediates. The active conformation that catalyzes GDP/GTP exchange in the G-protein (Gt) is generated from the metarhodopsin II intermediate (MII) and mediated by Schiff base proton translocation and proton uptake from the aqueous phase. In the stable nucleotide-free MII-Gt complex, any thermal transition of MII into other forms of rhodopsin is blocked. We have now studied how Gt affects flash-induced photochemical conversions of MII. Difference spectra from measured absorption changes show that MII photolyzes through two parallel pathways, with fast (1 ms) and slow (50 ms) kinetics (12 degrees C, pH 6). The slow pathway regenerates rhodopsin (9- or 11-cis) via Schiff base reprotonation and proton release. We infer a cis-isomerized early photoproduct (reverted meta, RM) preceding these thermal transitions. When MII is photolyzed in the MII-Gt complex, the slow absorption change is abolished, indicating that Gt blocks the completion of the regeneration process. This is due to the formation of a stable RM-Gt complex, as shown by successive photolysis of MII, RM, and ground state rhodopsin, and the application of GTP gamma S at different stages. The complex dissociates with GTP gamma S, and rhodopsin relaxes to the ground state. The results indicate that cis-retinal and Gt can bind to the receptor at the same time. We discuss the result that the protonations in the meta II state uncouple retinal geometry from Gt interaction.

Bound state and localization of excitation in many-body open systems

NASA Astrophysics Data System (ADS)

Cui, H. T.; Shen, H. Z.; Hou, S. C.; Yi, X. X.

2018-04-01

We study the exact bound state and time evolution for single excitations in one-dimensional X X Z spin chains within a non-Markovian reservoir. For the bound state, a common feature is the localization of single excitations, which means the spontaneous emission of excitations into the reservoir is prohibited. Exceptionally, the pseudo-bound state can be found, for which the single excitation has a finite probability of emission into the reservoir. In addition, a critical energy scale for bound states is also identified, below which only one bound state exists, and it is also the pseudo-bound state. The effect of quasirandom disorder in the spin chain is also discussed; such disorder induces the single excitation to locate at some spin sites. Furthermore, to display the effect of bound state and disorder on the preservation of quantum information, the time evolution of single excitations in spin chains is studied exactly. An interesting observation is that the excitation can stay at its initial location with high probability only when the bound state and disorder coexist. In contrast, when either one of them is absent, the information of the initial state can be erased completely or becomes mixed. This finding shows that the combination of bound state and disorder can provide an ideal mechanism for quantum memory.

Bell-correlated activable bound entanglement in multiqubit systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bandyopadhyay, Somshubhro; Chattopadhyay, Indrani; Roychowdhury, Vwani

2005-06-15

We show that the Hilbert space of even number ({>=}4) of qubits can always be decomposed as a direct sum of four orthogonal subspaces such that the normalized projectors onto the subspaces are activable bound entangled (ABE) states. These states also show a surprising recursive relation in the sense that the states belonging to 2N+2 qubits are Bell correlated to the states of 2N qubits; hence, we refer to these states as Bell-correlated ABE (BCABE) states. We also study the properties of noisy BCABE states and show that they are very similar to that of two qubit Bell-diagonal states.

K-Ras Populates Conformational States Differently from Its Isoform H-Ras and Oncogenic Mutant K-RasG12D.

PubMed

Parker, Jillian A; Volmar, Alicia Y; Pavlopoulos, Spiro; Mattos, Carla

2018-06-05

Structures of wild-type K-Ras from crystals obtained in the presence of guanosine triphosphate (GTP) or its analogs have remained elusive. Of the K-Ras mutants, only K-RasG12D and K-RasQ61H are available in the PDB representing the activated form of the GTPase not in complex with other proteins. We present the crystal structure of wild-type K-Ras bound to the GTP analog GppCH 2 p, with K-Ras in the state 1 conformation. Signatures of conformational states obtained by one-dimensional proton NMR confirm that K-Ras has a more substantial population of state 1 in solution than H-Ras, which predominantly favors state 2. The oncogenic mutant K-RasG12D favors state 2, changing the balance of conformational states in favor of interactions with effector proteins. Differences in the population of conformational states between K-Ras and H-Ras, as well as between K-Ras and its mutants, can provide a structural basis for focused targeting of the K-Ras isoform in cancer-specific strategies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evolution of New Function in the GTP Cyclohydrolase II Proteins of Streptomyces coelicolor†

PubMed Central

Spoonamore, James E.; Dahlgran, Annie L.; Jacobsen, Neil E.; Bandarian, Vahe

2009-01-01

The genome sequence of Streptomyces coelicolor contains three open reading frames (sco1441, sco2687, and sco6655) that encode proteins with significant (>40%) amino acid identity to GTP cyclohydrolase II (GCH II), which catalyzes the committed step in the biosynthesis of riboflavin. The physiological significance of the redundancy of these proteins in S. coelicolor is not known. However, the gene contexts of the three proteins are different, suggesting that they may serve alternate biological niches. Each of the three proteins was overexpressed in Escherichia coli and characterized to determine if their functions are biologically overlapping. As purified, each protein contains 1 molar equiv of zinc/ mol of protein and utilizes guanosine 5′-triphosphate (GTP) as substrate. Two of these proteins (SCO 1441 and SCO 2687) produce the canonical product of GCH II, 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5′-phosphate (APy). Remarkably, however, one of the three proteins (SCO 6655) converts GTP to 2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone 5′-phosphate (FAPy), as shown by UV-visible spectrophotometry, mass spectrometry, and NMR. This activity has been reported for a GTP cyclohydrolase III protein from Methanocaldococcus jannaschii [Graham, D. E., Xu, H., and White, R. H. (2002) Biochemistry 41, 15074–15084], which has no amino acid sequence homology to SCO 6655. Comparison of the sequences of these proteins and mapping onto the structure of the E. coli GCH II protein [Ren, J., Kotaka, M., Lockyer, M., Lamb, H. K., Hawkins, A. R., and Stammers, D. K. (2005) J. Biol. Chem. 280, 36912–36919] allowed identification of a switch residue, Met120, which appears to be responsible for the altered fate of GTP observed with SCO 6655; a Tyr is found in the analogous position of all proteins that have been shown to catalyze the conversion of GTP to APy. The Met120Tyr variant of SCO 6655 acquires the ability to catalyze the conversion of GTP to APy, suggesting

Discovery of G protein signaling.

PubMed

Selinger, Zvi

2008-01-01

The mechanism of transmembrane signaling by the receptor-activated adenylyl cyclase was an enigma. It was suggested that hydrolysis of GTP is a turn-off mechanism that resets the active adenylyl cyclase to the inactive state. To test this hypothesis, we developed a specific GTPase assay and found that the catecholamine adrenergic agonists stimulated the hydrolysis of GTP. To resolve the question of how the hormone concurrently stimulates GTP hydrolysis and activates the adenylyl cyclase, we suggested the regulatory GTPase cycle. Thus, because the hormone facilitates the binding of GTP, which is subsequently hydrolyzed, the regulatory cycle results in a hormone-stimulated GTPase activity. This model also predicts that two mechanisms could account for stimulation of adenylyl cyclase activity-either by the familiar hormone stimulation of the activation reaction or by an inhibition of the turn-off reaction. Indeed, we showed that cholera toxin enhances adenylyl cyclase activity by inhibition of GTP hydrolysis. Finally, we also showed that the hormone-activated receptor stimulates adenylyl cyclase activity by facilitating the exchange of bound GDP for free GTP. Thus, we presented, for the first time, an explicit mechanism for receptor action.

Straight and Curved Conformations of FtsZ Are Regulated by GTP Hydrolysis

PubMed Central

Lu, Chunlin; Reedy, Mary; Erickson, Harold P.

2000-01-01

FtsZ assembles in vitro into protofilaments that can adopt two conformations—the straight conformation, which can assemble further into two-dimensional protofilament sheets, and the curved conformation, which forms minirings about 23 nm in diameter. Here, we describe the structure of FtsZ tubes, which are a variation of the curved conformation. In the tube the curved protofilament forms a shallow helix with a diameter of 23 nm and a pitch of 18 or 24°. We suggest that this shallow helix is the relaxed structure of the curved protofilament in solution. We provide evidence that GTP favors the straight conformation while GDP favors the curved conformation. In particular, exclusively straight protofilaments and protofilament sheets are assembled in GMPCPP, a nonhydrolyzable GTP analog, or in GTP following chelation of Mg, which blocks GTP hydrolysis. Assembly in GDP produces exclusively tubes. The transition from straight protofilaments to the curved conformation may provide a mechanism whereby the energy of GTP hydrolysis is used to generate force for the constriction of the FtsZ ring in cell division. PMID:10613876

Photon-assisted tunneling through a topological superconductor with Majorana bound states

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Han-Zhao; Zhang, Ying-Tao, E-mail: zhangyt@mail.hebtu.edu.cn; Liu, Jian-Jun, E-mail: liujj@mail.hebtu.edu.cn

Employing the Keldysh Nonequilibrium Green’s function method, we investigate time-dependent transport through a topological superconductor with Majorana bound states in the presence of a high frequency microwave field. It is found that Majorana bound states driven by photon-assisted tunneling can absorb(emit) photons and the resulting photon-assisted tunneling side band peaks can split the Majorana bound state that then appears at non-zero bias. This splitting breaks from the current opinion that Majorana bound states appear only at zero bias and thus provides a new experimental method for detecting Majorana bound states in the Non-zero-energy mode. We not only demonstrate that themore » photon-assisted tunneling side band peaks are due to Non-zero-energy Majorana bound states, but also that the height of the photon-assisted tunneling side band peaks is related to the intensity of the microwave field. It is further shown that the time-varying conductance induced by the Majorana bound states shows negative values for a certain period of time, which corresponds to a manifestation of the phase coherent time-varying behavior in mesoscopic systems.« less

Volume dependence of N-body bound states

NASA Astrophysics Data System (ADS)

König, Sebastian; Lee, Dean

2018-04-01

We derive the finite-volume correction to the binding energy of an N-particle quantum bound state in a cubic periodic volume. Our results are applicable to bound states with arbitrary composition and total angular momentum, and in any number of spatial dimensions. The only assumptions are that the interactions have finite range. The finite-volume correction is a sum of contributions from all possible breakup channels. In the case where the separation is into two bound clusters, our result gives the leading volume dependence up to exponentially small corrections. If the separation is into three or more clusters, there is a power-law factor that is beyond the scope of this work, however our result again determines the leading exponential dependence. We also present two independent methods that use finite-volume data to determine asymptotic normalization coefficients. The coefficients are useful to determine low-energy capture reactions into weakly bound states relevant for nuclear astrophysics. Using the techniques introduced here, one can even extract the infinite-volume energy limit using data from a single-volume calculation. The derived relations are tested using several exactly solvable systems and numerical examples. We anticipate immediate applications to lattice calculations of hadronic, nuclear, and cold atomic systems.

Propagating bound states in the continuum in dielectric gratings

NASA Astrophysics Data System (ADS)

Bulgakov, E. N.; Maksimov, D. N.; Semina, P. N.; Skorobogatov, S. A.

2018-06-01

We consider propagating bound states in the continuum in dielectric gratings. The gratings consist of a slab with ridges periodically arranged ether on top or on the both sides of the slab. Based on the Fourier modal approach we recover the leaky zones above the line of light to identify the geometries of the gratings supporting Bloch bound states propagating in the direction perpendicular to the ridges. Most importantly, it is demonstrated that if a two-side grating possesses either mirror or glide symmetry the Bloch bound states are stable to variation of parameters as far as the above symmetries are preserved.

“Gate-keeper” Residues and Active-Site Rearrangements in DNA Polymerase μ Help Discriminate Non-cognate Nucleotides

PubMed Central

Li, Yunlang; Schlick, Tamar

2013-01-01

Incorporating the cognate instead of non-cognate substrates is crucial for DNA polymerase function. Here we analyze molecular dynamics simulations of DNA polymerase μ (pol μ) bound to different non-cognate incoming nucleotides including A:dCTP, A:dGTP, A(syn):dGTP, A:dATP, A(syn):dATP, T:dCTP, and T:dGTP to study the structure-function relationships involved with aberrant base pairs in the conformational pathway; while a pol μ complex with the A:dTTP base pair is available, no solved non-cognate structures are available. We observe distinct differences of the non-cognate systems compared to the cognate system. Specifically, the motions of active-site residue His329 and Asp330 distort the active site, and Trp436, Gln440, Glu443 and Arg444 tend to tighten the nucleotide-binding pocket when non-cognate nucleotides are bound; the latter effect may further lead to an altered electrostatic potential within the active site. That most of these “gate-keeper” residues are located farther apart from the upstream primer in pol μ, compared to other X family members, also suggests an interesting relation to pol μ's ability to incorporate nucleotides when the upstream primer is not paired. By examining the correlated motions within pol μ complexes, we also observe different patterns of correlations between non-cognate systems and the cognate system, especially decreased interactions between the incoming nucleotides and the nucleotide-binding pocket. Altered correlated motions in non-cognate systems agree with our recently proposed hybrid conformational selection/induced-fit models. Taken together, our studies propose the following order for difficulty of non-cognate system insertions by pol μ: T:dGTPGTP, which may be more sensitive to the template sequence. The structures and conformational aspects

Electron teleportation via Majorana bound states in a mesoscopic superconductor.

PubMed

Fu, Liang

2010-02-05

Zero-energy Majorana bound states in superconductors have been proposed to be potential building blocks of a topological quantum computer, because quantum information can be encoded nonlocally in the fermion occupation of a pair of spatially separated Majorana bound states. However, despite intensive efforts, nonlocal signatures of Majorana bound states have not been found in charge transport. In this work, we predict a striking nonlocal phase-coherent electron transfer process by virtue of tunneling in and out of a pair of Majorana bound states. This teleportation phenomenon only exists in a mesoscopic superconductor because of an all-important but previously overlooked charging energy. We propose an experimental setup to detect this phenomenon in a superconductor-quantum-spin-Hall-insulator-magnetic-insulator hybrid system.

Ethylene Regulates Monomeric GTP-Binding Protein Gene Expression and Activity in Arabidopsis1

PubMed Central

Moshkov, Igor E.; Mur, Luis A.J.; Novikova, Galina V.; Smith, Aileen R.; Hall, Michael A.

2003-01-01

Ethylene rapidly and transiently up-regulates the activity of several monomeric GTP-binding proteins (monomeric G proteins) in leaves of Arabidopsis as determined by two-dimensional gel electrophoresis and autoradiographic analyses. The activation is suppressed by the receptor-directed inhibitor 1-methylcyclopropene. In the etr1-1 mutant, constitutive activity of all the monomeric G proteins activated by ethylene is down-regulated relative to wild type, and ethylene treatment has no effect on the levels of activity. Conversely, in the ctr1-1 mutant, several of the monomeric G proteins activated by ethylene are constitutively up-regulated. However, the activation profile of ctr1-1 does not exactly mimic that of ethylene-treated wild type. Biochemical and molecular evidence suggested that some of these monomeric G proteins are of the Rab class. Expression of the genes for a number of monomeric G proteins in response to ethylene was investigated by reverse transcriptase-PCR. Rab8 and Ara3 expression was increased within 10 min of ethylene treatment, although levels fell back significantly by 40 min. In the etr1-1 mutant, expression of Rab8 was lower than wild type and unaffected by ethylene; in ctr1-1, expression of Rab8 was much higher than wild type and comparable with that seen in ethylene treatments. Expression in ctr1-1 was also unaffected by ethylene. Thus, the data indicate a role for monomeric G proteins in ethylene signal transduction. PMID:12692329

Symmetry-breaking instability of quadratic soliton bound states

DOE Office of Scientific and Technical Information (OSTI.GOV)

Delque, Michaeel; Departement d'Optique P.M. Duffieux, Institut FEMTO-ST, Universite de Franche-Comte, CNRS UMR 6174, F-25030 Besancon; Fanjoux, Gil

We study both numerically and experimentally two-dimensional soliton bound states in quadratic media and demonstrate their symmetry-breaking instability. The experiment is performed in a potassium titanyl phosphate crystal in a type-II configuration. The bound state is generated by the copropagation of the antisymmetric fundamental beam locked in phase with the symmetrical second harmonic one. Experimental results are in good agreement with numerical simulations of the nonlinear wave equations.

Identification of a botulinum C3-like enzyme in bovine brain that catalyzes ADP-ribosylation of GTP-binding proteins.

PubMed

Maehama, T; Takahashi, K; Ohoka, Y; Ohtsuka, T; Ui, M; Katada, T

1991-06-05

A novel enzyme activity was found in bovine brain cytosol that transfers the ADP-ribosyl moiety of NAD to proteins with Mr values of 22,000 and 25,000. The substrates were the same GTP-binding proteins serving as the substrate of an ADP-ribosyltransferase C3 which was produced by a type C strain of Clostridium botulinum. The brain enzyme was partially purified from the cytosol and had a molecular mass of approximately 20,000 on a gel filtration column. The brain endogenous enzyme displayed unique properties similar to those observed with botulinum C3 enzyme. The enzyme activity was markedly stimulated by a protein factor that had been initially found in the cytosol as an activator for botulinum C3-catalyzed ADP-ribosylation (Ohtsuka, T., Nagata, K., Iiri, T., Nozawa, Y., Ueno, K., Ui, M., and Katada, T. (1989) J. Biol. Chem. 264, 15000-15005). The activity of the brain enzyme was also affected by certain types of detergents or phospholipids. The substrate of the brain enzyme was specific for GTP-binding proteins serving as the substrate of botulinum C3 enzyme; the alpha-subunits of trimeric GTP-binding proteins which served as the substrate of cholera or pertussis toxin were not ADP-ribosylated by the endogenous enzyme. Thus, this is the first report showing an endogenous enzyme in mammalian cells that catalyzes ADP-ribosylation of small molecular weight GTP-binding proteins.

Bound states of moving potential wells in discrete wave mechanics

NASA Astrophysics Data System (ADS)

Longhi, S.

2017-10-01

Discrete wave mechanics describes the evolution of classical or matter waves on a lattice, which is governed by a discretized version of the Schrödinger equation. While for a vanishing lattice spacing wave evolution of the continuous Schrödinger equation is retrieved, spatial discretization and lattice effects can deeply modify wave dynamics. Here we discuss implications of breakdown of exact Galilean invariance of the discrete Schrödinger equation on the bound states sustained by a smooth potential well which is uniformly moving on the lattice with a drift velocity v. While in the continuous limit the number of bound states does not depend on the drift velocity v, as one expects from the covariance of ordinary Schrödinger equation for a Galilean boost, lattice effects can lead to a larger number of bound states for the moving potential well as compared to the potential well at rest. Moreover, for a moving potential bound states on a lattice become rather generally quasi-bound (resonance) states.

Structural Changes and Proapoptotic Peroxidase Activity of Cardiolipin-Bound Mitochondrial Cytochrome c

PubMed Central

Mandal, Abhishek; Hoop, Cody L.; DeLucia, Maria; Kodali, Ravindra; Kagan, Valerian E.; Ahn, Jinwoo; van der Wel, Patrick C.A.

2015-01-01

The cellular process of intrinsic apoptosis relies on the peroxidation of mitochondrial lipids as a critical molecular signal. Lipid peroxidation is connected to increases in mitochondrial reactive oxygen species, but there is also a required role for mitochondrial cytochrome c (cyt-c). In apoptotic mitochondria, cyt-c gains a new function as a lipid peroxidase that catalyzes the reactive oxygen species-mediated chemical modification of the mitochondrial lipid cardiolipin (CL). This peroxidase activity is caused by a conformational change in the protein, resulting from interactions between cyt-c and CL. The nature of the conformational change and how it causes this gain-of-function remain uncertain. Via a combination of functional, structural, and biophysical experiments we investigate the structure and peroxidase activity of cyt-c in its membrane-bound state. We reconstituted cyt-c with CL-containing lipid vesicles, and determined the increase in peroxidase activity resulting from membrane binding. We combined these assays of CL-induced proapoptotic activity with structural and dynamic studies of the membrane-bound protein via solid-state NMR and optical spectroscopy. Multidimensional magic angle spinning (MAS) solid-state NMR of uniformly 13C,15N-labeled protein was used to detect site-specific conformational changes in oxidized and reduced horse heart cyt-c bound to CL-containing lipid bilayers. MAS NMR and Fourier transform infrared measurements show that the peripherally membrane-bound cyt-c experiences significant dynamics, but also retains most or all of its secondary structure. Moreover, in two-dimensional and three-dimensional MAS NMR spectra the CL-bound cyt-c displays a spectral resolution, and thus structural homogeneity, that is inconsistent with extensive membrane-induced unfolding. Cyt-c is found to interact primarily with the membrane interface, without significantly disrupting the lipid bilayer. Thus, membrane binding results in cyt-c gaining the

Maximum and minimum entropy states yielding local continuity bounds

NASA Astrophysics Data System (ADS)

Hanson, Eric P.; Datta, Nilanjana

2018-04-01

Given an arbitrary quantum state (σ), we obtain an explicit construction of a state ρɛ * ( σ ) [respectively, ρ * , ɛ ( σ ) ] which has the maximum (respectively, minimum) entropy among all states which lie in a specified neighborhood (ɛ-ball) of σ. Computing the entropy of these states leads to a local strengthening of the continuity bound of the von Neumann entropy, i.e., the Audenaert-Fannes inequality. Our bound is local in the sense that it depends on the spectrum of σ. The states ρɛ * ( σ ) and ρ * , ɛ (σ) depend only on the geometry of the ɛ-ball and are in fact optimizers for a larger class of entropies. These include the Rényi entropy and the minimum- and maximum-entropies, providing explicit formulas for certain smoothed quantities. This allows us to obtain local continuity bounds for these quantities as well. In obtaining this bound, we first derive a more general result which may be of independent interest, namely, a necessary and sufficient condition under which a state maximizes a concave and Gâteaux-differentiable function in an ɛ-ball around a given state σ. Examples of such a function include the von Neumann entropy and the conditional entropy of bipartite states. Our proofs employ tools from the theory of convex optimization under non-differentiable constraints, in particular Fermat's rule, and majorization theory.

Wronskian Method for Bound States

ERIC Educational Resources Information Center

Fernandez, Francisco M.

2011-01-01

We propose a simple and straightforward method based on Wronskians for the calculation of bound-state energies and wavefunctions of one-dimensional quantum-mechanical problems. We explicitly discuss the asymptotic behaviour of the wavefunction and show that the allowed energies make the divergent part vanish. As illustrative examples we consider…

Interacting quantum walkers: two-body bosonic and fermionic bound states

NASA Astrophysics Data System (ADS)

Krapivsky, P. L.; Luck, J. M.; Mallick, K.

2015-11-01

We investigate the dynamics of bound states of two interacting particles, either bosons or fermions, performing a continuous-time quantum walk on a one-dimensional lattice. We consider the situation where the distance between both particles has a hard bound, and the richer situation where the particles are bound by a smooth confining potential. The main emphasis is on the velocity characterizing the ballistic spreading of these bound states, and on the structure of the asymptotic distribution profile of their center-of-mass coordinate. The latter profile generically exhibits many internal fronts.

[Alcohol intake and gamma -GTP observed from the viewpoint of an occupational physician].

PubMed

Oikawa, Takamitsu

2007-06-01

Alcohol is an important basic factor in health management at the workplace. The fact is, however, when alcohol is pervasive in a worker's daily life, effective measures are very difficult to carry out. We examined an intervention program based on serum y -GTP (IU/l) measurements at physical examination. Subjects were clients of the Keio Counseling Center in2005 (male, 5568: female, 1725). Among nondrinkers, gamma-GTP values were under 50 in 83% of men and 93% of women. Relative risk of lifestyle-related diseases (obesity, hypertension, hyperlipidemia, hyperuricemia, hyperglycemia and fatty liver) among male drinkers increased dramatically when gamma-GTP exceeded 50,with a further gradual increase for gamma-GTP over 100. Moreover, relative risk of over two concurrent diseases among obesity, hypertension, hyperlipidemia and hyperglycemia increased when gamma-GTP exceeded 25 and greatly increased beyond 50. While the findings suggest 25 or less as an ideal gamma-GTP values, a workplace program might more practically regard values over 50 as a threshold for management measures and values over 100 as indicating enforced management. At the workplace, management of other diseases including lifestyle-related diseases, alcoholism per se, and mental health issues needs to be carried out in a balanced, coordinated manner. Cooperation of related medical institutions and effective alcohol treatment program, and efforts to enlist the understanding and trust of all workers are needed.

The GAP arginine finger movement into the catalytic site of Ras increases the activation entropy

PubMed Central

Kötting, Carsten; Kallenbach, Angela; Suveyzdis, Yan; Wittinghofer, Alfred; Gerwert, Klaus

2008-01-01

Members of the Ras superfamily of small G proteins play key roles in signal transduction pathways, which they control by GTP hydrolysis. They are regulated by GTPase activating proteins (GAPs). Mutations that prevent hydrolysis cause severe diseases including cancer. A highly conserved “arginine finger” of GAP is a key residue. Here, we monitor the GTPase reaction of the Ras·RasGAP complex at high temporal and spatial resolution by time-resolved FTIR spectroscopy at 260 K. After triggering the reaction, we observe as the first step a movement of the switch-I region of Ras from the nonsignaling “off” to the signaling “on” state with a rate of 3 s−1. The next step is the movement of the “arginine finger” into the active site of Ras with a rate of k2 = 0.8 s−1. Once the arginine points into the binding pocket, cleavage of GTP is fast and the protein-bound Pi intermediate forms. The switch-I reversal to the “off” state, the release of Pi, and the movement of arginine back into an aqueous environment is observed simultaneously with k3 = 0.1 s−1, the rate-limiting step. Arrhenius plots for the partial reactions show that the activation energy for the cleavage reaction is lowered by favorable positive activation entropy. This seems to indicate that protein-bound structured water molecules are pushed by the “arginine finger” movement out of the binding pocket into the bulk water. The proposed mechanism shows how the high activation barrier for phosphoryl transfer can be reduced by splitting into partial reactions separated by a Pi-intermediate. PMID:18434546

Bound entangled states with a private key and their classical counterpart.

PubMed

Ozols, Maris; Smith, Graeme; Smolin, John A

2014-03-21

Entanglement is a fundamental resource for quantum information processing. In its pure form, it allows quantum teleportation and sharing classical secrets. Realistic quantum states are noisy and their usefulness is only partially understood. Bound-entangled states are central to this question--they have no distillable entanglement, yet sometimes still have a private classical key. We present a construction of bound-entangled states with a private key based on classical probability distributions. From this emerge states possessing a new classical analogue of bound entanglement, distinct from the long-sought bound information. We also find states of smaller dimensions and higher key rates than previously known. Our construction has implications for classical cryptography: we show that existing protocols are insufficient for extracting private key from our distributions due to their "bound-entangled" nature. We propose a simple extension of existing protocols that can extract a key from them.

Molecular modeling study for interaction between Bacillus subtilis Obg and Nucleotides.

PubMed

Lee, Yuno; Bang, Woo Young; Kim, Songmi; Lazar, Prettina; Kim, Chul Wook; Bahk, Jeong Dong; Lee, Keun Woo

2010-09-07

The bacterial Obg proteins (Spo0B-associated GTP-binding protein) belong to the subfamily of P-loop GTPase proteins that contain two equally and highly conserved domains, a C-terminal GTP binding domain and an N-terminal glycine-rich domain which is referred as the "Obg fold" and now it is considered as one of the new targets for antibacterial drug. When the Obg protein is associated with GTP, it becomes activated, because conformation of Obg fold changes due to the structural changes of GTPase switch elements in GTP binding site. In order to investigate the effects and structural changes in GTP bound to Obg and GTPase switch elements for activation, four different molecular dynamics (MD) simulations were performed with/without the three different nucleotides (GTP, GDP, and GDP + Pi) using the Bacillus subtilis Obg (BsObg) structure. The protein structures generated from the four different systems were compared using their representative structures. The pattern of C(alpha)-C(alpha) distance plot and angle between the two Obg fold domains of simulated apo form and each system (GTP, GDP, and GDP+Pi) were significantly different in the GTP-bound system from the others. The switch 2 element was significantly changed in GTP-bound system. Also root-mean-square fluctuation (RMSF) analysis revealed that the flexibility of the switch 2 element region was much higher than the others. This was caused by the characteristic binding mode of the nucleotides. When GTP was bound to Obg, its gamma-phosphate oxygen was found to interact with the key residue (D212) of the switch 2 element, on the contrary there was no such interaction found in other systems. Based on the results, we were able to predict the possible binding conformation of the activated form of Obg with L13, which is essential for the assembly with ribosome.

Minimal determinants for binding activated G-alpha from the structure of a G-alpha-i1/peptide dimer†

PubMed Central

Johnston, Christopher A.; Lobanova, Ekaterina S.; Shavkunov, Alexander S.; Low, Justin; Ramer, J. Kevin; Blaesius, Rainer; Fredericks, Zoey; Willard, Francis S.; Kuhlman, Brian; Arshavsky, Vadim Y.; Siderovski, David P.

2008-01-01

G-proteins cycle between an inactive GDP-bound state and active GTP-bound state, serving as molecular switches that coordinate cellular signaling. We recently used phage-display to identify a series of peptides that bind Gα subunits in a nucleotide-dependent manner [Johnston, C. A., Willard, F. S., Jezyk, M. R., Fredericks, Z., Bodor, E. T., Jones, M. B., Blaesius, R., Watts, V. J., Harden, T. K., Sondek, J., Ramer, J. K., and Siderovski, D. P. (2005) Structure 13, 1069–1080]. Here we describe the structural features and functions of KB-1753, a peptide that binds selectively to GDP·AlF4−- and GTPγS-bound states of Gαi subunits. KB-1753 blocks interaction of Gαtransducin with its effector, cGMP phosphodiesterase, and inhibits transducin-mediated activation of cGMP degradation. Additionally, KB-1753 interferes with RGS protein binding and resultant GAP activity. A fluorescent KB-1753 variant was found to act as a sensor for activated Gα in vitro. The crystal structure of KB-1753 bound to Gαi1·GDP·AlF4− reveals binding to a conserved hydrophobic groove between switch II and α3 helices, and, along with supporting biochemical data and previous structural analyses, supports the notion that this is the site of effector interactions for Gαi subunits. PMID:16981699

Vibrational studies of phosphoryl transfer enzymes: ras- p21(*)magnesium-GTP and Myosin S1(*)magnesium-ADP- vanadate

NASA Astrophysics Data System (ADS)

Wang, Jianghua

1999-07-01

We have measured the Raman spectra of monophosphate compounds in aqueous solution. The measured frequencies were correlated with P••O valence bond order by using a modification of the Hardcastle- Wachs procedure. The P••O bond order and bond length in phosphates can be determined from vibrational spectra by using the derived bond order/stretching frequency correlation and the bond length/bond order correlation of Brown and Wu. The Raman and infrared spectra of guanosine 5'-diphosphate (GDP) and guanosine 5'-triphosphate (GTP) in aqueous solution were also examined. Frequency shifts were observed as Mg2+ complexes with GDP and GTP in aqueous solution. These results suggested that Mg2+ binds to GDP in a bidentate manner to the α,β P••O bonds and in a tridentate manner to the α,β and γ P••O bonds of Mg•GTP . We have analyzed the previously obtained isotope edited Raman difference spectra of 1:1 complexes of Mg•GDP and Mg•GTP in ras-p21. Frequency changes of the phosphate groups were observed when Mg•GDP , Mg•GTP bind to the protein. Employing both the previous empirical relationships between bond orders/lengths and frequencies as well as vibrational analysis from ab initio calculations, the spectral changes can be explained by the change of the Mg2+ binding sites and hydrogen-bonding. Implications of these structural results for the reaction mechanism of GTP hydrolysis catalyzed by the GTPase are discussed. We have analyzed previously obtained isotope edited Raman difference spectra of the non-bridging V••O bonds of vanadates, both in solution, and when bound to the myosin S1•MgADP complex. By use of ab initio calculations on a model of the vanadate binding site in myosin, the angles between the non-bridging V••O bonds and between these bonds and the apical bonds in the myosin S1•MgADP -Vi complex were determined. The summed bond order of the two apical bonds

Majorana bound states in the finite-length chain

NASA Astrophysics Data System (ADS)

Zvyagin, A. A.

2015-08-01

Recent experiments investigating edge states in ferromagnetic atomic chains on superconducting substrate are analyzed. In particular, finite size effects are considered. It is shown how the energy of the Majorana bound state depends on the length of the chain, as well as on the parameters of the model. Oscillations of the energy of the bound edge state in the chain as a function of the length of the chain, and as a function of the applied voltage (or the chemical potential) are studied. In particular, it has been shown that oscillations can exist only for some values of the effective potential.

Observation of topologically protected bound states in photonic quantum walks.

PubMed

Kitagawa, Takuya; Broome, Matthew A; Fedrizzi, Alessandro; Rudner, Mark S; Berg, Erez; Kassal, Ivan; Aspuru-Guzik, Alán; Demler, Eugene; White, Andrew G

2012-06-06

Topological phases exhibit some of the most striking phenomena in modern physics. Much of the rich behaviour of quantum Hall systems, topological insulators, and topological superconductors can be traced to the existence of robust bound states at interfaces between different topological phases. This robustness has applications in metrology and holds promise for future uses in quantum computing. Engineered quantum systems--notably in photonics, where wavefunctions can be observed directly--provide versatile platforms for creating and probing a variety of topological phases. Here we use photonic quantum walks to observe bound states between systems with different bulk topological properties and demonstrate their robustness to perturbations--a signature of topological protection. Although such bound states are usually discussed for static (time-independent) systems, here we demonstrate their existence in an explicitly time-dependent situation. Moreover, we discover a new phenomenon: a topologically protected pair of bound states unique to periodically driven systems.

GTP-Binding Proteins Inhibit cAMP Activation of Chloride Channels in Cystic Fibrosis Airway Epithelial Cells

NASA Astrophysics Data System (ADS)

Schwiebert, Erik M.; Kizer, Neil; Gruenert, Dieter C.; Stanton, Bruce A.

1992-11-01

Cystic fibrosis (CF) is a genetic disease characterized, in part, by defective regulation of Cl^- secretion by airway epithelial cells. In CF, cAMP does not activate Cl^- channels in the apical membrane of airway epithelial cells. We report here whole-cell patch-clamp studies demonstrating that pertussis toxin, which uncouples heterotrimeric GTP-binding proteins (G proteins) from their receptors, and guanosine 5'-[β-thio]diphosphate, which prevents G proteins from interacting with their effectors, increase Cl^- currents and restore cAMP-activated Cl^- currents in airway epithelial cells isolated from CF patients. In contrast, the G protein activators guanosine 5'-[γ-thio]triphosphate and AlF^-_4 reduce Cl^- currents and inhibit cAMP from activating Cl^- currents in normal airway epithelial cells. In CF cells treated with pertussis toxin or guanosine 5'-[β-thio]diphosphate and in normal cells, cAMP activates a Cl^- conductance that has properties similar to CF transmembrane-conductance regulator Cl^- channels. We conclude that heterotrimeric G proteins inhibit cAMP-activated Cl^- currents in airway epithelial cells and that modulation of the inhibitory G protein signaling pathway may have the therapeutic potential for improving cAMP-activated Cl^- secretion in CF.

Impurity bound states in d-wave superconductors with subdominant order parameters

NASA Astrophysics Data System (ADS)

Mashkoori, Mahdi; Björnson, Kristofer; Black-Schaffer, Annica

Single magnetic impurity induces intra-gap bound states in conventional s-wave superconductors (SCs) but, in d-wave SCs only virtual bound states can be induced. However, in small cuprate islands a fully gapped spectrum has recently been discovered. In this work, we investigate the real bound states due to potential and magnetic impurities in the two candidate fully gapped states for this system: the topologically trivial d + is -wave state and the topologically non-trivial d + id' -wave (chiral d-wave state). Using the analytic T-matrix formalism and self-consistent numerical tight-binding lattice calculations, we show that potential and magnetic impurities create entirely different intra-gap bound states in d + is -wave and chiral d-wave SCs. Therefore, our results suggest that the bound states mainly depend on the subdominant order parameter. Considering that recent experiments have demonstrated an access to adjustable coupling J, impurities thus offer an intriguing way to clearly distinguish between the chiral d-wave and topologically trivial d + is -wave state. This work was supported by Swedish Research Council, Swedish Foundation for Strategic Research, the Wallenberg Academy Fellows program and the Göran Gustafsson Foundation. The computations were performed on resources provided by SNIC at LUNARC.

Bound exciton and free exciton states in GaSe thin slab.

PubMed

Wei, Chengrong; Chen, Xi; Li, Dian; Su, Huimin; He, Hongtao; Dai, Jun-Feng

2016-09-22

The photoluminescence (PL) and absorption experiments have been performed in GaSe slab with incident light polarized perpendicular to c-axis of sample at 10 K. An obvious energy difference of about 34 meV between exciton absorption peak and PL peak (the highest energy peak) is observed. By studying the temperature dependence of PL and absorption spectra, we attribute it to energy difference between free exciton and bound exciton states, where main exciton absorption peak comes from free exciton absorption, and PL peak is attributed to recombination of bound exciton at 10 K. This strong bound exciton effect is stable up to 50 K. Moreover, the temperature dependence of integrated PL intensity and PL lifetime reveals that a non-radiative process, with activation energy extracted as 0.5 meV, dominates PL emission.

Tsirelson's bound and supersymmetric entangled states

PubMed Central

Borsten, L.; Brádler, K.; Duff, M. J.

2014-01-01

A superqubit, belonging to a (2|1)-dimensional super-Hilbert space, constitutes the minimal supersymmetric extension of the conventional qubit. In order to see whether superqubits are more non-local than ordinary qubits, we construct a class of two-superqubit entangled states as a non-local resource in the CHSH game. Since super Hilbert space amplitudes are Grassmann numbers, the result depends on how we extract real probabilities and we examine three choices of map: (1) DeWitt (2) Trigonometric and (3) Modified Rogers. In cases (1) and (2), the winning probability reaches the Tsirelson bound pwin=cos2π/8≃0.8536 of standard quantum mechanics. Case (3) crosses Tsirelson's bound with pwin≃0.9265. Although all states used in the game involve probabilities lying between 0 and 1, case (3) permits other changes of basis inducing negative transition probabilities. PMID:25294964

The Kinesin-5 Chemomechanical Cycle Is Dominated by a Two-heads-bound State*♦

PubMed Central

Mickolajczyk, Keith J.

2016-01-01

Single-molecule microscopy and stopped-flow kinetics assays were carried out to understand the microtubule polymerase activity of kinesin-5 (Eg5). Four lines of evidence argue that the motor primarily resides in a two-heads-bound (2HB) state. First, upon microtubule binding, dimeric Eg5 releases both bound ADPs. Second, microtubule dissociation in saturating ADP is 20-fold slower for the dimer than for the monomer. Third, ATP-triggered mant-ADP release is 5-fold faster than the stepping rate. Fourth, ATP binding is relatively fast when the motor is locked in a 2HB state. Shortening the neck-linker does not facilitate rear-head detachment, suggesting a minimal role for rear-head-gating. This 2HB state may enable Eg5 to stabilize incoming tubulin at the growing microtubule plus-end. The finding that slowly hydrolyzable ATP analogs trigger slower nucleotide release than ATP suggests that ATP hydrolysis in the bound head precedes stepping by the tethered head, leading to a mechanochemical cycle in which processivity is determined by the race between unbinding of the bound head and attachment of the tethered head. PMID:27402829

Two Active Site Divalent Ions in the Crystal Structure of the Hammerhead Ribozyme Bound to a Transition State Analogue.

PubMed

Mir, Aamir; Golden, Barbara L

2016-02-02

The crystal structure of the hammerhead ribozyme bound to the pentavalent transition state analogue vanadate reveals significant rearrangements relative to the previously determined structures. The active site contracts, bringing G10.1 closer to the cleavage site and repositioning a divalent metal ion such that it could, ultimately, interact directly with the scissile phosphate. This ion could also position a water molecule to serve as a general acid in the cleavage reaction. A second divalent ion is observed coordinated to O6 of G12. This metal ion is well-placed to help tune the pKA of G12. On the basis of this crystal structure as well as a wealth of biochemical studies, we propose a mechanism in which G12 serves as the general base and a magnesium-bound water serves as a general acid.

Search for bound states of the eta-meson in light nuclei

NASA Technical Reports Server (NTRS)

Chrien, R. E.; Bart, S.; Pile, P.; Sutter, R.; Tsoupas, N.; Funsten, H. O.; Finn, J. M.; Lyndon, C.; Punjabi, V.; Perdrisat, C. F.

1988-01-01

A search for nuclear-bound states of the eta meson was carried out. Targets of lithium, carbon, oxygen, and aluminum were placed in a pion(+) beam at 800 MeV/c. A predicted eta bound state in O-15* (E sub x approx. = 540 MeV) with a width of approx. 9 MeV was not observed. A bound state of a size 1/3 of the predicted cross section would have been seen in this experiment at a confidence level of 3sigma (P is greater than 0.9987).

A High-Throughput Assay for Rho Guanine Nucleotide Exchange Factors Based on the Transcreener GDP Assay.

PubMed

Reichman, Melvin; Schabdach, Amanda; Kumar, Meera; Zielinski, Tom; Donover, Preston S; Laury-Kleintop, Lisa D; Lowery, Robert G

2015-12-01

Ras homologous (Rho) family GTPases act as molecular switches controlling cell growth, movement, and gene expression by cycling between inactive guanosine diphosphate (GDP)- and active guanosine triphosphate (GTP)-bound conformations. Guanine nucleotide exchange factors (GEFs) positively regulate Rho GTPases by accelerating GDP dissociation to allow formation of the active, GTP-bound complex. Rho proteins are directly involved in cancer pathways, especially cell migration and invasion, and inhibiting GEFs holds potential as a therapeutic strategy to diminish Rho-dependent oncogenesis. Methods for measuring GEF activity suitable for high-throughput screening (HTS) are limited. We developed a simple, generic biochemical assay method for measuring GEF activity based on the fact that GDP dissociation is generally the rate-limiting step in the Rho GTPase catalytic cycle, and thus addition of a GEF causes an increase in steady-state GTPase activity. We used the Transcreener GDP Assay, which relies on selective immunodetection of GDP, to measure the GEF-dependent stimulation of steady-state GTP hydrolysis by small GTPases using Dbs (Dbl's big sister) as a GEF for Cdc42, RhoA, and RhoB. The assay is well suited for HTS, with a homogenous format and far red fluorescence polarization (FP) readout, and it should be broadly applicable to diverse Rho GEF/GTPase pairs. © 2015 Society for Laboratory Automation and Screening.

De novo GTP Biosynthesis Is Critical for Virulence of the Fungal Pathogen Cryptococcus neoformans

PubMed Central

Morrow, Carl A.; Valkov, Eugene; Stamp, Anna; Chow, Eve W. L.; Lee, I. Russel; Wronski, Ania; Williams, Simon J.; Hill, Justine M.; Djordjevic, Julianne T.; Kappler, Ulrike; Kobe, Bostjan; Fraser, James A.

2012-01-01

We have investigated the potential of the GTP synthesis pathways as chemotherapeutic targets in the human pathogen Cryptococcus neoformans, a common cause of fatal fungal meningoencephalitis. We find that de novo GTP biosynthesis, but not the alternate salvage pathway, is critical to cryptococcal dissemination and survival in vivo. Loss of inosine monophosphate dehydrogenase (IMPDH) in the de novo pathway results in slow growth and virulence factor defects, while loss of the cognate phosphoribosyltransferase in the salvage pathway yielded no phenotypes. Further, the Cryptococcus species complex displays variable sensitivity to the IMPDH inhibitor mycophenolic acid, and we uncover a rare drug-resistant subtype of C. gattii that suggests an adaptive response to microbial IMPDH inhibitors in its environmental niche. We report the structural and functional characterization of IMPDH from Cryptococcus, revealing insights into the basis for drug resistance and suggesting strategies for the development of fungal-specific inhibitors. The crystal structure reveals the position of the IMPDH moveable flap and catalytic arginine in the open conformation for the first time, plus unique, exploitable differences in the highly conserved active site. Treatment with mycophenolic acid led to significantly increased survival times in a nematode model, validating de novo GTP biosynthesis as an antifungal target in Cryptococcus. PMID:23071437

Universal bounds on charged states in 2d CFT and 3d gravity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benjamin, Nathan; Dyer, Ethan; Fitzpatrick, A. Liam

2016-08-04

We derive an explicit bound on the dimension of the lightest charged state in two dimensional conformal field theories with a global abelian symmetry. We find that the bound scales with c and provide examples that parametrically saturate this bound. We also prove that any such theory must contain a state with charge-to-mass ratio above a minimal lower bound. As a result, we comment on the implications for charged states in three dimensional theories of gravity.

Shooting quasiparticles from Andreev bound states in a superconducting constriction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riwar, R.-P.; Houzet, M.; Meyer, J. S.

2014-12-15

A few-channel superconducting constriction provides a set of discrete Andreev bound states that may be populated with quasiparticles. Motivated by recent experimental research, we study the processes in an a.c. driven constriction whereby a quasiparticle is promoted to the delocalized states outside the superconducting gap and flies away. We distinguish two processes of this kind. In the process of ionization, a quasiparticle present in the Andreev bound state is transferred to the delocalized states leaving the constriction. The refill process involves two quasiparticles: one flies away while another one appears in the Andreev bound state. We notice an interesting asymmetrymore » of these processes. The electron-like quasiparticles are predominantly emitted to one side of the constriction while the hole-like ones are emitted to the other side. This produces a charge imbalance of accumulated quasiparticles, that is opposite on opposite sides of the junction. The imbalance may be detected with a tunnel contact to a normal metal lead.« less

Computational Simulation of the Activation Cycle of Gα Subunit in the G Protein Cycle Using an Elastic Network Model

PubMed Central

Kim, Min Hyeok; Kim, Young Jin; Kim, Hee Ryung; Jeon, Tae-Joon; Choi, Jae Boong; Chung, Ka Young; Kim, Moon Ki

2016-01-01

Agonist-activated G protein-coupled receptors (GPCRs) interact with GDP-bound G protein heterotrimers (Gαβγ) promoting GDP/GTP exchange, which results in dissociation of Gα from the receptor and Gβγ. The GTPase activity of Gα hydrolyzes GTP to GDP, and the GDP-bound Gα interacts with Gβγ, forming a GDP-bound G protein heterotrimer. The G protein cycle is allosterically modulated by conformational changes of the Gα subunit. Although biochemical and biophysical methods have elucidated the structure and dynamics of Gα, the precise conformational mechanisms underlying the G protein cycle are not fully understood yet. Simulation methods could help to provide additional details to gain further insight into G protein signal transduction mechanisms. In this study, using the available X-ray crystal structures of Gα, we simulated the entire G protein cycle and described not only the steric features of the Gα structure, but also conformational changes at each step. Each reference structure in the G protein cycle was modeled as an elastic network model and subjected to normal mode analysis. Our simulation data suggests that activated receptors trigger conformational changes of the Gα subunit that are thermodynamically favorable for opening of the nucleotide-binding pocket and GDP release. Furthermore, the effects of GTP binding and hydrolysis on mobility changes of the C and N termini and switch regions are elucidated. In summary, our simulation results enabled us to provide detailed descriptions of the structural and dynamic features of the G protein cycle. PMID:27483005

Two active site divalent ions in the crystal structure of the hammerhead ribozyme bound to a transition state analogue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mir, Aamir; Golden, Barbara L.

2015-11-09

The crystal structure of the hammerhead ribozyme bound to the pentavalent transition state analogue vanadate reveals significant rearrangements relative to the previously determined structures. The active site contracts, bringing G10.1 closer to the cleavage site and repositioning a divalent metal ion such that it could, ultimately, interact directly with the scissile phosphate. This ion could also position a water molecule to serve as a general acid in the cleavage reaction. A second divalent ion is observed coordinated to O6 of G12. This metal ion is well-placed to help tune the p K A of G12. Finally, on the basis ofmore » this crystal structure as well as a wealth of biochemical studies, in this paper we propose a mechanism in which G12 serves as the general base and a magnesium-bound water serves as a general acid.« less

Quantum state discrimination bounds for finite sample size

DOE Office of Scientific and Technical Information (OSTI.GOV)

Audenaert, Koenraad M. R.; Mosonyi, Milan; Mathematical Institute, Budapest University of Technology and Economics, Egry Jozsef u 1., Budapest 1111

2012-12-15

In the problem of quantum state discrimination, one has to determine by measurements the state of a quantum system, based on the a priori side information that the true state is one of the two given and completely known states, {rho} or {sigma}. In general, it is not possible to decide the identity of the true state with certainty, and the optimal measurement strategy depends on whether the two possible errors (mistaking {rho} for {sigma}, or the other way around) are treated as of equal importance or not. Results on the quantum Chernoff and Hoeffding bounds and the quantum Stein'smore » lemma show that, if several copies of the system are available then the optimal error probabilities decay exponentially in the number of copies, and the decay rate is given by a certain statistical distance between {rho} and {sigma} (the Chernoff distance, the Hoeffding distances, and the relative entropy, respectively). While these results provide a complete solution to the asymptotic problem, they are not completely satisfying from a practical point of view. Indeed, in realistic scenarios one has access only to finitely many copies of a system, and therefore it is desirable to have bounds on the error probabilities for finite sample size. In this paper we provide finite-size bounds on the so-called Stein errors, the Chernoff errors, the Hoeffding errors, and the mixed error probabilities related to the Chernoff and the Hoeffding errors.« less

Observation of three-photon bound states in a quantum nonlinear medium

NASA Astrophysics Data System (ADS)

Liang, Qi-Yu; Venkatramani, Aditya V.; Cantu, Sergio H.; Nicholson, Travis L.; Gullans, Michael J.; Gorshkov, Alexey V.; Thompson, Jeff D.; Chin, Cheng; Lukin, Mikhail D.; Vuletić, Vladan

2018-02-01

Bound states of massive particles, such as nuclei, atoms, or molecules, constitute the bulk of the visible world around us. By contrast, photons typically only interact weakly. We report the observation of traveling three-photon bound states in a quantum nonlinear medium where the interactions between photons are mediated by atomic Rydberg states. Photon correlation and conditional phase measurements reveal the distinct bunching and phase features associated with three-photon and two-photon bound states. Such photonic trimers and dimers possess shape-preserving wave functions that depend on the constituent photon number. The observed bunching and strongly nonlinear optical phase are described by an effective field theory of Rydberg-induced photon-photon interactions. These observations demonstrate the ability to realize and control strongly interacting quantum many-body states of light.

Ensemble-based characterization of unbound and bound states on protein energy landscape

PubMed Central

Ruvinsky, Anatoly M; Kirys, Tatsiana; Tuzikov, Alexander V; Vakser, Ilya A

2013-01-01

Physicochemical description of numerous cell processes is fundamentally based on the energy landscapes of protein molecules involved. Although the whole energy landscape is difficult to reconstruct, increased attention to particular targets has provided enough structures for mapping functionally important subspaces associated with the unbound and bound protein structures. The subspace mapping produces a discrete representation of the landscape, further called energy spectrum. We compiled and characterized ensembles of bound and unbound conformations of six small proteins and explored their spectra in implicit solvent. First, the analysis of the unbound-to-bound changes points to conformational selection as the binding mechanism for four proteins. Second, results show that bound and unbound spectra often significantly overlap. Moreover, the larger the overlap the smaller the root mean square deviation (RMSD) between the bound and unbound conformational ensembles. Third, the center of the unbound spectrum has a higher energy than the center of the corresponding bound spectrum of the dimeric and multimeric states for most of the proteins. This suggests that the unbound states often have larger entropy than the bound states. Fourth, the exhaustively long minimization, making small intrarotamer adjustments (all-atom RMSD ≤ 0.7 Å), dramatically reduces the distance between the centers of the bound and unbound spectra as well as the spectra extent. It condenses unbound and bound energy levels into a thin layer at the bottom of the energy landscape with the energy spacing that varies between 0.8–4.6 and 3.5–10.5 kcal/mol for the unbound and bound states correspondingly. Finally, the analysis of protein energy fluctuations showed that protein vibrations itself can excite the interstate transitions, including the unbound-to-bound ones. PMID:23526684

A Framework for Bounding Nonlocality of State Discrimination

NASA Astrophysics Data System (ADS)

Childs, Andrew M.; Leung, Debbie; Mančinska, Laura; Ozols, Maris

2013-11-01

We consider the class of protocols that can be implemented by local quantum operations and classical communication (LOCC) between two parties. In particular, we focus on the task of discriminating a known set of quantum states by LOCC. Building on the work in the paper Quantum nonlocality without entanglement (Bennett et al., Phys Rev A 59:1070-1091, 1999), we provide a framework for bounding the amount of nonlocality in a given set of bipartite quantum states in terms of a lower bound on the probability of error in any LOCC discrimination protocol. We apply our framework to an orthonormal product basis known as the domino states and obtain an alternative and simplified proof that quantifies its nonlocality. We generalize this result for similar bases in larger dimensions, as well as the “rotated” domino states, resolving a long-standing open question (Bennett et al., Phys Rev A 59:1070-1091, 1999).

Study of molecular N D bound states in the Bethe-Salpeter equation approach

NASA Astrophysics Data System (ADS)

Wang, Zhen-Yang; Qi, Jing-Juan; Guo, Xin-Heng; Wei, Ke-Wei

2018-05-01

We study the Λc(2595 )+ and Σc(2800 )0 states as the N D bound systems in the Bethe-Salpeter formalism in the ladder and instantaneous approximations. With the kernel induced by ρ , ω and σ exchanges, we solve the Bethe-Salpeter equations for the N D bound systems numerically and find that the bound states may exist. We assume that the observed states Λc(2595 )+ and Σc(2800 )0 are S -wave N D molecular bound states and calculate the decay widths of Λc(2595 )+→Σc0π+ and Σc(2800 )0→Λc+π-.

Stationary and oscillatory bound states of dissipative solitons created by third-order dispersion

NASA Astrophysics Data System (ADS)

Sakaguchi, Hidetsugu; Skryabin, Dmitry V.; Malomed, Boris A.

2018-06-01

We consider the model of fiber-laser cavities near the zero-dispersion point, based on the complex Ginzburg-Landau equation with the cubic-quintic nonlinearity, including the third-order dispersion (TOD) term. It is well known that this model supports stable dissipative solitons. We demonstrate that the same model gives rise to several families of robust bound states of the solitons, which exists only in the presence of the TOD. There are both stationary and dynamical bound states, with oscillating separation between the bound solitons. Stationary states are multistable, corresponding to different values of the separation. With the increase of the TOD coefficient, the bound state with the smallest separation gives rise the oscillatory state through the Hopf bifurcation. Further growth of TOD leads to a bifurcation transforming the oscillatory limit cycle into a strange attractor, which represents a chaotically oscillating dynamical bound state. Families of multistable three- and four-soliton complexes are found too, the ones with the smallest separation between the solitons again ending by a transition to oscillatory states through the Hopf bifurcation.

Matrix algorithms for solving (in)homogeneous bound state equations

PubMed Central

Blank, M.; Krassnigg, A.

2011-01-01

In the functional approach to quantum chromodynamics, the properties of hadronic bound states are accessible via covariant integral equations, e.g. the Bethe–Salpeter equation for mesons. In particular, one has to deal with linear, homogeneous integral equations which, in sophisticated model setups, use numerical representations of the solutions of other integral equations as part of their input. Analogously, inhomogeneous equations can be constructed to obtain off-shell information in addition to bound-state masses and other properties obtained from the covariant analogue to a wave function of the bound state. These can be solved very efficiently using well-known matrix algorithms for eigenvalues (in the homogeneous case) and the solution of linear systems (in the inhomogeneous case). We demonstrate this by solving the homogeneous and inhomogeneous Bethe–Salpeter equations and find, e.g. that for the calculation of the mass spectrum it is as efficient or even advantageous to use the inhomogeneous equation as compared to the homogeneous. This is valuable insight, in particular for the study of baryons in a three-quark setup and more involved systems. PMID:21760640

Tunable hybridization of Majorana bound states at the quantum spin Hall edge

NASA Astrophysics Data System (ADS)

Keidel, Felix; Burset, Pablo; Trauzettel, Björn

2018-02-01

Confinement at the helical edge of a topological insulator is possible in the presence of proximity-induced magnetic (F) or superconducting (S) order. The interplay of both phenomena leads to the formation of localized Majorana bound states (MBS) or likewise (under certain resonance conditions) the formation of ordinary Andreev bound states (ABS). We investigate the properties of bound states in junctions composed of alternating regions of F or S barriers. Interestingly, the direction of magnetization in F regions and the relative superconducting phase between S regions can be exploited to hybridize MBS or ABS at will. We show that the local properties of MBS translate into a particular nonlocal superconducting pairing amplitude. Remarkably, the symmetry of the pairing amplitude contains information about the nature of the bound state that it stems from. Hence this symmetry can in principle be used to distinguish MBS from ABS, owing to the strong connection between local density of states and nonlocal pairing in our setup.

Insight into Temperature Dependence of GTPase Activity in Human Guanylate Binding Protein-1

PubMed Central

Rahman, Safikur; Deep, Shashank; Sau, Apurba Kumar

2012-01-01

Interferon-γ induced human guanylate binding protein-1(hGBP1) belongs to a family of dynamin related large GTPases. Unlike all other GTPases, hGBP1 hydrolyzes GTP to a mixture of GDP and GMP with GMP being the major product at 37°C but GDP became significant when the hydrolysis reaction was carried out at 15°C. The hydrolysis reaction in hGBP1 is believed to involve with a number of catalytic steps. To investigate the effect of temperature in the product formation and on the different catalytic complexes of hGBP1, we carried out temperature dependent GTPase assays, mutational analysis, chemical and thermal denaturation studies. The Arrhenius plot for both GDP and GMP interestingly showed nonlinear behaviour, suggesting that the product formation from the GTP-bound enzyme complex is associated with at least more than one step. The negative activation energy for GDP formation and GTPase assay with external GDP together indicate that GDP formation occurs through the reversible dissociation of GDP-bound enzyme dimer to monomer, which further reversibly dissociates to give the product. Denaturation studies of different catalytic complexes show that unlike other complexes the free energy of GDP-bound hGBP1 decreases significantly at lower temperature. GDP formation is found to be dependent on the free energy of the GDP-bound enzyme complex. The decrease in the free energy of this complex at low temperature compared to at high is the reason for higher GDP formation at low temperature. Thermal denaturation studies also suggest that the difference in the free energy of the GTP-bound enzyme dimer compared to its monomer plays a crucial role in the product formation; higher stability favours GMP but lower favours GDP. Thus, this study provides the first thermodynamic insight into the effect of temperature in the product formation of hGBP1. PMID:22859948

Andreev bound states. Some quasiclassical reflections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Y., E-mail: yiriolin@illinois.edu; Leggett, A. J.

2014-12-15

We discuss a very simple and essentially exactly solvable model problem which illustrates some nice features of Andreev bound states, namely, the trapping of a single Bogoliubov quasiparticle in a neutral s-wave BCS superfluid by a wide and shallow Zeeman trap. In the quasiclassical limit, the ground state is a doublet with a splitting which is proportional to the exponentially small amplitude for “normal” reflection by the edges of the trap. We comment briefly on a prima facie paradox concerning the continuity equation and conjecture a resolution to it.

Andreev bound states. Some quasiclassical reflections

NASA Astrophysics Data System (ADS)

Lin, Y.; Leggett, A. J.

2014-12-01

We discuss a very simple and essentially exactly solvable model problem which illustrates some nice features of Andreev bound states, namely, the trapping of a single Bogoliubov quasiparticle in a neutral s-wave BCS superfluid by a wide and shallow Zeeman trap. In the quasiclassical limit, the ground state is a doublet with a splitting which is proportional to the exponentially small amplitude for "normal" reflection by the edges of the trap. We comment briefly on a prima facie paradox concerning the continuity equation and conjecture a resolution to it.

Impurity bound states in fully gapped d-wave superconductors with subdominant order parameters

PubMed Central

Mashkoori, Mahdi; Björnson, Kristofer; Black-Schaffer, Annica M.

2017-01-01

Impurities in superconductors and their induced bound states are important both for engineering novel states such as Majorana zero-energy modes and for probing bulk properties of the superconducting state. The high-temperature cuprates offer a clear advantage in a much larger superconducting order parameter, but the nodal energy spectrum of a pure d-wave superconductor only allows virtual bound states. Fully gapped d-wave superconducting states have, however, been proposed in several cuprate systems thanks to subdominant order parameters producing d + is- or d + id′-wave superconducting states. Here we study both magnetic and potential impurities in these fully gapped d-wave superconductors. Using analytical T-matrix and complementary numerical tight-binding lattice calculations, we show that magnetic and potential impurities behave fundamentally different in d + is- and d + id′-wave superconductors. In a d + is-wave superconductor, there are no bound states for potential impurities, while a magnetic impurity produces one pair of bound states, with a zero-energy level crossing at a finite scattering strength. On the other hand, a d + id′-wave symmetry always gives rise to two pairs of bound states and only produce a reachable zero-energy level crossing if the normal state has a strong particle-hole asymmetry. PMID:28281570

Interconversion of two GDP-bound conformations and their selection in an Arf-family small G protein.

PubMed

Okamura, Hideyasu; Nishikiori, Masaki; Xiang, Hongyu; Ishikawa, Masayuki; Katoh, Etsuko

2011-07-13

ADP-ribosylation factor (Arf) and other Arf-family small G proteins participate in many cellular functions via their characteristic GTP/GDP conformational cycles, during which a nucleotide(∗)Mg(2+)-binding site communicates with a remote N-terminal helix. However, the conformational interplay between the nucleotides, the helix, the protein core, and Mg(2+) has not been fully delineated. Herein, we report a study of the dynamics of an Arf-family protein, Arl8, under various conditions by means of NMR relaxation spectroscopy. The data indicated that, when GDP is bound, the protein core, which does not include the N-terminal helix, reversibly transition between an Arf-family GDP form and another conformation that resembles the Arf-family GTP form. Additionally, we found that the N-terminal helix and Mg(2+), respectively, stabilize the aforementioned former and latter conformations in a population-shift manner. Given the dynamics of the conformational changes, we can describe the Arl8 GTP/GDP cycle in terms of an energy diagram. Copyright © 2011 Elsevier Ltd. All rights reserved.

Two-polariton bound states in the Jaynes-Cummings-Hubbard model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, Max T. C.; Law, C. K.

2011-05-15

We examine the eigenstates of the one-dimensional Jaynes-Cummings-Hubbard model in the two-excitation subspace. We discover that two-excitation bound states emerge when the ratio of vacuum Rabi frequency to the tunneling rate between cavities exceeds a critical value. We determine the critical value as a function of the quasimomentum quantum number, and indicate that the bound states carry a strong correlation in which the two polaritons appear to be spatially confined together.

Mitochondrial rhodanese: membrane-bound and complexed activity.

PubMed

Ogata, K; Volini, M

1990-05-15

We have proposed that phosphorylated and dephosphorylated forms of the mitochondrial sulfurtransferase, rhodanese, function as converter enzymes that interact with membrane-bound iron-sulfur centers of the electron transport chain to modulate the rate of mitochondrial respiration (Ogata, K., Dai, X., and Volini, M. (1989) J. Biol. Chem. 204, 2718-2725). In the present studies, we have explored some structural aspects of the mitochondrial rhodanese system. By sequential extraction of lysed mitochondria with phosphate buffer and phosphate buffer containing 20 mM cholate, we have shown that 30% of the rhodanese activity of bovine liver is membrane-bound. Resolution of cholate extracts on Sephadex G-100 indicates that part of the bound rhodanese is complexed with other mitochondrial proteins. Tests with the complex show that it forms iron-sulfur centers when incubated with the rhodanese sulfur-donor substrate thiosulfate, iron ions, and a reducing agent. Experiments on the rhodanese activity of rat liver mitochondria give similar results. Taken together, the findings indicate that liver rhodanese is in part bound to the mitochondrial membrane as a component of a multiprotein complex that forms iron-sulfur centers. The findings are consistent with the role we propose for rhodanese in the modulation of mitochondrial respiratory activity.

Metastable Bound States of Two-Dimensional Magnetoexcitons in the Lowest Landau Levels Approximation

NASA Astrophysics Data System (ADS)

Moskalenko, S. A.; Khadzhi, P. I.; Podlesny, I. V.; Dumanov, E. V.; Liberman, M. A.; Zubac, I. A.

2017-12-01

The possible existence of the two-dimensional bimagnetoexcitons and metastable bound states formed by two magnetoexcitons with opposite in-plane wave vectors k and -k has been studied. Magnetoexcitons taking part in the formation of molecules look as two electric dipoles with the arms oriented in-plane perpendicular to the respective wave vectors and with the length of the arms d=k(l_0)^2, where l_0 is the magnetic length. Two antiparallel dipoles moving with equal, yet antiparallel, wave vectors have the possibility of moving with equal probability in any direction of the plane, which is determined by the trial wave function of relative motion φ_n(|k|), depending on modulus k. The magnetoexcitons are composed of electrons and holes situated on the lowest Landau levels with the cyclotron energies greater than the binding energy of the 2D Wannier-Mott exciton. The description has been made in Landau gauge. The spin states of two electrons have been chosen in the form of antisymmetric or symmetric combinations with parameter η=+/-1. The effective spins of two heavy holes have been combined in the same resultant spinor states as the spin of the electrons. Because the projections of the both spinor states with η=+/-1 are equal to zero, the influence of the Zeeman splitting effect vanishes. In the case of trial wave function, the maximal density of the magnetoexcitons in the momentum space is concentrated on the in-plane ring. In the approximation of the lowest Landau levels, when the influence of the excited Landau levels is neglected, stable bound states of bimagnetoexcitons do not exist for both spin orientations. Instead, in the case of α=0.5 and η=1, a deep metastable bound state with the activation barrier comparable with two magnetoexciton ionization potentials 2I_l has been revealed. In the case of η=-1 and α=3.4, only a shallow metastable bound state can appear.

Structural model of FeoB, the iron transporter from Pseudomonas aeruginosa, predicts a cysteine lined, GTP-gated pore

PubMed Central

Seyedmohammad, Saeed; Fuentealba, Natalia Alveal; Marriott, Robert A.J.; Goetze, Tom A.; Edwardson, J. Michael; Barrera, Nelson P.; Venter, Henrietta

2016-01-01

Iron is essential for the survival and virulence of pathogenic bacteria. The FeoB transporter allows the bacterial cell to acquire ferrous iron from its environment, making it an excellent drug target in intractable pathogens. The protein consists of an N-terminal GTP-binding domain and a C-terminal membrane domain. Despite the availability of X-ray crystal structures of the N-terminal domain, many aspects of the structure and function of FeoB remain unclear, such as the structure of the membrane domain, the oligomeric state of the protein, the molecular mechanism of iron transport, and how this is coupled to GTP hydrolysis at the N-terminal domain. In the present study, we describe the first homology model of FeoB. Due to the lack of sequence homology between FeoB and other transporters, the structures of four different proteins were used as templates to generate the homology model of full-length FeoB, which predicts a trimeric structure. We confirmed this trimeric structure by both blue-native-PAGE (BN-PAGE) and AFM. According to our model, the membrane domain of the trimeric protein forms a central pore lined by highly conserved cysteine residues. This pore aligns with a central pore in the N-terminal GTPase domain (G-domain) lined by aspartate residues. Biochemical analysis of FeoB from Pseudomonas aeruginosa further reveals a putative iron sensor domain that could connect GTP binding/hydrolysis to the opening of the pore. These results indicate that FeoB might not act as a transporter, but rather as a GTP-gated channel. PMID:26934982

Ethylene Rapidly Up-Regulates the Activities of Both Monomeric GTP-Binding Proteins and Protein Kinase(s) in Epicotyls of Pea1

PubMed Central

Moshkov, Igor E.; Novikova, Galina V.; Mur, Luis A.J.; Smith, Aileen R.; Hall, Michael A.

2003-01-01

It is demonstrated that, in etiolated pea (Pisum sativum) epicotyls, ethylene affects the activation of both monomeric GTP-binding proteins (monomeric G-proteins) and protein kinases. For monomeric G-proteins, the effect may be a rapid (2 min) and bimodal up-regulation, a transiently unimodal activation, or a transient down-regulation. Pretreatment with 1-methylcyclopropene abolishes the response to ethylene overall. Immunoprecipitation studies indicate that some of the monomeric G-proteins affected may be of the Rab class. Protein kinase activity is rapidly up-regulated by ethylene, the effect is inhibited by 1-methylcyclopropene, and the activation is bimodal. Immunoprecipitation indicates that the kinase(s) are of the MAP kinase ERK1 group. It is proposed that the data support the hypothesis that a transduction chain exists that is separate and antagonistic to that currently revealed by studies on Arabidopsis mutants. PMID:12692330

S-matrix method for the numerical determination of bound states.

NASA Technical Reports Server (NTRS)

Bhatia, A. K.; Madan, R. N.

1973-01-01

A rapid numerical technique for the determination of bound states of a partial-wave-projected Schroedinger equation is presented. First, one needs to integrate the equation only outwards as in the scattering case, and second, the number of trials necessary to determine the eigenenergy and the corresponding eigenfunction is considerably less than in the usual method. As a nontrivial example of the technique, bound states are calculated in the exchange approximation for the e-/He+ system and l equals 1 partial wave.

What makes Ras an efficient molecular switch: a computational, biophysical, and structural study of Ras-GDP interactions with mutants of Raf.

PubMed

Filchtinski, Daniel; Sharabi, Oz; Rüppel, Alma; Vetter, Ingrid R; Herrmann, Christian; Shifman, Julia M

2010-06-11

Ras is a small GTP-binding protein that is an essential molecular switch for a wide variety of signaling pathways including the control of cell proliferation, cell cycle progression and apoptosis. In the GTP-bound state, Ras can interact with its effectors, triggering various signaling cascades in the cell. In the GDP-bound state, Ras looses its ability to bind to known effectors. The interaction of the GTP-bound Ras (Ras(GTP)) with its effectors has been studied intensively. However, very little is known about the much weaker interaction between the GDP-bound Ras (Ras(GDP)) and Ras effectors. We investigated the factors underlying the nucleotide-dependent differences in Ras interactions with one of its effectors, Raf kinase. Using computational protein design, we generated mutants of the Ras-binding domain of Raf kinase (Raf) that stabilize the complex with Ras(GDP). Most of our designed mutations narrow the gap between the affinity of Raf for Ras(GTP) and Ras(GDP), producing the desired shift in binding specificity towards Ras(GDP). A combination of our best designed mutation, N71R, with another mutation, A85K, yielded a Raf mutant with a 100-fold improvement in affinity towards Ras(GDP). The Raf A85K and Raf N71R/A85K mutants were used to obtain the first high-resolution structures of Ras(GDP) bound to its effector. Surprisingly, these structures reveal that the loop on Ras previously termed the switch I region in the Ras(GDP).Raf mutant complex is found in a conformation similar to that of Ras(GTP) and not Ras(GDP). Moreover, the structures indicate an increased mobility of the switch I region. This greater flexibility compared to the same loop in Ras(GTP) is likely to explain the natural low affinity of Raf and other Ras effectors to Ras(GDP). Our findings demonstrate that an accurate balance between a rigid, high-affinity conformation and conformational flexibility is required to create an efficient and stringent molecular switch. Copyright 2010 Elsevier Ltd

Directional detection of dark matter in universal bound states

DOE PAGES

Laha, Ranjan

2015-10-06

It has been suggested that several small-scale structure anomalies in Λ CDM cosmology can be solved by strong self-interaction between dark matter particles. It was shown in Ref. [1] that the presence of a near threshold S-wave resonance can make the scattering cross section at nonrelativistic speeds come close to saturating the unitarity bound. This can result in the formation of a stable bound state of two asymmetric dark matter particles (which we call darkonium). Ref. [2] studied the nuclear recoil energy spectrum in dark matter direct detection experiments due to this incident bound state. Here we study the angularmore » recoil spectrum, and show that it is uniquely determined up to normalization by the S-wave scattering length. Furthermore, observing this angular recoil spectrum in a dark matter directional detection experiment will uniquely determine many of the low-energy properties of dark matter independent of the underlying dark matter microphysics.« less

Resolving the Spatial Structures of Bound Hole States in Black Phosphorus.

PubMed

Qiu, Zhizhan; Fang, Hanyan; Carvalho, Alexandra; Rodin, A S; Liu, Yanpeng; Tan, Sherman J R; Telychko, Mykola; Lv, Pin; Su, Jie; Wang, Yewu; Castro Neto, A H; Lu, Jiong

2017-11-08

Understanding the local electronic properties of individual defects and dopants in black phosphorus (BP) is of great importance for both fundamental research and technological applications. Here, we employ low-temperature scanning tunnelling microscope (LT-STM) to probe the local electronic structures of single acceptors in BP. We demonstrate that the charge state of individual acceptors can be reversibly switched by controlling the tip-induced band bending. In addition, acceptor-related resonance features in the tunnelling spectra can be attributed to the formation of Rydberg-like bound hole states. The spatial mapping of the quantum bound states shows two distinct shapes evolving from an extended ellipse shape for the 1s ground state to a dumbbell shape for the 2p x excited state. The wave functions of bound hole states can be well-described using the hydrogen-like model with anisotropic effective mass, corroborated by our theoretical calculations. Our findings not only provide new insight into the many-body interactions around single dopants in this anisotropic two-dimensional material but also pave the way to the design of novel quantum devices.

Calculations of binding affinity between C8-substituted GTP analogs and the bacterial cell-division protein FtsZ

PubMed Central

Hritz, Jozef; Läppchen, Tilman

2010-01-01

The FtsZ protein is a self-polymerizing GTPase that plays a central role in bacterial cell division. Several C8-substituted GTP analogs are known to inhibit the polymerization of FtsZ by competing for the same binding site as its endogenous activating ligand GTP. Free energy calculations of the relative binding affinities to FtsZ for a set of five C8-substituted GTP analogs were performed. The calculated values agree well with the available experimental data, and the main contribution to the free energy differences is determined to be the conformational restriction of the ligands. The dihedral angle distributions around the glycosidic bond of these compounds in water are known to vary considerably depending on the physicochemical properties of the substituent at C8. However, within the FtsZ protein, this substitution has a negligible influence on the dihedral angle distributions, which fall within the narrow range of −140° to −90° for all investigated compounds. The corresponding ensemble average of the coupling constants 3J(C4,H1′) is calculated to be 2.95 ± 0.1 Hz. The contribution of the conformational selection of the GTP analogs upon binding was quantified from the corresponding populations. The obtained restraining free energy values follow the same trend as the relative binding affinities to FtsZ, indicating their dominant contribution. PMID:20559630

GTP requirement for inositol-1,4,5-trisphosphate-induced Ca2+ release from sarcoplasmic reticulum in smooth muscle.

PubMed

Saida, K; van Breemen, C

1987-05-14

We have examined inositol-1,4,5-trisphosphate (IP3)-induced Ca2+ release from the sarcoplasmic reticulum (SR) in the skinned vascular smooth muscle. The amount of Ca2+ in the SR was estimated indirectly by caffeine-induced contraction of the skinned preparation. The Ca2+ release from the SR by IP3 required GTP. A non-hydrolyzable analogue of GTP, guanosine 5'-(beta gamma-imido) triphosphate (GppNHp) could substitute for GTP in the IP3-induced Ca2+ release. These results suggest an involvement of GTP-binding protein in the mechanism of Ca2+ release from the SR by IP3 in smooth muscle.

IκB Kinase γ/Nuclear Factor-κB-Essential Modulator (IKKγ/NEMO) Facilitates RhoA GTPase Activation, which, in Turn, Activates Rho-associated Kinase (ROCK) to Phosphorylate IKKβ in Response to Transforming Growth Factor (TGF)-β1*

PubMed Central

Kim, Hee-Jun; Kim, Jae-Gyu; Moon, Mi-Young; Park, Seol-Hye; Park, Jae-Bong

2014-01-01

Transforming growth factor (TGF)-β1 plays several roles in a variety of cellular functions. TGF-β1 transmits its signal through Smad transcription factor-dependent and -independent pathways. It was reported that TGF-β1 activates NF-κB and RhoA, and RhoA activates NF-κB in several kinds of cells in a Smad-independent pathway. However, the activation molecular mechanism of NF-κB by RhoA upon TGF-β1 has not been clearly elucidated. We observed that RhoA-GTP level was increased by TGF-β1 in RAW264.7 cells. RhoA-GDP and RhoGDI were bound to N- and C-terminal domains of IKKγ, respectively. Purified IKKγ facilitated GTP binding to RhoA complexed with RhoGDI. Furthermore, Dbs, a guanine nucletotide exchange factor of RhoA much more enhanced GTP binding to RhoA complexed with RhoGDI in the presence of IKKγ. Indeed, si-IKKγ abolished RhoA activation in response to TGF-β1 in cells. However, TGF-β1 stimulated the release of RhoA-GTP from IKKγ and Rho-associated kinase (ROCK), an active RhoA effector protein, directly phosphorylated IKKβ in vitro, whereas TGF-β1-activated kinase 1 activated RhoA upon TGF-β1 stimulation. Taken together, our data indicate that IKKγ facilitates RhoA activation via a guanine nucletotide exchange factor, which in turn activates ROCK to phosphorylate IKKβ, leading to NF-κB activation that induced the chemokine expression and cell migration upon TGF-β1. PMID:24240172

Magnetoconductance signatures of chiral domain-wall bound states in magnetic topological insulators

NASA Astrophysics Data System (ADS)

Tiwari, Kunal L.; Coish, W. A.; Pereg-Barnea, T.

2017-12-01

Recent magnetoconductance measurements performed on magnetic topological insulator candidates have revealed butterfly-shaped hysteresis. This hysteresis has been attributed to the formation of gapless chiral domain-wall bound states during a magnetic-field sweep. We treat this phenomenon theoretically, providing a link between microscopic magnetization dynamics and butterfly hysteresis in magnetoconductance. Further, we illustrate how a spatially resolved conductance measurement can probe the most striking feature of the domain-wall bound states: their chirality. This work establishes a regime where a definitive link between butterfly hysteresis in longitudinal magneto-conductance and domain-wall bound states can be made. This analysis provides an important tool for the identification of magnetic topological insulators.

Tunneling spectroscopy of quasiparticle bound states in a spinful Josephson junction.

PubMed

Chang, W; Manucharyan, V E; Jespersen, T S; Nygård, J; Marcus, C M

2013-05-24

The spectrum of a segment of InAs nanowire, confined between two superconducting leads, was measured as function of gate voltage and superconducting phase difference using a third normal-metal tunnel probe. Subgap resonances for odd electron occupancy-interpreted as bound states involving a confined electron and a quasiparticle from the superconducting leads, reminiscent of Yu-Shiba-Rusinov states-evolve into Kondo-related resonances at higher magnetic fields. An additional zero-bias peak of unknown origin is observed to coexist with the quasiparticle bound states.

Exotic lepton searches via bound state production at the LHC

NASA Astrophysics Data System (ADS)

Barrie, Neil D.; Kobakhidze, Archil; Liang, Shelley; Talia, Matthew; Wu, Lei

2018-06-01

Heavy long-lived multi-charged leptons (MCLs) are predicted by various new physics models. These hypothetical MCLs can form bound states, due to their high electric charges and long life times. In this work, we propose a novel strategy of searching for MCLs through their bound state productions and decays. By utilising LHC-8 TeV data in searching for resonances in the diphoton channel, we exclude the masses of isospin singlet heavy leptons with electric charge | q | ≥ 6 (in units of electron charge) lower than ∼1.2 TeV, which are much stronger than the corresponding 8 TeV LHC bounds from analysing the high ionisation and the long time-of-flight of MCLs. By utilising the current 13 TeV LHC diphoton channel measurements the bound can further exclude MCL masses up to ∼1.6 TeV for | q | ≥ 6. Also, we demonstrate that the conventional LHC limits from searching for MCLs produced via Drell-Yan processes can be enhanced by including the contribution of photon fusion processes.

Emergent gauge field for a chiral bound state on curved surface

NASA Astrophysics Data System (ADS)

Shi, Zhe-Yu; Zhai, Hui

2017-09-01

Emergent physics is one of the most important concepts in modern physics, and one of the most intriguing examples is the emergent gauge field. Here we show that a gauge field emerges for a chiral bound state formed by two attractively interacting particles on a curved surface. We demonstrate explicitly that the center-of-mass wave function of such a deeply bound state is monopole harmonic instead of spherical harmonic, which means that the bound state experiences a magnetic monopole at the center of the sphere. This emergent gauge field is due to the coupling between the center-of-mass and the relative motion on a curved surface, and our results can be generalized to an arbitrary curved surface. This result establishes an intriguing connection between the space curvature and gauge field, and paves an alternative way to engineer a topological state with space curvature, and may be observed in a cold atom system.

Understanding the nucleon as a Borromean bound-state

DOE PAGES

Segovia, Jorge; Roberts, Craig D.; Schmidt, Sebastian M.

2015-08-20

Analyses of the three valence-quark bound-state problem in relativistic quantum field theory predict that the nucleon may be understood primarily as a Borromean bound-state, in which binding arises mainly from two separate effects. One originates in non-Abelian facets of QCD that are expressed in the strong running coupling and generate confined but strongly-correlated colourantitriplet diquark clusters in both the scalar-isoscalar and pseudovector-isotriplet channels. That attraction is magnified by quark exchange associated with diquark breakup and reformation. Diquark clustering is driven by the same mechanism which dynamically breaks chiral symmetry in the Standard Model. It has numerous observable consequences, the completemore » elucidation of which requires a framework that also simultaneously expresses the running of the coupling and masses in the strong interaction. Moreover, planned experiments are capable of validating this picture.« less

ARF1·GTP, Tyrosine-based Signals, and Phosphatidylinositol 4,5-Bisphosphate Constitute a Minimal Machinery to Recruit the AP-1 Clathrin Adaptor to Membranes

PubMed Central

Crottet, Pascal; Meyer, Daniel M.; Rohrer, Jack; Spiess, Martin

2002-01-01

At the trans-Golgi network, clathrin coats containing AP-1 adaptor complexes are formed in an ARF1-dependent manner, generating vesicles transporting cargo proteins to endosomes. The mechanism of site-specific targeting of AP-1 and the role of cargo are poorly understood. We have developed an in vitro assay to study the recruitment of purified AP-1 adaptors to chemically defined liposomes presenting peptides corresponding to tyrosine-based sorting motifs. AP-1 recruitment was found to be dependent on myristoylated ARF1, GTP or nonhydrolyzable GTP-analogs, tyrosine signals, and small amounts of phosphoinositides, most prominently phosphatidylinositol 4,5-bisphosphate, in the absence of any additional cytosolic or membrane bound proteins. AP-1 from cytosol could be recruited to a tyrosine signal independently of the lipid composition, but the rate of recruitment was increased by phosphatidylinositol 4,5-bisphosphate. The results thus indicate that cargo proteins are involved in coat recruitment and that the local lipid composition contributes to specifying the site of vesicle formation. PMID:12388765

Topological bound states of a quantum walk with cold atoms

NASA Astrophysics Data System (ADS)

Mugel, Samuel; Celi, Alessio; Massignan, Pietro; Asbóth, János K.; Lewenstein, Maciej; Lobo, Carlos

2016-08-01

We suggest a method for engineering a quantum walk, with cold atoms as walkers, which presents topologically nontrivial properties. We derive the phase diagram, and show that we are able to produce a boundary between topologically distinct phases using the finite beam width of the applied lasers. A topologically protected bound state can then be observed, which is pinned to the interface and is robust to perturbations. We show that it is possible to identify this bound state by averaging over spin sensitive measures of the atom's position, based on the spin distribution that these states display. Interestingly, there exists a parameter regime in which our system maps on to the Creutz ladder.

Elevated small GTPase activation influences the cell proliferation signaling control in Niemann-Pick type C fibroblasts.

PubMed

Corey, Deborah A; Kelley, Thomas J

2007-07-01

Niemann-Pick type C (NPC) disease is characterized at the cellular level by the intracellular accumulation of free cholesterol. We have previously identified a similar phenotype in cystic fibrosis (CF) cell models that results in the activation of the small GTPase RhoA. The hypothesis of this study was that NPC cells would also exhibit an increase in small GTPase activation. An examination of the active, GTP-bound form of GTPases revealed a basal increase in the content of the active-form Ras and RhoA small GTPases in NPC fibroblasts compared to wt controls. To assess whether this increase in GTP-bound Ras and RhoA manifests a functional outcome, the expression of the proliferation control proteins p21/waf1 and cyclin D were examined. Consistent with increased GTPase signaling, p21/waf1 expression is reduced and cyclin D expression is elevated in NPC fibroblasts. Interestingly, cell growth rate is not altered in NPC fibroblasts compared to wt cells. However, NPC sensitivity to statin treatment is reversed by addition of the isoprenoid geranylgeranyl pyrophosphate (GGPP), a modifier of RhoA. It is concluded that Ras and RhoA basal activation is elevated in NPC fibroblasts and has an impact on cell survival pathways.

The engine of microtubule dynamics comes into focus.

PubMed

Mitchison, T J

2014-05-22

In this issue, Alushin et al. report high-resolution structures of three states of the microtubule lattice: GTP-bound, which is stable to depolymerization; unstable GDP-bound; and stable Taxol and GDP-bound. By comparing these structures at near-atomic resolution, they are able to propose a detailed model for how GTP hydrolysis destabilizes the microtubule and thus powers dynamic instability and chromosome movement. Destabilization of cytoskeleton filaments by nucleotide hydrolysis is an important general principle in cell dynamics, and this work represents a major step forward on a problem with a long history. Copyright © 2014 Elsevier Inc. All rights reserved.

Majorana bound states from exceptional points in non-topological superconductors

PubMed Central

San-Jose, Pablo; Cayao, Jorge; Prada, Elsa; Aguado, Ramón

2016-01-01

Recent experimental efforts towards the detection of Majorana bound states have focused on creating the conditions for topological superconductivity. Here we demonstrate an alternative route, which achieves fully localised zero-energy Majorana bound states when a topologically trivial superconductor is strongly coupled to a helical normal region. Such a junction can be experimentally realised by e.g. proximitizing a finite section of a nanowire with spin-orbit coupling, and combining electrostatic depletion and a Zeeman field to drive the non-proximitized (normal) portion into a helical phase. Majorana zero modes emerge in such an open system without fine-tuning as a result of charge-conjugation symmetry, and can be ultimately linked to the existence of ‘exceptional points’ (EPs) in parameter space, where two quasibound Andreev levels bifurcate into two quasibound Majorana zero modes. After the EP, one of the latter becomes non-decaying as the junction approaches perfect Andreev reflection, thus resulting in a Majorana dark state (MDS) localised at the NS junction. We show that MDSs exhibit the full range of properties associated to conventional closed-system Majorana bound states (zero-energy, self-conjugation, 4π-Josephson effect and non-Abelian braiding statistics), while not requiring topological superconductivity. PMID:26865011

ADP-ribosylation by cholera toxin: functional analysis of a cellular system that stimulates the enzymic activity of cholera toxin fragment A/sub 1/

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gill, D.M.; Coburn, J.

1987-10-06

The authors have clarified relationships between cholera toxin, cholera toxin substrates, a membrane protein S that is required for toxin activity, and a soluble protein CF that is needed for the function of S. The toxin has little intrinsic ability to catalyze ADP-ribosylations unless it encounters the active form of the S protein, which is S liganded to GTP or to a GTP analogue. In the presence of CF, S x GTP forms readily, though reversibly, but a more permanent active species, S-guanosine 5'-O-(3-thiotriphosphate) (S x GTP..gamma..S), forms over a period of 10-15 min at 37/sup 0/C. Both guanosine 5'-O-(2-thiodiphosphate)more » and GTP block this quasi-permanent activation. Some S x GTP..gamma..S forms in membranes that are exposed to CF alone and then to GTP..gamma..S, with a wash in between, and it is possible that CF facilitates a G nucleotide exchange. S x GTP..gamma..S dissolved by nonionic detergents persists in solution and can be used to support the ADP-ribosylation of nucleotide-free substrates. In this circumstance, added guanyl nucleotides have no further effect. This active form of S is unstable, especially when heated, but the thermal inactivation above 45/sup 0/C is decreased by GTP..gamma..S. Active S is required equally for the ADP-ribosylation of all of cholera toxin's protein substrates, regardless of whether they bind GTP or not. They suggest that active S interacts directly with the enzymic A/sub 1/ fragments of cholera toxin and not with any toxin substrate. The activation and activity of S are independent of the state, or even the presence, of adenylate cyclase and seem to be involved with the cyclase system only via cholera toxin. S is apparently not related by function to certain other GTP binding proteins, including p21/sup ras/, and appears to be a new GTP binding protein whose physiologic role remains to be identified.« less

Generation of bound states of pulses in a SESAM mode-locked Cr:ZnSe laser

NASA Astrophysics Data System (ADS)

Bu, Xiangbao; Shi, Yuhang; Xu, Jia; Li, Huijuan; Wang, Pu

2018-06-01

We report on the generation of bound states of pulses in a SESAM mode-locked Cr:ZnSe laser around 2415 nm. A thulium-doped double-clad fiber laser at 1908 nm was used as the pump source. Bound states with various pulse separations at different dispersion regimes were obtained. Especially, in the anomalous dispersion regime, vibrating bound state of solitons exhibiting an evolving phase was obtained.

Finite-Momentum Dimer Bound State in Spin-Orbit Coupled Fermi Gas

NASA Astrophysics Data System (ADS)

Dong, Lin; Jiang, Lei; Hu, Hui; Pu, Han

2013-03-01

We investigate the two-body properties of a spin-1/2 Fermi gas subject to a spin-orbit coupling induced by laser fields. When attractive s-wave interaction between unlike spins is present, the system may form a dimer bound state. Surprisingly, under proper conditions, the bound state obtains finite center-of-mass momentum, whereas under the same condition but in the absence of the two-body interaction, the system has zero total momentum. This unusual result can be regarded as a consequence of the broken Galilean invariance by the spin-orbit coupling. Such a finite-momentum bound state will have profound effects on the many-body properties of the system. HP is supported by the NSF, the Welch Foundation (Grant No. C-1669), and DARPA. HH is supported by the ARC Discovery Projects (Grant No. DP0984522) and the National Basic Research Program of China (NFRP-China, Grant No. 2011CB921502).

Binding of the 3' terminus of tRNA to 23S rRNA in the ribosomal exit site actively promotes translocation.

PubMed Central

Lill, R; Robertson, J M; Wintermeyer, W

1989-01-01

A key event in ribosomal protein synthesis is the translocation of deacylated tRNA, peptidyl tRNA and mRNA, which is catalyzed by elongation factor G (EF-G) and requires GTP. To address the molecular mechanism of the reaction we have studied the functional role of a tRNA exit site (E site) for tRNA release during translocation. We show that modifications of the 3' end of tRNAPhe, which considerably decrease the affinity of E-site binding, lower the translocation rate up to 40-fold. Furthermore, 3'-end modifications lower or abolish the stimulation by P site-bound tRNA of the GTPase activity of EF-G on the ribosome. The results suggest that a hydrogen-bonding interaction of the 3'-terminal adenine of the leaving tRNA in the E site, most likely base-pairing with 23S rRNA, is essential for the translocation reaction. Furthermore, this interaction stimulates the GTP hydrolyzing activity of EF-G on the ribosome. We propose the following molecular model of translocation: after the binding of EF-G.GTP, the P site-bound tRNA, by a movement of the 3'-terminal single-stranded ACCA tail, establishes an interaction with 23S rRNA in the adjacent E site, thereby initiating the tRNA transfer from the P site to the E site and promoting GTP hydrolysis. The co-operative interaction between the E site and the EF-G binding site, which are distantly located on the 50S ribosomal subunit, is probably mediated by a conformational change of 23S rRNA. PMID:2583120

Extending Quantum Chemistry of Bound States to Electronic Resonances

NASA Astrophysics Data System (ADS)

Jagau, Thomas-C.; Bravaya, Ksenia B.; Krylov, Anna I.

2017-05-01

Electronic resonances are metastable states with finite lifetime embedded in the ionization or detachment continuum. They are ubiquitous in chemistry, physics, and biology. Resonances play a central role in processes as diverse as DNA radiolysis, plasmonic catalysis, and attosecond spectroscopy. This review describes novel equation-of-motion coupled-cluster (EOM-CC) methods designed to treat resonances and bound states on an equal footing. Built on complex-variable techniques such as complex scaling and complex absorbing potentials that allow resonances to be associated with a single eigenstate of the molecular Hamiltonian rather than several continuum eigenstates, these methods extend electronic-structure tools developed for bound states to electronic resonances. Selected examples emphasize the formal advantages as well as the numerical accuracy of EOM-CC in the treatment of electronic resonances. Connections to experimental observables such as spectra and cross sections, as well as practical aspects of implementing complex-valued approaches, are also discussed.

Reduced conservatism in stability robustness bounds by state transformation

NASA Technical Reports Server (NTRS)

Yedavalli, R. K.; Liang, Z.

1986-01-01

This note addresses the issue of 'conservatism' in the time domain stability robustness bounds obtained by the Liapunov approach. A state transformation is employed to improve the upper bounds on the linear time-varying perturbation of an asymptotically stable linear time-invariant system for robust stability. This improvement is due to the variance of the conservatism of the Liapunov approach with respect to the basis of the vector space in which the Liapunov function is constructed. Improved bounds are obtained, using a transformation, on elemental and vector norms of perturbations (i.e., structured perturbations) as well as on a matrix norm of perturbations (i.e., unstructured perturbations). For the case of a diagonal transformation, an algorithm is proposed to find the 'optimal' transformation. Several examples are presented to illustrate the proposed analysis.

Structure of Escherichia coli dGTP Triphosphohydrolase: A Hexameric Enzyme with DNA Effector Molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Deepa; Gawel, Damian; Itsko, Mark

The Escherichia coli dgt gene encodes a dGTP triphosphohydrolase whose detailed role still remains to be determined. Deletion of dgt creates a mutator phenotype, indicating that the dGTPase has a fidelity role, possibly by affecting the cellular dNTP pool. In the present paper, we have investigated the structure of the Dgt protein at 3.1-Å resolution. One of the obtained structures revealed a protein hexamer that contained two molecules of single-stranded DNA. The presence of DNA caused significant conformational changes in the enzyme, including in the catalytic site of the enzyme. Dgt preparations lacking DNA were able to bind single-stranded DNAmore » with high affinity (K d ~ 50 nM). DNA binding positively affected the activity of the enzyme: dGTPase activity displayed sigmoidal (cooperative) behavior without DNA but hyperbolic (Michaelis-Menten) kinetics in its presence, consistent with a specific lowering of the apparent K m for dGTP. A mutant Dgt enzyme was also created containing residue changes in the DNA binding cleft. This mutant enzyme, whereas still active, was incapable of DNA binding and could no longer be stimulated by addition of DNA. We also created an E. coli strain containing the mutant dgt gene on the chromosome replacing the wild-type gene. The mutant also displayed a mutator phenotype. Finally, our results provide insight into the allosteric regulation of the enzyme and support a physiologically important role of DNA binding.« less

Structure of Escherichia coli dGTP Triphosphohydrolase: A Hexameric Enzyme with DNA Effector Molecules

DOE PAGES

Singh, Deepa; Gawel, Damian; Itsko, Mark; ...

2015-02-18

The Escherichia coli dgt gene encodes a dGTP triphosphohydrolase whose detailed role still remains to be determined. Deletion of dgt creates a mutator phenotype, indicating that the dGTPase has a fidelity role, possibly by affecting the cellular dNTP pool. In the present paper, we have investigated the structure of the Dgt protein at 3.1-Å resolution. One of the obtained structures revealed a protein hexamer that contained two molecules of single-stranded DNA. The presence of DNA caused significant conformational changes in the enzyme, including in the catalytic site of the enzyme. Dgt preparations lacking DNA were able to bind single-stranded DNAmore » with high affinity (K d ~ 50 nM). DNA binding positively affected the activity of the enzyme: dGTPase activity displayed sigmoidal (cooperative) behavior without DNA but hyperbolic (Michaelis-Menten) kinetics in its presence, consistent with a specific lowering of the apparent K m for dGTP. A mutant Dgt enzyme was also created containing residue changes in the DNA binding cleft. This mutant enzyme, whereas still active, was incapable of DNA binding and could no longer be stimulated by addition of DNA. We also created an E. coli strain containing the mutant dgt gene on the chromosome replacing the wild-type gene. The mutant also displayed a mutator phenotype. Finally, our results provide insight into the allosteric regulation of the enzyme and support a physiologically important role of DNA binding.« less

Upper bounds on the error probabilities and asymptotic error exponents in quantum multiple state discrimination

NASA Astrophysics Data System (ADS)

Audenaert, Koenraad M. R.; Mosonyi, Milán

2014-10-01

We consider the multiple hypothesis testing problem for symmetric quantum state discrimination between r given states σ1, …, σr. By splitting up the overall test into multiple binary tests in various ways we obtain a number of upper bounds on the optimal error probability in terms of the binary error probabilities. These upper bounds allow us to deduce various bounds on the asymptotic error rate, for which it has been hypothesized that it is given by the multi-hypothesis quantum Chernoff bound (or Chernoff divergence) C(σ1, …, σr), as recently introduced by Nussbaum and Szkoła in analogy with Salikhov's classical multi-hypothesis Chernoff bound. This quantity is defined as the minimum of the pairwise binary Chernoff divergences min _{jstates the bound is actually achieved. It was known to be achieved, in particular, when the state pair that is closest together in Chernoff divergence is more than 6 times closer than the next closest pair. Our results improve on this in two ways. First, we show that the optimal asymptotic rate must lie between C/2 and C. Second, we show that the Chernoff bound is already achieved when the closest state pair is more than 2 times closer than the next closest pair. We also show that the Chernoff bound is achieved when at least r - 2 of the states are pure, improving on a previous result by Nussbaum and Szkoła. Finally, we indicate a number of potential pathways along which a proof (or disproof) may eventually be found that the multi-hypothesis quantum Chernoff bound is always achieved.

Switching of the positive feedback for RAS activation by a concerted function of SOS membrane association domains.

PubMed

Nakamura, Yuki; Hibino, Kayo; Yanagida, Toshio; Sako, Yasushi

2016-01-01

Son of sevenless (SOS) is a guanine nucleotide exchange factor that regulates cell behavior by activating the small GTPase RAS. Recent in vitro studies have suggested that an interaction between SOS and the GTP-bound active form of RAS generates a positive feedback loop that propagates RAS activation. However, it remains unclear how the multiple domains of SOS contribute to the regulation of the feedback loop in living cells. Here, we observed single molecules of SOS in living cells to analyze the kinetics and dynamics of SOS behavior. The results indicate that the histone fold and Grb2-binding domains of SOS concertedly produce an intermediate state of SOS on the cell surface. The fraction of the intermediated state was reduced in positive feedback mutants, suggesting that the feedback loop functions during the intermediate state. Translocation of RAF, recognizing the active form of RAS, to the cell surface was almost abolished in the positive feedback mutants. Thus, the concerted functions of multiple membrane-associating domains of SOS governed the positive feedback loop, which is crucial for cell fate decision regulated by RAS.

Systematic assignment of Feshbach resonances via an asymptotic bound state model

NASA Astrophysics Data System (ADS)

Goosen, Maikel; Kokkelmans, Servaas

2008-05-01

We present an Asymptotic Bound state Model (ABM), which is useful to predict Feshbach resonances. The model utilizes asymptotic properties of the interaction potentials to represent coupled molecular wavefunctions. The bound states of this system give rise to Feshbach resonances, localized at the magnetic fields of intersection of these bound states with the scattering threshold. This model was very successful to assign measured Feshbach resonances in an ultra cold mixture of ^6Li and ^40K atomsootnotetextE. Wille, F.M. Spiegelhalder, G. Kerner, D. Naik, A. Trenkwalder, G. Hendl, F. Schreck, R. Grimm, T.G. Tiecke, J.T.M. Walraven, S.J.J.M.F. Kokkelmans, E. Tiesinga, P.S. Julienne, arXiv:0711.2916. For this system, the accuracy of the determined scattering lengths is comparable to full coupled channels results. However, it was not possible to predict the width of the resonances. We discuss how an incorporation of threshold effects will improve the model, and we apply it to a mixture of ^87Rb and ^133Cs atoms, where recently Feshbach resonances have been measured.

Emergent low-energy bound states in the two-orbital Hubbard model

NASA Astrophysics Data System (ADS)

Núñez-Fernández, Y.; Kotliar, G.; Hallberg, K.

2018-03-01

A repulsive Coulomb interaction between electrons in different orbitals in correlated materials can give rise to bound quasiparticle states. We study the nonhybridized two-orbital Hubbard model with intra- (inter)orbital interaction U (U12) and different bandwidths using an improved dynamical mean-field theory numerical technique which leads to reliable spectra on the real energy axis directly at zero temperature. We find that a finite density of states at the Fermi energy in one band is correlated with the emergence of well-defined quasiparticle states at excited energies Δ =U -U12 in the other band. These excitations are interband holon-doublon bound states. At the symmetric point U =U12 , the quasiparticle peaks are located at the Fermi energy, leading to a simultaneous and continuous Mott transition settling a long-standing controversy.

Bounds on internal state variables in viscoplasticity

NASA Technical Reports Server (NTRS)

Freed, Alan D.

1993-01-01

A typical viscoplastic model will introduce up to three types of internal state variables in order to properly describe transient material behavior; they are as follows: the back stress, the yield stress, and the drag strength. Different models employ different combinations of these internal variables--their selection and description of evolution being largely dependent on application and material selection. Under steady-state conditions, the internal variables cease to evolve and therefore become related to the external variables (stress and temperature) through simple functional relationships. A physically motivated hypothesis is presented that links the kinetic equation of viscoplasticity with that of creep under steady-state conditions. From this hypothesis one determines how the internal variables relate to one another at steady state, but most importantly, one obtains bounds on the magnitudes of stress and back stress, and on the yield stress and drag strength.

The Structural Basis of Oncogenic Mutations G12, G13 and Q61 in Small GTPase K-Ras4B

NASA Astrophysics Data System (ADS)

Lu, Shaoyong; Jang, Hyunbum; Nussinov, Ruth; Zhang, Jian

2016-02-01

Ras mediates cell proliferation, survival and differentiation. Mutations in K-Ras4B are predominant at residues G12, G13 and Q61. Even though all impair GAP-assisted GTP → GDP hydrolysis, the mutation frequencies of K-Ras4B in human cancers vary. Here we aim to figure out their mechanisms and differential oncogenicity. In total, we performed 6.4 μs molecular dynamics simulations on the wild-type K-Ras4B (K-Ras4BWT-GTP/GDP) catalytic domain, the K-Ras4BWT-GTP-GAP complex, and the mutants (K-Ras4BG12C/G12D/G12V-GTP/GDP, K-Ras4BG13D-GTP/GDP, K-Ras4BQ61H-GTP/GDP) and their complexes with GAP. In addition, we simulated ‘exchanged’ nucleotide states. These comprehensive simulations reveal that in solution K-Ras4BWT-GTP exists in two, active and inactive, conformations. Oncogenic mutations differentially elicit an inactive-to-active conformational transition in K-Ras4B-GTP; in K-Ras4BG12C/G12D-GDP they expose the bound nucleotide which facilitates the GDP-to-GTP exchange. These mechanisms may help elucidate the differential mutational statistics in K-Ras4B-driven cancers. Exchanged nucleotide simulations reveal that the conformational transition is more accessible in the GTP-to-GDP than in the GDP-to-GTP exchange. Importantly, GAP not only donates its R789 arginine finger, but stabilizes the catalytically-competent conformation and pre-organizes catalytic residue Q61; mutations disturb the R789/Q61 organization, impairing GAP-mediated GTP hydrolysis. Together, our simulations help provide a mechanistic explanation of key mutational events in one of the most oncogenic proteins in cancer.

The hyperbolic step potential: Anti-bound states, SUSY partners and Wigner time delays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gadella, M.; Kuru, Ş.; Negro, J., E-mail: jnegro@fta.uva.es

We study the scattering produced by a one dimensional hyperbolic step potential, which is exactly solvable and shows an unusual interest because of its asymmetric character. The analytic continuation of the scattering matrix in the momentum representation has a branch cut and an infinite number of simple poles on the negative imaginary axis which are related with the so called anti-bound states. This model does not show resonances. Using the wave functions of the anti-bound states, we obtain supersymmetric (SUSY) partners which are the series of Rosen–Morse II potentials. We have computed the Wigner reflection and transmission time delays formore » the hyperbolic step and such SUSY partners. Our results show that the more bound states a partner Hamiltonian has the smaller is the time delay. We also have evaluated time delays for the hyperbolic step potential in the classical case and have obtained striking similitudes with the quantum case. - Highlights: • The scattering matrix of hyperbolic step potential is studied. • The scattering matrix has a branch cut and an infinite number of poles. • The poles are associated to anti-bound states. • Susy partners using antibound states are computed. • Wigner time delays for the hyperbolic step and partner potentials are compared.« less

On bound-states of the Gross Neveu model with massive fundamental fermions

NASA Astrophysics Data System (ADS)

Frishman, Yitzhak; Sonnenschein, Jacob

2018-01-01

In the search for QFT's that admit boundstates, we reinvestigate the two dimensional Gross-Neveu model, but with massive fermions. By computing the self-energy for the auxiliary boundstate field and the effective potential, we show that there are no bound states around the lowest minimum, but there is a meta-stable bound state around the other minimum, a local one. The latter decays by tunneling. We determine the dependence of its lifetime on the fermion mass and coupling constant.

Emergent low-energy bound states in the two-orbital Hubbard model

DOE PAGES

Nunez-Fernandez, Y.; Kotliar, G.; Hallberg, K.

2018-03-30

A repulsive Coulomb interaction between electrons in different orbitals in correlated materials can give rise to bound quasiparticle states. We study the nonhybridized two-orbital Hubbard model with intra- (inter)orbital interaction U (U 12) and different bandwidths using an improved dynamical mean-field theory numerical technique which leads to reliable spectra on the real energy axis directly at zero temperature. We find that a finite density of states at the Fermi energy in one band is correlated with the emergence of well-defined quasiparticle states at excited energies Δ = U - U 12 in the other band. These excitations are interband holon-doublonmore » bound states. At the symmetric point U = U 12, the quasiparticle peaks are located at the Fermi energy, leading to a simultaneous and continuous Mott transition settling a long-standing controversy.« less

Bounds on the entanglement entropy of droplet states in the XXZ spin chain

NASA Astrophysics Data System (ADS)

Beaud, V.; Warzel, S.

2018-01-01

We consider a class of one-dimensional quantum spin systems on the finite lattice Λ ⊂Z , related to the XXZ spin chain in its Ising phase. It includes in particular the so-called droplet Hamiltonian. The entanglement entropy of energetically low-lying states over a bipartition Λ = B ∪ Bc is investigated and proven to satisfy a logarithmic bound in terms of min{n, |B|, |Bc|}, where n denotes the maximal number of down spins in the considered state. Upon addition of any (positive) random potential, the bound becomes uniformly constant on average, thereby establishing an area law. The proof is based on spectral methods: a deterministic bound on the local (many-body integrated) density of states is derived from an energetically motivated Combes-Thomas estimate.

Integration of G protein α (Gα) signaling by the regulator of G protein signaling 14 (RGS14).

PubMed

Brown, Nicole E; Goswami, Devrishi; Branch, Mary Rose; Ramineni, Suneela; Ortlund, Eric A; Griffin, Patrick R; Hepler, John R

2015-04-03

RGS14 contains distinct binding sites for both active (GTP-bound) and inactive (GDP-bound) forms of Gα subunits. The N-terminal regulator of G protein signaling (RGS) domain binds active Gαi/o-GTP, whereas the C-terminal G protein regulatory (GPR) motif binds inactive Gαi1/3-GDP. The molecular basis for how RGS14 binds different activation states of Gα proteins to integrate G protein signaling is unknown. Here we explored the intramolecular communication between the GPR motif and the RGS domain upon G protein binding and examined whether RGS14 can functionally interact with two distinct forms of Gα subunits simultaneously. Using complementary cellular and biochemical approaches, we demonstrate that RGS14 forms a stable complex with inactive Gαi1-GDP at the plasma membrane and that free cytosolic RGS14 is recruited to the plasma membrane by activated Gαo-AlF4(-). Bioluminescence resonance energy transfer studies showed that RGS14 adopts different conformations in live cells when bound to Gα in different activation states. Hydrogen/deuterium exchange mass spectrometry revealed that RGS14 is a very dynamic protein that undergoes allosteric conformational changes when inactive Gαi1-GDP binds the GPR motif. Pure RGS14 forms a ternary complex with Gαo-AlF4(-) and an AlF4(-)-insensitive mutant (G42R) of Gαi1-GDP, as observed by size exclusion chromatography and differential hydrogen/deuterium exchange. Finally, a preformed RGS14·Gαi1-GDP complex exhibits full capacity to stimulate the GTPase activity of Gαo-GTP, demonstrating that RGS14 can functionally engage two distinct forms of Gα subunits simultaneously. Based on these findings, we propose a working model for how RGS14 integrates multiple G protein signals in host CA2 hippocampal neurons to modulate synaptic plasticity. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Bound states, scattering states, and resonant states in PT -symmetric open quantum systems

NASA Astrophysics Data System (ADS)

Garmon, Savannah; Gianfreda, Mariagiovanna; Hatano, Naomichi

2015-08-01

We study a simple open quantum system with a PT -symmetric defect potential as a prototype in order to illustrate a number of general features of PT -symmetric open quantum systems; however, the potential itself could be mimicked by a number of PT systems that have been experimentally studied quite recently. One key feature is the resonance in continuum (RIC), which appears in both the discrete spectrum and the scattering spectrum of such systems. The RIC wave function forms a standing wave extending throughout the spatial extent of the system and in this sense represents a resonance between the open environment associated with the leads of our model and the central PT -symmetric potential. We also illustrate that as one deforms the system parameters, the RIC may exit the continuum by splitting into a bound state and a virtual bound state at the band edge, a process which should be experimentally observable. We also study the exceptional points appearing in the discrete spectrum at which two eigenvalues coalesce; we categorize these as either EP2As, at which two real-valued solutions coalesce before becoming complex-valued, and EP2Bs, for which the two solutions are complex on either side of the exceptional point. The EP2As are associated with PT -symmetry breaking; we argue that these are more stable against parameter perturbation than the EP2Bs. We also study complex-valued solutions of the discrete spectrum for which the wave function is nevertheless spatially localized, something that is not allowed in traditional open quantum systems; we illustrate that these may form quasibound states in continuum under some circumstances. We also study the scattering properties of the system, including states that support invisible propagation and some general features of perfect transmission states. We finally use our model as a prototype for the construction of scattering states that satisfy PT -symmetric boundary conditions; while these states do not conserve the

Dynamic spin injection into a quantum well coupled to a spin-split bound state

NASA Astrophysics Data System (ADS)

Maslova, N. S.; Rozhansky, I. V.; Mantsevich, V. N.; Arseyev, P. I.; Averkiev, N. S.; Lähderanta, E.

2018-05-01

We present a theoretical analysis of dynamic spin injection due to spin-dependent tunneling between a quantum well (QW) and a bound state split in spin projection due to an exchange interaction or external magnetic field. We focus on the impact of Coulomb correlations at the bound state on spin polarization and sheet density kinetics of the charge carriers in the QW. The theoretical approach is based on kinetic equations for the electron occupation numbers taking into account high order correlation functions for the bound state electrons. It is shown that the on-site Coulomb repulsion leads to an enhanced dynamic spin polarization of the electrons in the QW and a delay in the carriers tunneling into the bound state. The interplay of these two effects leads to nontrivial dependence of the spin polarization degree, which can be probed experimentally using time-resolved photoluminescence experiments. It is demonstrated that the influence of the Coulomb interactions can be controlled by adjusting the relaxation rates. These findings open a new way of studying the Hubbard-like electron interactions experimentally.

Transfer Function Bounds for Partial-unit-memory Convolutional Codes Based on Reduced State Diagram

NASA Technical Reports Server (NTRS)

Lee, P. J.

1984-01-01

The performance of a coding system consisting of a convolutional encoder and a Viterbi decoder is analytically found by the well-known transfer function bounding technique. For the partial-unit-memory byte-oriented convolutional encoder with m sub 0 binary memory cells and (k sub 0 m sub 0) inputs, a state diagram of 2(K) (sub 0) was for the transfer function bound. A reduced state diagram of (2 (m sub 0) +1) is used for easy evaluation of transfer function bounds for partial-unit-memory codes.

Extrapolating bound state data of anions into the metastable domain

NASA Astrophysics Data System (ADS)

Feuerbacher, Sven; Sommerfeld, Thomas; Cederbaum, Lorenz S.

2004-10-01

Computing energies of electronically metastable resonance states is still a great challenge. Both scattering techniques and quantum chemistry based L2 methods are very time consuming. Here we investigate two more economical extrapolation methods. Extrapolating bound states energies into the metastable region using increased nuclear charges has been suggested almost 20 years ago. We critically evaluate this attractive technique employing our complex absorbing potential/Green's function method that allows us to follow a bound state into the continuum. Using the 2Πg resonance of N2- and the 2Πu resonance of CO2- as examples, we found that the extrapolation works suprisingly well. The second extrapolation method involves increasing of bond lengths until the sought resonance becomes stable. The keystone is to extrapolate the attachment energy and not the total energy of the system. This method has the great advantage that the whole potential energy curve is obtained with quite good accuracy by the extrapolation. Limitations of the two techniques are discussed.

Structure of the Branched-chain Amino Acid and GTP-sensing Global Regulator, CodY, from Bacillus subtilis.

PubMed

Levdikov, Vladimir M; Blagova, Elena; Young, Vicki L; Belitsky, Boris R; Lebedev, Andrey; Sonenshein, Abraham L; Wilkinson, Anthony J

2017-02-17

CodY is a branched-chain amino acid (BCAA) and GTP sensor and a global regulator of transcription in low G + C Gram-positive bacteria. It controls the expression of over 100 genes and operons, principally by repressing during growth genes whose products are required for adaptations to nutrient limitation. However, the mechanism by which BCAA binding regulates transcriptional changes is not clear. It is known that CodY consists of a GAF (c G MP-stimulated phosphodiesterases, a denylate cyclases, F hlA) domain that binds BCAAs and a winged helix-turn-helix (wHTH) domain that binds to DNA, but the way in which these domains interact and the structural basis of the BCAA dependence of this interaction are unknown. To gain new insights, we determined the crystal structure of unliganded CodY from Bacillus subtilis revealing a 10-turn α-helix linking otherwise discrete GAF and wHTH domains. The structure of CodY in complex with isoleucine revealed a reorganized GAF domain. In both complexes CodY was tetrameric. Size exclusion chromatography with multiangle laser light scattering (SEC-MALLS) experiments showed that CodY is a dimer at concentrations found in bacterial cells. Comparison of structures of dimers of unliganded CodY and CodY-Ile derived from the tetramers showed a splaying of the wHTH domains when Ile was bound; splaying is likely to account for the increased affinity of Ile-bound CodY for DNA. Electrophoretic mobility shift and SEC-MALLS analyses of CodY binding to 19-36-bp operator fragments are consistent with isoleucine-dependent binding of two CodY dimers per duplex. The implications of these observations for effector control of CodY activity are discussed. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Non-Abelian fermion parity interferometry of Majorana bound states in a Fermi sea

NASA Astrophysics Data System (ADS)

Dahan, Daniel; Tanhayi Ahari, Mostafa; Ortiz, Gerardo; Seradjeh, Babak; Grosfeld, Eytan

We study the quantum dynamics of Majorana and regular fermion bound states coupled to a one-dimensional lead. The dynamics following the quench in the coupling to the lead exhibits a series of dynamical revivals as the bound state propagates in the lead and reflects from the boundaries. We show that the nature of revivals for a single Majorana bound state depends uniquely on the presence of a resonant level in the lead. When two spatially separated Majorana modes are coupled to the lead, the revivals depend only on the phase difference between their host superconductors. Remarkably, the quench in this case effectively performs a fermion-parity interferometry between Majorana bound states, revealing their unique non-Abelian braiding. Using both analytical and numerical techniques, we find the pattern of fermion parity transfers following the quench, study its evolution in the presence of disorder and interactions, and thus, ascertain the fate of Majorana in a rough Fermi sea. Work supported in part by BSF Grant No. 2014345, ISF Grant Nos. 401/12 and 1626/16, EU Seventh Framework Programme (FP7/2007-2013) Grant No. 303742, NSF CAREER Grant DMR-1350663 and the College of Arts and Sciences at Indiana University.

A balance for dark matter bound states

NASA Astrophysics Data System (ADS)

Nozzoli, F.

2017-05-01

Massive particles with self interactions of the order of 0.2 barn/GeV are intriguing Dark Matter candidates from an astrophysical point of view. Current and past experiments for direct detection of massive Dark Matter particles are focusing to relatively low cross sections with ordinary matter, however they cannot rule out very large cross sections, σ/M > 0.01 barn/GeV, due to atmosphere and material shielding. Cosmology places a strong indirect limit for the presence of large interactions among Dark Matter and baryons in the Universe, however such a limit cannot rule out the existence of a small sub-dominant component of Dark Matter with non negligible interactions with ordinary matter in our galactic halo. Here, the possibility of the existence of bound states with ordinary matter, for a similar Dark Matter candidate with not negligible interactions, is considered. The existence of bound states, with binding energy larger than ∼ 1 meV, would offer the possibility to test in laboratory capture cross sections of the order of a barn (or larger). The signature of the detection for a mass increasing of cryogenic samples, due to the possible particle accumulation, would allow the investigation of these Dark Matter candidates with mass up to the GUT scale. A proof of concept for a possible detection set-up and the evaluation of some noise sources are described.

Ras activation by SOS: Allosteric regulation by altered fluctuation dynamics

PubMed Central

Iversen, Lars; Tu, Hsiung-Lin; Lin, Wan-Chen; Christensen, Sune M.; Abel, Steven M.; Iwig, Jeff; Wu, Hung-Jen; Gureasko, Jodi; Rhodes, Christopher; Petit, Rebecca S.; Hansen, Scott D.; Thill, Peter; Yu, Cheng-Han; Stamou, Dimitrios; Chakraborty, Arup K.; Kuriyan, John; Groves, Jay T.

2014-01-01

Activation of the small guanosine triphosphatase H-Ras by the exchange factor Son of Sevenless (SOS) is an important hub for signal transduction. Multiple layers of regulation, through protein and membrane interactions, govern activity of SOS. We characterized the specific activity of individual SOS molecules catalyzing nucleotide exchange in H-Ras. Single-molecule kinetic traces revealed that SOS samples a broad distribution of turnover rates through stochastic fluctuations between distinct, long-lived (more than 100 seconds), functional states. The expected allosteric activation of SOS by Ras–guanosine triphosphate (GTP) was conspicuously absent in the mean rate. However, fluctuations into highly active states were modulated by Ras-GTP. This reveals a mechanism in which functional output may be determined by the dynamical spectrum of rates sampled by a small number of enzymes, rather than the ensemble average. PMID:24994643

Synthetic inhibitors of bacterial cell division targeting the GTP-binding site of FtsZ.

PubMed

Ruiz-Avila, Laura B; Huecas, Sonia; Artola, Marta; Vergoñós, Albert; Ramírez-Aportela, Erney; Cercenado, Emilia; Barasoain, Isabel; Vázquez-Villa, Henar; Martín-Fontecha, Mar; Chacón, Pablo; López-Rodríguez, María L; Andreu, José M

2013-09-20

Cell division protein FtsZ is the organizer of the cytokinetic Z-ring in most bacteria and a target for new antibiotics. FtsZ assembles with GTP into filaments that hydrolyze the nucleotide at the association interface between monomers and then disassemble. We have replaced FtsZ's GTP with non-nucleotide synthetic inhibitors of bacterial division. We searched for these small molecules among compounds from the literature, from virtual screening (VS), and from our in-house synthetic library (UCM), employing a fluorescence anisotropy primary assay. From these screens we have identified the polyhydroxy aromatic compound UCM05 and its simplified analogue UCM44 that specifically bind to Bacillus subtilis FtsZ monomers with micromolar affinities and perturb normal assembly, as examined with light scattering, polymer sedimentation, and negative stain electron microscopy. On the other hand, these ligands induce the cooperative assembly of nucleotide-devoid archaeal FtsZ into distinct well-ordered polymers, different from GTP-induced filaments. These FtsZ inhibitors impair localization of FtsZ into the Z-ring and inhibit bacterial cell division. The chlorinated analogue UCM53 inhibits the growth of clinical isolates of antibiotic-resistant Staphylococcus aureus and Enterococcus faecalis. We suggest that these interfacial inhibitors recapitulate binding and some assembly-inducing effects of GTP but impair the correct structural dynamics of FtsZ filaments and thus inhibit bacterial division, possibly by binding to a small fraction of the FtsZ molecules in a bacterial cell, which opens a new approach to FtsZ-based antibacterial drug discovery.

Carbon-Ion Irradiation Suppresses Migration and Invasiveness of Human Pancreatic Carcinoma Cells MIAPaCa-2 via Rac1 and RhoA Degradation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujita, Mayumi; Imadome, Kaori; Shoji, Yoshimi

2015-09-01

Purpose: To investigate the mechanisms underlying the inhibition of cancer cell migration and invasion by carbon (C)-ion irradiation. Methods and Materials: Human pancreatic cancer cells MIAPaCa-2, AsPC-1, and BxPC-3 were treated by x-ray (4 Gy) or C-ion (0.5, 1, 2, or 4 Gy) irradiation, and their migration and invasion were assessed 2 days later. The levels of guanosine triphosphate (GTP)-bound Rac1 and RhoA were determined by the active GTPase pull-down assay with or without a proteasome inhibitor, and the binding of E3 ubiquitin ligase to GTP-bound Rac1 was examined by immunoprecipitation. Results: Carbon-ion irradiation reduced the levels of GTP-bound Rac1 and RhoA, 2more » major regulators of cell motility, in MIAPaCa-2 cells and GTP-bound Rac1 in AsPC-1 and BxPC-3 cells. Proteasome inhibition reversed the effect, indicating that C-ion irradiation induced Rac1 and RhoA degradation via the ubiquitin (Ub)-proteasome pathway. E3 Ub ligase X-linked inhibitor of apoptosis protein (XIAP), which directly targets Rac1, was selectively induced in C-ion–irradiated MIAPaCa-2 cells and coprecipitated with GTP-bound Rac1 in C-ion–irradiated cells, which was associated with Rac1 ubiquitination. Cell migration and invasion reduced by C-ion radiation were restored by short interfering RNA–mediated XIAP knockdown, indicating that XIAP is involved in C-ion–induced inhibition of cell motility. Conclusion: In contrast to x-ray irradiation, C-ion treatment inhibited the activity of Rac1 and RhoA in MIAPaCa-2 cells and Rac1 in AsPC-1 and BxPC-3 cells via Ub-mediated proteasomal degradation, thereby blocking the motility of these pancreatic cancer cells.« less

Search for a hidden strange baryon-meson bound state from ϕ production in a nuclear medium

NASA Astrophysics Data System (ADS)

Gao, Haiyan; Huang, Hongxia; Liu, Tianbo; Ping, Jialun; Wang, Fan; Zhao, Zhiwen

2017-05-01

We investigate the hidden strange light baryon-meson system. With the resonating-group method, two bound states, η'-N and ϕ -N , are found in the quark delocalization color screening model. Focusing on the ϕ -N bound state around 1950 MeV, we obtain the total decay width of about 4 MeV by calculating the phase shifts in the resonance scattering processes. To study the feasibility of an experimental search for the ϕ -N bound state, we perform a Monte Carlo simulation of the bound state production with an electron beam and a gold target. In the simulation, we use the CLAS12 detector with the Forward Tagger and the BONUS12 detector in Hall B at Jefferson Lab. Both the signal and the background channels are estimated. We demonstrate that the signal events can be separated from the background with some momentum cuts. Therefore it is feasible to experimentally search for the ϕ -N bound state through the near threshold ϕ meson production from heavy nuclei.

Climate change impact of livestock CH4 emission in India: Global temperature change potential (GTP) and surface temperature response.

PubMed

Kumari, Shilpi; Hiloidhari, Moonmoon; Kumari, Nisha; Naik, S N; Dahiya, R P

2018-01-01

Two climate metrics, Global surface Temperature Change Potential (GTP) and the Absolute GTP (AGTP) are used for studying the global surface temperature impact of CH 4 emission from livestock in India. The impact on global surface temperature is estimated for 20 and 100 year time frames due to CH 4 emission. The results show that the CH 4 emission from livestock, worked out to 15.3 Tg in 2012. In terms of climate metrics GTP of livestock-related CH 4 emission in India in 2012 were 1030 Tg CO 2 e (GTP 20 ) and 62 Tg CO 2 e (GTP 100 ) at the 20 and 100 year time horizon, respectively. The study also illustrates that livestock-related CH 4 emissions in India can cause a surface temperature increase of up to 0.7mK and 0.036mK over the 20 and 100 year time periods, respectively. The surface temperature response to a year of Indian livestock emission peaks at 0.9mK in the year 2021 (9 years after the time of emission). The AGTP gives important information in terms of temperature change due to annual CH 4 emissions, which is useful when comparing policies that address multiple gases. Copyright © 2017 Elsevier Inc. All rights reserved.

Expression and GTP sensitivity of peptide histidine isoleucine high-affinity-binding sites in rat.

PubMed

Debaigt, Colin; Meunier, Annie-Claire; Goursaud, Stephanie; Montoni, Alicia; Pineau, Nicolas; Couvineau, Alain; Laburthe, Marc; Muller, Jean-Marc; Janet, Thierry

2006-07-01

High-affinity-binding sites for the vasoactive intestinal peptide (VIP) analogs peptide histidine/isoleucine-amide (PHI)/carboxyterminal methionine instead of isoleucine (PHM) are expressed in numerous tissues in the body but the nature of their receptors remains to be elucidated. The data presented indicate that PHI discriminated a high-affinity guanosine 5'-triphosphate (GTP)-insensitive-binding subtype that represented the totality of the PHI-binding sites in newborn rat tissues but was differentially expressed in adult animals. The GTP-insensitive PHI/PHM-binding sites were also observed in CHO cells over expressing the VPAC2 but not the VPAC1 VIP receptor.

Bounds on stochastic chemical kinetic systems at steady state

NASA Astrophysics Data System (ADS)

Dowdy, Garrett R.; Barton, Paul I.

2018-02-01

The method of moments has been proposed as a potential means to reduce the dimensionality of the chemical master equation (CME) appearing in stochastic chemical kinetics. However, attempts to apply the method of moments to the CME usually result in the so-called closure problem. Several authors have proposed moment closure schemes, which allow them to obtain approximations of quantities of interest, such as the mean molecular count for each species. However, these approximations have the dissatisfying feature that they come with no error bounds. This paper presents a fundamentally different approach to the closure problem in stochastic chemical kinetics. Instead of making an approximation to compute a single number for the quantity of interest, we calculate mathematically rigorous bounds on this quantity by solving semidefinite programs. These bounds provide a check on the validity of the moment closure approximations and are in some cases so tight that they effectively provide the desired quantity. In this paper, the bounded quantities of interest are the mean molecular count for each species, the variance in this count, and the probability that the count lies in an arbitrary interval. At present, we consider only steady-state probability distributions, intending to discuss the dynamic problem in a future publication.

Excitation-contraction coupling in skeletal muscle fibres of rat and toad in the presence of GTP gamma S.

PubMed Central

Lamb, G D; Stephenson, D G

1991-01-01

1. Rapid force responses were elicited in single mechanically skinned fibres from extensor digitorum longus (EDL) muscle of the rat when the fibres were depolarized by substituting K+ in the bathing solution with Na+. The properties of these depolarization-induced responses, the responses to lowered [Mg2+], and the characteristics of the slow prolonged response ('second component') produced in 'loaded' fibres by choline chloride (ChCl) substitution, were virtually identical to those observed previously in skinned fibres from toad muscle. 2. At physiological levels of [Mg2+] (1 mM) and Ca2+ loading, application of 50 microM- to 1 mM-GTP gamma S (guanosine-5'-O-(3-thiotriphosphate), a non-hydrolysable analogue of GTP) did not produce a response in any mammalian or amphibian fibre, even though the depolarization-induced coupling was totally functional. Furthermore, the presence of GTP gamma S had no apparent effect on the size, the threshold or the maximum number of responses which could be elicited by depolarization. 3. GTP gamma S did not elicit any response when excitation-contraction coupling was abolished by prolonged depolarization or by chemically skinning the fibre with saponin or by 24 h exposure to low [Ca2+] (5 mM-EGTA). 4. GDP beta S (guanosine-5'-O-(2-thiodiphosphate), 250 microM or 1 mM) neither evoked a response nor affected the responses to depolarization or caffeine. 5. When the [Mg2+] was lowered to 0.2 mM and the fibres were heavily loaded with Ca2+, addition of GTP gamma S (250 microM or 1 mM) induced a small response in about 50% of fibres, but depolarization-induced responses were not affected in any fibres. 6. Asymmetric charge movement recorded in EDL fibres with the vaseline-gap voltage clamp was not affected by the application of 1 mM-GTP gamma S to the cut ends of the fibres for up to 1 h. 7. These data imply that GTP-binding proteins (G-proteins) are not involved in coupling the voltage sensors to Ca2+ release in skeletal muscle

Excitation-contraction coupling in skeletal muscle fibres of rat and toad in the presence of GTP gamma S.

PubMed

Lamb, G D; Stephenson, D G

1991-12-01

1. Rapid force responses were elicited in single mechanically skinned fibres from extensor digitorum longus (EDL) muscle of the rat when the fibres were depolarized by substituting K+ in the bathing solution with Na+. The properties of these depolarization-induced responses, the responses to lowered [Mg2+], and the characteristics of the slow prolonged response ('second component') produced in 'loaded' fibres by choline chloride (ChCl) substitution, were virtually identical to those observed previously in skinned fibres from toad muscle. 2. At physiological levels of [Mg2+] (1 mM) and Ca2+ loading, application of 50 microM- to 1 mM-GTP gamma S (guanosine-5'-O-(3-thiotriphosphate), a non-hydrolysable analogue of GTP) did not produce a response in any mammalian or amphibian fibre, even though the depolarization-induced coupling was totally functional. Furthermore, the presence of GTP gamma S had no apparent effect on the size, the threshold or the maximum number of responses which could be elicited by depolarization. 3. GTP gamma S did not elicit any response when excitation-contraction coupling was abolished by prolonged depolarization or by chemically skinning the fibre with saponin or by 24 h exposure to low [Ca2+] (5 mM-EGTA). 4. GDP beta S (guanosine-5'-O-(2-thiodiphosphate), 250 microM or 1 mM) neither evoked a response nor affected the responses to depolarization or caffeine. 5. When the [Mg2+] was lowered to 0.2 mM and the fibres were heavily loaded with Ca2+, addition of GTP gamma S (250 microM or 1 mM) induced a small response in about 50% of fibres, but depolarization-induced responses were not affected in any fibres. 6. Asymmetric charge movement recorded in EDL fibres with the vaseline-gap voltage clamp was not affected by the application of 1 mM-GTP gamma S to the cut ends of the fibres for up to 1 h. 7. These data imply that GTP-binding proteins (G-proteins) are not involved in coupling the voltage sensors to Ca2+ release in skeletal muscle

Upper bounds on the error probabilities and asymptotic error exponents in quantum multiple state discrimination

DOE Office of Scientific and Technical Information (OSTI.GOV)

Audenaert, Koenraad M. R., E-mail: koenraad.audenaert@rhul.ac.uk; Department of Physics and Astronomy, University of Ghent, S9, Krijgslaan 281, B-9000 Ghent; Mosonyi, Milán, E-mail: milan.mosonyi@gmail.com

2014-10-01

We consider the multiple hypothesis testing problem for symmetric quantum state discrimination between r given states σ₁, …, σ{sub r}. By splitting up the overall test into multiple binary tests in various ways we obtain a number of upper bounds on the optimal error probability in terms of the binary error probabilities. These upper bounds allow us to deduce various bounds on the asymptotic error rate, for which it has been hypothesized that it is given by the multi-hypothesis quantum Chernoff bound (or Chernoff divergence) C(σ₁, …, σ{sub r}), as recently introduced by Nussbaum and Szkoła in analogy with Salikhov'smore » classical multi-hypothesis Chernoff bound. This quantity is defined as the minimum of the pairwise binary Chernoff divergences min{sub j« less

Dissociation of Rac1(GDP)·RhoGDI Complexes by the Cooperative Action of Anionic Liposomes Containing Phosphatidylinositol 3,4,5-Trisphosphate, Rac Guanine Nucleotide Exchange Factor, and GTP*

PubMed Central

Ugolev, Yelena; Berdichevsky, Yevgeny; Weinbaum, Carolyn; Pick, Edgar

2008-01-01

Rac plays a pivotal role in the assembly of the superoxide-generating NADPH oxidase of phagocytes. In resting cells, Rac is found in the cytosol in complex with Rho GDP dissociation inhibitor (RhoGDI). NADPH oxidase assembly involves dissociation of the Rac·RhoGDI complex and translocation of Rac to the membrane. We reported that liposomes containing high concentrations of monovalent anionic phospholipids cause Rac·RhoGDI complex dissociation (Ugolev, Y., Molshanski-Mor, S., Weinbaum, C., and Pick, E. (2006) J. Biol. Chem.281 ,19204 -1921916702219). We now designed an in vitro model mimicking membrane phospholipid remodeling during phagocyte stimulation in vivo. We showed that liposomes of “resting cell membrane” composition (less than 20 mol % monovalent anionic phospholipids), supplemented with 1 mol % of polyvalent anionic phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) in conjunction with constitutively active forms of the guanine nucleotide exchange factors (GEFs) for Rac, Trio, or Tiam1 and a non-hydrolyzable GTP analogue, cause dissociation of Rac1(GDP)·RhoGDI complexes, GDP to GTP exchange on Rac1, and binding of Rac1(GTP) to the liposomes. Complexes were not dissociated in the absence of GEF and GTP, and optimal dissociation required the presence of PtdIns(3,4,5)P3 in the liposomes. Dissociation of Rac1(GDP)·RhoGDI complexes was correlated with the affinity of particular GEF constructs, via the N-terminal pleckstrin homology domain, for PtdIns(3,4,5)P3 and involved GEF-mediated GDP to GTP exchange on Rac1. Phagocyte membranes enriched in PtdIns(3,4,5)P3 responded by NADPH oxidase activation upon exposure in vitro to Rac1(GDP)·RhoGDI complexes, p67phox, GTP, and Rac GEF constructs with affinity for PtdIns(3,4,5)P3 at a level superior to that of native membranes. PMID:18505730

Characterization of a plasma membrane-associated prenylcysteine-directed alpha carboxyl methyltransferase in human neutrophils.

PubMed

Pillinger, M H; Volker, C; Stock, J B; Weissmann, G; Philips, M R

1994-01-14

Signal transduction in human neutrophils requires prenylcysteine-directed carboxyl methylation of ras-related low molecular weight GTP-binding proteins. We now report the subcellular localization and characterization of a neutrophil prenylcysteine alpha carboxyl methyltransferase. The highest carboxyl methyltransferase activity copurified with biotinylated neutrophil surface membranes, supporting a plasma membrane localization of the enzyme. Neutrophil nuclear fractions contained little or no methyltransferase activity. Methyltransferase activity was detergent-sensitive but could be reconstituted by removal of detergent in the presence of phosphatidyl choline and an anionic phospholipid. N-Acetyl-S-trans,trans-farnesyl-L-cysteine (AFC) and N-acetyl-S-all-trans-geranylgeranyl-L-cysteine (AGGC) were effective substrates for neutrophil prenylcysteine-directed methyltransferase; Vmax values for AFC and AGGC (16.4 and 22.1 pmol of methylated/mg protein/min, respectively) are among the highest yet reported. Although both GTP gamma S and the chemoattractant fMet-Leu-Phe stimulated methylation of ras-related proteins, neither affected methylation of AFC. These data suggest that neutrophil plasma membranes contain a phospholipid-dependent, prenylcysteine-directed carboxyl methyltransferase of relatively high specific activity that modifies ras-related protein substrates in the GTP-bound, activated state.

Switching of the positive feedback for RAS activation by a concerted function of SOS membrane association domains

PubMed Central

Nakamura, Yuki; Hibino, Kayo; Yanagida, Toshio; Sako, Yasushi

2016-01-01

Son of sevenless (SOS) is a guanine nucleotide exchange factor that regulates cell behavior by activating the small GTPase RAS. Recent in vitro studies have suggested that an interaction between SOS and the GTP-bound active form of RAS generates a positive feedback loop that propagates RAS activation. However, it remains unclear how the multiple domains of SOS contribute to the regulation of the feedback loop in living cells. Here, we observed single molecules of SOS in living cells to analyze the kinetics and dynamics of SOS behavior. The results indicate that the histone fold and Grb2-binding domains of SOS concertedly produce an intermediate state of SOS on the cell surface. The fraction of the intermediated state was reduced in positive feedback mutants, suggesting that the feedback loop functions during the intermediate state. Translocation of RAF, recognizing the active form of RAS, to the cell surface was almost abolished in the positive feedback mutants. Thus, the concerted functions of multiple membrane-associating domains of SOS governed the positive feedback loop, which is crucial for cell fate decision regulated by RAS. PMID:27924253

GTP effects in rat brain slices support the non-interconvertability of M/sub 1/ and M/sub 2/ muscarinic acetylcholine receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spencer, D.G. Jr.; Horvath, E.; Traber, J.

GTP (guanosine-5'-triphosphate) markedly reduced high-affinity /sup 3/H-oxotremorine-M binding to M/sub 2/ receptors on brain slices in autoradiographic experiments while /sup 3/H-pirenzepine binding to M/sub 1/ receptors was largely unaffected. The distribution of M/sub 1/ receptors so labelled was also not altered by GTP to include former M/sub 2/-rich regions, thus indicating that GTP could not, by itself, interconvert high agonist-affinity M/sub 2/ receptors to M/sub 1/ receptors. 18 references, 1 figure.

GDP-bound and nucleotide-free intermediates of the guanine nucleotide exchange in the Rab5·Vps9 system.

PubMed

Uejima, Tamami; Ihara, Kentaro; Goh, Tatsuaki; Ito, Emi; Sunada, Mariko; Ueda, Takashi; Nakano, Akihiko; Wakatsuki, Soichi

2010-11-19

Many GTPases regulate intracellular transport and signaling in eukaryotes. Guanine nucleotide exchange factors (GEFs) activate GTPases by catalyzing the exchange of their GDP for GTP. Here we present crystallographic and biochemical studies of a GEF reaction with four crystal structures of Arabidopsis thaliana ARA7, a plant homolog of Rab5 GTPase, in complex with its GEF, VPS9a, in the nucleotide-free and GDP-bound forms, as well as a complex with aminophosphonic acid-guanylate ester and ARA7·VPS9a(D185N) with GDP. Upon complex formation with ARA7, VPS9 wedges into the interswitch region of ARA7, inhibiting the coordination of Mg(2+) and decreasing the stability of GDP binding. The aspartate finger of VPS9a recognizes GDP β-phosphate directly and pulls the P-loop lysine of ARA7 away from GDP β-phosphate toward switch II to further destabilize GDP for its release during the transition from the GDP-bound to nucleotide-free intermediates in the nucleotide exchange reaction.

GTP cyclohydrolase I gene transfer augments intracellular tetrahydrobiopterin in human endothelial cells: effects on nitric oxide synthase activity, protein levels and dimerisation.

PubMed

Cai, Shijie; Alp, Nicholas J; McDonald, Denise; Smith, Ian; Kay, Jonathan; Canevari, Laura; Heales, Simon; Channon, Keith M

2002-09-01

Tetrahydrobiopterin (BH4) is an essential cofactor for endothelial nitric oxide synthase (eNOS) activity. BH4 levels are regulated by de novo biosynthesis; the rate-limiting enzyme is GTP cyclohydrolase I (GTPCH). BH4 activates and promotes homodimerisation of purified eNOS protein, but the intracellular mechanisms underlying BH4-mediated eNOS regulation in endothelial cells remain less clear. We aimed to investigate the role of BH4 levels in intracellular eNOS regulation, by targeting the BH4 synthetic pathway as a novel strategy to modulate intracellular BH4 levels. We constructed a recombinant adenovirus, AdGCH, encoding human GTPCH. We infected human endothelial cells with AdGCH, investigated the changes in intracellular biopterin levels, and determined the effects on eNOS enzymatic activity, protein levels and dimerisation. GTPCH gene transfer in EAhy926 endothelial cells increased BH4 >10-fold compared with controls (cells alone or control adenovirus infection), and greatly enhanced NO production in a dose-dependent, eNOS-specific manner. We found that eNOS was principally monomeric in control cells, whereas GTPCH gene transfer resulted in a striking increase in eNOS homodimerisation. Furthermore, the total amounts of both native eNOS protein and a recombinant eNOS-GFP fusion protein were significantly increased following GTPCH gene transfer. These findings suggest that GTPCH gene transfer is a valid approach to increase BH4 levels in human endothelial cells, and provide new evidence for the relative importance of different mechanisms underlying BH4-mediated eNOS regulation in intact human endothelial cells. Additionally, these observations suggest that GTPCH may be a rational target to augment endothelial BH4 and normalise eNOS activity in endothelial dysfunction states.

Absorption enhancement in type-II coupled quantum rings due to existence of quasi-bound states

NASA Astrophysics Data System (ADS)

Hsieh, Chi-Ti; Lin, Shih-Yen; Chang, Shu-Wei

2018-02-01

The absorption of type-II nanostructures is often weaker than type-I counterpart due to spatially separated electrons and holes. We model the bound-to-continuum absorption of type-II quantum rings (QRs) using a multiband source-radiation approach using the retarded Green function in the cylindrical coordinate system. The selection rules due to the circular symmetry for allowed transitions of absorption are utilized. The bound-tocontinuum absorptions of type-II GaSb coupled and uncoupled QRs embedded in GaAs matrix are compared here. The GaSb QRs act as energy barriers for electrons but potential wells for holes. For the coupled QR structure, the region sandwiched between two QRs forms a potential reservoir of quasi-bound electrons. Electrons in these states, though look like bound ones, would ultimately tunnel out of the reservoir through barriers. Multiband perfectly-matched layers are introduced to model the tunneling of quasi-bound states into open space. Resonance peaks are observed on the absorption spectra of type-II coupled QRs due to the formation of quasi-bound states in conduction bands, but no resonance exist in the uncoupled QR. The tunneling time of these metastable states can be extracted from the resonance and is in the order of ten femtoseconds. Absorption of coupled QRs is significantly enhanced as compared to that of uncoupled ones in certain spectral windows of interest. These features may improve the performance of photon detectors and photovoltaic devices based on type-II semiconductor nanostructures.

Bounds on the cross-correlation functions of state m-sequences

NASA Astrophysics Data System (ADS)

Woodcock, C. F.; Davies, Phillip A.; Shaar, Ahmed A.

1987-03-01

Lower and upper bounds on the peaks of the periodic Hamming cross-correlation function for state m-sequences, which are often used in frequency-hopped spread-spectrum systems, are derived. The state position mapped (SPM) sequences of the state m-sequences are described. The use of SPM sequences for OR-channel code division multiplexing is studied. The relation between the Hamming cross-correlation function and the correlation function of SPM sequence is examined. Numerical results which support the theoretical data are presented.

Conformational dynamics of a G-protein α subunit is tightly regulated by nucleotide binding.

PubMed

Goricanec, David; Stehle, Ralf; Egloff, Pascal; Grigoriu, Simina; Plückthun, Andreas; Wagner, Gerhard; Hagn, Franz

2016-06-28

Heterotrimeric G proteins play a pivotal role in the signal-transduction pathways initiated by G-protein-coupled receptor (GPCR) activation. Agonist-receptor binding causes GDP-to-GTP exchange and dissociation of the Gα subunit from the heterotrimeric G protein, leading to downstream signaling. Here, we studied the internal mobility of a G-protein α subunit in its apo and nucleotide-bound forms and characterized their dynamical features at multiple time scales using solution NMR, small-angle X-ray scattering, and molecular dynamics simulations. We find that binding of GTP analogs leads to a rigid and closed arrangement of the Gα subdomain, whereas the apo and GDP-bound forms are considerably more open and dynamic. Furthermore, we were able to detect two conformational states of the Gα Ras domain in slow exchange whose populations are regulated by binding to nucleotides and a GPCR. One of these conformational states, the open state, binds to the GPCR; the second conformation, the closed state, shows no interaction with the receptor. Binding to the GPCR stabilizes the open state. This study provides an in-depth analysis of the conformational landscape and the switching function of a G-protein α subunit and the influence of a GPCR in that landscape.

Conformational dynamics of a G-protein α subunit is tightly regulated by nucleotide binding

PubMed Central

Goricanec, David; Stehle, Ralf; Egloff, Pascal; Grigoriu, Simina; Wagner, Gerhard; Hagn, Franz

2016-01-01

Heterotrimeric G proteins play a pivotal role in the signal-transduction pathways initiated by G-protein–coupled receptor (GPCR) activation. Agonist–receptor binding causes GDP-to-GTP exchange and dissociation of the Gα subunit from the heterotrimeric G protein, leading to downstream signaling. Here, we studied the internal mobility of a G-protein α subunit in its apo and nucleotide-bound forms and characterized their dynamical features at multiple time scales using solution NMR, small-angle X-ray scattering, and molecular dynamics simulations. We find that binding of GTP analogs leads to a rigid and closed arrangement of the Gα subdomain, whereas the apo and GDP-bound forms are considerably more open and dynamic. Furthermore, we were able to detect two conformational states of the Gα Ras domain in slow exchange whose populations are regulated by binding to nucleotides and a GPCR. One of these conformational states, the open state, binds to the GPCR; the second conformation, the closed state, shows no interaction with the receptor. Binding to the GPCR stabilizes the open state. This study provides an in-depth analysis of the conformational landscape and the switching function of a G-protein α subunit and the influence of a GPCR in that landscape. PMID:27298341

Mobile bound states of Rydberg excitations in a lattice

NASA Astrophysics Data System (ADS)

Letscher, Fabian; Petrosyan, David

2018-04-01

Spin-lattice models play a central role in the studies of quantum magnetism and nonequilibrium dynamics of spin excitations—-magnons. We show that a spin lattice with strong nearest-neighbor interactions and tunable long-range hopping of excitations can be realized by a regular array of laser-driven atoms, with an excited Rydberg state representing the spin-up state and a Rydberg-dressed ground state corresponding to the spin-down state. We find exotic interaction-bound states of magnons that propagate in the lattice via the combination of resonant two-site hopping and nonresonant second-order hopping processes. Arrays of trapped Rydberg-dressed atoms can thus serve as a flexible platform to simulate and study fundamental few-body dynamics in spin lattices.

Improved key-rate bounds for practical decoy-state quantum-key-distribution systems

NASA Astrophysics Data System (ADS)

Zhang, Zhen; Zhao, Qi; Razavi, Mohsen; Ma, Xiongfeng

2017-01-01

The decoy-state scheme is the most widely implemented quantum-key-distribution protocol in practice. In order to account for the finite-size key effects on the achievable secret key generation rate, a rigorous statistical fluctuation analysis is required. Originally, a heuristic Gaussian-approximation technique was used for this purpose, which, despite its analytical convenience, was not sufficiently rigorous. The fluctuation analysis has recently been made rigorous by using the Chernoff bound. There is a considerable gap, however, between the key-rate bounds obtained from these techniques and that obtained from the Gaussian assumption. Here we develop a tighter bound for the decoy-state method, which yields a smaller failure probability. This improvement results in a higher key rate and increases the maximum distance over which secure key exchange is possible. By optimizing the system parameters, our simulation results show that our method almost closes the gap between the two previously proposed techniques and achieves a performance similar to that of conventional Gaussian approximations.

Crystal structure of the GTPase domain and the bundle signalling element of dynamin in the GDP state

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anand, Roopsee; Eschenburg, Susanne; Reubold, Thomas F., E-mail: Reubold.Thomas@mh-hannover.de

Dynamin is the prototype of a family of large multi-domain GTPases. The 100 kDa protein is a key player in clathrin-mediated endocytosis, where it cleaves off vesicles from membranes using the energy from GTP hydrolysis. We have solved the high resolution crystal structure of a fusion protein of the GTPase domain and the bundle signalling element (BSE) of dynamin 1 liganded with GDP. The structure provides a hitherto missing snapshot of the GDP state of the hydrolytic cycle of dynamin and reveals how the switch I region moves away from the active site after GTP hydrolysis and release of inorganic phosphate.more » Comparing our structure of the GDP state with the known structures of the GTP state, the transition state and the nucleotide-free state of dynamin 1 we describe the structural changes through the hydrolytic cycle. - Highlights: • High resolution crystal structure of the GDP-state of a dynamin 1 GTPase-BSE fusion. • Visualizes one of the key states of the hydrolytic cycle of dynamin. • The dynamin-specific loop forms a helix as soon as a guanine base is present.« less

Topologically protected bound states in one-dimensional Floquet acoustic waveguide systems

NASA Astrophysics Data System (ADS)

Peng, Yu-Gui; Geng, Zhi-Guo; Zhu, Xue-Feng

2018-03-01

Topological manipulation of sound has recently been a hot spot in acoustics due to the fascinating property of defect immune transport. To the best of our knowledge, the studies on one-dimensional (1D) topological acoustic systems hitherto mainly focus on the case of the Su-Schrieffer-Heeger model. Here, we show that topologically protected bound states may also exist in 1D periodically modulated acoustic waveguide systems, viz., 1D Floquet topological insulators. The results show that tuning the coupling strength in a waveguide lattice could trigger topological phase transition, which gives rise to topologically protected interface states as we put together two waveguide lattices featured with different topological phases or winding numbers. However, for the combined lattice, input at the waveguides other than the interfacial ones will excite bulk states. We have further verified the robustness of interface bound states against the variation of coupling strengths between the two distinct waveguide lattices. This work extends the scope of topological acoustics and may promote potential applications for acoustic devices with topological functionalities.

Ab initio investigation on the valence and dipole-bound states of CNa - and SiNa -

NASA Astrophysics Data System (ADS)

Kalcher, Josef; Sax, Alexander F.

2000-08-01

CNa - and SiNa - have been studied by the CAS-ACPF method. The 3Σ- ground states have binding energies of 5420 and 7517 cm -1, respectively. The 5Σ- excited states are 494 and 1551 cm -1 above the respective ground states. The 1Δ , 3Π , and 1Π valence-excited states for SiNa - should be at least metastable. CNa - and SiNa - possess dipole-bound 5Σ- and 3Σ- states. Binding energies of these states in CNa - are 217 and 236 cm -1, respectively. SiNa - has two stable 5Σ- dipole-bound states, whose binding energies are 246 and 118 cm -1, respectively.

Upper bound on three-tangles of reduced states of four-qubit pure states

NASA Astrophysics Data System (ADS)

Sharma, S. Shelly; Sharma, N. K.

2017-06-01

Closed formulas for upper bounds on three-tangles of three-qubit reduced states in terms of three-qubit-invariant polynomials of pure four-qubit states are obtained. Our results offer tighter constraints on total three-way entanglement of a given qubit with the rest of the system than those used by Regula et al. [Phys. Rev. Lett. 113, 110501 (2014), 10.1103/PhysRevLett.113.110501 and Phys. Rev. Lett. 116, 049902(E) (2016)], 10.1103/PhysRevLett.116.049902 to verify monogamy of four-qubit quantum entanglement.

Explicit formula for the Holevo bound for two-parameter qubit-state estimation problem

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Jun, E-mail: junsuzuki@uec.ac.jp

The main contribution of this paper is to derive an explicit expression for the fundamental precision bound, the Holevo bound, for estimating any two-parameter family of qubit mixed-states in terms of quantum versions of Fisher information. The obtained formula depends solely on the symmetric logarithmic derivative (SLD), the right logarithmic derivative (RLD) Fisher information, and a given weight matrix. This result immediately provides necessary and sufficient conditions for the following two important classes of quantum statistical models; the Holevo bound coincides with the SLD Cramér-Rao bound and it does with the RLD Cramér-Rao bound. One of the important results ofmore » this paper is that a general model other than these two special cases exhibits an unexpected property: the structure of the Holevo bound changes smoothly when the weight matrix varies. In particular, it always coincides with the RLD Cramér-Rao bound for a certain choice of the weight matrix. Several examples illustrate these findings.« less

7-methylguanosine diphosphate (m(7)GDP) is not hydrolyzed but strongly bound by decapping scavenger (DcpS) enzymes and potently inhibits their activity.

PubMed

Wypijewska, Anna; Bojarska, Elzbieta; Lukaszewicz, Maciej; Stepinski, Janusz; Jemielity, Jacek; Davis, Richard E; Darzynkiewicz, Edward

2012-10-09

Decapping scavenger (DcpS) enzymes catalyze the cleavage of a residual cap structure following 3' → 5' mRNA decay. Some previous studies suggested that both m(7)GpppG and m(7)GDP were substrates for DcpS hydrolysis. Herein, we show that mononucleoside diphosphates, m(7)GDP (7-methylguanosine diphosphate) and m(3)(2,2,7)GDP (2,2,7-trimethylguanosine diphosphate), resulting from mRNA decapping by the Dcp1/2 complex in the 5' → 3' mRNA decay, are not degraded by recombinant DcpS proteins (human, nematode, and yeast). Furthermore, whereas mononucleoside diphosphates (m(7)GDP and m(3)(2,2,7)GDP) are not hydrolyzed by DcpS, mononucleoside triphosphates (m(7)GTP and m(3)(2,2,7)GTP) are, demonstrating the importance of a triphosphate chain for DcpS hydrolytic activity. m(7)GTP and m(3)(2,2,7)GTP are cleaved at a slower rate than their corresponding dinucleotides (m(7)GpppG and m(3)(2,2,7)GpppG, respectively), indicating an involvement of the second nucleoside for efficient DcpS-mediated digestion. Although DcpS enzymes cannot hydrolyze m(7)GDP, they have a high binding affinity for m(7)GDP and m(7)GDP potently inhibits DcpS hydrolysis of m(7)GpppG, suggesting that m(7)GDP may function as an efficient DcpS inhibitor. Our data have important implications for the regulatory role of m(7)GDP in mRNA metabolic pathways due to its possible interactions with different cap-binding proteins, such as DcpS or eIF4E.

Silica-coated gold nanorods as saturable absorber for bound-state pulse generation in a fiber laser with near-zero dispersion

NASA Astrophysics Data System (ADS)

Wang, Xude; Luo, Aiping; Luo, Zhichao; Liu, Meng; Zou, Feng; Zhu, Yanfang; Xue, Jianping; Xu, Wencheng

2017-11-01

We presented a bound-state operation in a fiber laser with near-zero anomalous dispersion based on a silica-coated gold nanorods (GNRs@SiO2) saturable absorber (SA). Using a balanced twin detector measurement technique, the modulation depth and nonsaturable loss of the GNRs@SiO2 SA were measured to be approximately 3.5% and 39.3%, respectively. By virtue of the highly nonlinear effect of the GNRs@SiO2 SA, the bound-state pulses could be easily observed. Besides the lower-order bound-state pulses with two, three, and four solitons, the higher-order bound states with up to 12 solitons were also obtained in the laser cavity. The pulse profiles of the higher-order bound states were further reconstructed theoretically. The experimental results would give further insight towards understanding the complex nonlinear dynamics of bound-state pulses in fiber lasers.

Quarkonium-nucleus bound states from lattice QCD

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beane, S.  R.; Chang, E.; Cohen, S.  D.

2015-06-11

Quarkonium-nucleus systems are composed of two interacting hadronic states without common valence quarks, which interact primarily through multi-gluon exchanges, realizing a color van der Waals force. We present lattice QCD calculations of the interactions of strange and charm quarkonia with light nuclei. Both the strangeonium-nucleus and charmonium-nucleus systems are found to be relatively deeply bound when the masses of the three light quarks are set equal to that of the physical strange quark. Extrapolation of these results to the physical light-quark masses suggests that the binding energy of charmonium to nuclear matter is B < 40 MeV.

Spontaneous reverse movement of mRNA-bound tRNA through the ribosome.

PubMed

Konevega, Andrey L; Fischer, Niels; Semenkov, Yuri P; Stark, Holger; Wintermeyer, Wolfgang; Rodnina, Marina V

2007-04-01

During the translocation step of protein synthesis, a complex of two transfer RNAs bound to messenger RNA (tRNA-mRNA) moves through the ribosome. The reaction is promoted by an elongation factor, called EF-G in bacteria, which, powered by GTP hydrolysis, induces an open, unlocked conformation of the ribosome that allows for spontaneous tRNA-mRNA movement. Here we show that, in the absence of EF-G, there is spontaneous backward movement, or retrotranslocation, of two tRNAs bound to mRNA. Retrotranslocation is driven by the gain in affinity when a cognate E-site tRNA moves into the P site, which compensates the affinity loss accompanying the movement of peptidyl-tRNA from the P to the A site. These results lend support to the diffusion model of tRNA movement during translocation. In the cell, tRNA movement is biased in the forward direction by EF-G, which acts as a Brownian ratchet and prevents backward movement.

Molecular kinetics. Ras activation by SOS: allosteric regulation by altered fluctuation dynamics.

PubMed

Iversen, Lars; Tu, Hsiung-Lin; Lin, Wan-Chen; Christensen, Sune M; Abel, Steven M; Iwig, Jeff; Wu, Hung-Jen; Gureasko, Jodi; Rhodes, Christopher; Petit, Rebecca S; Hansen, Scott D; Thill, Peter; Yu, Cheng-Han; Stamou, Dimitrios; Chakraborty, Arup K; Kuriyan, John; Groves, Jay T

2014-07-04

Activation of the small guanosine triphosphatase H-Ras by the exchange factor Son of Sevenless (SOS) is an important hub for signal transduction. Multiple layers of regulation, through protein and membrane interactions, govern activity of SOS. We characterized the specific activity of individual SOS molecules catalyzing nucleotide exchange in H-Ras. Single-molecule kinetic traces revealed that SOS samples a broad distribution of turnover rates through stochastic fluctuations between distinct, long-lived (more than 100 seconds), functional states. The expected allosteric activation of SOS by Ras-guanosine triphosphate (GTP) was conspicuously absent in the mean rate. However, fluctuations into highly active states were modulated by Ras-GTP. This reveals a mechanism in which functional output may be determined by the dynamical spectrum of rates sampled by a small number of enzymes, rather than the ensemble average. Copyright © 2014, American Association for the Advancement of Science.

Activation of the Lbc Rho Exchange Factor Proto-Oncogene by Truncation of an Extended C Terminus That Regulates Transformation and Targeting

PubMed Central

Sterpetti, Paola; Hack, Andrew A.; Bashar, Mariam P.; Park, Brian; Cheng, Sou-De; Knoll, Joan H. M.; Urano, Takeshi; Feig, Larry A.; Toksoz, Deniz

1999-01-01

The human lbc oncogene product is a guanine nucleotide exchange factor that specifically activates the Rho small GTP binding protein, thus resulting in biologically active, GTP-bound Rho, which in turn mediates actin cytoskeletal reorganization, gene transcription, and entry into the mitotic S phase. In order to elucidate the mechanism of onco-Lbc transformation, here we report that while proto- and onco-lbc cDNAs encode identical N-terminal dbl oncogene homology (DH) and pleckstrin homology (PH) domains, proto-Lbc encodes a novel C terminus absent in the oncoprotein that includes a predicted α-helical region homologous to cyto-matrix proteins, followed by a proline-rich region. The lbc proto-oncogene maps to chromosome 15, and onco-lbc represents a fusion of the lbc proto-oncogene N terminus with a short, unrelated C-terminal sequence from chromosome 7. Both onco- and proto-Lbc can promote formation of GTP-bound Rho in vivo. Proto-Lbc transforming activity is much reduced compared to that of onco-Lbc, and a significant increase in transforming activity requires truncation of both the α-helical and proline-rich regions in the proto-Lbc C terminus. Deletion of the chromosome 7-derived C terminus of onco-Lbc does not destroy transforming activity, demonstrating that it is loss of the proto-Lbc C terminus, rather than gain of an unrelated C-terminus by onco-Lbc, that confers transforming activity. Mutations of onco-Lbc DH and PH domains demonstrate that both domains are necessary for full transforming activity. The proto-Lbc product localizes to the particulate (membrane) fraction, while the majority of the onco-Lbc product is cytosolic, and mutations of the PH domain do not affect this localization. The proto-Lbc C-terminus alone localizes predominantly to the particulate fraction, indicating that the C terminus may play a major role in the correct subcellular localization of proto-Lbc, thus providing a mechanism for regulating Lbc oncogenic potential. PMID:9891067

Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS.

PubMed

Yao, Zhan; Yaeger, Rona; Rodrik-Outmezguine, Vanessa S; Tao, Anthony; Torres, Neilawattie M; Chang, Matthew T; Drosten, Matthias; Zhao, Huiyong; Cecchi, Fabiola; Hembrough, Todd; Michels, Judith; Baumert, Hervé; Miles, Linde; Campbell, Naomi M; de Stanchina, Elisa; Solit, David B; Barbacid, Mariano; Taylor, Barry S; Rosen, Neal

2017-08-10

Approximately 200 BRAF mutant alleles have been identified in human tumours. Activating BRAF mutants cause feedback inhibition of GTP-bound RAS, are RAS-independent and signal either as active monomers (class 1) or constitutively active dimers (class 2). Here we characterize a third class of BRAF mutants-those that have impaired kinase activity or are kinase-dead. These mutants are sensitive to ERK-mediated feedback and their activation of signalling is RAS-dependent. The mutants bind more tightly than wild-type BRAF to RAS-GTP, and their binding to and activation of wild-type CRAF is enhanced, leading to increased ERK signalling. The model suggests that dysregulation of signalling by these mutants in tumours requires coexistent mechanisms for maintaining RAS activation despite ERK-dependent feedback. Consistent with this hypothesis, melanomas with these class 3 BRAF mutations also harbour RAS mutations or NF1 deletions. By contrast, in lung and colorectal cancers with class 3 BRAF mutants, RAS is typically activated by receptor tyrosine kinase signalling. These tumours are sensitive to the inhibition of RAS activation by inhibitors of receptor tyrosine kinases. We have thus defined three distinct functional classes of BRAF mutants in human tumours. The mutants activate ERK signalling by different mechanisms that dictate their sensitivity to therapeutic inhibitors of the pathway.

Machineries regulating the activity of the small GTPase Arf6 in cancer cells are potential targets for developing innovative anti-cancer drugs.

PubMed

Yamauchi, Yohei; Miura, Yuki; Kanaho, Yasunori

2017-01-01

The Small GTPase ADP-ribosylation factor 6 (Arf6) functions as the molecular switch in cellular signaling pathways by cycling between GDP-bound inactive and GTP-bound active form, which is precisely regulated by two regulators, guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Numerous studies have shown that these machineries play critical roles in tumor angiogenesis/growth and cancer cell invasion/metastasis through regulating the cycling of Arf6. Here, we summarize accumulating knowledge for involvement of Arf6 GEFs/GAPs and small molecule inhibitors of Arf6 signaling/cycling in cancer progression, and discuss possible strategies for developing innovative anti-cancer drugs targeting Arf6 signaling/cycling. Copyright © 2016 Elsevier Ltd. All rights reserved.

Invariant criteria for bound states, degree of ionization, and plasma phase transition

NASA Technical Reports Server (NTRS)

Girardeau, M. D.

1990-01-01

Basis invariant characterizations of bound states and bound fraction of a partially ionized hydrogen plasma are given in terms of properties of the spectrum of eigenvalues and eigenfunctions of the equilibrium quantum statistical one-proton-one-electron reduced density matrix. It is suggested that these can be used to place theories of a proposed plasma-ionization phase transition on a firm foundation. This general approach may be relevant to cosmological questions such as the quark deconfinement-confinement transition.

What can Andreev bound states tell us about superconductors?

PubMed

Millo, Oded; Koren, Gad

2018-08-06

Zero-energy Andreev bound states, which manifest themselves in the tunnelling spectra as zero-bias conductance peaks (ZBCPs), are abundant at interfaces between superconductors and other materials and on the nodal surface of high-temperature superconductors. In this review, we focus on the information such excitations can provide on the properties of superconductor systems. First, a general introduction to the physics of Andreev bound states in superconductor/normal metal interfaces is given with a particular emphasis on why they appear at zero energy in d -wave superconductors. Then, specific spectroscopic tunnelling studies of thin films, bilayers and junctions are described, focusing on the corresponding ZBCP features. Scanning tunnelling spectroscopy (STS) studies show that the ZBCPs on the c -axis YBa 2 Cu 3 O 7- δ (YBCO) films are correlated with the surface morphology and appear only in proximity to (110) facets. STS on c -axis La 1.88 Sr 0.12 CuO 4 (LSCO) films exhibiting the 1/8 anomaly shows spatially modulated peaks near zero bias associated with the anti-phase ordering of the d -wave order parameter predicted at this doping level. ZBCPs were also found in micrometre-size edge junctions of YBCO/SrRuO 3 /YBCO, where SrRuO 3 is ferromagnetic. Here, the results are consistent with a crossed Andreev reflection effect (CARE) at the narrow domain walls of the SrRuO 3 ZBCPs measured in STS studies of manganite/cuprate bilayers could not be attributed to CARE because the manganite's domain wall is much larger than the coherence length in YBCO, and instead are attributed to proximity-induced triplet-pairing superconductivity with non-conventional symmetry. And finally, ZBCPs found in junctions of non-intentionally doped topological insulator films of Bi 2 Se 3 and the s -wave superconductor NbN are attributed to proximity-induced p x  + ip y triplet order parameter in the topological material.This article is part of the theme issue 'Andreev bound states'. �

Entanglement negativity bounds for fermionic Gaussian states

NASA Astrophysics Data System (ADS)

Eisert, Jens; Eisler, Viktor; Zimborás, Zoltán

2018-04-01

The entanglement negativity is a versatile measure of entanglement that has numerous applications in quantum information and in condensed matter theory. It can not only efficiently be computed in the Hilbert space dimension, but for noninteracting bosonic systems, one can compute the negativity efficiently in the number of modes. However, such an efficient computation does not carry over to the fermionic realm, the ultimate reason for this being that the partial transpose of a fermionic Gaussian state is no longer Gaussian. To provide a remedy for this state of affairs, in this work, we introduce efficiently computable and rigorous upper and lower bounds to the negativity, making use of techniques of semidefinite programming, building upon the Lagrangian formulation of fermionic linear optics, and exploiting suitable products of Gaussian operators. We discuss examples in quantum many-body theory and hint at applications in the study of topological properties at finite temperature.

Structure of a nanobody-stabilized active state of the β(2) adrenoceptor.

PubMed

Rasmussen, Søren G F; Choi, Hee-Jung; Fung, Juan Jose; Pardon, Els; Casarosa, Paola; Chae, Pil Seok; Devree, Brian T; Rosenbaum, Daniel M; Thian, Foon Sun; Kobilka, Tong Sun; Schnapp, Andreas; Konetzki, Ingo; Sunahara, Roger K; Gellman, Samuel H; Pautsch, Alexander; Steyaert, Jan; Weis, William I; Kobilka, Brian K

2011-01-13

G protein coupled receptors (GPCRs) exhibit a spectrum of functional behaviours in response to natural and synthetic ligands. Recent crystal structures provide insights into inactive states of several GPCRs. Efforts to obtain an agonist-bound active-state GPCR structure have proven difficult due to the inherent instability of this state in the absence of a G protein. We generated a camelid antibody fragment (nanobody) to the human β(2) adrenergic receptor (β(2)AR) that exhibits G protein-like behaviour, and obtained an agonist-bound, active-state crystal structure of the receptor-nanobody complex. Comparison with the inactive β(2)AR structure reveals subtle changes in the binding pocket; however, these small changes are associated with an 11 Å outward movement of the cytoplasmic end of transmembrane segment 6, and rearrangements of transmembrane segments 5 and 7 that are remarkably similar to those observed in opsin, an active form of rhodopsin. This structure provides insights into the process of agonist binding and activation.

Relativistic bound states in three space-time dimensions in Minkowski space

NASA Astrophysics Data System (ADS)

Gutierrez, C.; Gigante, V.; Frederico, T.; Tomio, Lauro

2016-01-01

With the aim to derive a workable framework for bound states in Minkowski space, we have investigated the Nakanishi perturbative integral representation of the Bethe-Salpeter (BS) amplitude in two-dimensions (2D) in space and time (2+1). The homogeneous BS amplitude, projected onto the light-front plane, is used to derive an equation for the Nakanishi weight function. The formal development is illustrated in detail and applied to the bound system composed by two scalar particles interacting through the exchange of a massive scalar. The explicit forms of the integral equations are obtained in ladder approximation.

Relativistic bound-state problem in the light-front Yukawa model

NASA Astrophysics Data System (ADS)

Głazek, Stanisław; Harindranath, Avaroth; Pinsky, Stephen; Shigemitsu, Junko; Wilson, Kenneth

1993-02-01

We study the renormalization problem on the light front for the two-fermion bound state in the (3+1)-dimensional Yukawa model, working within the lowest-order Tamm-Dancoff approximation. In addition to traditional mass and wave-function renormalization, new types of counterterms are required. These are nonlocal and involve arbitrary functions of the longitudinal momenta. Their appearance is consistent with general power-counting arguments on the light front. We estimate the ``arbitrary function'' in two ways: (1) by using perturbation theory as a guide and (2) by considering the asymptotic large transverse momentum behavior of the kernel in the bound-state equations. The latter method, as it is currently implemented, is applicable only to the helicity-zero sector of the theory. Because of triviality, in the Yukawa model one must retain a finite cutoff Λ in order to have a nonvanishing renormalized coupling. For the range of renormalized couplings (and cutoffs) allowed by triviality, one finds that the perturbative counterterm does a good job in eliminating cutoff dependence in the low-energy spectrum (masses <<Λ).

Subgap in the Surface Bound States Spectrum of Superfluid (3) 3 He-B with Rough Surface

NASA Astrophysics Data System (ADS)

Nagato, Y.; Higashitani, S.; Nagai, K.

2018-03-01

The subgap structure in the surface bound states spectrum of superfluid ^3He-B with rough surface is discussed. The subgap is formed by the level repulsion between the surface bound state and the continuum states in the course of multiple scattering by the surface roughness. We show that the level repulsion is originated from the nature of the wave function of the surface bound state that is now recognized as Majorana fermion. We study the superfluid ^3He-B with a rough surface and in a magnetic field perpendicular to the surface using the quasi-classical Green function together with a random S-matrix model. We calculate the self-consistent order parameters, the spin polarization density and the surface density of states. It is shown that the subgap is found also in a magnetic field perpendicular to the surface. The magnetic field dependence of the transverse acoustic impedance is also discussed.

NES consensus redefined by structures of PKI-type and Rev-type nuclear export signals bound to CRM1.

PubMed

Güttler, Thomas; Madl, Tobias; Neumann, Piotr; Deichsel, Danilo; Corsini, Lorenzo; Monecke, Thomas; Ficner, Ralf; Sattler, Michael; Görlich, Dirk

2010-11-01

Classic nuclear export signals (NESs) confer CRM1-dependent nuclear export. Here we present crystal structures of the RanGTP-CRM1 complex alone and bound to the prototypic PKI or HIV-1 Rev NESs. These NESs differ markedly in the spacing of their key hydrophobic (Φ) residues, yet CRM1 recognizes them with the same rigid set of five Φ pockets. The different Φ spacings are compensated for by different conformations of the bound NESs: in the case of PKI, an α-helical conformation, and in the case of Rev, an extended conformation with a critical proline docking into a Φ pocket. NMR analyses of CRM1-bound and CRM1-free PKI NES suggest that CRM1 selects NES conformers that pre-exist in solution. Our data lead to a new structure-based NES consensus, and explain why NESs differ in their affinities for CRM1 and why supraphysiological NESs bind the exportin so tightly.

STATIC QUARK ANTI-QUARK FREE AND INTERNAL ENERGY IN 2-FLAVOR QCD AND BOUND STATES IN THE QGP.

DOE Office of Scientific and Technical Information (OSTI.GOV)

ZANTOW, F.; KACZMAREK, O.

2005-07-25

We present results on heavy quark free energies in 2-flavour QCD. The temperature dependence of the interaction between static quark anti-quark pairs will be analyzed in terms of temperature dependent screening radii, which give a first estimate on the medium modification of (heavy quark) bound states in the quark gluon plasma. Comparing those radii to the (zero temperature) mean squared charge radii of chasmonium states indicates that the J/{Psi} may survive the phase transition as a bound state, while {chi}{sub c} and {Psi}{prime} are expected to show significant thermal modifications at temperatures close to the transition. Furthermore we will analyzemore » the relation between heavy quark free energies, entropy contributions and internal energy and discuss their relation to potential models used to analyze the melting of heavy quark bound states above the deconfinement temperature. Results of different groups and various potential models for bound states in the deconfined phase of QCD are compared.« less

Lasing action from photonic bound states in continuum

NASA Astrophysics Data System (ADS)

Kodigala, Ashok; Lepetit, Thomas; Gu, Qing; Bahari, Babak; Fainman, Yeshaiahu; Kanté, Boubacar

2017-01-01

In 1929, only three years after the advent of quantum mechanics, von Neumann and Wigner showed that Schrödinger’s equation can have bound states above the continuum threshold. These peculiar states, called bound states in the continuum (BICs), manifest themselves as resonances that do not decay. For several decades afterwards the idea lay dormant, regarded primarily as a mathematical curiosity. In 1977, Herrick and Stillinger revived interest in BICs when they suggested that BICs could be observed in semiconductor superlattices. BICs arise naturally from Feshbach’s quantum mechanical theory of resonances, as explained by Friedrich and Wintgen, and are thus more physical than initially realized. Recently, it was realized that BICs are intrinsically a wave phenomenon and are thus not restricted to the realm of quantum mechanics. They have since been shown to occur in many different fields of wave physics including acoustics, microwaves and nanophotonics. However, experimental observations of BICs have been limited to passive systems and the realization of BIC lasers has remained elusive. Here we report, at room temperature, lasing action from an optically pumped BIC cavity. Our results show that the lasing wavelength of the fabricated BIC cavities, each made of an array of cylindrical nanoresonators suspended in air, scales with the radii of the nanoresonators according to the theoretical prediction for the BIC mode. Moreover, lasing action from the designed BIC cavity persists even after scaling down the array to as few as 8-by-8 nanoresonators. BIC lasers open up new avenues in the study of light-matter interaction because they are intrinsically connected to topological charges and represent natural vector beam sources (that is, there are several possible beam shapes), which are highly sought after in the fields of optical trapping, biological sensing and quantum information.

Excited states of neutral donor bound excitons in GaN

NASA Astrophysics Data System (ADS)

Callsen, G.; Kure, T.; Wagner, M. R.; Butté, R.; Grandjean, N.

2018-06-01

We investigate the excited states of a neutral donor bound exciton (D0X) in bulk GaN by means of high-resolution, polychromatic photoluminescence excitation (PLE) spectroscopy. The optically most prominent donor in our sample is silicon accompanied by only a minor contribution of oxygen—the key for an unambiguous assignment of excited states. Consequently, we can observe a multitude of Si0X-related excitation channels with linewidths down to 200 μeV. Two groups of excitation channels are identified, belonging either to rotational-vibrational or electronic excited states of the hole in the Si0X complex. Such identification is achieved by modeling the excited states based on the equations of motion for a Kratzer potential, taking into account the particularly large anisotropy of effective hole masses in GaN. Furthermore, several ground- and excited states of the exciton-polaritons and the dominant bound exciton are observed in the photoluminescence (PL) and PLE spectra, facilitating an estimate of the associated complex binding energies. Our data clearly show that great care must be taken if only PL spectra of D0X centers in GaN are analyzed. Every PL feature we observe at higher emission energies with regard to the Si0X ground state corresponds to an excited state. Hence, any unambiguous peak identification renders PLE spectra highly valuable, as important spectral features are obscured in common PL spectra. Here, GaN represents a particular case among the wide-bandgap, wurtzite semiconductors, as comparably low localization energies for common D0X centers are usually paired with large emission linewidths and the prominent optical signature of exciton-polaritons, making the sole analysis of PL spectra a challenging task.

Temporal analysis of nonresonant two-photon coherent control involving bound and dissociative molecular states

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su Jing; Chen Shaohao; Jaron-Becker, Agnieszka

We theoretically study the control of two-photon excitation to bound and dissociative states in a molecule induced by trains of laser pulses, which are equivalent to certain sets of spectral phase modulated pulses. To this end, we solve the time-dependent Schroedinger equation for the interaction of molecular model systems with an external intense laser field. Our numerical results for the temporal evolution of the population in the excited states show that, in the case of an excited dissociative state, control schemes, previously validated for the atomic case, fail due to the coupling of electronic and nuclear motion. In contrast, formore » excitation to bound states the two-photon excitation probability is controlled via the time delay and the carrier-envelope phase difference between two consecutive pulses in the train.« less

Structures of rat cytosolic PEPCK: insight into the mechanism of phosphorylation and decarboxylation of oxaloacetic acid.

PubMed

Sullivan, Sarah M; Holyoak, Todd

2007-09-04

The structures of the rat cytosolic isoform of phosphoenolpyruvate carboxykinase (PEPCK) reported in the PEPCK-Mn2+, -Mn2+-oxaloacetic acid (OAA), -Mn2+-OAA-Mn2+-guanosine-5'-diphosphate (GDP), and -Mn2+-Mn2+-guanosine-5'-tri-phosphate (GTP) complexes provide insight into the mechanism of phosphoryl transfer and decarboxylation mediated by this enzyme. OAA is observed to bind in a number of different orientations coordinating directly to the active site metal. The Mn2+-OAA and Mn2+-OAA-Mn2+GDP structures illustrate inner-sphere coordination of OAA to the manganese ion through the displacement of two of the three water molecules coordinated to the metal in the holo-enzyme by the C3 and C4 carbonyl oxygens. In the PEPCK-Mn2+-OAA complex, an alternate bound conformation of OAA is present. In this conformation, in addition to the previous interactions, the C1 carboxylate is directly coordinated to the active site Mn2+, displacing all of the waters coordinated to the metal in the holo-enzyme. In the PEPCK-Mn2+-GTP structure, the same water molecule displaced by the C1 carboxylate of OAA is displaced by one of the gamma-phosphate oxygens of the triphosphate nucleotide. The structures are consistent with a mechanism of direct in-line phosphoryl transfer, supported by the observed stereochemistry of the reaction. In the catalytically competent binding mode, the C1 carboxylate of OAA is sandwiched between R87 and R405 in an environment that would serve to facilitate decarboxylation. In the reverse reaction, these two arginines would form the CO2 binding site. Comparison of the Mn2+-OAA-Mn2+GDP and Mn2+-Mn2+GTP structures illustrates a marked difference in the bound conformations of the nucleotide substrates in which the GTP nucleotide is bound in a high-energy state resulting from the eclipsing of all three of the phosphoryl groups along the triphosphate chain. This contrasts a previously determined structure of PEPCK in complex with a triphosphate nucleotide analogue in

Bound and resonance states of positronic copper atoms

NASA Astrophysics Data System (ADS)

Yamashita, Takuma; Umair, Muhammad; Kino, Yasushi

2017-10-01

We report a theoretical calculation for the bound and S-wave resonance states of the positronic copper atom (e+Cu). A positron is a positively charged particle; therefore, a positronic atom has an attractive correlation between the positron and electron. A Gaussian expansion method is adopted to directly describe this correlation as well as the strong repulsive interaction with the nucleus. The correlation between the positron and electron is much more important than that between electrons in an analogous system of Cu-, although the formation of a positronium (Ps) in e+Cu is not expressed in the ground state structure explicitly. Resonance states are calculated with a complex scaling method and identified above the first excited state of the copper atom. Resonance states below Ps (n = 2) + Cu+ classified to a dipole series show agreement with a simple analytical law. Comparison of the resonance energies and widths of e+Cu with those of e+K, of which the potential energy of the host atom resembles that of e+Cu, reveals that the positions of the resonance for the e+Cu dipole series deviate equally from those of e+K.

Hadamard States for the Klein-Gordon Equation on Lorentzian Manifolds of Bounded Geometry

NASA Astrophysics Data System (ADS)

Gérard, Christian; Oulghazi, Omar; Wrochna, Michał

2017-06-01

We consider the Klein-Gordon equation on a class of Lorentzian manifolds with Cauchy surface of bounded geometry, which is shown to include examples such as exterior Kerr, Kerr-de Sitter spacetime and the maximal globally hyperbolic extension of the Kerr outer region. In this setup, we give an approximate diagonalization and a microlocal decomposition of the Cauchy evolution using a time-dependent version of the pseudodifferential calculus on Riemannian manifolds of bounded geometry. We apply this result to construct all pure regular Hadamard states (and associated Feynman inverses), where regular refers to the state's two-point function having Cauchy data given by pseudodifferential operators. This allows us to conclude that there is a one-parameter family of elliptic pseudodifferential operators that encodes both the choice of (pure, regular) Hadamard state and the underlying spacetime metric.

All the adiabatic bound states of NO{sub 2}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salzgeber, R.F.; Mandelshtam, V.; Schlier, C.

1998-07-01

We calculated all 2967 even and odd bound states of the adiabatic ground state of NO{sub 2}, using a modification of the abthinspinitio potential energy surface of Leonardi {ital et al.} [J. Chem. Phys. {bold 105}, 9051 (1996)]. The calculation was performed by harmonic inversion of the Chebyshev correlation function generated by a DVR Hamiltonian in Radau coordinates. The relative error for the computed eigenenergies (measured from the potential minimum), is 10{sup {minus}4} or better, corresponding to an absolute error of less than about 2.5thinspcm{sup {minus}1}. Near the dissociation threshold the average density of states is about 0.2/cm{sup {minus}1} formore » each symmetry. Statistical analysis of the states shows some interesting structure of the rigidity parameter {Delta}{sub 3} as a function of energy. {copyright} {ital 1998 American Institute of Physics.}« less

Diabetes Among United States-Bound Adult Refugees, 2009-2014.

PubMed

Benoit, Stephen R; Gregg, Edward W; Zhou, Weigong; Painter, John A

2016-12-01

We reported diabetes prevalence among all US-bound adult refugees and assessed factors associated with disease. We analyzed overseas medical evaluations of US-bound refugees from 2009 through 2014 by using CDC's Electronic Disease Notification System. We identified refugees with diabetes by searching for diabetes-related keywords and medications in examination forms with text-parsing techniques. Age-adjusted prevalence rates were reported and factors associated with diabetes were assessed by using logistic regression. Of 248,850 refugees aged ≥18 years examined over 5 years, 5767 (2.3 %) had diabetes. Iraqis had the highest crude (5.1 %) and age-adjusted (8.9 %) prevalence of disease. Higher age group and body mass index were associated with diabetes in all regions. Diabetes prevalence varied by refugee nationality. Although the absolute rates were lower than rates in the United States, the prevalence is still concerning given the younger age of the population and their need for health services upon resettlement.

Algorithms for Differential Games with Bounded Control and States.

DTIC Science & Technology

1982-03-01

D-R124 642 ALGORITHMS FOR DIFFERENTIAL GAMES WI1TH BOUNDED CONTROL 1/2 AND STATES(U) CALIFORNIA UNIV LOS ANGELES SCHOOL OF ENGINEERING AND APPLIED...RECIPILNT’S CATALOG NUMBER None ~_________ TITLE (end Subtitle) S. TYPE OF REPORT P ERIOD COVERED ALGORITHMS FOR DIFFERENTIAL GAMES WITH Final, 11/29/79-11/28...problems are probably the most natural application of differential game theory and have been treated by many authors as such. Very few problems of this

The light bound states of N=1 supersymmetric SU(3) Yang-Mills theory on the lattice

NASA Astrophysics Data System (ADS)

Ali, Sajid; Bergner, Georg; Gerber, Henning; Giudice, Pietro; Montvay, Istvan; Münster, Gernot; Piemonte, Stefano; Scior, Philipp

2018-03-01

In this article we summarise our results from numerical simulations of N=1 supersymmetric Yang-Mills theory with gauge group SU(3). We use the formulation of Curci and Veneziano with clover-improved Wilson fermions. The masses of various bound states have been obtained at different values of the gluino mass and gauge coupling. Extrapolations to the limit of vanishing gluino mass indicate that the bound states form mass-degenerate supermultiplets.

78 FR 18326 - Agency Information Collection Activities; Comment Request; Upward Bound and Upward Bound Math...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

...; Comment Request; Upward Bound and Upward Bound Math Science Annual Performance Report AGENCY: The Office... considered public records. Title of Collection: Upward Bound and Upward Bound Math Science Annual Performance...) and Upward Bound Math and Science (UBMS) Programs. The Department is requesting a new APR because of...

Structural plasticity mediates distinct GAP-dependent GTP hydrolysis mechanisms in Rab33 and Rab5.

PubMed

Majumdar, Soneya; Acharya, Abhishek; Prakash, Balaji

2017-12-01

The classical GTP hydrolysis mechanism, as seen in Ras, employs a catalytic glutamine provided in cis by the GTPase and an arginine supplied in trans by a GTPase activating protein (GAP). The key idea emergent from a large body of research on small GTPases is that GTPases employ a variety of different hydrolysis mechanisms; evidently, these variations permit diverse rates of GTPase inactivation, crucial for temporal regulation of different biological processes. Recently, we unified these variations and argued that a steric clash between active site residues (corresponding to positions 12 and 61 of Ras) governs whether a GTPase utilizes the cis-Gln or the trans-Gln (from the GAP) for catalysis. As the cis-Gln encounters a steric clash, the Rab GTPases employ the so-called dual finger mechanism where the interacting GAP supplies a trans-Gln for catalysis. Using experimental and computational methods, we demonstrate how the cis-Gln of Rab33 overcomes the steric clash when it is stabilized by a residue in the vicinity. In effect, this demonstrates how both cis-Gln- and trans-Gln-mediated mechanisms could operate in the same GTPase in different contexts, i.e. depending on the GAP that regulates its action. Interestingly, in the case of Rab5, which possesses a higher intrinsic GTP hydrolysis rate, a similar stabilization of the cis-Gln appears to overcome the steric clash. Taken together with the mechanisms seen for Rab1, it is evident that the observed variations in Rab and their GAP partners allow structural plasticity, or in other words, the choice of different catalytic mechanisms. © 2017 Federation of European Biochemical Societies.

Light-Front Hamiltonian Approach to the Bound-State Problem in Quantum Electrodynamics

NASA Astrophysics Data System (ADS)

Jones, Billy D.

1997-10-01

Why is the study of the Lamb shift in hydrogen, which at the level of detail found in this paper was largely completed by Bethe in 1947, of any real interest today? While completing such a calculation using new techniques may be very interesting for formal and academic reasons, our primary motivation is to lay groundwork for precision bound-state calculations in QCD. The Lamb shift provides an excellent pedagogical tool for illustrating light-front Hamiltonian techniques, which are not widely known; but more importantly it presents three of the central dynamical and computational problems that we must face to make these techniques useful for solving QCD: How does a constituent picture emerge in a gauge field theory? How do bound-state energy scales emerge non-perturbatively? How does rotational symmetry emerge in a non-perturbative light-front calculation?

Bound States in Dimerized and Frustrated Heisenberg Chains

NASA Astrophysics Data System (ADS)

Bouzerar, G.; Sil, S.

Using the Bond-Operator Technique (BOT), we have studied the low energy excitation spectrum of a frustrated dimerized antiferromagnetic Heisenberg chain. In particular, we have compared our analytical results with previous Exact Diagonalization (ED) data. Qualitatively, the BOT results are in good agreement with the ED data. And even a very good quantitative agreement is obtained in some parameter region. It is clearly shown that there is only one elementary excitation branch (lowest triplet branch) and that the two other well defined excitations which appear below the continuum, one singlet and one triplet, are bound states of two elementary triplets.

Hyperquarks and bosonic preon bound states

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmid, Michael L.; Buchmann, Alfons J.

2009-11-01

In a model in which leptons, quarks, and the recently introduced hyperquarks are built up from two fundamental spin-(1/2) preons, the standard model weak gauge bosons emerge as preon bound states. In addition, the model predicts a host of new composite gauge bosons, in particular, those responsible for hyperquark and proton decay. Their presence entails a left-right symmetric extension of the standard model weak interactions and a scheme for a partial and grand unification of nongravitational interactions based on, respectively, the effective gauge groups SU(6){sub P} and SU(9){sub G}. This leads to a prediction of the Weinberg angle at lowmore » energies in good agreement with experiment. Furthermore, using evolution equations for the effective coupling strengths, we calculate the partial and grand unification scales, the hyperquark mass scale, as well as the mass and decay rate of the lightest hyperhadron.« less

Index theorem for the flat Andreev bound states at a dirty surface of a nodal superconductor

NASA Astrophysics Data System (ADS)

Ikegaya, Satoshi; Asano, Yasuhiro

2018-03-01

We discuss the stability of at-band Andreev bound states appearing at a surface of a nodal unconventional superconductor. In the clean limit, the existence of the surface bound states is topologically characterized by a momentum-dependent topological invariant: one-dimensional winding number de ned in the restricted Brillouin zone. Thus, such topological invariant is ill-defined in the presence of potential disorder which is inevitable in experiments. By paying attention to chiral symmetry of the Hamiltonian, we provide an alternative topological index N ZES that predicts the number of Andreev bound states at a dirty surface of an unconventional superconductor. Moreover, we demonstrate that the zero-bias differential conductance in a normal metal/unconventional superconductor junction is quantized at (4e 2 /h)|N ZES | in the limit of strong impurity scattering in the normal metal.

Universal bounds on current fluctuations.

PubMed

Pietzonka, Patrick; Barato, Andre C; Seifert, Udo

2016-05-01

For current fluctuations in nonequilibrium steady states of Markovian processes, we derive four different universal bounds valid beyond the Gaussian regime. Different variants of these bounds apply to either the entropy change or any individual current, e.g., the rate of substrate consumption in a chemical reaction or the electron current in an electronic device. The bounds vary with respect to their degree of universality and tightness. A universal parabolic bound on the generating function of an arbitrary current depends solely on the average entropy production. A second, stronger bound requires knowledge both of the thermodynamic forces that drive the system and of the topology of the network of states. These two bounds are conjectures based on extensive numerics. An exponential bound that depends only on the average entropy production and the average number of transitions per time is rigorously proved. This bound has no obvious relation to the parabolic bound but it is typically tighter further away from equilibrium. An asymptotic bound that depends on the specific transition rates and becomes tight for large fluctuations is also derived. This bound allows for the prediction of the asymptotic growth of the generating function. Even though our results are restricted to networks with a finite number of states, we show that the parabolic bound is also valid for three paradigmatic examples of driven diffusive systems for which the generating function can be calculated using the additivity principle. Our bounds provide a general class of constraints for nonequilibrium systems.

Casein kinase II protein kinase is bound to lamina-matrix and phosphorylates lamin-like protein in isolated pea nuclei

NASA Technical Reports Server (NTRS)

Li, H.; Roux, S. J.

1992-01-01

A casein kinase II (CK II)-like protein kinase was identified and partially isolated from a purified envelope-matrix fraction of pea (Pisum sativum L.) nuclei. When [gamma-32P]ATP was directly added to the envelope-matrix preparation, the three most heavily labeled protein bands had molecular masses near 71, 48, and 46 kDa. Protein kinases were removed from the preparation by sequential extraction with Triton X-100, EGTA, 0.3 M NaCl, and a pH 10.5 buffer, but an active kinase still remained bound to the remaining lamina-matrix fraction after these treatments. This kinase had properties resembling CK II kinases previously characterized from animal and plant sources: it preferred casein as an artificial substrate, could use GTP as efficiently as ATP as the phosphoryl donor, was stimulated by spermine, was calcium independent, and had a catalytic subunit of 36 kDa. Some animal and plant CK II kinases have regulatory subunits near 29 kDa, and a lamina-matrix-bound protein of this molecular mass was recognized on immunoblot by anti-Drosophila CK II polyclonal antibodies. Also found associated with the envelope-matrix fraction of pea nuclei were p34cdc2-like and Ca(2+)-dependent protein kinases, but their properties could not account for the protein kinase activity bound to the lamina. The 71-kDa substrate of the CK II-like kinase was lamin A-like, both in its molecular mass and in its cross-reactivity with anti-intermediate filament antibodies. Lamin phosphorylation is considered a crucial early step in the entry of cells into mitosis, so lamina-bound CK II kinases may be important control points for cellular proliferation.

A potential link between insulin signaling and GLUT4 translocation: Association of Rab10-GTP with the exocyst subunit Exoc6/6b

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sano, Hiroyuki; Peck, Grantley R.; Blachon, Stephanie

Insulin increases glucose transport in fat and muscle cells by stimulating the exocytosis of specialized vesicles containing the glucose transporter GLUT4. This process, which is referred to as GLUT4 translocation, increases the amount of GLUT4 at the cell surface. Previous studies have provided evidence that insulin signaling increases the amount of Rab10-GTP in the GLUT4 vesicles and that GLUT4 translocation requires the exocyst, a complex that functions in the tethering of vesicles to the plasma membrane, leading to exocytosis. In the present study we show that Rab10 in its GTP form binds to Exoc6 and Exoc6b, which are the twomore » highly homologous isotypes of an exocyst subunit, that both isotypes are found in 3T3-L1 adipocytes, and that knockdown of Exoc6, Exoc6b, or both inhibits GLUT4 translocation in 3T3-L1 adipocytes. These results suggest that the association of Rab10-GTP with Exoc6/6b is a molecular link between insulin signaling and the exocytic machinery in GLUT4 translocation. - Highlights: • Insulin stimulates the fusion of vesicles containing GLUT4 with the plasma membrane. • This requires vesicular Rab10-GTP and the exocyst plasma membrane tethering complex. • We find that Rab10-GTP associates with the Exoc6 subunit of the exocyst. • We find that knockdown of Exoc6 inhibits fusion of GLUT4 vesicles with the membrane. • The interaction of Rab10-GTP with Exoc6 potentially links signaling to exocytosis.« less

Fluoride-Mediated Capture of a Noncovalent Bound State of a Reversible Covalent Enzyme Inhibitor: X-ray Crystallographic Analysis of an Exceptionally Potent [alpha]-Ketoheterocycle Inhibitor of Fatty Acid Amide Hydrolase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mileni, Mauro; Garfunkle, Joie; Ezzili, Cyrine

2011-11-02

Two cocrystal X-ray structures of the exceptionally potent {alpha}-ketoheterocycle inhibitor 1 (K{sub i} = 290 pM) bound to a humanized variant of rat fatty acid amide hydrolase (FAAH) are disclosed, representing noncovalently and covalently bound states of the same inhibitor with the enzyme. Key to securing the structure of the noncovalently bound state of the inhibitor was the inclusion of fluoride ion in the crystallization conditions that is proposed to bind the oxyanion hole precluding inhibitor covalent adduct formation with stabilization of the tetrahedral hemiketal. This permitted the opportunity to detect important noncovalent interactions stabilizing the binding of the inhibitormore » within the FAAH active site independent of the covalent reaction. Remarkably, noncovalently bound 1 in the presence of fluoride appears to capture the active site in the same 'in action' state with the three catalytic residues Ser241-Ser217-Lys142 occupying essentially identical positions observed in the covalently bound structure of 1, suggesting that this technique of introducing fluoride may have important applications in structural studies beyond inhibiting substrate or inhibitor oxyanion hole binding. Key insights to emerge from the studies include the observations that noncovalently bound 1 binds in its ketone (not gem diol) form, that the terminal phenyl group in the acyl side chain of the inhibitor serves as the key anchoring interaction overriding the intricate polar interactions in the cytosolic port, and that the role of the central activating heterocycle is dominated by its intrinsic electron-withdrawing properties. These two structures are also briefly compared with five X-ray structures of {alpha}-ketoheterocycle-based inhibitors bound to FAAH recently disclosed.« less

Ultrafast dynamics of low-energy electron attachment via a non-valence correlation-bound state

NASA Astrophysics Data System (ADS)

Rogers, Joshua P.; Anstöter, Cate S.; Verlet, Jan R. R.

2018-03-01

The primary electron-attachment process in electron-driven chemistry represents one of the most fundamental chemical transformations with wide-ranging importance in science and technology. However, the mechanistic detail of the seemingly simple reaction of an electron and a neutral molecule to form an anion remains poorly understood, particularly at very low electron energies. Here, time-resolved photoelectron imaging was used to probe the electron-attachment process to a non-polar molecule using time-resolved methods. An initially populated diffuse non-valence state of the anion that is bound by correlation forces evolves coherently in ∼30 fs into a valence state of the anion. The extreme efficiency with which the correlation-bound state serves as a doorway state for low-energy electron attachment explains a number of electron-driven processes, such as anion formation in the interstellar medium and electron attachment to fullerenes.

Ran-dependent TPX2 activation promotes acentrosomal microtubule nucleation in neurons

PubMed Central

Chen, Wen-Shin; Chen, Yi-Ju; Huang, Yung-An; Hsieh, Bing-Yuan; Chiu, Ho-Chieh; Kao, Pei-Ying; Chao, Chih-Yuan; Hwang, Eric

2017-01-01

The microtubule (MT) cytoskeleton is essential for the formation of morphologically appropriate neurons. The existence of the acentrosomal MT organizing center in neurons has been proposed but its identity remained elusive. Here we provide evidence showing that TPX2 is an important component of this acentrosomal MT organizing center. First, neurite elongation is compromised in TPX2-depleted neurons. In addition, TPX2 localizes to the centrosome and along the neurite shaft bound to MTs. Depleting TPX2 decreases MT formation frequency specifically at the tip and the base of the neurite, and these correlate precisely with the regions where active GTP-bound Ran proteins are enriched. Furthermore, overexpressing the downstream effector of Ran, importin, compromises MT formation and neuronal morphogenesis. Finally, applying a Ran-importin signaling interfering compound phenocopies the effect of TPX2 depletion on MT dynamics. Together, these data suggest a model in which Ran-dependent TPX2 activation promotes acentrosomal MT nucleation in neurons. PMID:28205572

Crystal structure of a Schistosoma mansoni septin reveals the phenomenon of strand slippage in septins dependent on the nature of the bound nucleotide.

PubMed

Zeraik, Ana E; Pereira, Humberto M; Santos, Yuri V; Brandão-Neto, José; Spoerner, Michael; Santos, Maiara S; Colnago, Luiz A; Garratt, Richard C; Araújo, Ana P U; DeMarco, Ricardo

2014-03-14

Septins are filament-forming GTP-binding proteins involved in important cellular events, such as cytokinesis, barrier formation, and membrane remodeling. Here, we present two crystal structures of the GTPase domain of a Schistosoma mansoni septin (SmSEPT10), one bound to GDP and the other to GTP. The structures have been solved at an unprecedented resolution for septins (1.93 and 2.1 Å, respectively), which has allowed for unambiguous structural assignment of regions previously poorly defined. Consequently, we provide a reliable model for functional interpretation and a solid foundation for future structural studies. Upon comparing the two complexes, we observe for the first time the phenomenon of a strand slippage in septins. Such slippage generates a front-back communication mechanism between the G and NC interfaces. These data provide a novel mechanistic framework for the influence of nucleotide binding to the GTPase domain, opening new possibilities for the study of the dynamics of septin filaments.

Numerical Solutions of One Reduced Bethe-Salpeter Equation for the Coulombic Bound States Composed of Virtual Constituents

NASA Astrophysics Data System (ADS)

Chen, Jiao-Kai

2018-04-01

We present one reduction of the Bethe-Salpeter equation for the bound states composed of two off-mass-shell constituents. Both the relativistic effects and the virtuality effects can be considered in the obtained spinless virtuality distribution equation. The eigenvalues of the spinless virtuality distribution equation are perturbatively calculated and the bound states e+e-, μ+μ-, τ+τ-, μ+e-, and τ+e- are discussed.

Scattering and bound states of spinless particles in a mixed vector-scalar smooth step potential

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garcia, M.G.; Castro, A.S. de

2009-11-15

Scattering and bound states for a spinless particle in the background of a kink-like smooth step potential, added with a scalar uniform background, are considered with a general mixing of vector and scalar Lorentz structures. The problem is mapped into the Schroedinger-like equation with an effective Rosen-Morse potential. It is shown that the scalar uniform background present subtle and trick effects for the scattering states and reveals itself a high-handed element for formation of bound states. In that process, it is shown that the problem of solving a differential equation for the eigenenergies is transmuted into the simpler and moremore » efficient problem of solving an irrational algebraic equation.« less

Lower bounds to energies for cusped-gaussian wavefunctions. [hydrogen atom ground state

NASA Technical Reports Server (NTRS)

Eaves, J. O.; Walsh, B. C.; Steiner, E.

1974-01-01

Calculations for the ground states of H, He, and Be, conducted by Steiner and Sykes (1972), show that the inclusion of a very small number of cusp functions can lead to a substantial enhancement of the quality of the Gaussian basis used in molecular wavefunction computations. The properties of the cusped-Gaussian basis are investigated by a calculation of lower bounds concerning the ground state energy of the hydrogen atom.

Plant Rho-type (Rop) GTPase-dependent activation of receptor-like cytoplasmic kinases in vitro.

PubMed

Dorjgotov, Dulguun; Jurca, Manuela E; Fodor-Dunai, Csilla; Szucs, Attila; Otvös, Krisztina; Klement, Eva; Bíró, Judit; Fehér, Attila

2009-04-02

Plants have evolved distinct mechanisms to link Rho-type (Rop) GTPases to downstream signaling pathways as compared to other eukaryotes. Here, experimental data are provided that members of the Medicago, as well as Arabidopsis, receptor-like cytoplasmic kinase family (RLCK Class VI) were strongly and specifically activated by GTP-bound Rop GTPases in vitro. Deletion analysis indicated that the residues implicated in the interaction might be distributed on various parts of the kinases. Using a chimaeric Rop GTPase protein, the importance of the Rho-insert region in kinase activation could also be verified. These data strengthen the possibility that RLCKs may serve as Rop GTPase effectors in planta.

Dynamics at Lys-553 of the acto-myosin interface in the weakly and strongly bound states.

PubMed Central

MacLean, J J; Chrin, L R; Berger, C L

2000-01-01

Lys-553 of skeletal muscle myosin subfragment 1 (S1) was specifically labeled with the fluorescent probe FHS (6-[fluorescein-5(and 6)-carboxamido]hexanoic acid succinimidyl ester) and fluorescence quenching experiments were carried out to determine the accessibility of this probe at Lys-553 in both the strongly and weakly actin-bound states of the MgATPase cycle. Solvent quenchers of varying charge [nitromethane, (2,2,6, 6-tetramethyl-1-piperinyloxy) (TEMPO), iodide (I(-)), and thallium (Tl(+))] were used to assess both the steric and electrostatic accessibilities of the FHS probe at Lys-553. In the strongly bound rigor (nucleotide-free) and MgADP states, actin offered no protection from solvent quenching of FHS by nitromethane, TEMPO, or thallium, but did decrease the Stern-Volmer constant by almost a factor of two when iodide was used as the quencher. The protection from iodide quenching was almost fully reversed with the addition of 150 mM KCl, suggesting this effect is ionic in nature rather than steric. Conversely, actin offered no protection from iodide quenching at low ionic strength during steady-state ATP hydrolysis, even with a significant fraction of the myosin heads bound to actin. Thus, the lower 50 kD subdomain of myosin containing Lys-553 appears to interact differently with actin in the weakly and strongly bound states. PMID:10692329

Localization behavior at bound Bi complex states in GaA s 1 - x B i x

DOE PAGES

Alberi, K.; Christian, T. M.; Fluegel, B.; ...

2017-07-01

While bismuth-related states are known to localize carriers in GaAs 1-xBi x alloys, the localization behavior of distinct Bi pair, triplet and cluster states bound above the valence band is less well understood. We probe localization at three different Bi complex states in dilute GaAs 1-xBi x alloys using magneto-photoluminescence and time-resolved photoluminescence spectroscopy. The mass of electrons Coulomb-bound to holes trapped at Bi pair states is found to increase relative to the average electron mass in the alloy. This increase is attributed to enhanced local compressive strain in the immediate vicinity of the pairs. The dependence of energy transfermore » between these states on composition is also explored.« less

Quartified leptonic color, bound states, and future electron–positron collider

DOE PAGES

Kownacki, Corey; Ma, Ernest; Pollard, Nicholas; ...

2017-04-04

The [SU(3)] 4 quartification model of Babu, Ma, and Willenbrock (BMW), proposed in 2003, predicts a confining leptonic color SU(2)gauge symmetry, which becomes strong at the keV scale. Also, it predicts the existence of three families of half-charged leptons (hemions) below the TeV scale. These hemions are confined to form bound states which are not so easy to discover at the Large Hadron Collider (LHC). But, just as J/ψand Υ appeared as sharp resonances in e -e +colliders of the 20th century, the corresponding ‘hemionium’ states are expected at a future e -e +collider of the 21st century.

Observation of Excited Quadrupole-Bound States in Cold Anions

NASA Astrophysics Data System (ADS)

Zhu, Guo-Zhu; Liu, Yuan; Wang, Lai-Sheng

2017-07-01

We report the first observation of an excited quadrupole-bound state (QBS) in an anion. High-resolution photoelectron imaging of cryogenically cooled 4-cyanophenoxide (4 CP- ) anions yields an electron detachment threshold of 24 927 cm-1 . The photodetachment spectrum reveals a resonant transition 20 cm-1 below the detachment threshold, which is attributed to an excited QBS of 4 CP- because neutral 4CP has a large quadrupole moment with a negligible dipole moment. The QBS is confirmed by observation of seventeen above-threshold resonances due to autodetachment from vibrational levels of the QBS.

On the spin- 1/2 Aharonov–Bohm problem in conical space: Bound states, scattering and helicity nonconservation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andrade, F.M., E-mail: fmandrade@uepg.br; Silva, E.O., E-mail: edilbertoo@gmail.com; Pereira, M., E-mail: marciano@uepg.br

2013-12-15

In this work the bound state and scattering problems for a spin- 1/2 particle undergone to an Aharonov–Bohm potential in a conical space in the nonrelativistic limit are considered. The presence of a δ-function singularity, which comes from the Zeeman spin interaction with the magnetic flux tube, is addressed by the self-adjoint extension method. One of the advantages of the present approach is the determination of the self-adjoint extension parameter in terms of physics of the problem. Expressions for the energy bound states, phase-shift and S matrix are determined in terms of the self-adjoint extension parameter, which is explicitly determinedmore » in terms of the parameters of the problem. The relation between the bound state and zero modes and the failure of helicity conservation in the scattering problem and its relation with the gyromagnetic ratio g are discussed. Also, as an application, we consider the spin- 1/2 Aharonov–Bohm problem in conical space plus a two-dimensional isotropic harmonic oscillator. -- Highlights: •Planar dynamics of a spin- 1/2 neutral particle. •Bound state for Aharonov–Bohm systems. •Aharonov–Bohm scattering. •Helicity nonconservation. •Determination of the self-adjoint extension parameter.« less

Conformation-selective resonant photoelectron imaging from dipole-bound states of cold 3-hydroxyphenoxide

NASA Astrophysics Data System (ADS)

Zhu, Guo-Zhu; Huang, Dao-Ling; Wang, Lai-Sheng

2017-07-01

We report a photoelectron imaging and photodetachment study of cryogenically cooled 3-hydroxyphenoxide (3HOP) anions, m-HO(C6H4)O-. In a previous preliminary study, two conformations of the cold 3HOP anions with different dipole bound states were observed [D. L. Huang et al., J. Phys. Chem. Lett. 6, 2153 (2015)]. Five near-threshold vibrational resonances were revealed in the photodetachment spectrum from the dipole-bound excited states of the two conformations. Here, we report a more extensive investigation of the two conformers with observation of thirty above-threshold vibrational resonances in a wide spectral range between 18 850 and 19 920 cm-1 (˜1000 cm-1 above the detachment thresholds). By tuning the detachment laser to the vibrational resonances in the photodetachment spectrum, high-resolution conformation-selective resonant photoelectron images are obtained. Using information of the autodetachment channels and theoretical vibrational frequencies, we are able to assign the resonant peaks in the photodetachment spectrum: seventeen are assigned to vibrational levels of anti-3HOP, eight to syn-3HOP, and five to overlapping vibrational levels of both conformers. From the photodetachment spectrum and the conformation-selective resonant photoelectron spectra, we have obtained fourteen fundamental vibrational frequencies for the neutral syn- and anti-m-HO(C6H4)Oṡ radicals. The possibility to produce conformation-selected neutral beams using resonant photodetachment via dipole-bound excited states of anions is discussed.

Structural Dynamics Control Allosteric Activation of Cytohesin Family Arf GTPase Exchange Factors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malaby, Andrew W.; Das, Sanchaita; Chakravarthy, Srinivas

Membrane dynamic processes including vesicle biogenesis depend on Arf guanosine triphosphatase (GTPase) activation by guanine nucleotide exchange factors (GEFs) containing a catalytic Sec7 domain and a membrane-targeting module such as a pleckstrin homology (PH) domain. The catalytic output of cytohesin family Arf GEFs is controlled by autoinhibitory interactions that impede accessibility of the exchange site in the Sec7 domain. These restraints can be relieved through activator Arf-GTP binding to an allosteric site comprising the PH domain and proximal autoinhibitory elements (Sec7-PH linker and C-terminal helix). Small-angle X-ray scattering and negative-stain electron microscopy were used to investigate the structural organization andmore » conformational dynamics of cytohesin-3 (Grp1) in autoinhibited and active states. The results support a model in which hinge dynamics in the autoinhibited state expose the activator site for Arf-GTP binding, while subsequent C-terminal helix unlatching and repositioning unleash conformational entropy in the Sec7-PH linker to drive exposure of the exchange site.« less

Microtubule assembly governed by tubulin allosteric gain in flexibility and lattice induced fit

PubMed Central

2018-01-01

Microtubules (MTs) are key components of the cytoskeleton and play a central role in cell division and development. MT assembly is known to be associated with a structural change in αβ-tubulin dimers from kinked to straight conformations. How GTP binding renders individual dimers polymerization-competent, however, is still unclear. Here, we have characterized the conformational dynamics and energetics of unassembled tubulin using atomistic molecular dynamics and free energy calculations. Contrary to existing allosteric and lattice models, we find that GTP-tubulin favors a broad range of almost isoenergetic curvatures, whereas GDP-tubulin has a much lower bending flexibility. Moreover, irrespective of the bound nucleotide and curvature, two conformational states exist differing in location of the anchor point connecting the monomers that affects tubulin bending, with one state being strongly favored in solution. Our findings suggest a new combined model in which MTs incorporate and stabilize flexible GTP-dimers with a specific anchor point state. PMID:29652248

Surface Andreev Bound States and Odd-Frequency Pairing in Topological Superconductor Junctions

NASA Astrophysics Data System (ADS)

Tanaka, Yukio; Tamura, Shun

2018-04-01

In this review, we summarize the achievement of the physics of surface Andreev bound states (SABS) up to now. The route of this activity has started from the physics of SABS of unconventional superconductors where the pair potential has a sign change on the Fermi surface. It has been established that SABS can be regarded as a topological edge state with topological invariant defined in the bulk Hamiltonian. On the other hand, SABS accompanies odd-frequency pairing like spin-triplet s-wave or spin-singlet p-wave. In a spin-triplet superconductor junction, induced odd-frequency pairing can penetrate into a diffusive normal metal (DN) attached to the superconductor. It causes so called anomalous proximity effect where the local density of states of quasiparticle in DN has a zero energy peak. When bulk pairing symmetry is spin-triplet px-wave, the anomalous proximity effect becomes prominent and the zero bias voltage conductance is always quantized independent of the resistance in DN and interface. Finally, we show that the present anomalous proximity effect is realized in an artificial topological superconducting system, where a nanowire with spin-orbit coupling and Zeeman field is put on the conventional spin-singlet s-wave superconductor.

Stabilization and control of Majorana bound states with elongated skyrmions

DOE PAGES

Güngördü, Utkan; Sandhoefner, Shane; Kovalev, Alexey A.

2018-03-16

We show that elongated magnetic skyrmions can host Majorana bound states in a proximity-coupled two-dimensional electron gas sandwiched between a chiral magnet and an s-wave superconductor. Our proposal requires stable skyrmions with unit topological charge, which can be realized in a wide range of multilayer magnets, and it allows quantum information transfer by using standard methods in spintronics via skyrmion motion. Finally, we also show how braiding operations can be realized in our proposal.

Conformal mapping and bound states in bent waveguides

NASA Astrophysics Data System (ADS)

Sadurní, E.; Schleich, W. P.

2010-12-01

Is it possible to trap a quantum particle in an open geometry? In this work we deal with the boundary value problem of the stationary Schroedinger (or Helmholtz) equation within a waveguide with straight segments and a rectangular bending. The problem can be reduced to a one-dimensional matrix Schroedinger equation using two descriptions: oblique modes and conformal coordinates. We use a corner-corrected WKB formalism to find the energies of the one-dimensional problem. It is shown that the presence of bound states is an effect due to the boundary alone, with no classical counterpart for this geometry. The conformal description proves to be simpler, as the coupling of transversal modes is not essential in this case.

Bounded energy states in homogeneous turbulent shear flow: An alternative view

NASA Technical Reports Server (NTRS)

Bernard, Peter S.; Speziale, Charles G.

1990-01-01

The equilibrium structure of homogeneous turbulent shear flow is investigated from a theoretical standpoint. Existing turbulence models, in apparent agreement with physical and numerical experiments, predict an unbounded exponential time growth of the turbulent kinetic energy and dissipation rate; only the anisotropy tensor and turbulent time scale reach a structural equilibrium. It is shown that if vortex stretching is accounted for in the dissipation rate transport equation, then there can exist equilibrium solutions, with bounded energy states, where the turbulence production is balanced by its dissipation. Illustrative calculations are present for a k-epsilon model modified to account for vortex stretching. The calculations indicate an initial exponential time growth of the turbulent kinetic energy and dissipation rate for elapsed times that are as large as those considered in any of the previously conducted physical or numerical experiments on homogeneous shear flow. However, vortex stretching eventually takes over and forces a production-equals-dissipation equilibrium with bounded energy states. The validity of this result is further supported by an independent theoretical argument. It is concluded that the generally accepted structural equilibrium for homogeneous shear flow with unbounded component energies is in need of re-examination.

Evidence for a positron bound state on the surface of a topological insulator

NASA Astrophysics Data System (ADS)

Shastry, K.; Weiss, A. H.; Barbiellini, B.; Assaf, B. A.; Lim, Z. H.; Joglekar, P. V.; Heiman, D.

2015-06-01

We describe experiments aimed at probing the sticking of positrons to the surfaces of topological insulators using the Positron Annihilation induced Auger Electron Spectrometer (PAES). A magnetically guided beam was used to deposit positrons at the surface of Bi2Te2Se sample at energy of ∼2eV. Peaks observed in the energy spectra and intensities of electrons emitted as a result of positron annihilation showed peaks at energies corresponding to Auger peaks in Bi, Teand Se providing clear evidence of Auger emission associated with the annihilation of positrons in a surface bound state. Theoretical estimates of the binding energy of this state are compared with estimates obtained by measuring the incident beam energy threshold for secondary electron emission and the temperature dependence positronium(Ps) emission. The experiments provide strong evidence for the existence of a positron bound state at the surface of Bi2Te2Se and indicate the practicality of using positron annihilation to selectively probe the critically important top most layer of topological insulator system.

Probing the Vibrational Spectroscopy of the Deprotonated Thymine Radical by Photodetachment and State-Selective Autodetachment Photoelectron Spectroscopy via Dipole-Bound States

NASA Astrophysics Data System (ADS)

Huang, Dao-Ling; Zhu, Guo-Zhu; Wang, Lai-Sheng

2016-06-01

Deprotonated thymine can exist in two different forms, depending on which of its two N sites is deprotonated: N1[T-H]^- or N3[T-H]^-. Here we report a photodetachment study of the N1[T-H]^- isomer cooled in a cryogenic ion trap and the observation of an excited dipole-bound state. Eighteen vibrational levels of the dipole-bound state are observed, and its vibrational ground state is found to be 238 ± 5 wn below the detachment threshold of N1[T-H]^-. The electron affinity of the deprotonated thymine radical (N1[T-H]^.) is measured accruately to be 26 322 ± 5 wn (3.2635 ± 0.0006 eV). By tuning the detachment laser to the sixteen vibrational levels of the dipole-bound state that are above the detachment threshold, highly non-Franck-Condon resonant-enhanced photoelectron spectra are obtained due to state- and mode-selective vibrational autodetachment. Much richer vibrational information is obtained for the deprotonated thymine radical from the photodetachment and resonant-enhanced photoelectron spectroscopy. Eleven fundamental vibrational frequencies in the low-frequency regime are obtained for the N1[T-H]^. radical, including the two lowest-frequency internal rotational modes of the methyl group at 70 ± 8 wn and 92 ± 5 wn. D. L. Huang, H. T. Liu, C. G. Ning, G. Z. Zhu and L. S. Wang, Chem. Sci., 6, 3129-3138 (2015)

Dynamic studies of H-Ras•GTPγS interactions with nucleotide exchange factor Sos reveal a transient ternary complex formation in solution

PubMed Central

Vo, Uybach; Vajpai, Navratna; Embrey, Kevin J.; Golovanov, Alexander P.

2016-01-01

The cycling between GDP- and GTP- bound forms of the Ras protein is partly regulated by the binding of Sos. The structural/dynamic behavior of the complex formed between activated Sos and Ras at the point of the functional cycle where the nucleotide exchange is completed has not been described to date. Here we show that solution NMR spectra of H-Ras∙GTPγS mixed with a functional fragment of Sos (SosCat) at a 2:1 ratio are consistent with the formation of a rather dynamic assembly. H-Ras∙GTPγS binding was in fast exchange on the NMR timescale and retained a significant degree of molecular tumbling independent of SosCat, while SosCat also tumbled largely independently of H-Ras. Estimates of apparent molecular weight from both NMR data and SEC-MALS revealed that, at most, only one H-Ras∙GTPγS molecule appears stably bound to Sos. The weak transient interaction between Sos and the second H-Ras∙GTPγS may provide a necessary mechanism for complex dissociation upon the completion of the native GDP → GTP exchange reaction, but also explains measurable GTP → GTP exchange activity of Sos routinely observed in in vitro assays that use fluorescently-labelled analogs of GTP. Overall, the data presents the first dynamic snapshot of Ras functional cycle as controlled by Sos. PMID:27412770

Dynamic studies of H-Ras•GTPγS interactions with nucleotide exchange factor Sos reveal a transient ternary complex formation in solution.

PubMed

Vo, Uybach; Vajpai, Navratna; Embrey, Kevin J; Golovanov, Alexander P

2016-07-14

The cycling between GDP- and GTP- bound forms of the Ras protein is partly regulated by the binding of Sos. The structural/dynamic behavior of the complex formed between activated Sos and Ras at the point of the functional cycle where the nucleotide exchange is completed has not been described to date. Here we show that solution NMR spectra of H-Ras∙GTPγS mixed with a functional fragment of Sos (Sos(Cat)) at a 2:1 ratio are consistent with the formation of a rather dynamic assembly. H-Ras∙GTPγS binding was in fast exchange on the NMR timescale and retained a significant degree of molecular tumbling independent of Sos(Cat), while Sos(Cat) also tumbled largely independently of H-Ras. Estimates of apparent molecular weight from both NMR data and SEC-MALS revealed that, at most, only one H-Ras∙GTPγS molecule appears stably bound to Sos. The weak transient interaction between Sos and the second H-Ras∙GTPγS may provide a necessary mechanism for complex dissociation upon the completion of the native GDP → GTP exchange reaction, but also explains measurable GTP → GTP exchange activity of Sos routinely observed in in vitro assays that use fluorescently-labelled analogs of GTP. Overall, the data presents the first dynamic snapshot of Ras functional cycle as controlled by Sos.

An upper bound on the second order asymptotic expansion for the quantum communication cost of state redistribution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Datta, Nilanjana, E-mail: n.datta@statslab.cam.ac.uk; Hsieh, Min-Hsiu, E-mail: Min-Hsiu.Hsieh@uts.edu.au; Oppenheim, Jonathan, E-mail: j.oppenheim@ucl.ac.uk

State redistribution is the protocol in which given an arbitrary tripartite quantum state, with two of the subsystems initially being with Alice and one being with Bob, the goal is for Alice to send one of her subsystems to Bob, possibly with the help of prior shared entanglement. We derive an upper bound on the second order asymptotic expansion for the quantum communication cost of achieving state redistribution with a given finite accuracy. In proving our result, we also obtain an upper bound on the quantum communication cost of this protocol in the one-shot setting, by using the protocol ofmore » coherent state merging as a primitive.« less

Hydroxynonenal-stimulated activity of the uncoupling protein in Acanthamoeba castellanii mitochondria under phosphorylating conditions.

PubMed

Woyda-Ploszczyca, Andrzej; Jarmuszkiewicz, Wieslawa

2013-05-01

The influence of 4-hydroxy-2-nonenal (HNE), a lipid peroxidation end product, on the activity of the amoeba Acanthamoeba castellanii uncoupling protein (AcUCP) in isolated phosphorylating mitochondria was studied. Under phosphorylating conditions, exogenously added HNE induced GTP-sensitive AcUCP-mediated mitochondrial uncoupling. The HNE-induced proton leak decreased the yield of oxidative phosphorylation in an HNE concentration-dependent manner. The present study describes how the contributions of ATP synthase and HNE-induced AcUCP in phosphorylating respiration vary when the rate of succinate oxidation is decreased by limiting succinate uptake or inhibiting complex III activity within the range of a constant membrane potential. In phosphorylating mitochondria, at a given HNE concentration (100 μM), the efficiency of AcUCP in mitochondrial uncoupling increased as the respiratory rate decreased because the AcUCP contribution remained constant while the ATP synthase contribution decreased with the respiratory rate. HNE-induced uncoupling can be inhibited by GTP only when ubiquinone is sufficiently oxidized, indicating that in phosphorylating A. castellanii mitochondria, the sensitivity of AcUCP activity to GTP depends on the redox state of the membranous ubiquinone.

Association between housing type and γ-GTP increase after the Great East Japan Earthquake.

PubMed

Murakami, Aya; Sugawara, Yumi; Tomata, Yasutake; Sugiyama, Kemmyo; Kaiho, Yu; Tanji, Fumiya; Tsuji, Ichiro

2017-09-01

It has been reported that alcohol consumption increases after natural disasters, with an impact on health. However, the impact of relocation upon drinking behavior has been unclear. The aim of this study was to clarify the association between housing type and the impact of alcohol consumption on health after the Great East Japan Earthquake (GEJE) of 2011. We analyzed 569 residents living in devastated areas of Ishinomaki city, who had undergone assessment of their γ-GTP levels at health check-ups in both 2010 and 2013, and had given details of the type of housing they occupied in 2013. The housing types were categorized into five groups: "same housing as that before the GEJE", "prefabricated temporary housing", "privately rented temporary housing/rental housing", "homes of relatives", and "reconstructed housing". We used fixed-effect regression analysis to examine the association between housing type after the GEJE and changes in γ-GTP after adjustment for age, BMI, housing damage, number of people in household, smoking status, presence of illness, psychological distress, and social network. The mean age of the participants was 71.5 years and 46.2% of them were men. The proportion of individuals who drank heavily, and suffered from psychological distress and insomnia, was highest among those living in privately rented temporary housing/rental housing. Compared with individuals who continued to occupy the same housing as those before the GEJE, the effect of change in γ-GTP was significantly higher in individuals who had moved to privately rented temporary housing/rental housing (b = 9.5, SE = 4.4, p < 0.05). Our present findings reveal that disaster victims who have moved to privately rented temporary housing/rental housing are at highest risk of negative health effects due to alcohol drinking. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Dynamic clustering of dynamin-amphiphysin helices regulates membrane constriction and fission coupled with GTP hydrolysis

PubMed Central

Kozai, Toshiya; Yang, Huiran; Ishikuro, Daiki; Seyama, Kaho; Kumagai, Yusuke; Abe, Tadashi; Yamada, Hiroshi; Uchihashi, Takayuki

2018-01-01

Dynamin is a mechanochemical GTPase essential for membrane fission during clathrin-mediated endocytosis. Dynamin forms helical complexes at the neck of clathrin-coated pits and their structural changes coupled with GTP hydrolysis drive membrane fission. Dynamin and its binding protein amphiphysin cooperatively regulate membrane remodeling during the fission, but its precise mechanism remains elusive. In this study, we analyzed structural changes of dynamin-amphiphysin complexes during the membrane fission using electron microscopy (EM) and high-speed atomic force microscopy (HS-AFM). Interestingly, HS-AFM analyses show that the dynamin-amphiphysin helices are rearranged to form clusters upon GTP hydrolysis and membrane constriction occurs at protein-uncoated regions flanking the clusters. We also show a novel function of amphiphysin in size control of the clusters to enhance biogenesis of endocytic vesicles. Our approaches using combination of EM and HS-AFM clearly demonstrate new mechanistic insights into the dynamics of dynamin-amphiphysin complexes during membrane fission. PMID:29357276

Coordination of two sequential ester-transfer reactions: exogenous guanosine binding promotes the subsequent ωG binding to a group I intron

PubMed Central

Bao, Penghui; Wu, Qi-Jia; Yin, Ping; Jiang, Yanfei; Wang, Xu; Xie, Mao-Hua; Sun, Tao; Huang, Lin; Mo, Ding-Ding; Zhang, Yi

2008-01-01

Self-splicing of group I introns is accomplished by two sequential ester-transfer reactions mediated by sequential binding of two different guanosine ligands, but it is yet unclear how the binding is coordinated at a single G-binding site. Using a three-piece trans-splicing system derived from the Candida intron, we studied the effect of the prior GTP binding on the later ωG binding by assaying the ribozyme activity in the second reaction. We showed that adding GTP simultaneously with and prior to the esterified ωG in a substrate strongly accelerated the second reaction, suggesting that the early binding of GTP facilitates the subsequent binding of ωG. GTP-mediated facilitation requires C2 amino and C6 carbonyl groups on the Watson–Crick edge of the base but not the phosphate or sugar groups, suggesting that the base triple interactions between GTP and the binding site are important for the subsequent ωG binding. Strikingly, GTP binding loosens a few local structures of the ribozyme including that adjacent to the base triple, providing structural basis for a rapid exchange of ωG for bound GTP. PMID:18978026

Gravitationally self-bound quantum states in unstable potentials

NASA Astrophysics Data System (ADS)

Jääskeläinen, Markku

2018-04-01

Quantum mechanics at present cannot be unified with the theory of gravity at the deepest level, and to guide research towards the solution of this fundamental problem, we need to look for ways to observe or refute predictions originating from attempts to combine quantum theory with gravity. The influence of the gravitational field created by the material density given by the wave function itself gives rise to nontrivial phenomena. In this study I consider the wave function for the center-of-mass coordinate of a spherical mass distribution under the influence of the self-interaction of Newtonian gravity. I solve numerically for the ground state in the presence of an unstable potential and find that the energy of the free-space bound state can be lowered despite the nontrapping character of the potential. The center-of-mass ground state becomes increasingly localized for the used unstable potentials, although only in a limited parameter regime. The feebleness of the energy shift makes the observation of these effects demanding and requires further developments in the cooling of material particles. In addition, the influence of gravitational perturbations that are present in typical laboratory settings necessitates the use of extremely quiet and controlled environments such as those provided by recently proposed space-borne experiments.

Josephson Radiation from Gapless Andreev Bound States in HgTe-Based Topological Junctions

NASA Astrophysics Data System (ADS)

Deacon, R. S.; Wiedenmann, J.; Bocquillon, E.; Domínguez, F.; Klapwijk, T. M.; Leubner, P.; Brüne, C.; Hankiewicz, E. M.; Tarucha, S.; Ishibashi, K.; Buhmann, H.; Molenkamp, L. W.

2017-04-01

Frequency analysis of the rf emission of oscillating Josephson supercurrent is a powerful passive way of probing properties of topological Josephson junctions. In particular, measurements of the Josephson emission enable the detection of topological gapless Andreev bound states that give rise to emission at half the Josephson frequency fJ rather than conventional emission at fJ. Here, we report direct measurement of rf emission spectra on Josephson junctions made of HgTe-based gate-tunable topological weak links. The emission spectra exhibit a clear signal at half the Josephson frequency fJ/2 . The linewidths of emission lines indicate a coherence time of 0.3-4 ns for the fJ/2 line, much shorter than for the fJ line (3-4 ns). These observations strongly point towards the presence of topological gapless Andreev bound states and pave the way for a future HgTe-based platform for topological quantum computation.

All the nonadiabatic (J=0) bound states of NO{sub 2}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salzgeber, R.F.; Mandelshtam, V.A.; Schlier, C.

1999-02-01

We calculated all 3170 A{sub 1} and B{sub 2} (J=0) vibronic bound states of the coupled electronic ground ({tilde X}&hthinsp;{sup 2}A{sub 1}) and the first excited ({tilde A}&hthinsp;{sup 2}B{sub 2}) surfaces of NO{sub 2}, using a modification of the {ital ab initio} potentials of Leonardi {ital et al.} [J. Chem. Phys. {bold 105}, 9051 (1996)]. The calculation was performed by harmonic inversion of the Chebyshev correlation function generated from a DVR Hamiltonian in Radau coordinates. The rms error of the eigenenergies is about 2.5 cm{sup {minus}1}, corresponding to a relative error of 10{sup {minus}4} near the dissociation energy. The resultsmore » are compared with the adiabatic and diabatic levels calculated from the same surfaces, with experimental data, and with some approximations for the number of states function N(E). The experimental levels are reproduced fairly well up to an energy of 12&hthinsp;000 cm{sup {minus}1} above the potential minimum while the total number of bound levels agrees to within 2{percent} with that calculated from the phase space volume. {copyright} {ital 1999 American Institute of Physics.}« less

Calcium Modulation of Plant Plasma Membrane-Bound Atpase Activities

NASA Technical Reports Server (NTRS)

Caldwell, C.

1983-01-01

The kinetic properties of barley enzyme are discussed and compared with those of other plants. Possibilities for calcium transport in the plasma membrane by proton pump and ATPase-dependent calcium pumps are explored. Topics covered include the ph phase of the enzyme; high affinity of barley for calcium; temperature dependence, activation enthalpy, and the types of ATPase catalytic sites. Attention is given to lipids which are both screened and bound by calcium. Studies show that barley has a calmodulin activated ATPase that is found in the presence of magnesium and calcium.

Clostridial ADP-ribosylating toxins: effects on ATP and GTP-binding proteins.

PubMed

Aktories, K

1994-09-01

The actin cytoskeleton appears to be as the cellular target of various clostridial ADP-ribosyltransferases which have been described during recent years. Clostridium botulinum C2 toxin, Clostridium perfringens iota toxin and Clostridium spiroforme toxin ADP-ribosylate actin monomers and inhibit actin polymerization. Clostridium botulinum exoenzyme C3 and Clostridium limosum exoenzyme ADP-ribosylate the low-molecular-mass GTP-binding proteins of the Rho family, which participate in the regulation of the actin cytoskeleton. ADP-ribosylation inactivates the regulatory Rho proteins and disturbs the organization of the actin cytoskeleton.

Tetraquark bound states in a Bethe-Salpeter approach

NASA Astrophysics Data System (ADS)

Heupel, Walter; Eichmann, Gernot; Fischer, Christian S.

2012-12-01

We determine the mass of tetraquark bound states from a coupled system of covariant Bethe-Salpeter equations. Similar in spirit to the quark-diquark model of the nucleon, we approximate the full four-body equation for the tetraquark by a coupled set of two-body equations with meson and diquark constituents. These are calculated from their quark and gluon substructure using a phenomenologically well-established quark-gluon interaction. For the lightest scalar tetraquark we find a mass of the order of 400 MeV and a wave function dominated by the pion-pion constituents. Both results are in agreement with a meson molecule picture for the f0 (600). Our results furthermore suggest the presence of a potentially narrow all-charm tetraquark in the mass region 5-6 GeV.

Andreev bound states in a semiconducting nanowire Josephson junction, Part II: Quantum jumps and Fermion parity switching

NASA Astrophysics Data System (ADS)

Hays, M.; de Lange, G.; Serniak, K.; van Woerkom, D. J.; Väyrynen, J. I.; van Heck, B.; Vool, U.; Krogstrup, P.; Nygård, J.; Frunzio, L.; Geresdi, A.; Glazman, L. I.; Devoret, M. H.

Proximitized semiconducting nanowires subject to magnetic field should display topological superconductivity and support Majorana zero modes which have non-Abelian braiding statistics. The conventional Andreev levels formed in such wires in the absence of field are a precursor to these exotic zero modes. The fermion-parity switching time of Andreev levels sets a lower bound on the bandwidth required for experiments aimed at harnessing non-Abelian braiding statistics. We demonstrate the observation of quantum jumps between even and odd-parity states of an individual Andreev bound state in a non-topological junction, providing a direct measurement of the state populations and the parity lifetime. Work supported by: ARO, ONR, AFOSR, EU Marie Curie and YINQE.

The GTP- and Phospholipid-Binding Protein TTD14 Regulates Trafficking of the TRPL Ion Channel in Drosophila Photoreceptor Cells

PubMed Central

Cerny, Alexander C.; Altendorfer, André; Schopf, Krystina; Baltner, Karla; Maag, Nathalie; Sehn, Elisabeth; Wolfrum, Uwe; Huber, Armin

2015-01-01

Recycling of signaling proteins is a common phenomenon in diverse signaling pathways. In photoreceptors of Drosophila, light absorption by rhodopsin triggers a phospholipase Cβ-mediated opening of the ion channels transient receptor potential (TRP) and TRP-like (TRPL) and generates the visual response. The signaling proteins are located in a plasma membrane compartment called rhabdomere. The major rhodopsin (Rh1) and TRP are predominantly localized in the rhabdomere in light and darkness. In contrast, TRPL translocates between the rhabdomeral plasma membrane in the dark and a storage compartment in the cell body in the light, from where it can be recycled to the plasma membrane upon subsequent dark adaptation. Here, we identified the gene mutated in trpl translocation defective 14 (ttd14), which is required for both TRPL internalization from the rhabdomere in the light and recycling of TRPL back to the rhabdomere in the dark. TTD14 is highly conserved in invertebrates and binds GTP in vitro. The ttd14 mutation alters a conserved proline residue (P75L) in the GTP-binding domain and abolishes binding to GTP. This indicates that GTP binding is essential for TTD14 function. TTD14 is a cytosolic protein and binds to PtdIns(3)P, a lipid enriched in early endosome membranes, and to phosphatidic acid. In contrast to TRPL, rhabdomeral localization of the membrane proteins Rh1 and TRP is not affected in the ttd14 P75L mutant. The ttd14 P75L mutation results in Rh1-independent photoreceptor degeneration and larval lethality suggesting that other processes are also affected by the ttd14 P75L mutation. In conclusion, TTD14 is a novel regulator of TRPL trafficking, involved in internalization and subsequent sorting of TRPL into the recycling pathway that enables this ion channel to return to the plasma membrane. PMID:26509977

Finite state projection based bounds to compare chemical master equation models using single-cell data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fox, Zachary; Neuert, Gregor; Department of Pharmacology, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232

2016-08-21

Emerging techniques now allow for precise quantification of distributions of biological molecules in single cells. These rapidly advancing experimental methods have created a need for more rigorous and efficient modeling tools. Here, we derive new bounds on the likelihood that observations of single-cell, single-molecule responses come from a discrete stochastic model, posed in the form of the chemical master equation. These strict upper and lower bounds are based on a finite state projection approach, and they converge monotonically to the exact likelihood value. These bounds allow one to discriminate rigorously between models and with a minimum level of computational effort.more » In practice, these bounds can be incorporated into stochastic model identification and parameter inference routines, which improve the accuracy and efficiency of endeavors to analyze and predict single-cell behavior. We demonstrate the applicability of our approach using simulated data for three example models as well as for experimental measurements of a time-varying stochastic transcriptional response in yeast.« less

Extending the Diffuse Layer Model of Surface Acidity Behavior: III. Estimating Bound Site Activity Coefficients

EPA Science Inventory

Although detailed thermodynamic analyses of the 2-pK diffuse layer surface complexation model generally specify bound site activity coefficients for the purpose of accounting for those non-ideal excess free energies contributing to bound site electrochemical potentials, in applic...

A physiologically required G protein-coupled receptor (GPCR)-regulator of G protein signaling (RGS) interaction that compartmentalizes RGS activity.

PubMed

Croft, Wayne; Hill, Claire; McCann, Eilish; Bond, Michael; Esparza-Franco, Manuel; Bennett, Jeannette; Rand, David; Davey, John; Ladds, Graham

2013-09-20

G protein-coupled receptors (GPCRs) can interact with regulator of G protein signaling (RGS) proteins. However, the effects of such interactions on signal transduction and their physiological relevance have been largely undetermined. Ligand-bound GPCRs initiate by promoting exchange of GDP for GTP on the Gα subunit of heterotrimeric G proteins. Signaling is terminated by hydrolysis of GTP to GDP through intrinsic GTPase activity of the Gα subunit, a reaction catalyzed by RGS proteins. Using yeast as a tool to study GPCR signaling in isolation, we define an interaction between the cognate GPCR (Mam2) and RGS (Rgs1), mapping the interaction domains. This reaction tethers Rgs1 at the plasma membrane and is essential for physiological signaling response. In vivo quantitative data inform the development of a kinetic model of the GTPase cycle, which extends previous attempts by including GPCR-RGS interactions. In vivo and in silico data confirm that GPCR-RGS interactions can impose an additional layer of regulation through mediating RGS subcellular localization to compartmentalize RGS activity within a cell, thus highlighting their importance as potential targets to modulate GPCR signaling pathways.

Extracellular guanosine and GTP promote expression of differentiation markers and induce S-phase cell-cycle arrest in human SH-SY5Y neuroblastoma cells.

PubMed

Guarnieri, S; Pilla, R; Morabito, C; Sacchetti, S; Mancinelli, R; Fanò, G; Mariggiò, M A

2009-04-01

SH-SY5Y neuroblastoma cells, a model for studying neuronal differentiation, are able to differentiate into either cholinergic or dopaminergic/adrenergic phenotypes depending on media conditions. Using this system, we asked whether guanosine (Guo) or guanosine-5'-triphosphate (GTP) are able to drive differentiation towards one particular phenotype. Differentiation was determined by evaluating the frequency of cells bearing neurites and assessing neurite length after exposure to different concentrations of Guo or GTP for different durations. After 6 days, 0.3 mM Guo or GTP induced a significant increase in the number of cells bearing neurites and increased neurite length. Western blot analyses confirmed that purines induced differentiation; cells exposed to purines showed increases in the levels of GAP43, MAP2, and tyrosine hydroxylase. Proliferation assays and cytofluorimetric analyses indicated a significant anti-proliferative effect of purines, and a concentration-dependent accumulation of cells in S-phase, starting after 24 h of purine exposure and extending for up to 6 days. A transcriptional profile analysis using gene arrays showed that an up-regulation of cyclin E2/cdk2 evident after 24 h was responsible for S-phase entry, and a concurrent down-regulation of cell-cycle progression-promoting cyclin B1/B2 prevented S-phase exit. In addition, patch-clamp recordings revealed that 0.3 mM Guo or GTP, after 6 day incubation, significantly decreased Na(+) currents. In conclusion, we showed Guo- and GTP-induced cell-cycle arrest in neuroblastoma cells and suggest that this makes these cells more responsive to differentiation processes that favor the dopaminergic/adrenergic phenotype.

GDP-tubulin incorporation into growing microtubules modulates polymer stability.

PubMed

Valiron, Odile; Arnal, Isabelle; Caudron, Nicolas; Job, Didier

2010-06-04

Microtubule growth proceeds through the endwise addition of nucleotide-bound tubulin dimers. The microtubule wall is composed of GDP-tubulin subunits, which are thought to come exclusively from the incorporation of GTP-tubulin complexes at microtubule ends followed by GTP hydrolysis within the polymer. The possibility of a direct GDP-tubulin incorporation into growing polymers is regarded as hardly compatible with recent structural data. Here, we have examined GTP-tubulin and GDP-tubulin incorporation into polymerizing microtubules using a minimal assembly system comprised of nucleotide-bound tubulin dimers, in the absence of free nucleotide. We find that GDP-tubulin complexes can efficiently co-polymerize with GTP-tubulin complexes during microtubule assembly. GDP-tubulin incorporation into microtubules occurs with similar efficiency during bulk microtubule assembly as during microtubule growth from seeds or centrosomes. Microtubules formed from GTP-tubulin/GDP-tubulin mixtures display altered microtubule dynamics, in particular a decreased shrinkage rate, apparently due to intrinsic modifications of the polymer disassembly properties. Thus, although microtubules polymerized from GTP-tubulin/GDP-tubulin mixtures or from homogeneous GTP-tubulin solutions are both composed of GDP-tubulin subunits, they have different dynamic properties, and this may reveal a novel form of microtubule "structural plasticity."

Bound States and Field-Polarized Haldane Modes in a Quantum Spin Ladder.

PubMed

Ward, S; Mena, M; Bouillot, P; Kollath, C; Giamarchi, T; Schmidt, K P; Normand, B; Krämer, K W; Biner, D; Bewley, R; Guidi, T; Boehm, M; McMorrow, D F; Rüegg, Ch

2017-04-28

The challenge of one-dimensional systems is to understand their physics beyond the level of known elementary excitations. By high-resolution neutron spectroscopy in a quantum spin-ladder material, we probe the leading multiparticle excitation by characterizing the two-magnon bound state at zero field. By applying high magnetic fields, we create and select the singlet (longitudinal) and triplet (transverse) excitations of the fully spin-polarized ladder, which have not been observed previously and are close analogs of the modes anticipated in a polarized Haldane chain. Theoretical modeling of the dynamical response demonstrates our complete quantitative understanding of these states.

Secure key from bound entanglement.

PubMed

Horodecki, Karol; Horodecki, Michał; Horodecki, Paweł; Oppenheim, Jonathan

2005-04-29

We characterize the set of shared quantum states which contain a cryptographically private key. This allows us to recast the theory of privacy as a paradigm closely related to that used in entanglement manipulation. It is shown that one can distill an arbitrarily secure key from bound entangled states. There are also states that have less distillable private keys than the entanglement cost of the state. In general, the amount of distillable key is bounded from above by the relative entropy of entanglement. Relationships between distillability and distinguishability are found for a class of states which have Bell states correlated to separable hiding states. We also describe a technique for finding states exhibiting irreversibility in entanglement distillation.

Antioxidant Activities of Selected Berries and Their Free, Esterified, and Insoluble-Bound Phenolic Acid Contents

PubMed Central

2018-01-01

To explore the potential of berries as natural sources of bioactive compounds, the quantities of free, esterified, and insoluble-bound phenolic acids in a number of berries were determined. In addition, the antioxidant activities of the berries were determined using 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, ferric reducing antioxidant power, and Trolox equivalent antioxidant capacity assays, in addition to determination of their metal ion chelating activities. Furthermore, several phenolic compounds were detected using high-performance liquid chromatography. Of the 6 tested berries, black chokeberry and blackberry exhibited the strongest antioxidant activities, and the various berry samples were found to contain catechin, caffeic acid, p-coumaric acid, epicatechin, vanillic acid, quercitrin, resveratrol, morin, naringenin, and apigenin. Moreover, the antioxidant activities and total phenolic contents of the fractions containing insoluble-bound phenolic acids were higher than those containing the free and esterified phenolic acids. The results imply that the insoluble-bound fractions of these berries are important natural sources of antioxidants for the preparation of functional food ingredients and preventing diseases associated with oxidative stress. PMID:29662846

Impurity bound states in mesoscopic topological superconducting loops

NASA Astrophysics Data System (ADS)

Jin, Yan-Yan; Zha, Guo-Qiao; Zhou, Shi-Ping

2018-06-01

We study numerically the effect induced by magnetic impurities in topological s-wave superconducting loops with spin-orbit interaction based on spin-generalized Bogoliubov-de Gennes equations. In the case of a single magnetic impurity, it is found that the midgap bound states can cross the Fermi level at an appropriate impurity strength and the circulating spin current jumps at the crossing point. The evolution of the zero-energy mode can be effectively tuned by the located site of a single magnetic impurity. For the effect of many magnetic impurities, two independent midway or edge impurities cannot lead to the overlap of zero modes. The multiple zero-energy modes can be effectively realized by embedding a single Josephson junction with impurity scattering into the system, and the spin current displays oscillatory feature with increasing the layer thickness.

Antibacterial activity of the soil-bound antimicrobials oxytetracycline and ofloxacin.

PubMed

Peng, Feng-Jiao; Zhou, Li-Jun; Ying, Guang-Guo; Liu, You-Sheng; Zhao, Jian-Liang

2014-04-01

Soil contamination of antimicrobials has become an increasing concern because of the potential risks to the soil microbial ecosystem and human health. The present study investigated sorption and desorption behaviors of oxytetracycline (OTC) and ofloxacin (OFL) in 3 typical soils (A, B, and C), and evaluated the antibacterial activity of soil-adsorbed compounds to a pure sensitive strain Escherichia coli ATCC 25922. The results showed different sorption and desorption behaviors of OTC and OFL in the 3 soils, behaviors that were mainly influenced by soil organic matter content and cation exchange capacity (CEC) as well as pH value. In addition, complexation and cation-exchange reactions were shown to be the main sorption mechanisms. Strong adsorption was found in soil B (with a high organic matter content) and in soil C (with high CEC), whereas enhanced desorption was observed in soil A (with low organic matter content). The results also demonstrated that soil-bound antimicrobials retained antibacterial activity toward E. coli. Opposite patterns of antibacterial activity were found for the 2 antimicrobials in the 3 soils: A>B>C for OFL; and C>B>A for OTC. This finding suggests that soil-bound antimicrobials could still exert selective pressure on soil bacteria although less effectively in comparison with the dissolved forms. © 2014 SETAC.

Dissecting EB1-microtubule interactions from every direction: using single-molecule visualization and static and dynamic binding measurements

NASA Astrophysics Data System (ADS)

Lopez, Benjamin

2015-03-01

EB1 is an important microtubule associating protein (MAP) that acts as a master coordinator of protein activity at the growing plus-end of the microtubule. We can recapitulate the plus-end binding behavior of EB1 along the entire length of a static microtubule using microtubules polymerized in the presence of the nonhydrolyzable GTP analogs GMPCPP and GTP γS instead of GTP. Through the use of single-molecule TIRF imaging we find that EB1 is highly dynamic (with a sub-second characteristic binding lifetime) and continuously diffusive while bound to the microtubule. We measure the diffusion coefficient, D, through linear fitting to mean-squared displacement of individually labeled proteins, and the binding lifetime, τ, by fitting a single exponential decay to the probability distribution of trajectory lifetimes. In agreement with measurements of other diffusive MAPs, we find that D increases and τ decreases with increasing ionic strength. We also find that D is sensitive to the choice of GTP analog: EB1 proteins bound to GTP γS polymerized microtubules have a D half of that found with GMPCPP polymerized microtubules. To compare these single-molecule measurements to the bulk binding behavior of EB1, we use TIRF imaging to measure the intensity of microtubules coated with EB1-GFP as a function of EB1 concentration. We find that EB1 binding is cooperative and both the quantity of EB1 bound and the dissociation constant are sensitive to GTP analog and ionic concentration. The correlation between binding affinity and D and the cooperative nature of EB1-microtubule binding leads to a decrease in D with increasing EB1 concentration. Interestingly, we also find an increase in τ at high EB1 concentrations, consistent with attractive EB1-microtubule interactions driving the cooperativity. To further understand the nature of the cooperativity we estimate the interaction energy by measuring the association and dissociation rates (kon and koff respectively) at different

Combination of selenium-enriched green tea polysaccharides and Huo-ji polysaccharides synergistically enhances antioxidant and immune activity in mice.

PubMed

Yuan, Chengfu; Li, Zhihong; Peng, Fan; Xiao, Fangxiang; Ren, Dongming; Xue, Hui; Chen, Tao; Mushtaq, Gohar; Kamal, Mohammad Amjad

2015-12-01

The aim of this study was to investigate the influence of a combination of selenium-enriched green tea polysaccharides (Se-GTP) and Huo-ji polysaccharides (HJP) on the immune function and antioxidant activity in mice. The results showed that the indices of spleen and thymus were markedly increased, and the activity of natural killer (NK) cell was promoted in mice treated with the combination of Se-GTP and HJP. The combined treatment of Se-GTP and HJP also reduced the content of tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in splenocytes. In addition, the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were remarkably enhanced, and malondialdehyde (MDA) levels were significantly reduced in mice treated with combination of Se-GTP and HJP. Furthermore, the combined treatment of Se-GTP and HJP increased nuclear factor erythroid 2-related factor (Nrf2) expression at mRNA and protein levels in splenocytes. The effects of the combination treatment of Se-GTP and HJP in mice were stronger than with Se-GTP or HJP treatment alone. Our study suggests that the combined administration of Se-GTP and HJP can synergistically improve immune function and decrease the oxidative stress by enhancing the mechanisms involved in the clearance of free radicals. © 2015 Society of Chemical Industry.

Topological Defects in Topological Insulators and Bound States at Topological Superconductor Vortices.

PubMed

Parente, Vincenzo; Campagnano, Gabriele; Giuliano, Domenico; Tagliacozzo, Arturo; Guinea, Francisco

2014-03-04

The scattering of Dirac electrons by topological defects could be one of the most relevant sources of resistance in graphene and at the boundary surfaces of a three-dimensional topological insulator (3D TI). In the long wavelength, continuous limit of the Dirac equation, the topological defect can be described as a distortion of the metric in curved space, which can be accounted for by a rotation of the Gamma matrices and by a spin connection inherited with the curvature. These features modify the scattering properties of the carriers. We discuss the self-energy of defect formation with this approach and the electron cross-section for intra-valley scattering at an edge dislocation in graphene, including corrections coming from the local stress. The cross-section contribution to the resistivity, ρ, is derived within the Boltzmann theory of transport. On the same lines, we discuss the scattering of a screw dislocation in a two-band 3D TI, like Bi 1-x Sb x , and we present the analytical simplified form of the wavefunction for gapless helical states bound at the defect. When a 3D TI is sandwiched between two even-parity superconductors, Dirac boundary states acquire superconductive correlations by proximity. In the presence of a magnetic vortex piercing the heterostructure, two Majorana states are localized at the two interfaces and bound to the vortex core. They have a half integer total angular momentum each, to match with the unitary orbital angular momentum of the vortex charge.

Nucleon Viewed as a Borromean Bound-State

NASA Astrophysics Data System (ADS)

Segovia, Jorge; Mezrag, Cédric; Chang, Lei; Roberts, Craig D.

2018-05-01

We explain how the emergent phenomenon of dynamical chiral symmetry breaking ensures that Poincaré covariant analyses of the three valence-quark scattering problem in continuum quantum field theory yield a picture of the nucleon as a Borromean bound-state, in which binding arises primarily through the sum of two separate contributions. One involves aspects of the non-Abelian character of Quantum Chromodynamics that are expressed in the strong running coupling and generate tight, dynamical color-antitriplet quark-quark correlations in the scalar-isoscalar and pseudovector-isotriplet channels. This attraction is magnified by quark exchange associated with diquark breakup and reformation, which is required in order to ensure that each valence-quark participates in all diquark correlations to the complete extent allowed by its quantum numbers. Combining these effects, we arrive at a properly antisymmetrised Faddeev wave function for the nucleon and calculate, e.g. the flavor-separated versions of the Dirac and Pauli form factors and the proton's leading-twist parton distribution amplitude. We conclude that available data and planned experiments are capable of validating the proposed picture.

Structure of Mandelate Racemase with Bound Intermediate Analogues Benzohydroxamate and Cupferron†

PubMed Central

Lietzan, Adam D.; Nagar, Mitesh; Pellmann, Elise A.; Bourque, Jennifer R.; Bearne, Stephen L.; St Maurice, Martin

2012-01-01

Mandelate racemase (MR, EC 5.1.2.2) from Pseudomonas putida catalyzes the Mg2+-dependent interconversion of the enantiomers of mandelate, stabilizing the altered substrate in the transition state by 26 kcal/mol relative to the substrate in the ground state. To understand the origins of this binding discrimination, we solved the X-ray crystal structures of wild-type MR complexed with two analogues of the putative aci-carboxylate intermediate, benzohydroxamate and cupferron, to 2.2-Å resolution. Benzohydroxamate is shown to be a reasonable mimic of the transition state/intermediate since its binding affinity to 21 MR variants correlates well with changes in the free energy of transition state stabilization afforded by these variants. Both benzohydroxamate and cupferron chelate the active site divalent metal ion and are bound in a conformation with the phenyl ring coplanar with the hydroxamate and diazeniumdiolate moieties, respectively. Structural overlays of MR complexed with benzohydroxamate, cupferron, and the ground state analogue (S)-atrolacatate reveal that the para-carbon of the substrate phenyl ring moves by 0.8–1.2 Å between the ground state and intermediate state, consistent with the proposal that the phenyl ring moves during MR catalysis while the polar groups remain relatively fixed. Although the overall protein structure of MR with bound intermediate analogues is very similar to MR with bound (S)-atrolactate, the intermediate-Mg2+ distance shortens, suggesting a tighter complex with the catalytic Mg2+. In addition, Tyr 54 moves nearer to the phenyl ring of the bound intermediate analogues, contributing to an overall constriction of the active site cavity. However, site-directed mutagenesis experiments revealed that the role of Tyr 54 in MR catalysis is relatively minor, suggesting that alterations in enzyme structure that contribute to discrimination between the altered substrate in the transition state and the ground state by this proficient enzyme

K- absorption on two nucleons and ppK- bound state search in the Σ0p final state

NASA Astrophysics Data System (ADS)

Vázquez Doce, O.; Fabbietti, L.; Cargnelli, M.; Curceanu, C.; Marton, J.; Piscicchia, K.; Scordo, A.; Sirghi, D.; Tucakovic, I.; Wycech, S.; Zmeskal, J.; Anastasi, A.; Curciarello, F.; Czerwinski, E.; Krzemien, W.; Mandaglio, G.; Martini, M.; Moskal, P.; Patera, V.; Pérez del Rio, E.; Silarski, M.

2016-07-01

We report the measurement of K- absorption processes in the Σ0p final state and the first exclusive measurement of the two nucleon absorption (2NA) with the KLOE detector. The 2NA process without further interactions is found to be 9% of the sum of all other contributing processes, including absorption on three and more nucleons or 2NA followed by final state interactions with the residual nucleons. We also determine the possible contribution of the ppK- bound state to the Σ0p final state. The yield of ppK- /Kstop- is found to be (0.044 ± 0.009stat-0.005+0.004 syst) ṡ10-2 but its statistical significance based on an F-test is only 1σ.

Monitoring Ras Interactions with the Nucleotide Exchange Factor Son of Sevenless (Sos) Using Site-specific NMR Reporter Signals and Intrinsic Fluorescence*

PubMed Central

Vo, Uybach; Vajpai, Navratna; Flavell, Liz; Bobby, Romel; Breeze, Alexander L.; Embrey, Kevin J.; Golovanov, Alexander P.

2016-01-01

The activity of Ras is controlled by the interconversion between GTP- and GDP-bound forms partly regulated by the binding of the guanine nucleotide exchange factor Son of Sevenless (Sos). The details of Sos binding, leading to nucleotide exchange and subsequent dissociation of the complex, are not completely understood. Here, we used uniformly 15N-labeled Ras as well as [13C]methyl-Met,Ile-labeled Sos for observing site-specific details of Ras-Sos interactions in solution. Binding of various forms of Ras (loaded with GDP and mimics of GTP or nucleotide-free) at the allosteric and catalytic sites of Sos was comprehensively characterized by monitoring signal perturbations in the NMR spectra. The overall affinity of binding between these protein variants as well as their selected functional mutants was also investigated using intrinsic fluorescence. The data support a positive feedback activation of Sos by Ras·GTP with Ras·GTP binding as a substrate for the catalytic site of activated Sos more weakly than Ras·GDP, suggesting that Sos should actively promote unidirectional GDP → GTP exchange on Ras in preference of passive homonucleotide exchange. Ras·GDP weakly binds to the catalytic but not to the allosteric site of Sos. This confirms that Ras·GDP cannot properly activate Sos at the allosteric site. The novel site-specific assay described may be useful for design of drugs aimed at perturbing Ras-Sos interactions. PMID:26565026

Dissecting GRB7-mediated signals for proliferation and migration in HER2 overexpressing breast tumor cells: GTP-ase rules.

PubMed

Pradip, De; Bouzyk, Mark; Dey, Nandini; Leyland-Jones, Brian

2013-01-01

Amplification of human Her2 and its aberrant signaling in 20-30% of early breast cancer patients is responsible for highly aggressive tumors with poor outcome. Grb7 is reported to be co-amplified with Her2. We report a concurrent high expression of mRNA (from FFPE tumor samples; mRNA correlation, Pearson r(2)= 0.806), and high levels of GRB7 protein (immunoblot) in HER2+ breast cancer cell lines. We demonstrated the signaling mechanism of HER2 and downstream effectors that contributes to proliferation and migration. Using HER2+ and trastuzumab-resistant breast cancer cell lines, we identified the interaction between GRB7 and HER2 in the control of HER2+ cell proliferation. Our co-IP data show that GRB7 recruits SHC into the HER2-GRB7 signaling complex. This complex formation leads to activation of RAS-GTP. We also observed that following integrin engagement, GRB7 is phosphorylated at tyrosine in a p-FAK (Y397) dependent manner. This FAK-GRB7 complex leads to downstream activation of RAC1-GTP (responsible for migration) probably through the recruitment of VAV2. Our CO-IP data demonstrate that GRB7 directly binds with VAV2 following fibronectin engagement in HER2+ cells. To address whether GRB7 could serve as a pathway specific therapeutic target, we used siRNA to suppress GRB7 expression. Knockdown of GRB7 expression in the HER2+ breast cancer cell lines decreases RAS activation, cell proliferation, 2D and 3D colony formation and also blocked integrin-mediated RAC1 activation along with integrin-directed cell migration. These findings dissected the HER2-mediated signaling cascade into (1) HER2+ cell proliferation (HER2-GRB7-SHC-RAS) and (2) HER2+ cell migration (alpha5 beta1/alpha4 beta1-FAK-GRB7-VAV2-RAC1). Our data clearly demonstrate that a coupling of GRB7 with HER2 is required for the proliferative and migratory signals in HER2+ breast tumor cells.

Bound states of water in gelatin discriminated by near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Otsuka, Yukiko; Shirakashi, Ryo; Hirakawa, Kazuhiko

2017-11-01

By near-infrared spectroscopy, we classified water molecules in hydrated gelatin membranes in a drying process. Absorbance spectra in the frequency range of 4500-5500 cm-1 were resolved into three peaks, S0, S1, and S2, that correspond to water molecules with different hydrogen bond states. From the areas of the absorbance peaks as a function of the water content of gelatin, together with the information on the freezing properties of water measured by differential scanning calorimetry, we found that, when the water content is less than 20%, free water disappears and only weakly and strongly bound waters remain. We also found that the weakly bound water consists of S0, S1, and S2 water molecules with a simple composition of \\text{S}0:\\text{S}1:\\text{S}2 ≈ 1:2:0. Using this information, most of the freezable water was determined to be free water. Our classification provides a simple method of estimating the retention and freezing properties of processed foods or drugs by infrared spectroscopy.

Large enhancement of second harmonic generation from transition-metal dichalcogenide monolayer on grating near bound states in the continuum.

PubMed

Wang, Tiecheng; Zhang, Shihao

2018-01-08

Second harmonic generation from the two-layer structure where a transition-metal dichalcogenide monolayer is put on a one-dimensional grating has been studied. This grating supports bound states in the continuum which have no leakage lying within the continuum of radiation modes, we can enhance the second harmonic generation from the transition-metal dichalcogenide monolayer by more than four orders of magnitude based on the critical field enhancement near the bound states in the continuum. In order to complete this calculation, the scattering matrix theory has been extended to include the nonlinear effect and the scattering matrix of a two-dimensional material including nonlinear terms; furthermore, two methods to observe the bound states in the continuum are considered, where one is tuning the thickness of the grating and the other is changing the incident angle of the electromagnetic wave. We have also discussed various modulation of the second harmonic generation enhancement by adjusting the azimuthal angle of the transition-metal dichalcogenide monolayer.

Posttranslational modifications of Rab proteins cause effective displacement of GDP dissociation inhibitor.

PubMed

Oesterlin, Lena K; Goody, Roger S; Itzen, Aymelt

2012-04-10

Intracellular vesicular trafficking is regulated by approximately 60 members of the Rab subfamily of small Ras-like GDP/GTP binding proteins. Rab proteins cycle between inactive and active states as well as between cytosolic and membrane bound forms. Membrane extraction/delivery and cytosolic distribution of Rabs is mediated by interaction with the protein GDP dissociation inhibitor (GDI) that binds to prenylated inactive (GDP-bound) Rab proteins. Because the Rab:GDP:GDI complex is of high affinity, the question arises of how GDI can be displaced efficiently from Rab protein in order to allow the necessary recruitment of the Rab to its specific target membrane. While there is strong evidence that DrrA, as a bacterially encoded GDP/GTP exchange factor, contributes to this event, we show here that posttranslational modifications of Rabs can also modulate the affinity for GDI and thus cause effective displacement of GDI from Rab:GDI complexes. These activities have been found associated with the phosphocholination and adenylylation activities of the enzymes AnkX and DrrA/SidM, respectively, from the pathogenic bacterium Legionella pneumophila. Both modifications occur after spontaneous dissociation of Rab:GDI complexes within their natural equilibrium. Therefore, the effective GDI displacement that is observed is caused by inhibition of reformation of Rab:GDI complexes. Interestingly, in contrast to adenylylation by DrrA, AnkX can covalently modify inactive Rabs with high catalytic efficiency even when GDP is bound to the GTPase and hence can inhibit binding of GDI to Rab:GDP complexes. We therefore speculate that human cells could employ similar mechanisms in the absence of infection to effectively displace Rabs from GDI.

Probing the Dark Sector with Dark Matter Bound States

NASA Astrophysics Data System (ADS)

An, Haipeng; Echenard, Bertrand; Pospelov, Maxim; Zhang, Yue

2016-04-01

A model of the dark sector where O (few GeV ) mass dark matter particles χ couple to a lighter dark force mediator V , mV≪mχ, is motivated by the recently discovered mismatch between simulated and observed shapes of galactic halos. Such models, in general, provide a challenge for direct detection efforts and collider searches. We show that for a large range of coupling constants and masses, the production and decay of the bound states of χ , such as 0-+ and 1-- states, ηD and ϒD, is an important search channel. We show that e+e-→ηD+V or ϒD+γ production at B factories for αD>0.1 is sufficiently strong to result in multiple pairs of charged leptons and pions via ηD→2 V →2 (l+l-) and ϒD→3 V →3 (l+l-) (l =e ,μ ,π ). The absence of such final states in the existing searches performed at BABAR and Belle sets new constraints on the parameter space of the model. We also show that a search for multiple bremsstrahlung of dark force mediators, e+e-→χ χ ¯+n V , resulting in missing energy and multiple leptons, will further improve the sensitivity to self-interacting dark matter.

Bound and resonance states of the dipolar anion of hydrogen cyanide: Competition between threshold effects and rotation in an open quantum system

DOE PAGES

Fossez, K.; Michel, N.; Nazarewicz, W.; ...

2015-01-12

In this paper, bound and resonance states of the dipole-bound anion of hydrogen cyanide HCN – are studied using a nonadiabatic pseudopotential method and the Berggren expansion technique involving bound states, decaying resonant states, and nonresonant scattering continuum. We devise an algorithm to identify the resonant states in the complex energy plane. To characterize spatial distributions of electronic wave functions, we introduce the body-fixed density and use it to assign families of resonant states into collective rotational bands. We find that the nonadiabatic coupling of electronic motion to molecular rotation results in a transition from the strong-coupling to weak-coupling regime.more » In the strong-coupling limit, the electron moving in a subthreshold, spatially extended halo state follows the rotational motion of the molecule. Above the ionization threshold, the electron's motion in a resonance state becomes largely decoupled from molecular rotation. Finally, the widths of resonance-band members depend primarily on the electron orbital angular momentum.« less

Crater property in two-particle bound states: When and why

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chow, Chi-Keung

2000-06-01

Crater has shown that, for two particles (with masses m{sub 1} and m{sub 2}) in a Coulombic bound state, the charge distribution is equal to the sum of the two charge distributions obtained by taking m{sub 1}{yields}{infinity} and m{sub 2}{yields}{infinity}, respectively, while keeping the same Coulombic potential. We provide a simple scaling criterion to determine whether an arbitrary Hamiltonian possesses this property. In particular, we show that, for a Coulombic system, fine structure corrections preserve this Crater property while two-particle relativistic corrections and/or hyperfine corrections may destroy it. (c) 2000 American Association of Physics Teachers.

Quantum localization and bound-state formation in Bose-Einstein condensates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Franzosi, Roberto; Giampaolo, Salvatore M.; Illuminati, Fabrizio

2010-12-15

We discuss the possibility of exponential quantum localization in systems of ultracold bosonic atoms with repulsive interactions in open optical lattices without disorder. We show that exponential localization occurs in the maximally excited state of the lowest energy band. We establish the conditions under which the presence of the upper energy bands can be neglected, determine the successive stages and the quantum phase boundaries at which localization occurs, and discuss schemes to detect it experimentally by visibility measurements. The discussed mechanism is a particular type of quantum localization that is intuitively understood in terms of the interplay between nonlinearity andmore » a bounded energy spectrum.« less

Spontaneous nucleotide exchange in low molecular weight GTPases by fluorescently labeled γ-phosphate-linked GTP analogs

PubMed Central

Korlach, Jonas; Baird, Daniel W.; Heikal, Ahmed A.; Gee, Kyle R.; Hoffman, Gregory R.; Webb, Watt W.

2004-01-01

Regulated guanosine nucleotide exchange and hydrolysis constitute the fundamental activities of low molecular weight GTPases. We show that three guanosine 5′-triphosphate analogs with BODIPY fluorophores coupled via the gamma phosphate bind to the GTPases Cdc42, Rac1, RhoA, and Ras and displace guanosine 5′-diphosphate with high intrinsic exchange rates in the presence of Mg2+ ions, thereby acting as synthetic, low molecular weight guanine nucleotide exchange factors. The accompanying large fluorescence enhancements (as high as 12-fold), caused by a reduction in guanine quenching of the environmentally sensitive BODIPY dye fluorescence on protein binding, allow for real-time monitoring of this spontaneous nucleotide exchange in the visible spectrum with high signal-to-noise ratios. Binding affinities increased with longer aliphatic linkers connecting the nucleotide and BODIPY fluorophore and were in the 10–100 nM range. Steady-state and time-resolved fluorescence spectroscopy showed an inverse relationship between linker length and fluorescence enhancement factors and differences in protein-bound fluorophore mobilities, providing optimization criteria for future applications of such compounds as efficient elicitors and reporters of nucleotide exchange. EDTA markedly enhanced nucleotide exchange, enabling rapid loading of GTPases with these probes. Differences in active site geometries, in the absence of Mg2+, caused qualitatively different reporting of the bound state by the different analogs. The BODIPY analogs also prevented the interaction of Cdc42 with p21 activated kinase. Together, these results validate the use of these analogs as valuable tools for studying GTPase functions and for developing potent synthetic nucleotide exchange factors for this important class of signaling molecules. PMID:14973186

Structural and biochemical analysis of Escherichia coli ObgE, a central regulator of bacterial persistence.

PubMed

Gkekas, Sotirios; Singh, Ranjan Kumar; Shkumatov, Alexander V; Messens, Joris; Fauvart, Maarten; Verstraeten, Natalie; Michiels, Jan; Versées, Wim

2017-04-07

The Obg protein family belongs to the TRAFAC (translation factor) class of P-loop GTPases and is conserved from bacteria to eukaryotes. Essential roles in many different cellular processes have been suggested for the Obg protein from Escherichia coli (ObgE), and we recently showed that it is a central regulator of bacterial persistence. Here, we report the first crystal structure of ObgE at 1.85-Å resolution in the GDP-bound state, showing the characteristic N-terminal domain and a central G domain that are common to all Obg proteins. ObgE also contains an intrinsically disordered C-terminal domain, and we show here that this domain specifically contributed to GTP binding, whereas it did not influence GDP binding or GTP hydrolysis. Biophysical analysis, using small angle X-ray scattering and multi-angle light scattering experiments, revealed that ObgE is a monomer in solution, regardless of the bound nucleotide. In contrast to recent suggestions, our biochemical analyses further indicate that ObgE is neither activated by K + ions nor by homodimerization. However, the ObgE GTPase activity was stimulated upon binding to the ribosome, confirming the ribosome-dependent GTPase activity of the Obg family. Combined, our data represent an important step toward further unraveling the detailed molecular mechanism of ObgE, which might pave the way to further studies into how this GTPase regulates bacterial physiology, including persistence. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Hydroxycinnamic acid bound arabinoxylans from millet brans-structural features and antioxidant activity.

PubMed

Bijalwan, Vandana; Ali, Usman; Kesarwani, Atul Kumar; Yadav, Kamalendra; Mazumder, Koushik

2016-07-01

Hydroxycinnamic acid bound arabinoxylans (HCA-AXs) were extracted from brans of five Indian millet varieties and response surface methodology was used to optimize the extraction conditions. The optimal condition to obtain highest yield of millet HCA-AXs was determined as follows: time 61min, temperature 66°C, ratio of solvent to sample 12ml/g. Linkage analysis indicated that hydroxycinnamic acid bound arabinoxylan from kodo millet (KM-HCA-AX) contained comparatively low branched arabinoxylan consisting of 14.6% mono-substituted, 1.2% di-substituted and 41.2% un-substituted Xylp residues. The HPLC analysis of millet HCA-AXs showed significant variation in the content of three major bound hydroxycinnamic acids (caffeic, p-coumaric and ferulic acid). The antioxidant activity of millet HCA-AXs were evaluated using three in vitro assay methods (DPPH, FRAP and β-carotene linoleate emulsion assays) which suggested both phenolic acid composition and structural characteristics of arabinoxylans could be correlated to their antioxidant potential, the detailed structural analysis revealed that low substituted KM-HCA-AX exhibited relatively higher antioxidant activity compared to other medium and highly substituted HCA-AXs from finger (FM), proso (PM), barnyard (BM) and foxtail (FOXM) millet. Copyright © 2016. Published by Elsevier B.V.

Probable systemic lupus erythematosus with cell-bound complement activation products (CB-CAPS).

PubMed

Lamichhane, D; Weinstein, A

2016-08-01

Complement activation is a key feature of systemic lupus erythematosus (SLE). Detection of cell-bound complement activation products (CB-CAPS) occurs more frequently than serum hypocomplementemia in definite lupus. We describe a patient with normocomplementemic probable SLE who did not fulfill ACR classification criteria for lupus, but the diagnosis was supported by the presence of CB-CAPS. © The Author(s) 2016.

Activation of G-proteins by receptor-stimulated nucleoside diphosphate kinase in Dictyostelium.

PubMed Central

Bominaar, A A; Molijn, A C; Pestel, M; Veron, M; Van Haastert, P J

1993-01-01

Recently, interest in the enzyme nucleoside diphosphate kinase (EC2.7.4.6) has increased as a result of its possible involvement in cell proliferation and development. Since NDP kinase is one of the major sources of GTP in cells, it has been suggested that the effects of an altered NDP kinase activity on cellular processes might be the result of altered transmembrane signal transduction via guanine nucleotide-binding proteins (G-proteins). In the cellular slime mould Dictyostelium discoideum, extracellular cAMP induces an increase of phospholipase C activity via a surface cAMP receptor and G-proteins. In this paper it is demonstrated that part of the cellular NDP kinase is associated with the membrane and stimulated by cell surface cAMP receptors. The GTP produced by the action of NDP kinase is capable of activating G-proteins as monitored by altered G-protein-receptor interaction and the activation of the effector enzyme phospholipase C. Furthermore, specific monoclonal antibodies inhibit the effect of NDP kinase on G-protein activation. These results suggest that receptor-stimulated NDP kinase contributes to the mediation of hormone action by producing GTP for the activation of GTP-binding proteins. Images PMID:8389692

Topological Defects in Topological Insulators and Bound States at Topological Superconductor Vortices

PubMed Central

Parente, Vincenzo; Campagnano, Gabriele; Giuliano, Domenico; Tagliacozzo, Arturo; Guinea, Francisco

2014-01-01

The scattering of Dirac electrons by topological defects could be one of the most relevant sources of resistance in graphene and at the boundary surfaces of a three-dimensional topological insulator (3D TI). In the long wavelength, continuous limit of the Dirac equation, the topological defect can be described as a distortion of the metric in curved space, which can be accounted for by a rotation of the Gamma matrices and by a spin connection inherited with the curvature. These features modify the scattering properties of the carriers. We discuss the self-energy of defect formation with this approach and the electron cross-section for intra-valley scattering at an edge dislocation in graphene, including corrections coming from the local stress. The cross-section contribution to the resistivity, ρ, is derived within the Boltzmann theory of transport. On the same lines, we discuss the scattering of a screw dislocation in a two-band 3D TI, like Bi1−xSbx, and we present the analytical simplified form of the wavefunction for gapless helical states bound at the defect. When a 3D TI is sandwiched between two even-parity superconductors, Dirac boundary states acquire superconductive correlations by proximity. In the presence of a magnetic vortex piercing the heterostructure, two Majorana states are localized at the two interfaces and bound to the vortex core. They have a half integer total angular momentum each, to match with the unitary orbital angular momentum of the vortex charge. PMID:28788537

Two-sided estimates of minimum-error distinguishability of mixed quantum states via generalized Holevo-Curlander bounds

NASA Astrophysics Data System (ADS)

Tyson, Jon

2009-03-01

We prove a concise factor-of-2 estimate for the failure rate of optimally distinguishing an arbitrary ensemble of mixed quantum states, generalizing work of Holevo [Theor. Probab. Appl. 23, 411 (1978)] and Curlander [Ph.D. Thesis, MIT, 1979]. A modification to the minimal principle of Cocha and Poor [Proceedings of the 6th International Conference on Quantum Communication, Measurement, and Computing (Rinton, Princeton, NJ, 2003)] is used to derive a suboptimal measurement which has an error rate within a factor of 2 of the optimal by construction. This measurement is quadratically weighted and has appeared as the first iterate of a sequence of measurements proposed by Ježek et al. [Phys. Rev. A 65, 060301 (2002)]. Unlike the so-called pretty good measurement, it coincides with Holevo's asymptotically optimal measurement in the case of nonequiprobable pure states. A quadratically weighted version of the measurement bound by Barnum and Knill [J. Math. Phys. 43, 2097 (2002)] is proven. Bounds on the distinguishability of syndromes in the sense of Schumacher and Westmoreland [Phys. Rev. A 56, 131 (1997)] appear as a corollary. An appendix relates our bounds to the trace-Jensen inequality.

A novel, kinetically stable, catalytically active, all-ferric, nitrite-bound complex of Paracoccus pantotrophus cytochrome cd1.

PubMed Central

Allen, James W A; Higham, Christopher W; Zajicek, Richard S; Watmough, Nicholas J; Ferguson, Stuart J

2002-01-01

The oxidized form of Paracoccus pantotrophus cytochrome cd(1) nitrite reductase, as isolated, has bis-histidinyl co-ordination of the c haem and His/Tyr co-ordination of the d(1) haem. On reduction, the haem co-ordinations change to His/Met and His/vacant respectively. If the latter form of the enzyme is reoxidized, a conformer is generated in which the ferric c haem is His/Met co-ordinated; this can revert to the 'as isolated' state of the enzyme over approx. 20 min at room temperature. However, addition of nitrite to the enzyme after a cycle of reduction and reoxidation produces a kinetically stable, all-ferric complex with nitrite bound to the d(1) haem and His/Met co-ordination of the c haem. This complex is catalytically active with the physiological electron donor protein pseudoazurin. The effective dissociation constant for nitrite is 2 mM. Evidence is presented that d(1) haem is optimized to bind nitrite, as opposed to other anions that are commonly good ligands to ferric haem. The all-ferric nitrite bound state of the enzyme could not be generated stoichiometrically by mixing nitrite with the 'as isolated' conformer of cytochrome cd(1) without redox cycling. PMID:12086580

Free energy barrier for melittin reorientation from a membrane-bound state to a transmembrane state.

PubMed

Irudayam, Sheeba J; Pobandt, Tobias; Berkowitz, Max L

2013-10-31

An important step in a phospholipid membrane pore formation by melittin antimicrobial peptide is a reorientation of the peptide from a surface into a transmembrane conformation. Experiments measure the fraction of peptides in the surface state and the transmembrane state, but no computational study exists that quantifies the free energy curve for the reorientation. In this work we perform umbrella sampling simulations to calculate the potential of mean force (PMF) for the reorientation of melittin from a surface-bound state to a transmembrane state and provide a molecular level insight in understanding the peptide-lipid properties that influence the existence of the free energy barrier. The PMFs were calculated for a peptide to lipid (P/L) ratio of 1/128 and 4/128. We observe that the free energy barrier is reduced when the P/L ratio increases. In addition, we study the cooperative effect; specifically we investigate if the reorientation barrier is smaller for a second melittin, given that another neighboring melittin was already in the transmembrane orientation. We observe that indeed the barrier of the PMF curve is reduced in this case, thus confirming the presence of a cooperative effect.

Full-potential multiple scattering theory with space-filling cells for bound and continuum states.

PubMed

Hatada, Keisuke; Hayakawa, Kuniko; Benfatto, Maurizio; Natoli, Calogero R

2010-05-12

We present a rigorous derivation of a real-space full-potential multiple scattering theory (FP-MST) that is free from the drawbacks that up to now have impaired its development (in particular the need to expand cell shape functions in spherical harmonics and rectangular matrices), valid both for continuum and bound states, under conditions for space partitioning that are not excessively restrictive and easily implemented. In this connection we give a new scheme to generate local basis functions for the truncated potential cells that is simple, fast, efficient, valid for any shape of the cell and reduces to the minimum the number of spherical harmonics in the expansion of the scattering wavefunction. The method also avoids the need for saturating 'internal sums' due to the re-expansion of the spherical Hankel functions around another point in space (usually another cell center). Thus this approach provides a straightforward extension of MST in the muffin-tin (MT) approximation, with only one truncation parameter given by the classical relation l(max) = kR(b), where k is the electron wavevector (either in the excited or ground state of the system under consideration) and R(b) is the radius of the bounding sphere of the scattering cell. Moreover, the scattering path operator of the theory can be found in terms of an absolutely convergent procedure in the l(max) --> ∞ limit. Consequently, this feature provides a firm ground for the use of FP-MST as a viable method for electronic structure calculations and makes possible the computation of x-ray spectroscopies, notably photo-electron diffraction, absorption and anomalous scattering among others, with the ease and versatility of the corresponding MT theory. Some numerical applications of the theory are presented, both for continuum and bound states.

Stabilizing potentials in bound state analytic continuation methods for electronic resonances in polyatomic molecules

DOE PAGES

White, Alec F.; Head-Gordon, Martin; McCurdy, C. William

2017-01-30

The computation of Siegert energies by analytic continuation of bound state energies has recently been applied to shape resonances in polyatomic molecules by several authors. Here, we critically evaluate a recently proposed analytic continuation method based on low order (type III) Padé approximants as well as an analytic continuation method based on high order (type II) Padé approximants. We compare three classes of stabilizing potentials: Coulomb potentials, Gaussian potentials, and attenuated Coulomb potentials. These methods are applied to a model potential where the correct answer is known exactly and to the 2Π g shape resonance of N 2 - whichmore » has been studied extensively by other methods. Both the choice of stabilizing potential and method of analytic continuation prove to be important to the accuracy of the results. We then conclude that an attenuated Coulomb potential is the most effective of the three for bound state analytic continuation methods. With the proper potential, such methods show promise for algorithmic determination of the positions and widths of molecular shape resonances.« less

Stabilizing potentials in bound state analytic continuation methods for electronic resonances in polyatomic molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

White, Alec F.; Head-Gordon, Martin; McCurdy, C. William

The computation of Siegert energies by analytic continuation of bound state energies has recently been applied to shape resonances in polyatomic molecules by several authors. Here, we critically evaluate a recently proposed analytic continuation method based on low order (type III) Padé approximants as well as an analytic continuation method based on high order (type II) Padé approximants. We compare three classes of stabilizing potentials: Coulomb potentials, Gaussian potentials, and attenuated Coulomb potentials. These methods are applied to a model potential where the correct answer is known exactly and to the 2Π g shape resonance of N 2 - whichmore » has been studied extensively by other methods. Both the choice of stabilizing potential and method of analytic continuation prove to be important to the accuracy of the results. We then conclude that an attenuated Coulomb potential is the most effective of the three for bound state analytic continuation methods. With the proper potential, such methods show promise for algorithmic determination of the positions and widths of molecular shape resonances.« less

Do Reuss and Voigt Bounds Really Bound in High-Pressure Rheology Experiments?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen,J.; Li, L.; Yu, T.

2006-01-01

Energy dispersive synchrotron x-ray diffraction is carried out to measure differential lattice strains in polycrystalline Fe{sub 2}SiO{sub 4} (fayalite) and MgO samples using a multi-element solid state detector during high-pressure deformation. The theory of elastic modeling with Reuss (iso-stress) and Voigt (iso-strain) bounds is used to evaluate the aggregate stress and weight parameter, {alpha} (0{le}{alpha}{le}1), of the two bounds. Results under the elastic assumption quantitatively demonstrate that a highly stressed sample in high-pressure experiments reasonably approximates to an iso-stress state. However, when the sample is plastically deformed, the Reuss and Voigt bounds are no longer valid ({alpha} becomes beyond 1).more » Instead, if plastic slip systems of the sample are known (e.g. in the case of MgO), the aggregate property can be modeled using a visco-plastic self-consistent theory.« less

Real weights, bound states and duality orbits

NASA Astrophysics Data System (ADS)

Marrani, Alessio; Riccioni, Fabio; Romano, Luca

2016-01-01

We show that the duality orbits of extremal black holes in supergravity theories with symmetric scalar manifolds can be derived by studying the stabilizing subalgebras of suitable representatives, realized as bound states of specific weight vectors of the corresponding representation of the duality symmetry group. The weight vectors always correspond to weights that are real, where the reality properties are derived from the Tits-Satake diagram that identifies the real form of the Lie algebra of the duality symmetry group. Both 𝒩 = 2 magic Maxwell-Einstein supergravities and the semisimple infinite sequences of 𝒩 = 2 and 𝒩 = 4 theories in D = 4 and 5 are considered, and various results, obtained over the years in the literature using different methods, are retrieved. In particular, we show that the stratification of the orbits of these theories occurs because of very specific properties of the representations: in the case of the theory based on the real numbers, whose symmetry group is maximally noncompact and therefore all the weights are real, the stratification is due to the presence of weights of different lengths, while in the other cases it is due to the presence of complex weights.

Meson-nucleus potentials and the search for meson-nucleus bound states

NASA Astrophysics Data System (ADS)

Metag, V.; Nanova, M.; Paryev, E. Ya.

2017-11-01

Recent experiments studying the meson-nucleus interaction to extract meson-nucleus potentials are reviewed. The real part of the potentials quantifies whether the interaction is attractive or repulsive while the imaginary part describes the meson absorption in nuclei. The review is focused on mesons which are sufficiently long-lived to potentially form meson-nucleus quasi-bound states. The presentation is confined to meson production off nuclei in photon-, pion-, proton-, and light-ion induced reactions and heavy-ion collisions at energies near the production threshold. Tools to extract the potential parameters are presented. In most cases, the real part of the potential is determined by comparing measured meson momentum distributions or excitation functions with collision model or transport model calculations. The imaginary part is extracted from transparency ratio measurements. Results on K+ ,K0 ,K- , η ,η‧ , ω, and ϕ mesons are presented and compared with theoretical predictions. The interaction of K+ and K0 mesons with nuclei is found to be weakly repulsive, while the K- , η ,η‧ , ω and ϕ meson-nucleus potentials are attractive, however, with widely different strengths. Because of meson absorption in the nuclear medium the imaginary parts of the meson-nucleus potentials are all negative, again with a large spread. An outlook on planned experiments in the charm sector is given. In view of the determined potential parameters, the criteria and chances for experimentally observing meson-nucleus quasi-bound states are discussed. The most promising candidates appear to be the η and η‧ mesons.

Bounding species distribution models

USGS Publications Warehouse

Stohlgren, T.J.; Jarnevich, C.S.; Esaias, W.E.; Morisette, J.T.

2011-01-01

Species distribution models are increasing in popularity for mapping suitable habitat for species of management concern. Many investigators now recognize that extrapolations of these models with geographic information systems (GIS) might be sensitive to the environmental bounds of the data used in their development, yet there is no recommended best practice for "clamping" model extrapolations. We relied on two commonly used modeling approaches: classification and regression tree (CART) and maximum entropy (Maxent) models, and we tested a simple alteration of the model extrapolations, bounding extrapolations to the maximum and minimum values of primary environmental predictors, to provide a more realistic map of suitable habitat of hybridized Africanized honey bees in the southwestern United States. Findings suggest that multiple models of bounding, and the most conservative bounding of species distribution models, like those presented here, should probably replace the unbounded or loosely bounded techniques currently used. ?? 2011 Current Zoology.

Probing the Dark Sector with Dark Matter Bound States.

PubMed

An, Haipeng; Echenard, Bertrand; Pospelov, Maxim; Zhang, Yue

2016-04-15

A model of the dark sector where O(few  GeV) mass dark matter particles χ couple to a lighter dark force mediator V, m_{V}≪m_{χ}, is motivated by the recently discovered mismatch between simulated and observed shapes of galactic halos. Such models, in general, provide a challenge for direct detection efforts and collider searches. We show that for a large range of coupling constants and masses, the production and decay of the bound states of χ, such as 0^{-+} and 1^{--} states, η_{D} and ϒ_{D}, is an important search channel. We show that e^{+}e^{-}→η_{D}+V or ϒ_{D}+γ production at B factories for α_{D}>0.1 is sufficiently strong to result in multiple pairs of charged leptons and pions via η_{D}→2V→2(l^{+}l^{-}) and ϒ_{D}→3V→3(l^{+}l^{-}) (l=e,μ,π). The absence of such final states in the existing searches performed at BABAR and Belle sets new constraints on the parameter space of the model. We also show that a search for multiple bremsstrahlung of dark force mediators, e^{+}e^{-}→χχ[over ¯]+nV, resulting in missing energy and multiple leptons, will further improve the sensitivity to self-interacting dark matter.

Yeast Ras regulates the complex that catalyzes the first step in GPI-anchor biosynthesis at the ER.

PubMed

Sobering, Andrew K; Watanabe, Reika; Romeo, Martin J; Yan, Benjamin C; Specht, Charles A; Orlean, Peter; Riezman, Howard; Levin, David E

2004-05-28

The yeast ERI1 gene encodes a small ER-localized protein that associates in vivo with GTP bound Ras2 in an effector loop-dependent manner. We showed previously that loss of Eri1 function results in hyperactive Ras phenotypes. Here, we demonstrate that Eri1 is a component of the GPI-GlcNAc transferase (GPI-GnT) complex in the ER, which catalyzes transfer of GlcNAc from UDP-GlcNAc to an acceptor phosphatidylinositol, the first step in the production of GPI-anchors for cell surface proteins. We also show that GTP bound Ras2 associates with the GPI-GnT complex in vivo and inhibits its activity, indicating that yeast Ras uses the ER as a signaling platform from which to negatively regulate the GPI-GnT. We propose that diminished GPI-anchor protein production contributes to hyperactive Ras phenotypes.

Andreev bound states probed in three-terminal quantum dots

NASA Astrophysics Data System (ADS)

Gramich, J.; Baumgartner, A.; Schönenberger, C.

2017-11-01

Andreev bound states (ABSs) are well-defined many-body quantum states that emerge from the hybridization of individual quantum dot (QD) states with a superconductor and exhibit very rich and fundamental phenomena. We demonstrate several electron transport phenomena mediated by ABSs that form on three-terminal carbon nanotube (CNT) QDs, with one superconducting (S) contact in the center and two adjacent normal-metal (N) contacts. Three-terminal spectroscopy allows us to identify the coupling to the N contacts as the origin of the Andreev resonance (AR) linewidths and to determine the critical coupling strengths to S, for which a ground state (or quantum phase) transition in such S-QD systems can occur. In addition, we ascribe replicas of the lowest-energy ABS resonance to transitions between the ABS and odd-parity excited QD states, a process we call excited state ABS resonances. In the conductance between the two N contacts we find a characteristic pattern of positive and negative differential subgap conductance, which we explain by considering two nonlocal processes, the creation of Cooper pairs in S by electrons from both N terminals, and a transport mechanism we call resonant ABS tunneling, possible only in multiterminal QD devices. In the latter process, electrons are transferred via the ABS without effectively creating Cooper pairs in S. The three-terminal geometry also allows spectroscopy experiments with different boundary conditions, for example by leaving S floating. Surprisingly, we find that, depending on the boundary conditions and the device parameters, the experiments either show single-particle Coulomb blockade resonances, ABS characteristics, or both in the same measurements, seemingly contradicting the notion of ABSs replacing the single-particle states as eigenstates of the QD. We qualitatively explain these results as originating from the finite time scale required for the coherent oscillations between the superposition states after a single

Comparison of the free and bound phenolic profiles and cellular antioxidant activities of litchi pulp extracts from different solvents

PubMed Central

2014-01-01

Background The phenolic contents and antioxidant activities of fruits could be underestimated if the bound phenolic compounds are not considered. In the present study, the extraction efficiencies of various solvents were investigated in terms of the total content of the free and bound phenolic compounds, as well as the phenolic profiles and antioxidant activities of the extracts. Methods Five different solvent mixtures were used to extract the free phenolic compounds from litchi pulp. Alkaline and acidic hydrolysis methods were compared for the hydrolysis of bound phenolic compounds from litchi pulp residue. The phenolic compositions of the free and bound fractions from the litchi pulp were identified using HPLC-DAD. The antioxidant activities of the litchi pulp extracts were determined by oxygen radical absorbance capacity (ORAC) and cellular antioxidant activity (CAA) assays. Results Of the solvents tested, aqueous acetone extracted the largest amount of total free phenolic compounds (210.7 mg GAE/100 g FW) from litchi pulp, followed sequentially by aqueous mixtures of methanol, ethanol and ethyl acetate, and water itself. The acid hydrolysis method released twice as many bound phenolic compounds as the alkaline hydrolysis method. Nine phenolic compounds were detected in the aqueous acetone extract. In contrast, not all of these compounds were found in the other four extracts. The classification and content of the bound phenolic compounds released by the acid hydrolysis method were higher than those achieved by the alkaline hydrolysis. The aqueous acetone extract showing the highest ORAC value (3406.9 μmol TE/100 g FW) for the free phenolic extracts. For the CAA method, however, the aqueous acetone and methanol extracts (56.7 and 55.1 μmol QE/100 g FW) showed the highest levels of activity of the five extracts tested. The ORAC and CAA values of the bound phenolic compounds obtained by acid hydrolysis were 2.6- and 1.9-fold higher than those obtained using the

Estrogen Modification of Human Glutamate Dehydrogenases Is Linked to Enzyme Activation State*

PubMed Central

Borompokas, Nikolas; Papachatzaki, Maria-Martha; Kanavouras, Konstantinos; Mastorodemos, Vasileios; Zaganas, Ioannis; Spanaki, Cleanthe; Plaitakis, Andreas

2010-01-01

Mammalian glutamate dehydrogenase (GDH) is a housekeeping enzyme central to the metabolism of glutamate. Its activity is potently inhibited by GTP (IC50 = 0.1–0.3 μm) and thought to be controlled by the need of the cell in ATP. Estrogens are also known to inhibit mammalian GDH, but at relatively high concentrations. Because, in addition to this housekeeping human (h) GDH1, humans have acquired via a duplication event an hGDH2 isoform expressed in human cortical astrocytes, we tested here the interaction of estrogens with the two human isoenzymes. The results showed that, under base-line conditions, diethylstilbestrol potently inhibited hGDH2 (IC50 = 0.08 ± 0.01 μm) and with ∼18-fold lower affinity hGDH1 (IC50 = 1.67 ± 0.06 μm; p < 0.001). Similarly, 17β-estradiol showed a ∼18-fold higher affinity for hGDH2 (IC50 = 1.53 ± 0.24 μm) than for hGDH1 (IC50 = 26.94 ± 1.07 μm; p < 0.001). Also, estriol and progesterone were more potent inhibitors of hGDH2 than hGDH1. Structure/function analyses revealed that the evolutionary R443S substitution, which confers low basal activity, was largely responsible for sensitivity of hGDH2 to estrogens. Inhibition of both human GDHs by estrogens was inversely related to their state of activation induced by ADP, with the slope of this correlation being steeper for hGDH2 than for hGDH1. Also, the study of hGDH1 and hGDH2 mutants displaying different states of activation revealed that the affinity of estrogen for these enzymes correlated inversely (R = 0.99; p = 0.0001) with basal catalytic activity. Because astrocytes are known to synthesize estrogens, these hormones, by interacting potently with hGDH2 in its closed state, may contribute to regulation of glutamate metabolism in brain. PMID:20628048

Monitoring Ras Interactions with the Nucleotide Exchange Factor Son of Sevenless (Sos) Using Site-specific NMR Reporter Signals and Intrinsic Fluorescence.

PubMed

Vo, Uybach; Vajpai, Navratna; Flavell, Liz; Bobby, Romel; Breeze, Alexander L; Embrey, Kevin J; Golovanov, Alexander P

2016-01-22

The activity of Ras is controlled by the interconversion between GTP- and GDP-bound forms partly regulated by the binding of the guanine nucleotide exchange factor Son of Sevenless (Sos). The details of Sos binding, leading to nucleotide exchange and subsequent dissociation of the complex, are not completely understood. Here, we used uniformly (15)N-labeled Ras as well as [(13)C]methyl-Met,Ile-labeled Sos for observing site-specific details of Ras-Sos interactions in solution. Binding of various forms of Ras (loaded with GDP and mimics of GTP or nucleotide-free) at the allosteric and catalytic sites of Sos was comprehensively characterized by monitoring signal perturbations in the NMR spectra. The overall affinity of binding between these protein variants as well as their selected functional mutants was also investigated using intrinsic fluorescence. The data support a positive feedback activation of Sos by Ras·GTP with Ras·GTP binding as a substrate for the catalytic site of activated Sos more weakly than Ras·GDP, suggesting that Sos should actively promote unidirectional GDP → GTP exchange on Ras in preference of passive homonucleotide exchange. Ras·GDP weakly binds to the catalytic but not to the allosteric site of Sos. This confirms that Ras·GDP cannot properly activate Sos at the allosteric site. The novel site-specific assay described may be useful for design of drugs aimed at perturbing Ras-Sos interactions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Minimum-error quantum distinguishability bounds from matrix monotone functions: A comment on 'Two-sided estimates of minimum-error distinguishability of mixed quantum states via generalized Holevo-Curlander bounds' [J. Math. Phys. 50, 032106 (2009)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tyson, Jon

2009-06-15

Matrix monotonicity is used to obtain upper bounds on minimum-error distinguishability of arbitrary ensembles of mixed quantum states. This generalizes one direction of a two-sided bound recently obtained by the author [J. Tyson, J. Math. Phys. 50, 032106 (2009)]. It is shown that the previously obtained special case has unique properties.

Formation of Triplet Positron-helium Bound State by Stripping of Positronium Atoms in Collision with Ground State Helium

NASA Technical Reports Server (NTRS)

Drachman, Richard J.

2006-01-01

Formation of triplet positron-helium bound state by stripping of positronium atoms in collision with ground state helium JOSEPH DI RlENZI, College of Notre Dame of Maryland, RICHARD J. DRACHMAN, NASA/Goddard Space Flight Center - The system consisting of a positron and a helium atom in the triplet state e(+)He(S-3)(sup e) was conjectured long ago to be stable [1]. Its stability has recently been established rigorously [2], and the values of the energies of dissociation into the ground states of Ps and He(+) have also been reported [3] and [4]. We have evaluated the cross-section for this system formed by radiative attachment of a positron in triplet He state and found it to be small [5]. The mechanism of production suggested here should result in a larger cross-section (of atomic size) which we are determining using the Born approximation with simplified initial and final wave functions.

GTP analogues promote release of the alpha subunit of the guanine nucleotide binding protein, Gi2, from membranes of rat glioma C6 BU1 cells.

PubMed Central

Milligan, G; Mullaney, I; Unson, C G; Marshall, L; Spiegel, A M; McArdle, H

1988-01-01

The major pertussis-toxin-sensitive guanine nucleotide-binding protein of rat glioma C6 BU1 cells corresponded immunologically to Gi2. Antibodies which recognize the alpha subunit of this protein indicated that it has an apparent molecular mass of 40 kDa and a pI of 5.7. Incubation of membranes of these cells with guanosine 5'-[beta gamma-imido]triphosphate, or other analogues of GTP, caused release of this polypeptide from the membrane in a time-dependent manner. Analogues of GDP or of ATP did not mimic this effect. The GTP analogues similarly caused release of the alpha subunit of Gi2 from membranes of C6 cells in which this G-protein had been inactivated by pretreatment with pertussis toxin. The beta subunit was not released from the membrane under any of these conditions, indicating that the release process was a specific response to the dissociation of the G-protein after binding of the GTP analogue. Similar nucleotide profiles for release of the alpha subunits of forms of Gi were noted for membranes of both the neuroblastoma x glioma hybrid cell line NG108-15 and of human platelets. These data provide evidence that: (1) pertussis-toxin-sensitive G-proteins, in native membranes, do indeed dissociate into alpha and beta gamma subunits upon activation; (2) the alpha subunit of 'Gi-like' proteins need not always remain in intimate association with the plasma membrane; and (3) the alpha subunit of Gi2 can still dissociate from the beta/gamma subunits after pertussis-toxin-catalysed ADP-ribosylation. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:3140801

Bounding Species Distribution Models

NASA Technical Reports Server (NTRS)

Stohlgren, Thomas J.; Jarnevich, Cahterine S.; Morisette, Jeffrey T.; Esaias, Wayne E.

2011-01-01

Species distribution models are increasing in popularity for mapping suitable habitat for species of management concern. Many investigators now recognize that extrapolations of these models with geographic information systems (GIS) might be sensitive to the environmental bounds of the data used in their development, yet there is no recommended best practice for "clamping" model extrapolations. We relied on two commonly used modeling approaches: classification and regression tree (CART) and maximum entropy (Maxent) models, and we tested a simple alteration of the model extrapolations, bounding extrapolations to the maximum and minimum values of primary environmental predictors, to provide a more realistic map of suitable habitat of hybridized Africanized honey bees in the southwestern United States. Findings suggest that multiple models of bounding, and the most conservative bounding of species distribution models, like those presented here, should probably replace the unbounded or loosely bounded techniques currently used [Current Zoology 57 (5): 642-647, 2011].

Correlation of cholinergic drug induced quenching of acetylcholinesterase bound thioflavin-T fluorescence with their inhibition activity

NASA Astrophysics Data System (ADS)

Islam, Mullah Muhaiminul; Rohman, Mostofa Ataur; Gurung, Arun Bahadur; Bhattacharjee, Atanu; Aguan, Kripamoy; Mitra, Sivaprasad

2018-01-01

The development of new acetylcholinesterase inhibitors (AChEIs) and subsequent assay of their inhibition efficiency is considered to be a key step for AD treatment. The fluorescence intensity of thioflavin-T (ThT) bound in the active site of acetylcholinesterase (AChE) quenches substantially in presence of standard AChEI drugs due to the dynamic replacement of the fluorophore from the AChE active site as confirmed from steady state emission as well as time-resolved fluorescence anisotropy measurement and molecular dynamics simulation in conjunction with docking calculation. The parametrized % quenching data for individual system shows excellent correlation with enzyme inhibition activity measured independently by standard Ellman AChE assay method in a high throughput plate reader system. The results are encouraging towards design of a fluorescence intensity based AChE inhibition assay method and may provide a better toolset to rapidly evaluate as well as develop newer AChE-inhibitors for AD treatment.

Charm-beauty meson bound states from B (B*)D (D*) and B (B*)D \\xAF(D\\xAF*) interaction

NASA Astrophysics Data System (ADS)

Sakai, S.; Roca, L.; Oset, E.

2017-09-01

We evaluate the s -wave interaction of pseudoscalar and vector mesons with both charm and beauty to investigate the possible existence of molecular B D , B*D , B D*, B*D*, B D ¯, B*D ¯, B D¯*, or B*D¯* meson states. The scattering amplitude is obtained implementing unitarity starting from a tree level potential accounting for the dominant vector meson exchange. The diagrams are evaluated using suitable extensions to the heavy flavor sector of the hidden gauge symmetry Lagrangians involving vector and pseudoscalar mesons, respecting heavy quark spin symmetry. We obtain bound states at energies above 7 GeV for B D (JP=0+), B*D (1+), B D* (1+), and B*D* (0+, 1+, 2+), all in isospin 0. For B D ¯ (0+), B*D ¯ (1+), B D¯* (1+), and B*D¯* (0+, 1+, 2+) we also find similar bound states in I =0 , but much less bound, which would correspond to exotic meson states with b ¯ and c ¯ quarks, and for the I =1 we find a repulsive interaction. We also evaluate the scattering lengths in all cases, which can be tested in current investigations of lattice QCD.

Two-magnon bound state causes ultrafast thermally induced magnetisation switching

PubMed Central

Barker, J.; Atxitia, U.; Ostler, T. A.; Hovorka, O.; Chubykalo-Fesenko, O.; Chantrell, R. W.

2013-01-01

There has been much interest recently in the discovery of thermally induced magnetisation switching using femtosecond laser excitation, where a ferrimagnetic system can be switched deterministically without an applied magnetic field. Experimental results suggest that the reversal occurs due to intrinsic material properties, but so far the microscopic mechanism responsible for reversal has not been identified. Using computational and analytic methods we show that the switching is caused by the excitation of two-magnon bound states, the properties of which are dependent on material factors. This discovery allows us to accurately predict the onset of switching and the identification of this mechanism will allow new classes of materials to be identified or designed for memory devices in the THz regime. PMID:24253110

78 FR 44553 - Agency Information Collection Activities; Comment Request; Veterans Upward Bound Annual...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-24

... DEPARTMENT OF EDUCATION [Docket No. ED-2013-ICCD-0095] Agency Information Collection Activities; Comment Request; Veterans Upward Bound Annual Performance Report AGENCY: Office of Postsecondary Education (OPE), Department of Education (ED). ACTION: Notice. SUMMARY: In accordance with the Paperwork...

14-3-3 Proteins Interact with a Hybrid Prenyl-Phosphorylation Motif to Inhibit G Proteins

PubMed Central

Riou, Philippe; Kjær, Svend; Garg, Ritu; Purkiss, Andrew; George, Roger; Cain, Robert J.; Bineva, Ganka; Reymond, Nicolas; McColl, Brad; Thompson, Andrew J.; O’Reilly, Nicola; McDonald, Neil Q.; Parker, Peter J.; Ridley, Anne J.

2013-01-01

Summary Signaling through G proteins normally involves conformational switching between GTP- and GDP-bound states. Several Rho GTPases are also regulated by RhoGDI binding and sequestering in the cytosol. Rnd proteins are atypical constitutively GTP-bound Rho proteins, whose regulation remains elusive. Here, we report a high-affinity 14-3-3-binding site at the C terminus of Rnd3 consisting of both the Cys241-farnesyl moiety and a Rho-associated coiled coil containing protein kinase (ROCK)-dependent Ser240 phosphorylation site. 14-3-3 binding to Rnd3 also involves phosphorylation of Ser218 by ROCK and/or Ser210 by protein kinase C (PKC). The crystal structure of a phosphorylated, farnesylated Rnd3 peptide with 14-3-3 reveals a hydrophobic groove in 14-3-3 proteins accommodating the farnesyl moiety. Functionally, 14-3-3 inhibits Rnd3-induced cell rounding by translocating it from the plasma membrane to the cytosol. Rnd1, Rnd2, and geranylgeranylated Rap1A interact similarly with 14-3-3. In contrast to the canonical GTP/GDP switch that regulates most Ras superfamily members, our results reveal an unprecedented mechanism for G protein inhibition by 14-3-3 proteins. PMID:23622247

Highly excited bound-state resonances of short-range inverse power-law potentials

NASA Astrophysics Data System (ADS)

Hod, Shahar

2017-11-01

We study analytically the radial Schrödinger equation with long-range attractive potentials whose asymptotic behaviors are dominated by inverse power-law tails of the form V(r)=-β _n r^{-n} with n>2. In particular, assuming that the effective radial potential is characterized by a short-range infinitely repulsive core of radius R, we derive a compact analytical formula for the threshold energy E^{ {max}}_l=E^{ {max}}_l(n,β _n,R), which characterizes the most weakly bound-state resonance (the most excited energy level) of the quantum system.

Yrb4p, a yeast ran-GTP-binding protein involved in import of ribosomal protein L25 into the nucleus.

PubMed Central

Schlenstedt, G; Smirnova, E; Deane, R; Solsbacher, J; Kutay, U; Görlich, D; Ponstingl, H; Bischoff, F R

1997-01-01

Gsp1p, the essential yeast Ran homologue, is a key regulator of transport across the nuclear pore complex (NPC). We report the identification of Yrb4p, a novel Gsp1p binding protein. The 123 kDa protein was isolated from Saccharomyces cerevisiae cells and found to be related to importin-beta, the mediator of nuclear localization signal (NLS)-dependent import into the nucleus, and to Pse1p. Like importin-beta, Yrb4p and Pse1p specifically bind to Gsp1p-GTP, protecting it from GTP hydrolysis and nucleotide exchange. The GTPase block of Gsp1p complexed to Yrb4p or Pse1p is released by Yrb1p, which contains a Gsp1p binding domain distinct from that of Yrb4p. This might reflect an in vivo function for Yrb1p. Cells disrupted for YRB4 are defective in nuclear import of ribosomal protein L25, but show no defect in the import of proteins containing classical NLSs. Expression of a Yrb4p mutant deficient in Gsp1p-binding is dominant-lethal and blocks bidirectional traffic across the NPC in wild-type cells. L25 binds to Yrb4p and Pse1p and is released by Gsp1p-GTP. Consistent with its putative role as an import receptor for L25-like proteins, Yrb4p localizes to the cytoplasm, the nucleoplasm and the NPC. PMID:9321403

Bounded energy states in homogeneous turbulent shear flow - An alternative view

NASA Technical Reports Server (NTRS)

Bernard, P. S.; Speziale, C. G.

1992-01-01

The equilibrium structure of homogeneous turbulent shear flow is investigated from a theoretical standpoint. Existing turbulence models, in apparent agreement with physical and numerical experiments, predict an unbounded exponential time growth of the turbulent kinetic energy and dissipation rate; only the anisotropy tensor and turbulent time scale reach a structural equilibrium. It is shown that if a residual vortex stretching term is maintained in the dissipation rate transport equation, then there can exist equilibrium solutions, with bounded energy states, where the turbulence production is balanced by its dissipation. Illustrative calculations are presented for a k-epsilon model modified to account for net vortex stretching.

Structural basis for the binding of didemnins to human elongation factor eEF1A and rationale for the potent antitumor activity of these marine natural products.

PubMed

Marco, Esther; Martín-Santamaría, Sonsoles; Cuevas, Carmen; Gago, Federico

2004-08-26

Didemnins and tamandarins are closely related marine natural products with potent inhibitory effects on protein synthesis and cell viability. On the basis of available biochemical and structural evidence and results from molecular dynamics simulations, a model is proposed that accounts for the strong and selective binding of these compounds to human elongation factor eEF1A in the presence of GTP. We suggest that the p-methoxyphenyl ring of these cyclic depsipeptides is inserted into the same pocket in eEF1A that normally lodges either the 3' terminal adenine of aminoacylated tRNA, as inferred from two prokaryotic EF-Tu.GTP.tRNA complexes, or the aromatic side chain of Phe/Tyr-163 from the nucleotide exchange factor eEF1Balpha, as observed in several X-ray crystal structures of a yeast eEF1A:eEF1Balpha complex. This pocket, which has a strong hydrophobic character, is formed by two protruding loops on the surface of eEF1A domain 2. Further stabilization of the bound depsipeptide is brought about by additional crucial interactions involving eEF1A domain 1 in such a way that the molecule fits snugly at the interface between these two domains. In the GDP-bound form of eEF1A, this binding site exists only as two separate halves, which accounts for the much greater affinity of didemnins for the GTP-bound form of this elongation factor. This binding mode is entirely different from those seen in the complexes of the homologous prokaryotic EF-Tu with kirromycin-type antibiotics or the cyclic thiazolyl peptide antibiotic GE2270A. Interestingly, the set of interactions used by didemnins to bind to eEF1A is also distinct from that used by eEF1Balpha or eEF1Bbeta, thus establishing a competition for binding to a common site that goes beyond simple molecular mimicry. The model presented here is consistent with both available biochemical evidence and known structure-activity relationships for these two classes of natural compounds and synthetic analogues and provides fertile

The effects of bound state motion on macromolecular diffusion

NASA Astrophysics Data System (ADS)

Hough, Loren; Stefferson, Michael; Norris, Samantha; Maguire, Laura; Vernerey, Franck; Betterton, Meredith

The diffusion of macromolecules is modified in crowded environments by both inert obstacles and interaction sites. Molecules are generally slowed in their movement inducing transient anomalous subdiffusion. Obstacles also modify the kinetics and equilibrium behavior of interaction between mobile proteins. In some biophysical contexts, bound molecules can still experience mobility, for example transcription factors sliding along DNA, membrane proteins with some entry and diffusion within lipid domains, or proteins that can enter into non-membrane bound compartments such as the nucleolus. We used lattice and continuum models to study the diffusive behavior of tracer particles which bind to obstacles and can diffuse within them. We show that binding significantly alters the motion of tracers. The type and degree of motion while bound is a key determinant of the tracer mobility. Our work has implications for protein-protein movement and interactions within living cells, including those involving intrinsically disordered proteins.

StarD13 is a tumor suppressor in breast cancer that regulates cell motility and invasion

PubMed Central

HANNA, SAMER; KHALIL, BASSEM; NASRALLAH, ANITA; SAYKALI, BECHARA A.; SOBH, RANIA; NASSER, SELIM; EL-SIBAI, MIRVAT

2014-01-01

Breast cancer is one of the most commonly diagnosed cancers in women around the world. In general, the more aggressive the tumor, the more rapidly it grows and the more likely it metastasizes. Members of the Rho subfamily of small GTP-binding proteins (GTPases) play a central role in breast cancer cell motility and metastasis. The switch between active GTP-bound and inactive GDP-bound state is regulated by guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs) and guanine-nucleotide dissociation inhibitors (GDIs). We studied the role of StarD13, a recently identified Rho-GAP that specifically inhibits the function of RhoA and Cdc42. We aimed to investigate its role in breast cancer proliferation and metastasis. The levels of expression of this Rho-GAP in tumor tissues of different grades were assayed using immunohistochemistry. We observed that, while the level of StarD13 expression decreases in cancer tissues compared to normal tissues, it increases as the grade of the tumor increased. This was consistent with the fact that although StarD13 was indeed a tumor suppressor in our breast cancer cells, as seen by its effect on cell proliferation, it was needed for cancer cell motility. In fact, StarD13 knockdown resulted in an inhibition of cell motility and cells were not able to detach their tail and move forward. Our study describes, for the first time, a tumor suppressor that plays a positive role in cancer motility. PMID:24627003

Search For ɛ-Bound Nuclei

NASA Astrophysics Data System (ADS)

Machner, H.

2011-10-01

The η meson can be bound to atomic nuclei. Experimental search is discussed in the form of final state interaction for the reactions dp→3Heη and dd→4Heη. For the latter case tensor polarized deuterons were used in order to extract the s-wave strength. For both reactions complex scattering lengths are deduced: In a two-nucleon transfer reaction under quasi-free conditions, p27Al→3HeX, was investigated. The system X can be the bound 25Mg⊗η at rest. When a possible decay of an intermediate N*(1535) is required, a highly significant bump shows up in the missing mass spectrum. The data give for a bound state a binding energy of 13.3±1.6 MeV and a width of σ = 4.4±1.3 MeV.

Antioxidant activity of commercial buckwheat flours and their free and bound phenolic compositions

USDA-ARS?s Scientific Manuscript database

Buckwheat flours (Whole, Farinetta, Supreme, and Fancy) were investigated for their compositions, free and bound phenolic contents, antioxidant activities, and flavonoid contents using spectrophotometer and LC-ESI-IT- MS (LC-MS). Farinetta flour contained the highest oil, protein, and free and boun...

Generalized Hofmann quantum process fidelity bounds for quantum filters

NASA Astrophysics Data System (ADS)

Sedlák, Michal; Fiurášek, Jaromír

2016-04-01

We propose and investigate bounds on the quantum process fidelity of quantum filters, i.e., probabilistic quantum operations represented by a single Kraus operator K . These bounds generalize the Hofmann bounds on the quantum process fidelity of unitary operations [H. F. Hofmann, Phys. Rev. Lett. 94, 160504 (2005), 10.1103/PhysRevLett.94.160504] and are based on probing the quantum filter with pure states forming two mutually unbiased bases. Determination of these bounds therefore requires far fewer measurements than full quantum process tomography. We find that it is particularly suitable to construct one of the probe bases from the right eigenstates of K , because in this case the bounds are tight in the sense that if the actual filter coincides with the ideal one, then both the lower and the upper bounds are equal to 1. We theoretically investigate the application of these bounds to a two-qubit optical quantum filter formed by the interference of two photons on a partially polarizing beam splitter. For an experimentally convenient choice of factorized input states and measurements we study the tightness of the bounds. We show that more stringent bounds can be obtained by more sophisticated processing of the data using convex optimization and we compare our methods for different choices of the input probe states.

The bound-state properties summary and recommendations of working group 1

NASA Astrophysics Data System (ADS)

Friar, J. L.; Frois, B.

A dozen years ago virtually nothing was known about three-nucleon forces. In the intervening years we have learned to solve routinely the trinucleon bound-state Faddeev equations for what amounts to the complete (model) nucleon-nucleon potential, and to include complicated three-nucleon forces as well. The art of constructing those forces has dramatically improved, and modern versions of these forces contain components derived from the exchange of heavy mesons, in addition to pion exchange. Experimental sophistication in probing the trinucleon ground states has made similar improvements. The recent Saclay and MIT tritium form factor experiments have finally unravelled the isospin structure of the trinucleon charge densities, and have generated new challenges for theorists. Although there are few definite conclusions yet and much remains to be done, the progress has been exceptional. Perhaps it is not too pretentious to quote the final frame of the movie 41 Destination Moon: "This is the end of the beginning."

Characterization of the Deoxynucleotide Triphosphate Triphosphohydrolase (dNTPase) Activity of the EF1143 Protein from Enterococcus faecalis and Crystal Structure of the Activator-Substrate Complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vorontsov, Ivan I.; Minasov, George; Kiryukhina, Olga

2012-06-19

The EF1143 protein from Enterococcus faecalis is a distant homolog of deoxynucleotide triphosphate triphosphohydrolases (dNTPases) from Escherichia coli and Thermus thermophilus. These dNTPases are important components in the regulation of the dNTP pool in bacteria. Biochemical assays of the EF1143 dNTPase activity demonstrated nonspecific hydrolysis of all canonical dNTPs in the presence of Mn{sup 2+}. In contrast, with Mg{sup 2+} hydrolysis required the presence of dGTP as an effector, activating the degradation of dATP and dCTP with dGTP also being consumed in the reaction with dATP. The crystal structure of EF1143 and dynamic light scattering measurements in solution revealed amore » tetrameric oligomer as the most probable biologically active unit. The tetramer contains four dGTP specific allosteric regulatory sites and four active sites. Examination of the active site with the dATP substrate suggests an in-line nucleophilic attack on the {alpha}-phosphate center as a possible mechanism of the hydrolysis and two highly conserved residues, His-129 and Glu-122, as an acid-base catalytic dyad. Structural differences between EF1143 apo and holo forms revealed mobility of the {alpha}3 helix that can regulate the size of the active site binding pocket and could be stabilized in the open conformation upon formation of the tetramer and dGTP effector binding.« less

Structural studies of the nudix hydrolase DR1025 from deinococcus radiodurans and its ligand complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ranatunga, Wasantha; Hill, Emma E.; Mooster, Jana L.

We have determined the crystal structure, at 1.4, of the Nudix hydrolase DR1025 from the extremely radiation resistant bacterium Deinococcus radiodurans. The protein forms an intertwined homodimer by exchanging N-terminal segments between chains. We have identified additional conserved elements of the Nudix fold, including the metal-binding motif, a kinked b-strand characterized by a proline two positions upstream of the Nudix consensus sequence, and participation of the N-terminal extension in the formation of the substrate-binding pocket. Crystal structures were also solved of DR1025 crystallized in the presence of magnesium and either a GTP analog or Ap4A (both at 1.6 resolution). Inmore » the Ap4Aco-crystal, the electron density indicated that the product of asymmetric hydrolysis, ATP, was bound to the enzyme. The GTP analog bound structure showed that GTP was bound almost identically as ATP. Neither nucleoside triphosphate was further cleaved.« less

¹H, ¹³C and ¹⁵N resonance assignment for the human K-Ras at physiological pH.

PubMed

Vo, Uybach; Embrey, Kevin J; Breeze, Alexander L; Golovanov, Alexander P

2013-10-01

K-Ras, a member of the Ras family of small GTPases, is involved in cell growth, proliferation, differentiation and apoptosis and is frequently mutated in cancer. The activity of Ras is mediated by the inter-conversion between GTP- and GDP- bound states. This conversion is regulated by binding of effector proteins such as guanine nucleotide exchange factors and GTPase activating proteins. Previously, NMR signals from these effector-binding regions of Ras often remained unassigned and largely unobservable due to conformational exchange and polysterism inherent to this protein. In this paper, we report the complete backbone and C(β), as well as partial H(α), H(β) and C(γ), NMR assignment for human K-Ras (residues 1-166) in the GDP-bound form at a physiological pH of 7.4. These data thereby make possible detailed monitoring of the functional cycle of Ras and its interactions with nucleotides and effector proteins through the observation of fingerprint signals from all the functionally important regions of the protein.

Parkinson’s disease in GTP cyclohydrolase 1 mutation carriers

PubMed Central

Mencacci, Niccolò E.; Isaias, Ioannis U.; Reich, Martin M.; Ganos, Christos; Plagnol, Vincent; Polke, James M.; Bras, Jose; Hersheson, Joshua; Stamelou, Maria; Pittman, Alan M.; Noyce, Alastair J.; Mok, Kin Y.; Opladen, Thomas; Kunstmann, Erdmute; Hodecker, Sybille; Münchau, Alexander; Volkmann, Jens; Samnick, Samuel; Sidle, Katie; Nanji, Tina; Sweeney, Mary G.; Houlden, Henry; Batla, Amit; Zecchinelli, Anna L.; Pezzoli, Gianni; Marotta, Giorgio; Lees, Andrew; Alegria, Paulo; Krack, Paul; Cormier-Dequaire, Florence; Lesage, Suzanne; Brice, Alexis; Heutink, Peter; Gasser, Thomas; Lubbe, Steven J.; Morris, Huw R.; Taba, Pille; Koks, Sulev; Majounie, Elisa; Raphael Gibbs, J.; Singleton, Andrew; Hardy, John; Klebe, Stephan

2014-01-01

GTP cyclohydrolase 1, encoded by the GCH1 gene, is an essential enzyme for dopamine production in nigrostriatal cells. Loss-of-function mutations in GCH1 result in severe reduction of dopamine synthesis in nigrostriatal cells and are the most common cause of DOPA-responsive dystonia, a rare disease that classically presents in childhood with generalized dystonia and a dramatic long-lasting response to levodopa. We describe clinical, genetic and nigrostriatal dopaminergic imaging ([123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane single photon computed tomography) findings of four unrelated pedigrees with DOPA-responsive dystonia in which pathogenic GCH1 variants were identified in family members with adult-onset parkinsonism. Dopamine transporter imaging was abnormal in all parkinsonian patients, indicating Parkinson’s disease-like nigrostriatal dopaminergic denervation. We subsequently explored the possibility that pathogenic GCH1 variants could contribute to the risk of developing Parkinson’s disease, even in the absence of a family history for DOPA-responsive dystonia. The frequency of GCH1 variants was evaluated in whole-exome sequencing data of 1318 cases with Parkinson’s disease and 5935 control subjects. Combining cases and controls, we identified a total of 11 different heterozygous GCH1 variants, all at low frequency. This list includes four pathogenic variants previously associated with DOPA-responsive dystonia (Q110X, V204I, K224R and M230I) and seven of undetermined clinical relevance (Q110E, T112A, A120S, D134G, I154V, R198Q and G217V). The frequency of GCH1 variants was significantly higher (Fisher’s exact test P-value 0.0001) in cases (10/1318 = 0.75%) than in controls (6/5935 = 0.1%; odds ratio 7.5; 95% confidence interval 2.4–25.3). Our results show that rare GCH1 variants are associated with an increased risk for Parkinson’s disease. These findings expand the clinical and biological relevance of GTP cycloydrolase 1

Analytical study of bound states in graphene nanoribbons and carbon nanotubes: The variable phase method and the relativistic Levinson theorem

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miserev, D. S., E-mail: d.miserev@student.unsw.edu.au, E-mail: erazorheader@gmail.com

2016-06-15

The problem of localized states in 1D systems with a relativistic spectrum, namely, graphene stripes and carbon nanotubes, is studied analytically. The bound state as a superposition of two chiral states is completely described by their relative phase, which is the foundation of the variable phase method (VPM) developed herein. Based on our VPM, we formulate and prove the relativistic Levinson theorem. The problem of bound states can be reduced to the analysis of closed trajectories of some vector field. Remarkably, the Levinson theorem appears as the Poincaré index theorem for these closed trajectories. The VPM equation is also reducedmore » to the nonrelativistic and semiclassical limits. The limit of a small momentum p{sub y} of transverse quantization is applicable to an arbitrary integrable potential. In this case, a single confined mode is predicted.« less

Exact edge, bulk, and bound states of finite topological systems

NASA Astrophysics Data System (ADS)

Duncan, Callum W.; Öhberg, Patrik; Valiente, Manuel

2018-05-01

Finite topologically nontrivial systems are characterized, among many other unique properties, by the presence of bound states at their physical edges. These topological edge modes can be distinguished from usual Shockley waves energetically, as their energies remain finite and in gap even when the boundaries of the system represent an effectively infinite and sharp energetic barrier. Theoretically, the existence of topological edge modes can be shown by means of the bulk-edge correspondence and topological invariants. On a clean one-dimensional lattice and reducible two-dimensional models, in either the commensurate or semi-infinite case, the edge modes can be essentially obtained analytically, as shown previously [Y. Hatsugai, Phys. Rev. Lett. 71, 3697 (1993), 10.1103/PhysRevLett.71.3697; D. Hügel and B. Paredes, Phys. Rev. A 89, 023619 (2014), 10.1103/PhysRevA.89.023619]. In this work, we put forward a method for obtaining the spectrum and wave functions of topological edge modes for arbitrary finite lattices, including the incommensurate case. A small number of parameters are easily determined numerically, with the form of the eigenstates remaining fully analytical. We also obtain the bulk modes in the finite system analytically and their associated eigenenergies, which lie within the infinite-size limit continuum. Our method is general and can be easily applied to obtain the properties of nontopological models and/or extended to include impurities. As an example, we consider a relevant case of an impurity located next to one edge of a one-dimensional system, equivalent to a softened boundary in a separable two-dimensional model. We show that a localized impurity can have a drastic effect on the original topological edge modes of the system. Using the periodic Harper and Hofstadter models to illustrate our method, we find that, on increasing the impurity strength, edge states can enter or exit the continuum, and a trivial Shockley state bound to the impurity

Structural evidence for a copper-bound carbonate intermediate in the peroxidase and dismutase activities of superoxide dismutase.

PubMed

Strange, Richard W; Hough, Michael A; Antonyuk, Svetlana V; Hasnain, S Samar

2012-01-01

Copper-zinc superoxide dismutase (SOD) is of fundamental importance to our understanding of oxidative damage. Its primary function is catalysing the dismutation of superoxide to O(2) and H(2)O(2). SOD also reacts with H(2)O(2), leading to the formation of a strong copper-bound oxidant species that can either inactivate the enzyme or oxidise other substrates. In the presence of bicarbonate (or CO(2)) and H(2)O(2), this peroxidase activity is enhanced and produces the carbonate radical. This freely diffusible reactive oxygen species is proposed as the agent for oxidation of large substrates that are too bulky to enter the active site. Here, we provide direct structural evidence, from a 2.15 Å resolution crystal structure, of (bi)carbonate captured at the active site of reduced SOD, consistent with the view that a bound carbonate intermediate could be formed, producing a diffusible carbonate radical upon reoxidation of copper. The bound carbonate blocks direct access of substrates to Cu(I), suggesting that an adjunct to the accepted mechanism of SOD catalysed dismutation of superoxide operates, with Cu(I) oxidation by superoxide being driven via a proton-coupled electron transfer mechanism involving the bound carbonate rather than the solvent. Carbonate is captured in a different site when SOD is oxidised, being located in the active site channel adjacent to the catalytically important Arg143. This is the probable route of diffusion from the active site following reoxidation of the copper. In this position, the carbonate is poised for re-entry into the active site and binding to the reduced copper.

Structural Evidence for a Copper-Bound Carbonate Intermediate in the Peroxidase and Dismutase Activities of Superoxide Dismutase

PubMed Central

Strange, Richard W.; Hough, Michael A.; Antonyuk, Svetlana V.; Hasnain, S. Samar

2012-01-01

Copper-zinc superoxide dismutase (SOD) is of fundamental importance to our understanding of oxidative damage. Its primary function is catalysing the dismutation of superoxide to O2 and H2O2. SOD also reacts with H2O2, leading to the formation of a strong copper-bound oxidant species that can either inactivate the enzyme or oxidise other substrates. In the presence of bicarbonate (or CO2) and H2O2, this peroxidase activity is enhanced and produces the carbonate radical. This freely diffusible reactive oxygen species is proposed as the agent for oxidation of large substrates that are too bulky to enter the active site. Here, we provide direct structural evidence, from a 2.15 Å resolution crystal structure, of (bi)carbonate captured at the active site of reduced SOD, consistent with the view that a bound carbonate intermediate could be formed, producing a diffusible carbonate radical upon reoxidation of copper. The bound carbonate blocks direct access of substrates to Cu(I), suggesting that an adjunct to the accepted mechanism of SOD catalysed dismutation of superoxide operates, with Cu(I) oxidation by superoxide being driven via a proton-coupled electron transfer mechanism involving the bound carbonate rather than the solvent. Carbonate is captured in a different site when SOD is oxidised, being located in the active site channel adjacent to the catalytically important Arg143. This is the probable route of diffusion from the active site following reoxidation of the copper. In this position, the carbonate is poised for re-entry into the active site and binding to the reduced copper. PMID:22984565

Vesicle endocytosis requires dynamin-dependent GTP hydrolysis at a fast CNS synapse.

PubMed

Yamashita, Takayuki; Hige, Toshihide; Takahashi, Tomoyuki

2005-01-07

Molecular dependence of vesicular endocytosis was investigated with capacitance measurements at the calyx of Held terminal in brainstem slices. Intraterminal loading of botulinum toxin E revealed that the rapid capacitance transient implicated as "kiss-and-run" was unrelated to transmitter release. The release-related capacitance change decayed with an endocytotic time constant of 10 to 25 seconds, depending on the magnitude of exocytosis. Presynaptic loading of the nonhydrolyzable guanosine 5'-triphosphate (GTP) analog GTPgS or dynamin-1 proline-rich domain peptide abolished endocytosis. These compounds had no immediate effect on exocytosis, but caused a use-dependent rundown of exocytosis. Thus, the guanosine triphosphatase dynamin-1 is indispensable for vesicle endocytosis at this fast central nervous system (CNS) synapse.

Andreev Bound States Formation and Quasiparticle Trapping in Quench Dynamics Revealed by Time-Dependent Counting Statistics.

PubMed

Souto, R Seoane; Martín-Rodero, A; Yeyati, A Levy

2016-12-23

We analyze the quantum quench dynamics in the formation of a phase-biased superconducting nanojunction. We find that in the absence of an external relaxation mechanism and for very general conditions the system gets trapped in a metastable state, corresponding to a nonequilibrium population of the Andreev bound states. The use of the time-dependent full counting statistics analysis allows us to extract information on the asymptotic population of even and odd many-body states, demonstrating that a universal behavior, dependent only on the Andreev state energy, is reached in the quantum point contact limit. These results shed light on recent experimental observations on quasiparticle trapping in superconducting atomic contacts.

Sphingosine 1-phosphate (S1P) suppresses the collagen-induced activation of human platelets via S1P4 receptor.

PubMed

Onuma, Takashi; Tanabe, Kumiko; Kito, Yuko; Tsujimoto, Masanori; Uematsu, Kodai; Enomoto, Yukiko; Matsushima-Nishiwaki, Rie; Doi, Tomoaki; Nagase, Kiyoshi; Akamatsu, Shigeru; Tokuda, Haruhiko; Ogura, Shinji; Iwama, Toru; Kozawa, Osamu; Iida, Hiroki

2017-08-01

Sphingosine 1-phosphate (S1P) is as an extracellular factor that acts as a potent lipid mediator by binding to specific receptors, S1P receptors (S1PRs). However, the precise role of S1P in human platelets that express S1PRs has not yet been fully clarified. We previously reported that heat shock protein 27 (HSP27) is released from human platelets accompanied by its phosphorylation stimulated by collagen. In the present study, we investigated the effect of S1P on the collagen-induced platelet activation. S1P pretreatment markedly attenuated the collagen-induced aggregation. Co-stimulation with S1P and collagen suppressed collagen-induced platelet activation, but the effect was weaker than that of S1P-pretreatment. The collagen-stimulated secretion of platelet-derived growth factor (PDGF)-AB and the soluble CD40 ligand (sCD40L) release were significantly reduced by S1P. In addition, S1P suppressed the collagen-induced release of HSP27 as well as the phosphorylation of HSP27. S1P significantly suppressed the collagen-induced phosphorylation of p38 mitogen-activated protein kinase. S1P increased the levels of GTP-bound Gαi and GTP-bound Gα13 coupled to S1PPR1 and/or S1PR4. CYM50260, a selective S1PR4 agonist, but not SEW2871, a selective S1PR1 agonist, suppressed the collagen-stimulated platelet aggregation, PDGF-AB secretion and sCD40L release. In addition, CYM50260 reduced the release of phosphorylated-HSP27 by collagen as well as the phosphorylation of HSP27. The selective S1PR4 antagonist CYM50358, which failed to affect collagen-induced HSP27 phosphorylation, reversed the S1P-induced attenuation of HSP27 phosphorylation by collagen. These results strongly suggest that S1P inhibits the collagen-induced human platelet activation through S1PR4 but not S1PR1. Copyright © 2017 Elsevier Ltd. All rights reserved.

Northwest Outward Bound Instructor's Manual.

ERIC Educational Resources Information Center

Northwest Outward Bound School, Portland, OR.

Instructor responsibilities, procedures for completing activities safely, and instructional methods and techniques are outlined to assist instructors in the Northwest Outward Bound School (Portland, Oregon) as they strive for teaching excellence. Information is organized into six chapters addressing: history and philosophy of Outward Bound; course…

Existence of bound states of a polaron with a breather in soft potentials

NASA Astrophysics Data System (ADS)

Cuevas, J.; Kevrekidis, P. G.; Frantzeskakis, D. J.; Bishop, A. R.

2006-08-01

We consider polarons in models of coupled electronic and vibrational degrees of freedom, in the presence of a soft nonlinear substrate potential (Morse potential). In particular, we focus on a bound state of a polaron with a breather, a so-called “polarobreather.” We analyze the existence of these states based on frequency resonance conditions and illustrate their stability using Floquet spectrum techniques. Multisite solutions of this type are also obtained both in the stationary case (bond-centered and twisted polarons) and in the breathing case (bond-centered and twisted polarobreathers). For all the branches examined, the dynamical evolution of instabilities pertinent to the corresponding solutions are also briefly discussed. Finally, a different branch of so-called phantom polarobreathers is also demonstrated.

Differential regulation of serotonin-1A receptor-stimulated [35S]GTP gamma S binding in the dorsal raphe nucleus by citalopram and escitalopram.

PubMed

Rossi, Dania V; Burke, Teresa F; Hensler, Julie G

2008-03-31

The effect of chronic citalopram or escitalopram administration on 5-HT1A receptor function in the dorsal raphe nucleus was determined by measuring [35S]GTP gamma S binding stimulated by the 5-HT1A receptor agonist (R)-(+)-8-OH-DPAT (1nM-10 microM). Although chronic administration of citalopram or escitalopram has been shown to desensitize somatodendritic 5-HT1A autoreceptors, we found that escitalopram treatment decreased the efficacy of 5-HT1A receptors to activate G proteins, whereas citalopram treatment did not. The binding of [3H]8-OH-DPAT to the coupled, high affinity agonist state of the receptor was not altered by either treatment. Interestingly, escitalopram administration resulted in greater occupancy of serotonin transporter sites as measured by the inhibition of [3H]cyanoimipramine binding. As the binding and action of escitalopram is limited by the inactive enantiomer R-citalopram present in racemic citalopram, we propose that the regulation of 5-HT1A receptor function in the dorsal raphe nucleus at the level of receptor-G protein interaction may be a result of greater inhibition of the serotonin transporter by escitalopram.

Search for weakly decaying Λ n - and ΛΛ exotic bound states in central Pb–Pb collisions at s NN = 2.76  TeV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adam, J.; Adamová, D.; Aggarwal, M. M.

Here, we present results of a search for two hypothetical strange dibaryon states, i.e. the H-dibaryon and the possiblemore » $$\\overline{Λn}$$ bound state. The search is performed with the ALICE detector in central (0-10%) Pb-Pb collisions at $$\\sqrt{s}$$$_ {NN}$$ = 2.76 TeV, by invariant mass analysis in the decay modes $$\\overline{Λn}$$ → $$\\bar{d}$$π + and H-dibaryon →Λpπ -. No evidence for these bound states is observed. Upper limits are determined at 99% confidence level for a wide range of lifetimes and for the full range of branching ratios. The results are compared to thermal, coalescence and hybrid UrQMD model expectations, which describe correctly the production of other loosely bound states, like the deuteron and the hypertriton.« less

Search for weakly decaying Λ n - and ΛΛ exotic bound states in central Pb–Pb collisions at s NN = 2.76  TeV

DOE PAGES

Adam, J.; Adamová, D.; Aggarwal, M. M.; ...

2016-11-28

Here, we present results of a search for two hypothetical strange dibaryon states, i.e. the H-dibaryon and the possiblemore » $$\\overline{Λn}$$ bound state. The search is performed with the ALICE detector in central (0-10%) Pb-Pb collisions at $$\\sqrt{s}$$$_ {NN}$$ = 2.76 TeV, by invariant mass analysis in the decay modes $$\\overline{Λn}$$ → $$\\bar{d}$$π + and H-dibaryon →Λpπ -. No evidence for these bound states is observed. Upper limits are determined at 99% confidence level for a wide range of lifetimes and for the full range of branching ratios. The results are compared to thermal, coalescence and hybrid UrQMD model expectations, which describe correctly the production of other loosely bound states, like the deuteron and the hypertriton.« less

Quantum correlations beyond Tsirelson's bound

NASA Astrophysics Data System (ADS)

Berry, Dominic; Ringbauer, Martin; Fedrizzi, Alessandro; White, Andrew

2014-03-01

Violations of Bell inequalities show that there are correlations that cannot explained by any classical theory. Further violation, beyond Tsirelson's bound, shows that there are correlations that are not explained by quantum mechanics. Such super-quantum correlations would enable violation of information causality, where communication of one bit provides more than one bit of information [Nature 461, 1101 (2009)]. An unavoidable feature of all realistic Bell inequality experiments is loss. If one postselects on successful measurements, unentangled states can violate Bell inequalities. On the other hand, loss can be used to enhance the violation of Bell inequalities for entangled states. This can improve the ability to distinguish between entangled and unentangled states, despite loss. Here we report an optical experiment providing maximal violation of the CHSH-Bell inequality with entangled states. Due to loss and postselection, Tsirelson's bound is also violated. This enables us to more easily distinguish between entangled and unentangled states. In addition, it provides violation of information causality for the postselected data.

K-Ras protein as a drug target.

PubMed

McCormick, Frank

2016-03-01

K-Ras proteins are major drivers of human cancers, playing a direct causal role in about one million cancer cases/year. In cancers driven by mutant K-Ras, the protein is locked in the active, GTP-bound state constitutively, through a defect in the off-switch mechanism. As such, the mutant protein resembles the normal K-Ras protein from a structural perspective, making therapeutic attack extremely challenging. K-Ras is a member of a large family of related proteins, which share very similar GDP/GTP-binding domains, making specific therapies more difficult. Furthermore, Ras proteins lack pockets to which small molecules can bind with high affinity, with a few interesting exceptions. However, new insights into the structure and function of K-Ras proteins reveal opportunities for intervention that were not appreciated many years ago, when efforts were launched to develop K-Ras therapies. Furthermore, K-Ras undergoes post-translational modification and interactions with cellular signaling proteins that present additional therapeutic opportunities, such as specific binding to calmodulin and regulation of non-canonical Wnt signaling.

Controlling Directionality and Dimensionality of Radiation by Perturbing Separable Bound States in the Continuum

DOE PAGES

Rivera, Nicholas; Hsu, Chia Wei; Zhen, Bo; ...

2016-09-19

Here, a bound state in the continuum (BIC) is an unusual localized state that is embedded in a continuum of extended states. Here, we present the general condition for BICs to arise from wave equation separability. Then we show that by exploiting perturbations of certain symmetry such BICs can be turned into resonances that radiate with a tailorable directionality and dimensionality. Using this general framework, we construct new examples of separable BICs and resonances that can exist in optical potentials for ultracold atoms, photonic systems, and systems described by tight binding. Such resonances with easily reconfigurable radiation allow for applicationsmore » such as the storage and release of waves at a controllable rate and direction, as well systems that switch between different dimensions of confinement.« less

Structural and functional analysis of a FeoB A143S G5 loop mutant explains the accelerated GDP release rate.

PubMed

Guilfoyle, Amy P; Deshpande, Chandrika N; Vincent, Kimberley; Pedroso, Marcelo M; Schenk, Gerhard; Maher, Megan J; Jormakka, Mika

2014-05-01

GTPases (G proteins) hydrolyze the conversion of GTP to GDP and free phosphate, comprising an integral part of prokaryotic and eukaryotic signaling, protein biosynthesis and cell division, as well as membrane transport processes. The G protein cycle is brought to a halt after GTP hydrolysis, and requires the release of GDP before a new cycle can be initiated. For eukaryotic heterotrimeric Gαβγ proteins, the interaction with a membrane-bound G protein-coupled receptor catalyzes the release of GDP from the Gα subunit. Structural and functional studies have implicated one of the nucleotide binding sequence motifs, the G5 motif, as playing an integral part in this release mechanism. Indeed, a Gαs G5 mutant (A366S) was shown to have an accelerated GDP release rate, mimicking a G protein-coupled receptor catalyzed release state. In the present study, we investigate the role of the equivalent residue in the G5 motif (residue A143) in the prokaryotic membrane protein FeoB from Streptococcus thermophilus, which includes an N-terminal soluble G protein domain. The structure of this domain has previously been determined in the apo and GDP-bound states and in the presence of a transition state analogue, revealing conformational changes in the G5 motif. The A143 residue was mutated to a serine and analyzed with respect to changes in GTPase activity, nucleotide release rate, GDP affinity and structural alterations. We conclude that the identity of the residue at this position in the G5 loop plays a key role in the nucleotide release rate by allowing the correct positioning and hydrogen bonding of the nucleotide base. © 2014 FEBS.

Few-Body Techniques Using Coordinate Space for Bound and Continuum States

NASA Astrophysics Data System (ADS)

Garrido, E.

2018-05-01

These notes are a short summary of a set of lectures given within the frame of the "Critical Stability of Quantum Few-Body Systems" International School held in the Max Planck Institute for the Physics of Complex Systems (Dresden). The main goal of the lectures has been to provide the basic ingredients for the description of few-body systems in coordinate space. The hyperspherical harmonic and the adiabatic expansion methods are introduced in detail, and subsequently used to describe bound and continuum states. The expressions for the cross sections and reaction rates for three-body processes are derived. The case of resonant scattering and the complex scaling method as a tool to obtain the resonance energy and width is also introduced.

Tryptophan W207 in transducin T alpha is the fluorescence sensor of the G protein activation switch and is involved in the effector binding.

PubMed Central

Faurobert, E; Otto-Bruc, A; Chardin, P; Chabre, M

1993-01-01

We have produced a recombinant transducin alpha subunit (rT alpha) in sf9 cells, using a baculovirus system. Deletion of the myristoylation site near the N-terminal increased the solubility and allowed the purification of rT alpha. When reconstituted with excess T beta gamma on retinal membrane, rT alpha displayed functional characteristics of wild-type T alpha vis à vis its coupled receptor, rhodopsin and its effector, cGMP phosphodiesterase (PDE). We further mutated a tryptophan, W207, which is conserved in all G proteins and is suspected to elicit the fluorescence change correlated to their activation upon GDP/GTP exchange or aluminofluoride (AlFx) binding. [W207F]T alpha mutant displayed high affinity receptor binding and underwent a conformational switch upon receptor-catalysed GTP gamma S binding or upon AlFx binding, but this did not elicit any fluorescence change. Thus W207 is the only fluorescence sensor of the switch. Upon the switch the mutant remained unable to activate the PDE. To characterize better its effector-activating interaction we measured the affinity of [W207F]T alpha GDP-AlFx for PDE gamma, the effector subunit that binds most tightly to T alpha. [W207F]T alpha still bound in an activation-dependent way to PDE gamma, but with a 100-fold lower affinity than rT alpha. This suggests that W207 contributes to the G protein effector binding. Images PMID:8223434

Endothelium-specific GTP cyclohydrolase I overexpression accelerates refractory wound healing by suppressing oxidative stress in diabetes

PubMed Central

Tie, Lu; Li, Xue-Jun; Wang, Xian; Channon, Keith M.; Chen, Alex F.

2009-01-01

Refractory wound is a severe complication that leads to limb amputation in diabetes. Endothelial nitric oxide synthase (eNOS) plays a key role in normal wound repair but is uncoupled in streptozotocin (STZ)-induced type 1 diabetes because of reduced cofactor tetrahydrobiopterin (BH4). We tested the hypothesis that overexpression of GTP cyclohydrolase I (GTPCH I), the rate-limiting enzyme for de novo BH4 synthesis, retards NOS uncoupling and accelerates wound healing in STZ mice. Blood glucose levels were significantly increased in both male endothelium-specific GTPCH I transgenic mice (Tg-GCH; via a tie-2 promoter) and wild-type (WT) littermates 5 days after STZ regimen. A full-thickness excisional wound was created on mouse dorsal skin by a 4-mm punch biopsy. Wound closure was delayed in STZ mice, which was rescued in STZ Tg-GCH mice. Cutaneous BH4 level was significantly reduced in STZ mice vs. WT mice, which was maintained in STZ Tg-GCH mice. In STZ mice, constitutive NOS (cNOS) activity and nitrite levels were decreased compared with WT mice, paralleled by increased superoxide anion (O2−) level and inducible NOS (iNOS) activity. In STZ Tg-GCH mice, nitrite level and cNOS activity were potentiated and O2− level and iNOS activity were suppressed compared with STZ mice. Thus endothelium-specific BH4 overexpression accelerates wound healing in type 1 diabetic mice by enhancing cNOS activity and suppressing oxidative stress. PMID:19336662

Bound states in the continuum on periodic structures: perturbation theory and robustness.

PubMed

Yuan, Lijun; Lu, Ya Yan

2017-11-01

On periodic structures, a bound state in the continuum (BIC) is a standing or propagating Bloch wave with a frequency in the radiation continuum. Some BICs (e.g., antisymmetric standing waves) are symmetry protected, since they have incompatible symmetry with outgoing waves in the radiation channels. The propagating BICs do not have this symmetry mismatch, but they still crucially depend on the symmetry of the structure. In this Letter, a perturbation theory is developed for propagating BICs on two-dimensional periodic structures. The Letter shows that these BICs are robust against structural perturbations that preserve the symmetry, indicating that these BICs, in fact, are implicitly protected by symmetry.

Surface-Bound Casein Modulates the Adsorption and Activity of Kinesin on SiO2 Surfaces

PubMed Central

Ozeki, Tomomitsu; Verma, Vivek; Uppalapati, Maruti; Suzuki, Yukiko; Nakamura, Mikihiko; Catchmark, Jeffrey M.; Hancock, William O.

2009-01-01

Abstract Conventional kinesin is routinely adsorbed to hydrophilic surfaces such as SiO2. Pretreatment of surfaces with casein has become the standard protocol for achieving optimal kinesin activity, but the mechanism by which casein enhances kinesin surface adsorption and function is poorly understood. We used quartz crystal microbalance measurements and microtubule gliding assays to uncover the role that casein plays in enhancing the activity of surface-adsorbed kinesin. On SiO2 surfaces, casein adsorbs as both a tightly bound monolayer and a reversibly bound second layer that has a dissociation constant of 500 nM and can be desorbed by washing with casein-free buffer. Experiments using truncated kinesins demonstrate that in the presence of soluble casein, kinesin tails bind well to the surface, whereas kinesin head binding is blocked. Removing soluble casein reverses these binding profiles. Surprisingly, reversibly bound casein plays only a moderate role during kinesin adsorption, but it significantly enhances kinesin activity when surface-adsorbed motors are interacting with microtubules. These results point to a model in which a dynamic casein bilayer prevents reversible association of the heads with the surface and enhances association of the kinesin tail with the surface. Understanding protein-surface interactions in this model system should provide a framework for engineering surfaces for functional adsorption of other motor proteins and surface-active enzymes. PMID:19383474

The interaction of RNA helicase DDX3 with HIV-1 Rev-CRM1-RanGTP complex during the HIV replication cycle

DOE PAGES

Mahboobi, Seyed Hanif; Javanpour, Alex A.; Mofrad, Mohammad R. K.

2015-02-27

Molecular traffic between the nucleus and the cytoplasm is regulated by the nuclear pore complex (NPC), which acts as a highly selective channel perforating the nuclear envelope in eukaryotic cells. The human immunodeficiency virus (HIV) exploits the nucleocytoplasmic pathway to export its RNA transcripts across the NPC to the cytoplasm. Despite extensive study on the HIV life cycle and the many drugs developed to target this cycle, no current drugs have been successful in targeting the critical process of viral nuclear export, even though HIV’s reliance on a single host protein, CRM1, to export its unspliced and partially spliced RNAmore » transcripts makes it a tempting target. Due to recent findings implicating a DEAD-box helicase, DDX3, in HIV replication and a member of the export complex, it has become an appealing target for anti-HIV drug inhibition. In the present research, we have applied a hybrid computational protocol to analyze protein-protein interactions in the HIV mRNA export cycle. This method is based on molecular docking followed by molecular dynamics simulation and accompanied by approximate free energy calculation (MM/GBSA), computational alanine scanning, clustering, and evolutionary analysis. We highlight here some of the most likely binding modes and interfacial residues between DDX3 and CRM1 both in the absence and presence of RanGTP. This work shows that although DDX3 can bind to free CRM1, addition of RanGTP leads to more concentrated distribution of binding modes and stronger binding between CRM1 and RanGTP.« less

The interaction of RNA helicase DDX3 with HIV-1 Rev-CRM1-RanGTP complex during the HIV replication cycle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahboobi, Seyed Hanif; Javanpour, Alex A.; Mofrad, Mohammad R. K.

Molecular traffic between the nucleus and the cytoplasm is regulated by the nuclear pore complex (NPC), which acts as a highly selective channel perforating the nuclear envelope in eukaryotic cells. The human immunodeficiency virus (HIV) exploits the nucleocytoplasmic pathway to export its RNA transcripts across the NPC to the cytoplasm. Despite extensive study on the HIV life cycle and the many drugs developed to target this cycle, no current drugs have been successful in targeting the critical process of viral nuclear export, even though HIV’s reliance on a single host protein, CRM1, to export its unspliced and partially spliced RNAmore » transcripts makes it a tempting target. Due to recent findings implicating a DEAD-box helicase, DDX3, in HIV replication and a member of the export complex, it has become an appealing target for anti-HIV drug inhibition. In the present research, we have applied a hybrid computational protocol to analyze protein-protein interactions in the HIV mRNA export cycle. This method is based on molecular docking followed by molecular dynamics simulation and accompanied by approximate free energy calculation (MM/GBSA), computational alanine scanning, clustering, and evolutionary analysis. We highlight here some of the most likely binding modes and interfacial residues between DDX3 and CRM1 both in the absence and presence of RanGTP. This work shows that although DDX3 can bind to free CRM1, addition of RanGTP leads to more concentrated distribution of binding modes and stronger binding between CRM1 and RanGTP.« less

The Gem GTP-binding protein promotes morphological differentiation in neuroblastoma.

PubMed

Leone, A; Mitsiades, N; Ward, Y; Spinelli, B; Poulaki, V; Tsokos, M; Kelly, K

2001-05-31

Gem is a small GTP-binding protein within the Ras superfamily whose function has not been determined. We report here that ectopic Gem expression is sufficient to stimulate cell flattening and neurite extension in N1E-115 and SH-SY5Y neuroblastoma cells, suggesting a role for Gem in cytoskeletal rearrangement and/or morphological differentiation of neurons. Consistent with this potential function, in clinical samples of neuroblastoma, Gem protein was most highly expressed within cells which had differentiated to express ganglionic morphology. Gem was also observed in developing trigeminal nerve ganglia in 12.5 day mouse embryos, demonstrating that Gem expression is a property of normal ganglionic development. Although Gem expression is rare in epithelial and hematopoietic cancer cell lines, constitutive Gem levels were detected in several neuroblastoma cell lines and could be further induced as much as 10-fold following treatment with PMA or the acetylcholine muscarinic agonist, carbachol.

Search for weakly decaying Λn ‾ and ΛΛ exotic bound states in central Pb-Pb collisions at √{sNN} = 2.76 TeV

NASA Astrophysics Data System (ADS)

Adam, J.; Adamová, D.; Aggarwal, M. M.; Aglieri Rinella, G.; Agnello, M.; Agrawal, N.; Ahammed, Z.; Ahmed, I.; Ahn, S. U.; Aimo, I.; Aiola, S.; Ajaz, M.; Akindinov, A.; Alam, S. N.; Aleksandrov, D.; Alessandro, B.; Alexandre, D.; Alfaro Molina, R.; Alici, A.; Alkin, A.; Alme, J.; Alt, T.; Altinpinar, S.; Altsybeev, I.; Alves Garcia Prado, C.; Andrei, C.; Andronic, A.; Anguelov, V.; Anielski, J.; Antičić, T.; Antinori, F.; Antonioli, P.; Aphecetche, L.; Appelshäuser, H.; Arcelli, S.; Armesto, N.; Arnaldi, R.; Aronsson, T.; Arsene, I. C.; Arslandok, M.; Augustinus, A.; Averbeck, R.; Azmi, M. D.; Bach, M.; Badalà, A.; Baek, Y. W.; Bagnasco, S.; Bailhache, R.; Bala, R.; Baldisseri, A.; Ball, M.; Baltasar Dos Santos Pedrosa, F.; Baral, R. C.; Barbano, A. M.; Barbera, R.; Barile, F.; Barnaföldi, G. G.; Barnby, L. S.; Barret, V.; Bartalini, P.; Bartke, J.; Bartsch, E.; Basile, M.; Bastid, N.; Basu, S.; Bathen, B.; Batigne, G.; Batista Camejo, A.; Batyunya, B.; Batzing, P. C.; Bearden, I. G.; Beck, H.; Bedda, C.; Behera, N. K.; Belikov, I.; Bellini, F.; Bello Martinez, H.; Bellwied, R.; Belmont, R.; Belmont-Moreno, E.; Belyaev, V.; Bencedi, G.; Beole, S.; Berceanu, I.; Bercuci, A.; Berdnikov, Y.; Berenyi, D.; Bertens, R. A.; Berzano, D.; Betev, L.; Bhasin, A.; Bhat, I. R.; Bhati, A. K.; Bhattacharjee, B.; Bhom, J.; Bianchi, L.; Bianchi, N.; Bianchin, C.; Bielčík, J.; Bielčíková, J.; Bilandzic, A.; Biswas, S.; Bjelogrlic, S.; Blanco, F.; Blau, D.; Blume, C.; Bock, F.; Bogdanov, A.; Bøggild, H.; Boldizsár, L.; Bombara, M.; Book, J.; Borel, H.; Borissov, A.; Borri, M.; Bossú, F.; Botje, M.; Botta, E.; Böttger, S.; Braun-Munzinger, P.; Bregant, M.; Breitner, T.; Broker, T. A.; Browning, T. A.; Broz, M.; Brucken, E. J.; Bruna, E.; Bruno, G. E.; Budnikov, D.; Buesching, H.; Bufalino, S.; Buncic, P.; Busch, O.; Buthelezi, Z.; Buxton, J. T.; Caffarri, D.; Cai, X.; Caines, H.; Calero Diaz, L.; Caliva, A.; Calvo Villar, E.; Camerini, P.; Carena, F.; Carena, W.; Castillo Castellanos, J.; Castro, A. J.; Casula, E. A. R.; Cavicchioli, C.; Ceballos Sanchez, C.; Cepila, J.; Cerello, P.; Chang, B.; Chapeland, S.; Chartier, M.; Charvet, J. L.; Chattopadhyay, S.; Chattopadhyay, S.; Chelnokov, V.; Cherney, M.; Cheshkov, C.; Cheynis, B.; Chibante Barroso, V.; Chinellato, D. D.; Chochula, P.; Choi, K.; Chojnacki, M.; Choudhury, S.; Christakoglou, P.; Christensen, C. H.; Christiansen, P.; Chujo, T.; Chung, S. U.; Cicalo, C.; Cifarelli, L.; Cindolo, F.; Cleymans, J.; Colamaria, F.; Colella, D.; Collu, A.; Colocci, M.; Conesa Balbastre, G.; Conesa del Valle, Z.; Connors, M. E.; Contreras, J. G.; Cormier, T. M.; Corrales Morales, Y.; Cortés Maldonado, I.; Cortese, P.; Cosentino, M. R.; Costa, F.; Crochet, P.; Cruz Albino, R.; Cuautle, E.; Cunqueiro, L.; Dahms, T.; Dainese, A.; Danu, A.; Das, D.; Das, I.; Das, S.; Dash, A.; Dash, S.; De, S.; De Caro, A.; de Cataldo, G.; de Cuveland, J.; De Falco, A.; De Gruttola, D.; De Marco, N.; De Pasquale, S.; Deisting, A.; Deloff, A.; Dénes, E.; D'Erasmo, G.; Di Bari, D.; Di Mauro, A.; Di Nezza, P.; Diaz Corchero, M. A.; Dietel, T.; Dillenseger, P.; Divià, R.; Djuvsland, Ø.; Dobrin, A.; Dobrowolski, T.; Domenicis Gimenez, D.; Dönigus, B.; Dordic, O.; Dubey, A. K.; Dubla, A.; Ducroux, L.; Dupieux, P.; Ehlers, R. J.; Elia, D.; Engel, H.; Erazmus, B.; Erhardt, F.; Eschweiler, D.; Espagnon, B.; Estienne, M.; Esumi, S.; Evans, D.; Evdokimov, S.; Eyyubova, G.; Fabbietti, L.; Fabris, D.; Faivre, J.; Fantoni, A.; Fasel, M.; Feldkamp, L.; Felea, D.; Feliciello, A.; Feofilov, G.; Ferencei, J.; Fernández Téllez, A.; Ferreiro, E. G.; Ferretti, A.; Festanti, A.; Figiel, J.; Figueredo, M. A. S.; Filchagin, S.; Finogeev, D.; Fionda, F. M.; Fiore, E. M.; Fleck, M. G.; Floris, M.; Foertsch, S.; Foka, P.; Fokin, S.; Fragiacomo, E.; Francescon, A.; Frankenfeld, U.; Fuchs, U.; Furget, C.; Furs, A.; Fusco Girard, M.; Gaardhøje, J. J.; Gagliardi, M.; Gago, A. M.; Gallio, M.; Gangadharan, D. R.; Ganoti, P.; Gao, C.; Garabatos, C.; Garcia-Solis, E.; Gargiulo, C.; Gasik, P.; Germain, M.; Gheata, A.; Gheata, M.; Ghosh, P.; Ghosh, S. K.; Gianotti, P.; Giubellino, P.; Giubilato, P.; Gladysz-Dziadus, E.; Glässel, P.; Gomez Ramirez, A.; González-Zamora, P.; Gorbunov, S.; Görlich, L.; Gotovac, S.; Grabski, V.; Graczykowski, L. K.; Grelli, A.; Grigoras, A.; Grigoras, C.; Grigoriev, V.; Grigoryan, A.; Grigoryan, S.; Grinyov, B.; Grion, N.; Grosse-Oetringhaus, J. F.; Grossiord, J.-Y.; Grosso, R.; Guber, F.; Guernane, R.; Guerzoni, B.; Gulbrandsen, K.; Gulkanyan, H.; Gunji, T.; Gupta, A.; Gupta, R.; Haake, R.; Haaland, Ø.; Hadjidakis, C.; Haiduc, M.; Hamagaki, H.; Hamar, G.; Hanratty, L. D.; Hansen, A.; Harris, J. W.; Hartmann, H.; Harton, A.; Hatzifotiadou, D.; Hayashi, S.; Heckel, S. T.; Heide, M.; Helstrup, H.; Herghelegiu, A.; Herrera Corral, G.; Hess, B. A.; Hetland, K. F.; Hilden, T. E.; Hillemanns, H.; Hippolyte, B.; Hristov, P.; Huang, M.; Humanic, T. J.; Hussain, N.; Hussain, T.; Hutter, D.; Hwang, D. S.; Ilkaev, R.; Ilkiv, I.; Inaba, M.; Ionita, C.; Ippolitov, M.; Irfan, M.; Ivanov, M.; Ivanov, V.; Izucheev, V.; Jachołkowski, A.; Jacobs, P. M.; Jahnke, C.; Jang, H. J.; Janik, M. A.; Jayarathna, P. H. S. Y.; Jena, C.; Jena, S.; Jimenez Bustamante, R. T.; Jones, P. G.; Jung, H.; Jusko, A.; Kalinak, P.; Kalweit, A.; Kamin, J.; Kang, J. H.; Kaplin, V.; Kar, S.; Karasu Uysal, A.; Karavichev, O.; Karavicheva, T.; Karpechev, E.; Kebschull, U.; Keidel, R.; Keijdener, D. L. D.; Keil, M.; Khan, K. H.; Khan, M. M.; Khan, P.; Khan, S. A.; Khanzadeev, A.; Kharlov, Y.; Kileng, B.; Kim, B.; Kim, D. W.; Kim, D. J.; Kim, H.; Kim, J. S.; Kim, M.; Kim, M.; Kim, S.; Kim, T.; Kirsch, S.; Kisel, I.; Kiselev, S.; Kisiel, A.; Kiss, G.; Klay, J. L.; Klein, C.; Klein, J.; Klein-Bösing, C.; Kluge, A.; Knichel, M. L.; Knospe, A. G.; Kobayashi, T.; Kobdaj, C.; Kofarago, M.; Köhler, M. K.; Kollegger, T.; Kolojvari, A.; Kondratiev, V.; Kondratyeva, N.; Kondratyuk, E.; Konevskikh, A.; Kouzinopoulos, C.; Kovalenko, V.; Kowalski, M.; Kox, S.; Koyithatta Meethaleveedu, G.; Kral, J.; Králik, I.; Kravčáková, A.; Krelina, M.; Kretz, M.; Krivda, M.; Krizek, F.; Kryshen, E.; Krzewicki, M.; Kubera, A. M.; Kučera, V.; Kucheriaev, Y.; Kugathasan, T.; Kuhn, C.; Kuijer, P. G.; Kulakov, I.; Kumar, J.; Kumar, L.; Kurashvili, P.; Kurepin, A.; Kurepin, A. B.; Kuryakin, A.; Kushpil, S.; Kweon, M. J.; Kwon, Y.; La Pointe, S. L.; La Rocca, P.; Lagana Fernandes, C.; Lakomov, I.; Langoy, R.; Lara, C.; Lardeux, A.; Lattuca, A.; Laudi, E.; Lea, R.; Leardini, L.; Lee, G. R.; Lee, S.; Legrand, I.; Lehnert, J.; Lemmon, R. C.; Lenti, V.; Leogrande, E.; León Monzón, I.; Leoncino, M.; Lévai, P.; Li, S.; Li, X.; Lien, J.; Lietava, R.; Lindal, S.; Lindenstruth, V.; Lippmann, C.; Lisa, M. A.; Ljunggren, H. M.; Lodato, D. F.; Loenne, P. I.; Loggins, V. R.; Loginov, V.; Loizides, C.; Lopez, X.; López Torres, E.; Lowe, A.; Lu, X.-G.; Luettig, P.; Lunardon, M.; Luparello, G.; Maevskaya, A.; Mager, M.; Mahajan, S.; Mahmood, S. M.; Maire, A.; Majka, R. D.; Malaev, M.; Maldonado Cervantes, I.; Malinina, L.; Mal'Kevich, D.; Malzacher, P.; Mamonov, A.; Manceau, L.; Manko, V.; Manso, F.; Manzari, V.; Marchisone, M.; Mareš, J.; Margagliotti, G. V.; Margotti, A.; Margutti, J.; Marín, A.; Markert, C.; Marquard, M.; Martashvili, I.; Martin, N. A.; Martin Blanco, J.; Martinengo, P.; Martínez, M. I.; Martínez García, G.; Martinez Pedreira, M.; Martynov, Y.; Mas, A.; Masciocchi, S.; Masera, M.; Masoni, A.; Massacrier, L.; Mastroserio, A.; Matyja, A.; Mayer, C.; Mazer, J.; Mazzoni, M. A.; Mcdonald, D.; Meddi, F.; Menchaca-Rocha, A.; Meninno, E.; Mercado Pérez, J.; Meres, M.; Miake, Y.; Mieskolainen, M. M.; Mikhaylov, K.; Milano, L.; Milosevic, J.; Minervini, L. M.; Mischke, A.; Mishra, A. N.; Miśkowiec, D.; Mitra, J.; Mitu, C. M.; Mohammadi, N.; Mohanty, B.; Molnar, L.; Montaño Zetina, L.; Montes, E.; Morando, M.; Moretto, S.; Morreale, A.; Morsch, A.; Muccifora, V.; Mudnic, E.; Mühlheim, D.; Muhuri, S.; Mukherjee, M.; Müller, H.; Mulligan, J. D.; Munhoz, M. G.; Murray, S.; Musa, L.; Musinsky, J.; Nandi, B. K.; Nania, R.; Nappi, E.; Naru, M. U.; Nattrass, C.; Nayak, K.; Nayak, T. K.; Nazarenko, S.; Nedosekin, A.; Nellen, L.; Ng, F.; Nicassio, M.; Niculescu, M.; Niedziela, J.; Nielsen, B. S.; Nikolaev, S.; Nikulin, S.; Nikulin, V.; Noferini, F.; Nomokonov, P.; Nooren, G.; Norman, J.; Nyanin, A.; Nystrand, J.; Oeschler, H.; Oh, S.; Oh, S. K.; Ohlson, A.; Okatan, A.; Okubo, T.; Olah, L.; Oleniacz, J.; Oliveira Da Silva, A. C.; Oliver, M. H.; Onderwaater, J.; Oppedisano, C.; Ortiz Velasquez, A.; Oskarsson, A.; Otwinowski, J.; Oyama, K.; Ozdemir, M.; Pachmayer, Y.; Pagano, P.; Paić, G.; Pajares, C.; Pal, S. K.; Pan, J.; Pandey, A. K.; Pant, D.; Papikyan, V.; Pappalardo, G. S.; Pareek, P.; Park, W. J.; Parmar, S.; Passfeld, A.; Paticchio, V.; Paul, B.; Pawlak, T.; Peitzmann, T.; Pereira Da Costa, H.; Pereira De Oliveira Filho, E.; Peresunko, D.; Pérez Lara, C. E.; Peskov, V.; Pestov, Y.; Petráček, V.; Petrov, V.; Petrovici, M.; Petta, C.; Piano, S.; Pikna, M.; Pillot, P.; Pinazza, O.; Pinsky, L.; Piyarathna, D. B.; Płoskoń, M.; Planinic, M.; Pluta, J.; Pochybova, S.; Podesta-Lerma, P. L. M.; Poghosyan, M. G.; Polichtchouk, B.; Poljak, N.; Poonsawat, W.; Pop, A.; Porteboeuf-Houssais, S.; Porter, J.; Pospisil, J.; Prasad, S. K.; Preghenella, R.; Prino, F.; Pruneau, C. A.; Pshenichnov, I.; Puccio, M.; Puddu, G.; Pujahari, P.; Punin, V.; Putschke, J.; Qvigstad, H.; Rachevski, A.; Raha, S.; Rajput, S.; Rak, J.; Rakotozafindrabe, A.; Ramello, L.; Raniwala, R.; Raniwala, S.; Räsänen, S. S.; Rascanu, B. T.; Rathee, D.; Razazi, V.; Read, K. F.; Real, J. S.; Redlich, K.; Reed, R. J.; Rehman, A.; Reichelt, P.; Reicher, M.; Reidt, F.; Ren, X.; Renfordt, R.; Reolon, A. R.; Reshetin, A.; Rettig, F.; Revol, J.-P.; Reygers, K.; Riabov, V.; Ricci, R. A.; Richert, T.; Richter, M.; Riedler, P.; Riegler, W.; Riggi, F.; Ristea, C.; Rivetti, A.; Rocco, E.; Rodríguez Cahuantzi, M.; Rodriguez Manso, A.; Røed, K.; Rogochaya, E.; Rohr, D.; Röhrich, D.; Romita, R.; Ronchetti, F.; Ronflette, L.; Rosnet, P.; Rossi, A.; Roukoutakis, F.; Roy, A.; Roy, C.; Roy, P.; Rubio Montero, A. J.; Rui, R.; Russo, R.; Ryabinkin, E.; Ryabov, Y.; Rybicki, A.; Sadovsky, S.; Šafařík, K.; Sahlmuller, B.; Sahoo, P.; Sahoo, R.; Sahoo, S.; Sahu, P. K.; Saini, J.; Sakai, S.; Saleh, M. A.; Salgado, C. A.; Salzwedel, J.; Sambyal, S.; Samsonov, V.; Sanchez Castro, X.; Šándor, L.; Sandoval, A.; Sano, M.; Santagati, G.; Sarkar, D.; Scapparone, E.; Scarlassara, F.; Scharenberg, R. P.; Schiaua, C.; Schicker, R.; Schmidt, C.; Schmidt, H. R.; Schuchmann, S.; Schukraft, J.; Schulc, M.; Schuster, T.; Schutz, Y.; Schwarz, K.; Schweda, K.; Scioli, G.; Scomparin, E.; Scott, R.; Seeder, K. S.; Seger, J. E.; Sekiguchi, Y.; Selyuzhenkov, I.; Senosi, K.; Seo, J.; Serradilla, E.; Sevcenco, A.; Shabanov, A.; Shabetai, A.; Shadura, O.; Shahoyan, R.; Shangaraev, A.; Sharma, A.; Sharma, N.; Shigaki, K.; Shtejer, K.; Sibiriak, Y.; Siddhanta, S.; Sielewicz, K. M.; Siemiarczuk, T.; Silvermyr, D.; Silvestre, C.; Simatovic, G.; Simonetti, G.; Singaraju, R.; Singh, R.; Singha, S.; Singhal, V.; Sinha, B. C.; Sinha, T.; Sitar, B.; Sitta, M.; Skaali, T. B.; Slupecki, M.; Smirnov, N.; Snellings, R. J. M.; Snellman, T. W.; Søgaard, C.; Soltz, R.; Song, J.; Song, M.; Song, Z.; Soramel, F.; Sorensen, S.; Spacek, M.; Spiriti, E.; Sputowska, I.; Spyropoulou-Stassinaki, M.; Srivastava, B. K.; Stachel, J.; Stan, I.; Stefanek, G.; Steinpreis, M.; Stenlund, E.; Steyn, G.; Stiller, J. H.; Stocco, D.; Strmen, P.; Suaide, A. A. P.; Sugitate, T.; Suire, C.; Suleymanov, M.; Sultanov, R.; Šumbera, M.; Symons, T. J. M.; Szabo, A.; Szanto de Toledo, A.; Szarka, I.; Szczepankiewicz, A.; Szymanski, M.; Takahashi, J.; Tanaka, N.; Tangaro, M. A.; Tapia Takaki, J. D.; Tarantola Peloni, A.; Tariq, M.; Tarzila, M. G.; Tauro, A.; Tejeda Muñoz, G.; Telesca, A.; Terasaki, K.; Terrevoli, C.; Teyssier, B.; Thäder, J.; Thomas, D.; Tieulent, R.; Timmins, A. R.; Toia, A.; Trogolo, S.; Trubnikov, V.; Trzaska, W. H.; Tsuji, T.; Tumkin, A.; Turrisi, R.; Tveter, T. S.; Ullaland, K.; Uras, A.; Usai, G. L.; Utrobicic, A.; Vajzer, M.; Vala, M.; Valencia Palomo, L.; Vallero, S.; Van Der Maarel, J.; Van Hoorne, J. W.; van Leeuwen, M.; Vanat, T.; Vande Vyvre, P.; Varga, D.; Vargas, A.; Vargyas, M.; Varma, R.; Vasileiou, M.; Vasiliev, A.; Vauthier, A.; Vechernin, V.; Veen, A. M.; Veldhoen, M.; Velure, A.; Venaruzzo, M.; Vercellin, E.; Vergara Limón, S.; Vernet, R.; Verweij, M.; Vickovic, L.; Viesti, G.; Viinikainen, J.; Vilakazi, Z.; Villalobos Baillie, O.; Vinogradov, A.; Vinogradov, L.; Vinogradov, Y.; Virgili, T.; Vislavicius, V.; Viyogi, Y. P.; Vodopyanov, A.; Völkl, M. A.; Voloshin, K.; Voloshin, S. A.; Volpe, G.; von Haller, B.; Vorobyev, I.; Vranic, D.; Vrláková, J.; Vulpescu, B.; Vyushin, A.; Wagner, B.; Wagner, J.; Wang, H.; Wang, M.; Wang, Y.; Watanabe, D.; Weber, M.; Weber, S. G.; Wessels, J. P.; Westerhoff, U.; Wiechula, J.; Wikne, J.; Wilde, M.; Wilk, G.; Wilkinson, J.; Williams, M. C. S.; Windelband, B.; Winn, M.; Yaldo, C. G.; Yamaguchi, Y.; Yang, H.; Yang, P.; Yano, S.; Yasnopolskiy, S.; Yin, Z.; Yokoyama, H.; Yoo, I.-K.; Yurchenko, V.; Yushmanov, I.; Zaborowska, A.; Zaccolo, V.; Zaman, A.; Zampolli, C.; Zanoli, H. J. C.; Zaporozhets, S.; Zarochentsev, A.; Závada, P.; Zaviyalov, N.; Zbroszczyk, H.; Zgura, I. S.; Zhalov, M.; Zhang, H.; Zhang, X.; Zhang, Y.; Zhao, C.; Zhigareva, N.; Zhou, D.; Zhou, Y.; Zhou, Z.; Zhu, H.; Zhu, J.; Zhu, X.; Zichichi, A.; Zimmermann, A.; Zimmermann, M. B.; Zinovjev, G.; Zyzak, M.

2016-01-01

We present results of a search for two hypothetical strange dibaryon states, i.e. the H-dibaryon and the possible Λn ‾ bound state. The search is performed with the ALICE detector in central (0-10%) Pb-Pb collisions at √{sNN} = 2.76 TeV, by invariant mass analysis in the decay modes Λn ‾ → d ‾π+ and H-dibaryon → Λpπ-. No evidence for these bound states is observed. Upper limits are determined at 99% confidence level for a wide range of lifetimes and for the full range of branching ratios. The results are compared to thermal, coalescence and hybrid UrQMD model expectations, which describe correctly the production of other loosely bound states, like the deuteron and the hypertriton.

Robust Bounded Influence Tests in Linear Models

DTIC Science & Technology

1988-11-01

sensitivity analysis and bounded influence estimation. In: Evaluation of Econometric Models, J. Kmenta and J.B. Ramsey (eds.) Academic Press, New York...1R’OBUST bOUNDED INFLUENCE TESTS IN LINEA’ MODELS and( I’homas P. [lettmansperger* Tim [PennsylvanLa State UJniversity A M i0d fix pu111 rsos.p JJ 1 0...November 1988 ROBUST BOUNDED INFLUENCE TESTS IN LINEAR MODELS Marianthi Markatou The University of Iowa and Thomas P. Hettmansperger* The Pennsylvania

Bound states for an induced electric dipole in the presence of an azimuthal magnetic field and a disclination

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bakke, K.

2010-09-15

Based on the Wei-Han-Wei setup [H. Wei, R. Han, and X. Wei, Phys. Rev. Lett. 75, 2071 (1995)], where a neutral particle with an induced electric dipole moment interacts with a configuration of crossed electric and magnetic fields, in this paper we study the bound states that arise when we change the Wei-Han-Wei field configuration and consider a field configuration of crossed azimuthal magnetic field and a radial electric field. Moreover, we consider here a spin-half neutral particle and the presence of a linear topological defect called disclination. We obtain the bound states in two distinct cases: in the firstmore » case, we consider that the wave function of the neutral particle is well-behaved at the origin and vanishes at the asymptotic limit; in the second case, we consider the neutral particle confined to a parabolic potential like a quantum dot.« less

A Hidden Transhydrogen Activity of a FMN-Bound Diaphorase under Anaerobic Conditions

DTIC Science & Technology

2016-05-04

RESEARCH ARTICLE A Hidden Transhydrogen Activity of a FMN- Bound Diaphorase under Anaerobic Conditions John Collins1, Ting Zhang1, Scott Huston1... metabolic pathways for facilitating the electron transfer from one molecule to another in redox reactions. Transhy- drogenase plays an important role in...March 2, 2016 Accepted: April 20, 2016 Published: May 4, 2016 Copyright: © 2016 Collins et al. This is an open access article distributed under the

Interactions of a designed peptide with lipopolysaccharide: Bound conformation and anti-endotoxic activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhunia, Anirban; Chua, Geok Lin; Domadia, Prerna N.

Designed peptides that would selectively interact with lipopolysaccharide (LPS) or endotoxin and fold into specific conformations could serve as important scaffolds toward the development of antisepsis compounds. Here, we describe solution structure of a designed amphipathic peptide, H{sub 2}N-YVKLWRMIKFIR-CONH{sub 2} (YW12D) in complex with endotoxin as determined by transferred nuclear Overhauser effect spectroscopy. The conformation of the isolated peptide is highly flexible, but undergoes a dramatic structural stabilization in the presence of LPS. Structure calculations reveal that the peptide presents two amphipathic surfaces in its bound state to LPS whereby each surface is characterized by two positive charges and amore » number of aromatic and/or aliphatic residues. ITC data suggests that peptide interacts with two molecules of lipid A. In activity assays, YW12D exhibits neutralization of LPS toxicity with very little hemolysis of red blood cells. Structural and functional properties of YW12D would be applicable in designing low molecular weight non-toxic antisepsis molecules.« less

Reaching the Quantum Cramér-Rao Bound for Transmission Measurements

NASA Astrophysics Data System (ADS)

Woodworth, Timothy; Chan, Kam Wai Clifford; Marino, Alberto

2017-04-01

The quantum Cramér-Rao bound (QCRB) is commonly used to quantify the lower bound for the uncertainty in the estimation of a given parameter. Here, we calculate the QCRB for transmission measurements of an optical system probed by a beam of light. Estimating the transmission of an optical element is important as it is required for the calibration of optimal states for interferometers, characterization of high efficiency photodetectors, or as part of other measurements, such as those in plasmonic sensors or in ellipsometry. We use a beam splitter model for the losses introduced by the optical system to calculate the QCRB for different input states. We compare the bound for a coherent state, a two-mode squeezed-state (TMSS), a single-mode squeezed-state (SMSS), and a Fock state and show that it is possible to obtain an ultimate lower bound, regardless of the state used to probe the system. We prove that the Fock state gives the lowest possible uncertainty in estimating the transmission for any state and demonstrate that the TMSS and SMSS approach this ultimate bound for large levels of squeezing. Finally, we show that a simple measurement strategy for the TMSS, namely an intensity difference measurement, is able to saturate the QCRB. Work supported by the W.M. Keck Foundation.

Universality classes of order parameters composed of many-body bound states

DOE PAGES

Tsvelik, A. M.

2016-11-28

This theoretical paper discusses microscopic models giving rise to special types of order in which conduction electrons are bound together with localized spins to create composite order parameters. It is shown that composite order is related to the formation of a spin liquid with gapped excitations carrying quantum numbers which are a fraction of those of electron. These spin liquids are special in the sense that their formation necessarily involves spin degrees of freedom of both the conduction and the localized electrons and can be characterized by nonlocal order parameters. A detailed description of such spin liquid states is presentedmore » with a special care given to a demonstration of their robustness against local perturbations preserving the Lie group symmetry and the translational invariance.« less

Application of the bounds-analysis approach to arsenic and gallium antisite defects in gallium arsenide

DOE PAGES

Wright, A. F.; Modine, N. A.

2015-01-23

The As antisite in GaAs (AsGa) has been the subject of numerous experimental and theoretical studies. Recent density-functional-theory (DFT) studies report results in good agreement with experimental data for the +2, +1, and 0 charge states of the stable EL2 structure, the 0 charge state of the metastable EL2* structure, and the activation energy to transform from EL2* to EL2 in the 0 charge state. However, these studies did not report results for EL2* in the -1 charge state. In this paper, we report new DFT results for the +2, +1, 0, and -1 charge states of AsGa, obtained usingmore » a semilocal exchange-correlation functional and interpreted using a bounds-analysis approach. In good agreement with experimental data, we find a -1/0 EL2* level 0.06 eV below the conduction-band edge and an activation energy of 0.05 eV to transform from EL2* to EL2 in the -1 charge state. While the Ga antisite in GaAs (GaAs) has not been studied as extensively as AsGa, experimental studies report three charge states (-2, -1, 0) and two levels (-2/-1, -1/0) close to the valence-band edge. Recent DFT studies report the same charge states, but the levels are found to be well-separated from the valence-band edge. To resolve this disagreement, we performed new DFT calculations for GaAs and interpreted them using a bounds analysis. The analysis identified the -1 and 0 charge states as hole states weakly bound to a highly-localized -2 charge state. Moreover, the -2/-1, -1/0 levels were found to be near the valence-band edge, in good agreement with the experimental data.« less

Dynamic current susceptibility as a probe of Majorana bound states in nanowire-based Josephson junctions

NASA Astrophysics Data System (ADS)

Trif, Mircea; Dmytruk, Olesia; Bouchiat, Hélène; Aguado, Ramón; Simon, Pascal

2018-02-01

We theoretically study a Josephson junction based on a semiconducting nanowire subject to a time-dependent flux bias. We establish a general density-matrix approach for the dynamical response of the Majorana junction and calculate the resulting flux-dependent susceptibility using both microscopic and effective low-energy descriptions for the nanowire. We find that the diagonal component of the susceptibility, associated with the dynamics of the Majorana state populations, dominates over the standard Kubo contribution for a wide range of experimentally relevant parameters. The diagonal term, explored, in this Rapid Communication, in the context of Majorana physics, allows probing accurately the presence of Majorana bound states in the junction.

In vitro digestibility, free and bound phenolic profiles and antioxidant activity of thermally treated Eragrostis tef L.

PubMed

Koubová, Eva; Mrázková, Martina; Sumczynski, Daniela; Orsavová, Jana

2018-06-01

Total phenolic content, phenolic profile and antioxidant activity were determined in free and bound phenolic fractions of thermally treated brown and white teff grains. Phenolic content in raw brown and white teff (1540 and 992 mg gallic acid equivalent kg -1 ) as well as antioxidant activity (6.3 and 5.5 mmol trolox equivalent kg -1 ) were higher in free phenolic fractions. The most significant decrease in total phenolics was observed after application of the sous-vide method (35% for brown teff and 11% for white teff). Main free phenolics of heat-treated teff were ferulic, protocatechuic, p-coumaric and ellagic acids, rutin and epigallocatechin. Main bound phenolics were ferulic, gallic, sinapic and ellagic acids, catechin and epigallocatechin. The detrimental effect on free and bound quercetin and bound cinnamic acid concentrations was also examined during heat treatment. Thermally treated brown teff showed a high level of in vitro organic matter digestibility if water cooking and rice cooker (both 99.5%) and sous-vide (96.5%) methods were applied. The sous-vide method may be recommended as the most suitable hydrothermal treatment for grains of teff when compared with water cooking and rice cooker methods. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Insights into the Structural Dynamics of Nucleocytoplasmic Transport of tRNA by Exportin-t

PubMed Central

Gupta, Asmita; Kailasam, Senthilkumar; Bansal, Manju

2016-01-01

Exportin-t (Xpot) transports mature 5′- and 3′-end processed tRNA from the nucleus to the cytoplasm by associating with a small G-protein Ran (RAs-related nuclear protein), in the nucleus. The release of tRNA in cytoplasm involves RanGTP hydrolysis. Despite the availability of crystal structures of nuclear and cytosolic forms of Xpot, the molecular details regarding the sequential events leading to tRNA release and subsequent conformational changes occurring in Xpot remain unknown. We have performed a combination of classical all-atom and accelerated molecular dynamics simulations on a set of complexes involving Xpot to study a range of features including conformational flexibility of free and cargo-bound Xpot and functionally critical contacts between Xpot and its cargo. The systems investigated include free Xpot and its different complexes, bound either to Ran (GTP/GDP) or tRNA or both. This approach provided a statistically reliable estimate of structural dynamics of Xpot after cargo release. The mechanistic basis for Xpot opening after cargo release has been explained in terms of dynamic structural hinges, about which neighboring region could be displaced to facilitate the nuclear to cytosolic state transition. Post-RanGTP hydrolysis, a cascade of events including local conformational change in RanGTP and loss of critical contacts at Xpot/tRNA interface suggest factors responsible for eventual release of tRNA. The level of flexibility in different Xpot complexes varied depending on the arrangement of individual HEAT repeats. Current study provides one of the most comprehensive and robust analysis carried out on this protein using molecular dynamics schemes. PMID:27028637

Sound Velocity Bound and Neutron Stars

DOE PAGES

Bedaque, Paulo; Steiner, Andrew W.

2015-01-21

A conjecture that the velocity of sound in any medium is smaller than the velocity of light in vacuum divided by sqrt(3). Simple arguments support this bound in nonrelativistic and/or weakly coupled theories. Moreover, the bound has been demonstrated in several classes of strongly coupled theories with gravity duals and is saturated only in conformal theories. Here, we point out that the existence of neutron stars with masses around two solar masses combined with the knowledge of the equation of state of hadronic matter at low densities is in strong tension with this bound.

Effect of H2 binding on the nonadiabatic transition probability between singlet and triplet states of the [NiFe]-hydrogenase active site.

PubMed

Kaliakin, Danil S; Zaari, Ryan R; Varganov, Sergey A

2015-02-12

We investigate the effect of H2 binding on the spin-forbidden nonadiabatic transition probability between the lowest energy singlet and triplet electronic states of [NiFe]-hydrogenase active site model, using a velocity averaged Landau-Zener theory. Density functional and multireference perturbation theories were used to provide parameters for the Landau-Zener calculations. It was found that variation of the torsion angle between the terminal thiolate ligands around the Ni center induces an intersystem crossing between the lowest energy singlet and triplet electronic states in the bare active site and in the active site with bound H2. Potential energy curves between the singlet and triplet minima along the torsion angle and H2 binding energies to the two spin states were calculated. Upon H2 binding to the active site, there is a decrease in the torsion angle at the minimum energy crossing point between the singlet and triplet states. The probability of nonadiabatic transitions at temperatures between 270 and 370 K ranges from 35% to 32% for the active site with bound H2 and from 42% to 38% for the bare active site, thus indicating the importance of spin-forbidden nonadiabatic pathways for H2 binding on the [NiFe]-hydrogenase active site.

New method for taking into account finite nuclear mass in the determination of the absence of bound states: Application to e/sup +/H

DOE Office of Scientific and Technical Information (OSTI.GOV)

Armour, E.A.G.

1982-06-07

It has been known since the work of Aronson, Kleinman and Spruch, and Armour that, if the proton is considered to be infinitely massive, no bound state of a system made up of a positron and a hydrogen atom can exist. In this Letter a new method is introduced for taking into account finite nuclear mass. With use of this method it is shown that the inclusion of the finite mass of the proton does not result in the appearance of a bound state. This is the first time that this result has been established.

Cloud droplet activation through oxidation of organic aerosol influenced by temperature and particle phase state: CLOUD ACTIVATION BY AGED ORGANIC AEROSOL

DOE PAGES

Slade, Jonathan H.; Shiraiwa, Manabu; Arangio, Andrea; ...

2017-02-04

Chemical aging of organic aerosol (OA) through multiphase oxidation reactions can alter their cloud condensation nuclei (CCN) activity and hygroscopicity. However, the oxidation kinetics and OA reactivity depend strongly on the particle phase state, potentially influencing the hydrophobic-to-hydrophilic conversion rate of carbonaceous aerosol. Here, amorphous Suwannee River fulvic acid (SRFA) aerosol particles, a surrogate humic-like substance (HULIS) that contributes substantially to global OA mass, are oxidized by OH radicals at different temperatures and phase states. When oxidized at low temperature in a glassy solid state, the hygroscopicity of SRFA particles increased by almost a factor of two, whereas oxidation ofmore » liquid-like SRFA particles at higher temperatures did not affect CCN activity. Low-temperature oxidation appears to promote the formation of highly-oxygenated particle-bound fragmentation products with lower molar mass and greater CCN activity, underscoring the importance of chemical aging in the free troposphere and its influence on the CCN activity of OA.« less

34 CFR 645.42 - What are Upward Bound stipends?

Code of Federal Regulations, 2012 CFR

2012-07-01

... grantee is permitted to provide: (1) For Regular Upward Bound projects and Upward Bound Math and Science... What are Upward Bound stipends? (a) An Upward Bound project may provide stipends for all participants... evidence of satisfactory participation in activities of the project including— (1) Regular attendance; and...

34 CFR 645.42 - What are Upward Bound stipends?

Code of Federal Regulations, 2013 CFR

2013-07-01

... grantee is permitted to provide: (1) For Regular Upward Bound projects and Upward Bound Math and Science... What are Upward Bound stipends? (a) An Upward Bound project may provide stipends for all participants... evidence of satisfactory participation in activities of the project including— (1) Regular attendance; and...

34 CFR 645.42 - What are Upward Bound stipends?

Code of Federal Regulations, 2014 CFR

2014-07-01

... grantee is permitted to provide: (1) For Regular Upward Bound projects and Upward Bound Math and Science... What are Upward Bound stipends? (a) An Upward Bound project may provide stipends for all participants... evidence of satisfactory participation in activities of the project including— (1) Regular attendance; and...

Comparative analysis of solid-state bioprocessing and enzymatic treatment of finger millet for mobilization of bound phenolics.

PubMed

Yadav, Geetanjali; Singh, Anshu; Bhattacharya, Patrali; Yuvraj, Jude; Banerjee, Rintu

2013-11-01

The present work investigates the probable bioprocessing technique to mobilize the bound phenolics naturally found in finger millet cell wall for enriching it with dietary antioxidants. Comparative study was performed between the exogenous enzymatic treatment and solid-state fermentation of grain (SSF) with a food grade organism Rhizopus oryzae. SSF results indicated that at the 6th day of incubation, total phenolic content (18.64 mg gallic acid equivalent/gds) and antioxidant property (DPPH radical scavenging activity of 39.03 %, metal chelating ability of 54 % and better reducing power) of finger millet were drastically enhanced when fermented with GRAS filamentous fungi. During the enzymatic bioprocessing, most of the phenolics released during the hydrolysis, leached out into the liquid portion rather than retaining them within the millet grain, resulting in overall loss of dietary antioxidant. The present study establishes the most effective strategy to enrich the finger millet with phenolic antioxidants.

Experimental evidence for bounds on quantum correlations.

PubMed

Bovino, F A; Castagnoli, G; Degiovanni, I P; Castelletto, S

2004-02-13

We implemented the experiment proposed by Cabello in the preceding Letter to test the bounds of quantum correlation. As expected from the theory we found that, for certain choices of local observables, Tsirelson's bound of the Clauser-Horne-Shimony-Holt inequality (2 x square root of 2) is not reached by any quantum states.

Lead acetate induces EGFR activation upstream of SFK and PKC{alpha} linkage to the Ras/Raf-1/ERK signaling