Statistical transmutation in doped quantum dimer models.

Science.gov (United States)

Lamas, C A; Ralko, A; Cabra, D C; Poilblanc, D; Pujol, P

2012-07-06

We prove a "statistical transmutation" symmetry of doped quantum dimer models on the square, triangular, and kagome lattices: the energy spectrum is invariant under a simultaneous change of statistics (i.e., bosonic into fermionic or vice versa) of the holes and of the signs of all the dimer resonance loops. This exact transformation enables us to define the duality equivalence between doped quantum dimer Hamiltonians and provides the analytic framework to analyze dynamical statistical transmutations. We investigate numerically the doping of the triangular quantum dimer model with special focus on the topological Z(2) dimer liquid. Doping leads to four (instead of two for the square lattice) inequivalent families of Hamiltonians. Competition between phase separation, superfluidity, supersolidity, and fermionic phases is investigated in the four families.

Strain mediated interaction of adatom dimers

OpenAIRE

Kappus, Wolfgang

2013-01-01

An earlier model for substrate strain mediated interactions between monomer adatoms is extended to the interaction of monomers with dimers and the interaction of dimers. While monomers (sitting on high symmetric sites) are supposed to create isotropic stress on the substrate, dimers would create anisotropic stress caused by stretching their bond. Resulting interactions are strongly angle dependent and also reflect the elastic anisotropy of the substrate. The applicability of a continuum elast...

Selective amine catalysed steroidal dimerization

Indian Academy of Sciences (India)

of cholesterol is the formation of a green colour in concentrated sulphuric acid, and this was shown to be due to a polyenyl steroidal dimer carbocation.7–9 Many dimeric and oligomeric steroids exhibit interesting micellular, detergent and liquid crystal behaviour.10,11. Most of the steroidal dimmers are also well-known.

Photoionization of helium dimers

International Nuclear Information System (INIS)

Havermeier, Tilo

2010-01-01

The helium dimer is one of the most weakly bound systems in the universe. This makes it an interesting quantum mechanical object for investigation. These Van der Waals Clusters can be produced in an expansion of a cryogenic gas jet through a small nozzle into vacuum. In the present experiment we examine the interaction of He dimers with synchrotron radiation at an energy range from 64 to 78 eV. We observed different pathways leading to single ionization of both He atoms of the dimer compound. This two close standing ions begin now to dissociate in cause of their coulomb potential. All charged fragments were detected in coincidence with a COLTRIMS system. Especially Interatomic Coulombic Decay (ICD) and the two step process (TS1) were clearly identified. Furthermore a distribution of the internuclear distance was obtained from the measured Kinetic Energy Release (KER). (orig.)

Pyrimidine dimer formation and repair in human skin

International Nuclear Information System (INIS)

Sutherland, B.M.; Harber, L.C.; Kochevar, I.E.

1980-01-01

Cyclobutyl pyrimidine dimers have been detected in the DNA of human skin following in vivo irradiation with suberythermal doses of ultraviolet (UV) radiation from FS-20 sun lamp fluorescent tubes. Dimers were assayed by treatment of extracted DNA with Micrococus luteus UV-specific endonuclease, alkaline agarose electrophoresis, and ethidum bromide staining. This technique, in contrast to conventional dimer assays, can be used with nonradioactive DNA and is optimal at low UV light doses. These data suggest that some dimer disappearance by excision repair occurs within 20 min of UV irradiation and that photoreactivation of dimers can make a contribution to the total repair process

Adventures in holographic dimer models

International Nuclear Information System (INIS)

Kachru, Shamit; Karch, Andreas; Yaida, Sho

2011-01-01

We abstract the essential features of holographic dimer models, and develop several new applications of these models. Firstly, semi-holographically coupling free band fermions to holographic dimers, we uncover novel phase transitions between conventional Fermi liquids and non-Fermi liquids, accompanied by a change in the structure of the Fermi surface. Secondly, we make dimer vibrations propagate through the whole crystal by way of double trace deformations, obtaining nontrivial band structure. In a simple toy model, the topology of the band structure experiences an interesting reorganization as we vary the strength of the double trace deformations. Finally, we develop tools that would allow one to build, in a bottom-up fashion, a holographic avatar of the Hubbard model.

Dynamic interplay between adhesive and lateral E-cadherin dimers

DEFF Research Database (Denmark)

Klingelhöfer, Jörg; Laur, Oscar Y; Troyanovsky, Regina B

2002-01-01

M. The disappearance of adhesive dimers was counterbalanced by an increase in Trp156-dependent lateral dimers. Increasing the calcium concentration to a normal level rapidly restored the original balance between adhesive and lateral dimers. We also present evidence that E-cadherin dimers in vivo have a short lifetime...

Plasmonic nanospherical dimers for color pixels

KAUST Repository

Alrasheed, Salma

2018-04-20

Display technologies are evolving more toward higher resolution and miniaturization. Plasmonic color pixels can offer solutions to realize such technologies due to their sharp resonances and selective scattering and absorption at particular wavelengths. Metal nanosphere dimers are capable of supporting plasmon resonances that can be tuned to span the entire visible spectrum. In this article, we demonstrate numerically bright color pixels that are highly polarized and broadly tuned using periodic arrays of metal nanosphere dimers on a glass substrate. We show that it is possible to obtain RGB pixels in the reflection mode. The longitudinal plasmon resonance of nanosphere dimers along the axis of the dimer is the main contributor to the color of the pixel, while far-field diffractive coupling further enhances and tunes the plasmon resonance. The computational method used is the finite-difference time-domain method. The advantages of this approach include simplicity of the design, bright coloration, and highly polarized function. In addition, we show that it is possible to obtain different colors by varying the angle of incidence, the periodicity, the size of the dimer, the gap, and the substrate thickness.

Age-Adjusted D-Dimer in the Prediction of Pulmonary Embolism: Does a Normal Age-Adjusted D-Dimer Rule Out PE?

Directory of Open Access Journals (Sweden)

Jacob Ortiz

2017-01-01

Full Text Available Risk assessment for pulmonary embolism (PE currently relies on physician judgment, clinical decision rules (CDR, and D-dimer testing. There is still controversy regarding the role of D-dimer testing in low or intermediate risk patients. The objective of the study was to define the role of clinical decision rules and D-dimer testing in patients suspected of having a PE. Records of 894 patients referred for computed tomography pulmonary angiography (CTPA at a University medical center were analyzed. The clinical decision rules overall had an ROC of approximately 0.70, while signs of DVT had the highest ROC (0.80. A low probability CDR coupled with a negative age-adjusted D-dimer largely excluded PE. The negative predictive value (NPV of an intermediate CDR was 86–89%, while the addition of a negative D-dimer resulted in NPVs of 94%. Thus, in patients suspected of having a PE, a low or intermediate CDR does not exclude PE; however, in patients with an intermediate CDR, a normal age-adjusted D-dimer increases the NPV.

Peptides Interfering 3A Protein Dimerization Decrease FMDV Multiplication.

Directory of Open Access Journals (Sweden)

Mónica González-Magaldi

Full Text Available Nonstructural protein 3A is involved in relevant functions in foot-and-mouth disease virus (FMDV replication. FMDV 3A can form homodimers and preservation of the two hydrophobic α-helices (α1 and α2 that stabilize the dimer interface is essential for virus replication. In this work, small peptides mimicking residues involved in the dimer interface were used to interfere with dimerization and thus gain insight on its biological function. The dimer interface peptides α1, α2 and that spanning the two hydrophobic α-helices, α12, impaired in vitro dimer formation of a peptide containing the two α-helices, this effect being higher with peptide α12. To assess the effect of dimer inhibition in cultured cells, the interfering peptides were N-terminally fused to a heptaarginine (R7 sequence to favor their intracellular translocation. Thus, when fused to R7, interference peptides (100 μM were able to inhibit dimerization of transiently expressed 3A, the higher inhibitions being found with peptides α1 and α12. The 3A dimerization impairment exerted by the peptides correlated with significant, specific reductions in the viral yield recovered from peptide-treated FMDV infected cells. In this case, α2 was the only peptide producing significant reductions at concentrations lower than 100 μM. Thus, dimer interface peptides constitute a tool to understand the structure-function relationship of this viral protein and point to 3A dimerization as a potential antiviral target.

Mahler Measure, Eisenstein Series and Dimers

NARCIS (Netherlands)

Stienstra, J.

2007-01-01

This note reveals a mysterious link between the partition function of certain dimer models on 2-dimensional tori and the L-function of their spectral curves. It also relates the partition function in certain families of dimer models to Eisenstein series. http://www.arxiv.org/abs/math.NT/0502197

Effects of Dimers on Cooperation in the Spatial Prisoner's Dilemma Game

International Nuclear Information System (INIS)

Li Haihong; Cheng Hongyan; Dai Qionglin; Ju Ping; Yang Junzhong; Zhang Mei

2011-01-01

We investigate the evolutionary prisoner's dilemma game in structured populations by introducing dimers, which are defined as that two players in each dimer always hold a same strategy. We find that influences of dimers on cooperation depend on the type of dimers and the population structure. For those dimers in which players interact with each other, the cooperation level increases with the number of dimers though the cooperation improvement level depends on the type of network structures. On the other hand, the dimers, in which there are not mutual interactions, will not do any good to the cooperation level in a single community, but interestingly, will improve the cooperation level in a population with two communities. We explore the relationship between dimers and self-interactions and find that the effects of dimers are similar to that of self-interactions. Also, we find that the dimers, which are established over two communities in a multi-community network, act as one type of interaction through which information between communities is communicated by the requirement that two players in a dimer hold a same strategy. (general)

Structural insights into the intertwined dimer of fyn SH2.

Science.gov (United States)

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

2015-12-01

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

Kinetics of DNA tile dimerization.

Science.gov (United States)

Jiang, Shuoxing; Yan, Hao; Liu, Yan

2014-06-24

Investigating how individual molecular components interact with one another within DNA nanoarchitectures, both in terms of their spatial and temporal interactions, is fundamentally important for a better understanding of their physical behaviors. This will provide researchers with valuable insight for designing more complex higher-order structures that can be assembled more efficiently. In this report, we examined several spatial factors that affect the kinetics of bivalent, double-helical (DH) tile dimerization, including the orientation and number of sticky ends (SEs), the flexibility of the double helical domains, and the size of the tiles. The rate constants we obtained confirm our hypothesis that increased nucleation opportunities and well-aligned SEs accelerate tile-tile dimerization. Increased flexibility in the tiles causes slower dimerization rates, an effect that can be reversed by introducing restrictions to the tile flexibility. The higher dimerization rates of more rigid tiles results from the opposing effects of higher activation energies and higher pre-exponential factors from the Arrhenius equation, where the pre-exponential factor dominates. We believe that the results presented here will assist in improved implementation of DNA tile based algorithmic self-assembly, DNA based molecular robotics, and other specific nucleic acid systems, and will provide guidance to design and assembly processes to improve overall yield and efficiency.

Dimers in Piecewise Temperleyan Domains

Science.gov (United States)

Russkikh, Marianna

2018-03-01

We study the large-scale behavior of the height function in the dimer model on the square lattice. Richard Kenyon has shown that the fluctuations of the height function on Temperleyan discretizations of a planar domain converge in the scaling limit (as the mesh size tends to zero) to the Gaussian Free Field with Dirichlet boundary conditions. We extend Kenyon's result to a more general class of discretizations. Moreover, we introduce a new factorization of the coupling function of the double-dimer model into two discrete holomorphic functions, which are similar to discrete fermions defined in Smirnov (Proceedings of the international congress of mathematicians (ICM), Madrid, Spain, 2006; Ann Math (2) 172:1435-1467, 2010). For Temperleyan discretizations with appropriate boundary modifications, the results of Kenyon imply that the expectation of the double-dimer height function converges to a harmonic function in the scaling limit. We use the above factorization to extend this result to the class of all polygonal discretizations, that are not necessarily Temperleyan. Furthermore, we show that, quite surprisingly, the expectation of the double-dimer height function in the Temperleyan case is exactly discrete harmonic (for an appropriate choice of Laplacian) even before taking the scaling limit.

Dimer-based model for heptaspanning membrane receptors.

Science.gov (United States)

Franco, Rafael; Casadó, Vicent; Mallol, Josefa; Ferré, Sergi; Fuxe, Kjell; Cortés, Antonio; Ciruela, Francisco; Lluis, Carmen; Canela, Enric I

2005-07-01

The existence of intramembrane receptor-receptor interactions for heptaspanning membrane receptors is now fully accepted, but a model considering dimers as the basic unit that binds to two ligand molecules is lacking. Here, we propose a two-state-dimer model in which the ligand-induced conformational changes from one component of the dimer are communicated to the other. Our model predicts cooperativity in binding, which is relevant because the other current models fail to address this phenomenon satisfactorily. Our two-state-dimer model also predicts the variety of responses elicited by full or partial agonists, neutral antagonists and inverse agonists. This model can aid our understanding of the operation of heptaspanning receptors and receptor channels, and, potentially, be important for improving the treatment of cardiovascular, neurological and neuropsychyatric diseases.

Detection of cyclobutane thymine dimers in DNA of human cells with monoclonal antibodies raised against a thymine dimer-containing tetranucleotide

Energy Technology Data Exchange (ETDEWEB)

Roza, L; Wulp, K.J.M. van der; MacFarlane, S J; Lohman, P H.M.; Baan, R A

1988-11-01

A hybrid cell line (hybridoma) has been isolated after fusion between mouse-plasmacytoma cells and spleen cells from mice immunized with a thymine dimer-containing tetranucleotide coupled to a carrier protein. Monoclonal antibodies produced by this hybridoma were characterized by testing the effect of various inhibitors in a competitive enzyme-linked immunosorbent assay (ELISA). The antibodies have a high specificity for thymine dimers in single-stranded DNA or poly(dT), but do not bind UV-irradiated d(TpC)/sub 5/. Less binding is observed with short thymine dimer-containing sequences. In vitro treatment of UV-irradiated DNA with photoreactivating enzyme in the presence of light, or with Micrococcus luteus UV-endonuclease results in disappearance of antigenicity. Antibody-binding to DNA isolated from UV-irradiated human fibroblasts (at 254 nm) is linear with dose. Removal of thymine dimers in these cells during a post-irradiation incubation, as detected with the antibodies, is fast initially but the rate rapidly decreases (about 50% residual dimers at 20 h after 10 J/m/sup 2/). The induction of thymine dimers in human skin irradiated with low doses of UV-B, too, was demonstrated immunochemically, by ELISA as well as by quantitative immunofluorescence microscopy.

Hydrodynamic Torques and Rotations of Superparamagnetic Bead Dimers

Science.gov (United States)

Pease, Christopher; Etheridge, J.; Wijesinghe, H. S.; Pierce, C. J.; Prikockis, M. V.; Sooryakumar, R.

Chains of micro-magnetic particles are often rotated with external magnetic fields for many lab-on-a-chip technologies such as transporting beads or mixing fluids. These applications benefit from faster responses of the actuated particles. In a rotating magnetic field, the magnetization of superparamagnetic beads, created from embedded magnetic nano-particles within a polymer matrix, is largely characterized by induced dipoles mip along the direction of the field. In addition there is often a weak dipole mop that orients out-of-phase with the external rotating field. On a two-bead dimer, the simplest chain of beads, mop contributes a torque Γm in addition to the torque from mip. For dimers with beads unbound to each other, mop rotates individual beads which generate an additional hydrodynamic torque on the dimer. Whereas, mop directly torques bound dimers. Our results show that Γm significantly alters the average frequency-dependent dimer rotation rate for both bound and unbound monomers and, when mop exceeds a critical value, increases the maximum dimer rotation frequency. Models that include magnetic and hydrodynamics torques provide good agreement with the experimental findings over a range of field frequencies.

Adsorption of dimeric surfactants in lamellar silicates

Energy Technology Data Exchange (ETDEWEB)

Balcerzak, Mateusz; Pietralik, Zuzanna [Department of Macromolecular Physics, Faculty of Physics, A. Mickiewicz University, Umultowska 85, 61-614 Poznań (Poland); Domka, Ludwik [Department of Metalorganic Chemistry, Faculty of Chemistry, A. Mickiewicz University, Grunwaldzka 6, 60-780 Poznań (Poland); Skrzypczak, Andrzej [Institute of Chemical Technology, Poznań University of Technology, Berdychowo 4, 60-965 Poznań (Poland); Kozak, Maciej, E-mail: mkozak@amu.edu.pl [Department of Macromolecular Physics, Faculty of Physics, A. Mickiewicz University, Umultowska 85, 61-614 Poznań (Poland)

2015-12-01

Highlights: • The intercalation of dimeric surfactants changed the morphology of MMT samples. • XRD indicated structures formed by surfactant molecules in interlayer space. • The four-step thermal decomposition of dimeric surfactant, confirms intercalation. - Abstract: The adsorption of different types of cationic surfactants in lamellar silicates changes their surface character from hydrophilic to hydrophobic. This study was undertaken to obtain lamellar silicates modified by a series of novel dimeric (gemini) surfactants of different length alkyl chains and to characterise these organophilised materials. Synthetic sodium montmorillonite SOMASIF® ME 100 (M) and enriched bentonite of natural origin (Nanoclay – hydrophilic bentonite®) were organophilised with dimeric (gemini) surfactants (1,1′-(1,4-butanediyl)bis(alkoxymethyl)imidazolium dichlorides). As a result of surfactant molecule adsorption in interlamellar space, the d-spacing (d{sub 001}) increased from 0.97 nm (for the anhydrous structure) to 2.04 nm. A Fourier transform infrared spectroscopy (FTIR) analysis of the modified systems reveals bands assigned to the stretching vibrations of the CH{sub 2} and CH{sub 3} groups and the scissoring vibrations of the NH group from the structure of the dimeric surfactants. Thermogravimetric (TG) and derivative thermogravimetric (DTG) studies imply a four-stage process of surfactant decomposition. Scanning electron microscopy (SEM) images provide information on the influence of dimeric surfactant intercalation into the silicate structures. Particles of the modified systems show a tendency toward the formation of irregularly shaped agglomerates.

D-dimer Test

Science.gov (United States)

... 1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition]. Pagana, Kathleen D. & Pagana, ... www.itxm.org . Titus, K. (2003 January). Identity crisis persists: which D-dimer? CAP Today , In the ...

Molecular mechanics calculations on cobalt phthalocyanine dimers

NARCIS (Netherlands)

Heuts, J.P.A.; Schipper, E.T.W.M.; Piet, P.; German, A.L.

1995-01-01

In order to obtain insight into the structure of cobalt phthalocyanine dimers, molecular mechanics calculations were performed on dimeric cobalt phthalocyanine species. Molecular mechanics calculations are first presented on monomeric cobalt(II) phthalocyanine. Using the Tripos force field for the

Revealing the Dimeric Crystal and Solution Structure of β-Lactoglobulin at pH 4 and Its pH and Salt Dependent Monomer–Dimer Equilibrium

DEFF Research Database (Denmark)

Khan, Sanaullah; Ipsen, Richard; Almdal, Kristoffer

2018-01-01

The dimeric structure of bovine β-lactoglobulin A (BLGA) at pH 4.0 was solved to 2.0 Å resolution. Fitting the BLGA pH 4.0 structure to SAXS data at low ionic strength (goodness of fit R-factor = 3.6%) verified the dimeric state in solution. Analysis of the monomer–dimer equilibrium at varying pH...... and ionic strength by SAXS and scattering modeling showed that BLGA is dimeric at pH 3.0 and 4.0, shifting toward a monomer at pH 2.2, 2.6, and 7.0 yielding monomer/dimer ratios of 80/20%, 50/50%, and 25/75%, respectively. BLGA remained a dimer at pH 3.0 and 4.0 in 50–150 mM NaCl, whereas the electrostatic...... shielding raised the dimer content at pH 2.2, 2.6, and 7.0, i.e., below and above the pI. Overall, the findings provide new insights into the molecular characteristics of BLGA relevant for dairy product formulations and for various biotechnological and pharmaceutical applications....

Dynamics of the water dimer + nitric oxide collision

Energy Technology Data Exchange (ETDEWEB)

Ree, Jong Baik [Dept. of Chemistry Education, Chonnam National University, Gwangju (Korea, Republic of); Kim, Yoo Hang [Dept. of Chemistry, Inha University, Incheon (Korea, Republic of); Shin, Hyung Kyu [Dept. of Chemistry, University of Nevada, Nevada (Korea, Republic of)

2017-02-15

Collision-induced intermolecular energy transfer and intramolecular vibrational redistribution in the collision of a water dimer and nitric oxide are studied by use of quasiclassical procedures. Intermolecular energy flow is shown to occur mainly through a direct-mode mechanism transferring relatively large amounts in strong collisions. About a quarter of the energy initially deposited in the dimer transfers to the ground state NO, while the rest redistributes among internal motions of the collision system. The main portion of initial energy deposited in the dimer redistributes in the stretches of the donor monomer through the 1:1 resonance followed by in the bend through the 1:2 resonance. Energy transfer from the excited NO to the ground-state dimer is equally efficient, transferring more than half the initial excitation to the donor monomer, the efficiency that is attributed to the internal modes operating as energy reservoirs. The hydrogen bond shares about 15% of the initial excitation stored in both dimer-to-NO and NO-to-dimer processes as a result of strong coupling of the hydrogen bond with the proton-donor OH bond of the monomer. A small fraction of collisions proceeds through a complex-mode mechanism and lead to NO dissociation, the dissociated O atom showing a propensity to form a new hydrogen bond.

Determination of the Tetramer-Dimer Equilibrium Constant of Rabbit ...

African Journals Online (AJOL)

Hemoglobin is a tetrameric protein which is able to dissociate into dimers. The dimers can in turn dissociate into tetramers. It has been found that dimers are more reactive than tetramers. The difference in the reactivity of these two species has been used to determine the tetramerdimer dissociation constant of various ...

Dualism of Sensitivity and Selectivity of Porphyrin Dimers in Electroanalysis.

Science.gov (United States)

Lisak, Grzegorz; Tamaki, Takashi; Ogawa, Takuji

2017-04-04

This work uncovers the application of porphyrin dimers for the use in electroanalysis, such as potentiometric determination of ions. It also puts in question a current perception of an occurrence of the super-Nernstian response, as a result of the possible dimerization of single porphyrins within an ion-selective membrane. To study that, four various porphyrin dimers were used as ionophores, namely, freebase-freebase, Zn-Zn, Zn-freebase, and freebase-Zn. Since the Zn-freebase and freebase-Zn porphyrin dimers carried both anion- and cation-sensitive porphyrin units, their application in ISEs was utilized in both anion- and cation-sensitive sensors. With respect to the lipophilic salt added, both porphyrins dimers were found anion- and cation-sensitive. This allowed using a single molecule as novel type of versatile ionophore (anion- and cation-selective), simply by varying the membrane composition. All anion-sensitive sensors were perchlorate-sensitive, while the cation-selective sensors were silver-sensitive. The selectivity of the sensors depended primarily on the porphyrin dimers in the ion-selective membrane. Furthermore, the selectivity of cation-sensitive dimer based sensors was found significantly superior to the ones measured for the single porphyrin unit based sensors (precursors of the porphyrin dimers). Thus, the dimerization of single porphyrins may actually be a factor to increase or modulate porphyrin selectivity. Moreover, in the case of cation-sensitive sensors, the selectivity vastly depended on the order of porphyrin units in the dimer. This opens a new approach of regulating and adjusting sensitivity and selectivity of the sensor through the application of complex porphyrin systems with more than one porphyrin units with mix sensitive porphyrins.

Factors associated with D-dimer levels in HIV-infected individuals

DEFF Research Database (Denmark)

Borges, Alvaro H; O'Connor, Jemma L; Phillips, Andrew N

2014-01-01

BACKGROUND: Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood. METHODS: In this cross-sectional study, participants in three randomized controlled trials...... with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4+ count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6...... viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high...

Mechanism for Controlling the Dimer-Monomer Switch and Coupling Dimerization to Catalysis of the Severe Acute Respiratory Syndrome Coronavirus 3C-Like Protease

Energy Technology Data Exchange (ETDEWEB)

Shi,J.; Sivaraman, J.; Song, J.

2008-01-01

Unlike 3C protease, the severe acute respiratory syndrome coronavirus (SARS-CoV) 3C-like protease (3CLpro) is only enzymatically active as a homodimer and its catalysis is under extensive regulation by the unique extra domain. Despite intense studies, two puzzles still remain: (i) how the dimer-monomer switch is controlled and (ii) why dimerization is absolutely required for catalysis. Here we report the monomeric crystal structure of the SARS-CoV 3CLpro mutant R298A at a resolution of 1.75 Angstroms . Detailed analysis reveals that Arg298 serves as a key component for maintaining dimerization, and consequently, its mutation will trigger a cooperative switch from a dimer to a monomer. The monomeric enzyme is irreversibly inactivated because its catalytic machinery is frozen in the collapsed state, characteristic of the formation of a short 310-helix from an active-site loop. Remarkably, dimerization appears to be coupled to catalysis in 3CLpro through the use of overlapped residues for two networks, one for dimerization and another for the catalysis.

Study of molybdenum(VI) dimerization equilibrium in strongly acidic medium

International Nuclear Information System (INIS)

Esbelin, E.

2000-01-01

Molybdenum (VI) was investigated spectro-photometrically in non complexing and strongly acidic medium for the first time by Krumenacker. Cationic species of molybdenum were identified by electrophoresis on cellulose paper in highly acidic solutions. From these early results using absorption spectrophotometry, Krumenacker postulated the condensation of molybdenum in this medium. He studied the polymeric species by measuring diffusion coefficients and identified the polymeric form as a dimer. He described the system by equations (1) and (2). Cruywagen later added two equations (3) and (4) to supplement the description of the system. The aim of this work was to re-examine the conditional dimerization equilibrium between the various species of molybdenum(VI) in strongly acid medium by focussing on the influence of the medium. All Mo solution concentrations were analyzed by ICP-AES. Absorbance of the solutions were measured with a VARIAN model CARY5 spectrophotometer in double beam mode with air as reference; blank solutions contained all reagents except molybdenum. The quartz cell path length was 1 mm. The dimerization of monomeric molybdenum(VI) was investigated spectro-photometrically at perchloric acid concentrations of 0.5, 1.0, 2.0 and 3 M at 25 deg C. Two absorption bands at 215 and 245 nm were observed and attributed to monomeric and dimeric forms respectively. The variations in the conditional molar absorption coefficient of molybdenum with total molybdenum(VI) concentration is indicative of several molybdenum forms involved in the total absorbance. Dimerization equilibrium is defined by equation (5). By using the additivity of absorbance and mass conservation of molybdenum, a descriptive equation of the 'spectrochemical' system is developed. This equation is linearized into two forms (6) et (7). From them, two refinement methods were used to estimate the conditional dimerization constant K' d for various medium concentrations. This numerical procedure offers

Structural insights into lipid-dependent reversible dimerization of human GLTP

International Nuclear Information System (INIS)

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

2013-01-01

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

Association of atoms into universal dimers using an oscillating magnetic field.

Science.gov (United States)

Langmack, Christian; Smith, D Hudson; Braaten, Eric

2015-03-13

In a system of ultracold atoms near a Feshbach resonance, pairs of atoms can be associated into universal dimers by an oscillating magnetic field with a frequency near that determined by the dimer binding energy. We present a simple expression for the transition rate that takes into account many-body effects through a transition matrix element of the contact. In a thermal gas, the width of the peak in the transition rate as a function of the frequency is determined by the temperature. In a dilute Bose-Einstein condensate of atoms, the width is determined by the inelastic scattering rates of a dimer with zero-energy atoms. Near an atom-dimer resonance, there is a dramatic increase in the width from inelastic atom-dimer scattering and from atom-atom-dimer recombination. The recombination contribution provides a signature for universal tetramers that are Efimov states consisting of two atoms and a dimer.

Multiple regions of Harvey sarcoma virus RNA can dimerize in vitro.

Science.gov (United States)

Feng, Y X; Fu, W; Winter, A J; Levin, J G; Rein, A

1995-04-01

Retroviruses contain a dimeric RNA consisting of two identical molecules of plus-strand genomic RNA. The structure of the linkage between the two monomers is not known, but they are believed to be joined near their 5' ends. Darlix and coworkers have reported that transcripts of retroviral RNA sequences can dimerize spontaneously in vitro (see, for example, E. Bieth, C. Gabus, and J. L. Darlix, Nucleic Acids Res. 18:119-127, 1990). As one approach to identification of sequences which might participate in the linkage, we have mapped sequences derived from the 5' 378 bases of Harvey sarcoma virus (HaSV) RNA which can dimerize in vitro. We found that at least three distinct regions, consisting of nucleotides 37 to 229, 205 to 272, and 271 to 378, can form these dimers. Two of these regions contain nucleotides 205 to 226; computer analysis suggests that this region can form a stem-loop with an inverted repeat in the loop. We propose that this hypothetical structure is involved in dimer formation by these two transcripts. We also compared the thermal stabilities of each of these dimers with that of HaSV viral RNA. Dimers of nucleotides 37 to 229 and 205 to 272 both exhibited melting temperatures near that of viral RNA, while dimers of nucleotides 271 to 378 are quite unstable. We also found that dimers of nucleotides 37 to 378 formed at 37 degrees C are less thermostable than dimers of the same RNA formed at 55 degrees C. It seems possible that bases from all of these regions participate in the dimer linkage present in viral RNA.

Kinetics of thymine dimer excision in ultraviolet-irradiated human cells

International Nuclear Information System (INIS)

Ehmann, U.K.; Cook, K.H.; Friedberg, E.C.

1978-01-01

We have investigated the kinetics of the loss of thymine dimers from the acid-insoluble fraction of several ultraviolet (uv)-irradiated cultured human cell lines. Our results show that uv fluences between 10 and 40 J/m 2 produce an average of 21 to 85 x 10 5 thymine dimers per cell and an eventual maximal loss per cell of 12 to 20 x 10 5 thymine dimers. The time for half-maximal loss of dimers ranged from 12 to 22 h after uv irradiation. In contrast, the time for half-maximal repair synthesis of DNA measured by autoradiography was 4.5 h. This figure agrees well with reported half-maximal repair synthesis times, which range from 0.5 to 3.6 h based on our analysis. The discrepancy in the kinetics of the loss of thymine dimers from DNA and repair synthesis is discussed in terms of possible molecular mechanisms of thymine dimer excision in vivo and in terms of possible experimental artifacts

Role of cyclobutane dimers in UV-denaturation of DNA

International Nuclear Information System (INIS)

Zavil'gel'skij, G.B.; Zuev, A.V.

1978-01-01

UV irradiation of double-stranded DNA produces local denatured regions. The evidence presented indicates that these single-stranded regions arise from photoproducts other than pyrimidine dimers. The irradiation of T2 DNA at 8x10 4 erg/mm 2 (254 nm) produces 6-8% thymine dimers, amd Tsub(mel) drops by 12-14 deg C, accompanied by a significant broadening of the transition profile. The kinetics of denatured region formation and lowering Tsub(mel) corresponds to that of formation of crosslinkages and differs markedly from the kinetics of formation of cyclobutane pyrimidine dimers. Treatment of UV-irradiated DNA with light in the presence of yeast photoreactivating enzyme monomerizes almost all thymine dimers but does not change the Tsub(mel). Local denatured regions are detected in UV-irradiated DNA and are absent from AcPhM-sensibilized DNA, which contains 20-25% thymine dimers, as determined by the accridine orange fluorescence technique. S1 nuclease from Aspergillis oryzae produces single-strand breaks in UV-irradiated DNA of phage PM2 but is not active on AcPhM-treated PM2 DNA, which contains about 50 thymine dimers. It is supposed that the formation of a cyclobutane dimer only weakens the hydrogen bonds in the AT base pair rather than breaks them. Local denatured regions are thought to arise from the accumulation in UV-irradiated DNA (254 nm) of the sufficient number of photoproducts with impaired ability to base pairing

Family C 7TM receptor dimerization and activation

DEFF Research Database (Denmark)

Bonde, Marie Mi; Sheikh, Søren P; Hansen, Jakob Lerche

2006-01-01

The family C seven transmembrane (7TM) receptors constitutes a small and especially well characterized subfamily of the large 7TM receptor superfamily. Approximately 50% of current prescription drugs target 7TM receptors, this biologically important family represents the largest class of drug...... to be fully defined. This review presents the biochemical support for family C 7TM receptor dimerization and discusses its importance for receptor biosynthesis, surface expression, ligand binding and activation, since lessons learnt here may well be applicable to the whole superfamily of 7TM receptors.......-targets today. It is well established that family C 7TM receptors form homo- or hetero-dimers on the cell surface of living cells. The large extra-cellular domains (ECD) have been crystallized as a dimer in the presence and absence of agonist. Upon agonist binding, the dimeric ECD undergoes large conformational...

Characterization of oxygen dimer-enriched silicon detectors

CERN Document Server

Boisvert, V; Moll, M; Murin, L I; Pintilie, I

2005-01-01

Various types of silicon material and silicon p+n diodes have been treated to increase the concentration of the oxygen dimer (O2i) defect. This was done by exposing the bulk material and the diodes to 6 MeV electrons at a temperature of about 350 °C. FTIR spectroscopy has been performed on the processed material confirming the formation of oxygen dimer defects in Czochralski silicon pieces. We also show results from TSC characterization on processed diodes. Finally, we investigated the influence of the dimer enrichment process on the depletion voltage of silicon diodes and performed 24 GeV/c proton irradiations to study the evolution of the macroscopic diode characteristics as a function of fluence.

Dimeric Surfactants: Promising Ingredients of Cosmetics and Toiletries

Directory of Open Access Journals (Sweden)

Naveen Kumar

2013-11-01

Full Text Available Surfactants are an essential ingredient for cosmetic, toiletries and personal care products for enhancing their performance. Dimeric surfactants demonstrate superiority compared to conventional surfactants in all areas of application. Dimeric surfactants are extremely promising for utilization in various cosmetic formulations viz. shampoo, lotions, creams, conditioners etc. These surfactants possess extremely unique surface properties viz. lower surface tension, unique micellization, low critical micelle concentration (CMC and antimicrobial activity, higher solubilization etc. Dimerics enhance the performances of cosmetics in an extraordinary manner and provide eco-friendly preparations for human epidermis.

Two Populations Mean-Field Monomer-Dimer Model

Science.gov (United States)

Alberici, Diego; Mingione, Emanuele

2018-04-01

A two populations mean-field monomer-dimer model including both hard-core and attractive interactions between dimers is considered. The pressure density in the thermodynamic limit is proved to satisfy a variational principle. A detailed analysis is made in the limit of one population is much smaller than the other and a ferromagnetic mean-field phase transition is found.

Evaluation of Serum D-dimer Levels in Children with Pneumonia

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Nilgün Selçuk Duru

2016-03-01

Full Text Available Aim: The aim of this study was to investigate the relationship of plasma D-dimer levels with duration of hospitalization and radiological and laboratory findings in patients with pneumonia. Methods: Forty-seven patients with pneumonia (31 boys and 16 girls, mean age: 4.2±4.7 years were included in the study. The patients were divided into two groups according to duration of hospitalization and three groups according to radiological findings. D-dimer and other laboratory findings were compared between the groups. Results: The mean serum D-dimer level was 1333.5±1364.4 ng/L. There was no statistically significant difference in D-dimer, leukocyte, erythrocyte sedimentation rate (ESR and C-reactive protein (CRP between the groups divided according to duration of hospitalization. In addition, there was no statistically difference in D-dimer levels between the groups divided according to radiological findings. Age, percentage of neutrophils, ESR and fibrinogen levels were higher in patients with lobar pneumonia when compared with the other groups and CRP level was higher in lobar pneumonia group when compared to interstitial pneumonia group. D-dimer levels were negatively correlated with age and positively correlated with ESR, CRP, and fibrinogen. Conclusion: In our study, D-dimer levels were high in patient with pneumonia. Further studies with a larger number of patients are necessary to determine the role of D-dimer levels as an acutephase reactant in patients with pneumonia

Electron transfer reactions induced by the triplet state of thiacarbocyanine dimers

International Nuclear Information System (INIS)

Chibisov, Alexander K.; Slavnova, Tatyana D.; Goerner, Helmut

2004-01-01

The photoinduced electron transfer between either cationic 5,5 ' -dichloro-3,3 ' ,9-triethylthiacarbocyanine (1) or a structurally similar anionic dye (2) and appropriate donors, e.g. ascorbic acid, and acceptors, e.g. methyl viologen, was studied by ns-laser photolysis. In aqueous solution the dyes in the ground state are present as an equilibrated mixture of dimers and monomers, whereas the triplet state is mainly populated from dimers. The triplet states of both dimers and monomers are quenched by electron donors or acceptors and the rate constant for quenching is generally 2-4 times higher for dimers than for monomers. The kinetics of triplet decay and radical formation and decay as a result of primary and secondary electron transfer were analyzed. While the one-electron reduced dimer decays due to back reactions, the one-electron oxidized dimer rapidly dissociates into the monomer and the monomeric dye radical. For the dimeric dye/donor/acceptor systems the primary photoinduced electron transfer occurs either from the donor or to the acceptor yielding the dimeric dye radicals. The one-electron reduced dimer can be efficiently oxidized by acceptors, e.g. the rate constant for reaction of the dimeric dye radical of 1 with methyl viologen (photoreductive pathway of sensitization) is 1.6x10 9 M -1 s -1 . The photooxidative pathway of sensitization is more complicated; after dissociation of the dimeric dye radical, the monomeric dye radical is reduced in a secondary electron transfer from ascorbic acid, e.g. with a rate constant of 1x10 9 M -1 s -1 for 2, yielding the monomer. On increasing the donor concentration the photooxidative pathway of sensitization is switched to a photoreductive one

Tunneling anisotropic magnetoresistance via molecular π orbitals of Pb dimers

Science.gov (United States)

Schöneberg, Johannes; Ferriani, Paolo; Heinze, Stefan; Weismann, Alexander; Berndt, Richard

2018-01-01

Pb dimers on a ferromagnetic surface are shown to exhibit large tunneling anisotropic magnetoresistance (TAMR) due to molecular π orbitals. Dimers oriented differently with respect to the magnetization directions of a ferromagnetic Fe double layer on W(110) were made with a scanning tunneling microscope. Depending on the dimer orientations, TAMR is absent or as large as 20% at the Fermi level. General arguments and first-principles calculations show that mixing of molecular orbitals due to spin-orbit coupling, which leads to TAMR, is maximal when the magnetization is oriented parallel to the dimer axis.

VUV spectroscopy of rare gas van der Waals dimers

International Nuclear Information System (INIS)

Dehmer, P.M.; Pratt, S.T.

1982-01-01

We have undertaken a systematic study of the photoionization spectra of the homonuclear and heteronuclear rare gas dimers in order to better understand the nature of the bonding in the Rydberg states adnd ions of these molecules. We have obtained results for Ar 2 , Kr 2 , Xe 2 , NeAr, NeKr, NeXe, ArKr, ArXe, and KrXe. Of the remaining dimer species (Ne 2 and the Herare gas dimers), only Ne 2 has been studied using photoionization mass spectrometry. The results of the present series of experiments provide information both on the excited states of the neutral dimers and on the ground and excited states of the dimer ions. Using the data obtained in these measurements, we are able to compile for the first time a nearly complete list of ground state dissociation energies for the homonuclear and heteronuclear rare gas dimer ions. Somewhat less complete results are obtained for the excited states of these species. The observed trends in binding energy provide an excellent example of the systematic changes that occur as a result of changes in atomic orbital energies, polarizability, and internuclear distance, and these trends can be explained qualitatively in terms of simple molecular orbital theory

Pair Interaction of Catalytical Sphere Dimers in Chemically Active Media

Directory of Open Access Journals (Sweden)

Jing-Min Shi

2018-01-01

Full Text Available We study the pair dynamics of two self-propelled sphere dimers in the chemically active medium in which a cubic autocatalytic chemical reaction takes place. Concentration gradient around the dimer, created by reactions occurring on the catalytic sphere surface and responsible for the self-propulsion, is greatly influenced by the chemical activities of the environment. Consequently, the pair dynamics of two dimers mediated by the concentration field are affected. In the particle-based mesoscopic simulation, we combine molecular dynamics (MD for potential interactions and reactive multiparticle collision dynamics (RMPC for solvent flow and bulk reactions. Our results indicate three different configurations between a pair of dimers after the collision, i.e., two possible scenarios of bound dimer pairs and one unbound dimer pair. A phase diagram is sketched as a function of the rate coefficients of the environment reactions. Since the pair interactions are the basic elements of larger scale systems, we believe the results may shed light on the understanding of the collective dynamics.

Subsurface dimerization in III-V semiconductor (001) surfaces

DEFF Research Database (Denmark)

Kumpf, C.; Marks, L.D.; Ellis, D.

2001-01-01

We present the atomic structure of the c(8 X 2) reconstructions of InSb-, InAs-, and GaAs-(001) surfaces as determined by surface x-ray diffraction using direct methods. Contrary to common belief, group III dimers are not prominent on the surface, instead subsurface dimerization of group m atoms ...... takes place in the second bilayer, accompanied by a major rearrangement of the surface atoms above the dimers to form linear arrays. By varying the occupancies of four surface sites the (001)-c(8 X 2) reconstructions of III-V semiconductors can be described in a unified model....

The water dimer II: Theoretical investigations

Energy Technology Data Exchange (ETDEWEB)

Mukhopadhyay, Anamika; Xantheas, Sotiris S.; Saykally, Richard J.

2018-03-29

As the archetype of hydrogen bonding between water molecules, the water dimer has been extensively studied by both theory and experiment for nearly seven decades. In this article, we present a detailed chronological review of the theoretical advances using electronic structure methods pertaining to the structure, hydrogen bonding and vibrational spectroscopy of the water dimer as well as the role of its potential energy surface in the development of classical force fields to describe intermolecular interaction in clusters and liquid water.

In Situ Structural Characterization of Ferric Iron Dimers in Aqueous Solutions

DEFF Research Database (Denmark)

Zhu, Mengqiang; Puls, Brendan W.; Frandsen, Cathrine

2013-01-01

The structure of ferric iron (Fe3+) dimers in aqueous solutions has long been debated. In this work, we have determined the dimer structure in situ in aqueous solutions using extended X-ray absorption fine structure (EXAFS) spectroscopy. An Fe K-edge EXAFS analysis of 0.2 M ferric nitrate solutions...... at pH 1.28–1.81 identified a Fe–Fe distance at ∼3.6 Å, strongly indicating that the dimers take the μ-oxo form. The EXAFS analysis also indicates two short Fe–O bonds at ∼1.80 Å and ten long Fe–O bonds at ∼2.08 Å, consistent with the μ-oxo dimer structure. The scattering from the Fe–Fe paths interferes...... confirmed by Mössbauer analyses of analogous quick frozen solutions. This work also explores the electronic structure and the relative stability of the μ-oxo dimer in a comparison to the dihydroxo dimer using density function theory (DFT) calculations. The identification of such dimers in aqueous solutions...

SOXE transcription factors form selective dimers on non-compact DNA motifs through multifaceted interactions between dimerization and high-mobility group domains.

Science.gov (United States)

Huang, Yong-Heng; Jankowski, Aleksander; Cheah, Kathryn S E; Prabhakar, Shyam; Jauch, Ralf

2015-05-27

The SOXE transcription factors SOX8, SOX9 and SOX10 are master regulators of mammalian development directing sex determination, gliogenesis, pancreas specification and neural crest development. We identified a set of palindromic SOX binding sites specifically enriched in regulatory regions of melanoma cells. SOXE proteins homodimerize on these sequences with high cooperativity. In contrast to other transcription factor dimers, which are typically rigidly spaced, SOXE group proteins can bind cooperatively at a wide range of dimer spacings. Using truncated forms of SOXE proteins, we show that a single dimerization (DIM) domain, that precedes the DNA binding high mobility group (HMG) domain, is sufficient for dimer formation, suggesting that DIM : HMG rather than DIM:DIM interactions mediate the dimerization. All SOXE members can also heterodimerize in this fashion, whereas SOXE heterodimers with SOX2, SOX4, SOX6 and SOX18 are not supported. We propose a structural model where SOXE-specific intramolecular DIM:HMG interactions are allosterically communicated to the HMG of juxtaposed molecules. Collectively, SOXE factors evolved a unique mode to combinatorially regulate their target genes that relies on a multifaceted interplay between the HMG and DIM domains. This property potentially extends further the diversity of target genes and cell-specific functions that are regulated by SOXE proteins.

SOXE transcription factors form selective dimers on non-compact DNA motifs through multifaceted interactions between dimerization and high-mobility group domains

Science.gov (United States)

Huang, Yong-Heng; Jankowski, Aleksander; Cheah, Kathryn S. E.; Prabhakar, Shyam; Jauch, Ralf

2015-01-01

The SOXE transcription factors SOX8, SOX9 and SOX10 are master regulators of mammalian development directing sex determination, gliogenesis, pancreas specification and neural crest development. We identified a set of palindromic SOX binding sites specifically enriched in regulatory regions of melanoma cells. SOXE proteins homodimerize on these sequences with high cooperativity. In contrast to other transcription factor dimers, which are typically rigidly spaced, SOXE group proteins can bind cooperatively at a wide range of dimer spacings. Using truncated forms of SOXE proteins, we show that a single dimerization (DIM) domain, that precedes the DNA binding high mobility group (HMG) domain, is sufficient for dimer formation, suggesting that DIM : HMG rather than DIM:DIM interactions mediate the dimerization. All SOXE members can also heterodimerize in this fashion, whereas SOXE heterodimers with SOX2, SOX4, SOX6 and SOX18 are not supported. We propose a structural model where SOXE-specific intramolecular DIM:HMG interactions are allosterically communicated to the HMG of juxtaposed molecules. Collectively, SOXE factors evolved a unique mode to combinatorially regulate their target genes that relies on a multifaceted interplay between the HMG and DIM domains. This property potentially extends further the diversity of target genes and cell-specific functions that are regulated by SOXE proteins. PMID:26013289

Asymmetric monometallic nanorod nanoparticle dimer and related compositions and methods

KAUST Repository

Han, Yu

2016-03-31

The fabrication of asymmetric monometallic nanocrystals with novel properties for plasmonics, nanophotonics and nanoelectronics. Asymmetric monometallic plasmonic nanocrystals are of both fundamental synthetic challenge and practical significance. In an example, a thiol-ligand mediated growth strategy that enables the synthesis of unprecedented Au Nanorod-Au Nanoparticle (AuNR-AuNP) dimers from pre-synthesized AuNR seeds. Using high-resolution electron microscopy and tomography, crystal structure and three-dimensional morphology of the dimer, as well as the growth pathway of the AuNP on the AuNR seed, was investigated for this example. The dimer exhibits an extraordinary broadband optical extinction spectrum spanning the UV, visible, and near infrared regions (300 - 1300 nm). This unexpected property makes the AuNR-AuNP dimer example useful for many nanophotonic applications. In two experiments, the dimer example was tested as a surface- enhanced Raman scattering (SERS) substrate and a solar light harvester for photothermal conversion, in comparison with the mixture of AuNR and AuNP. In the SERS experiment, the dimer example showed an enhancement factor about 10 times higher than that of the mixture, when the excitation wavelength (660 nm) was off the two surface plasmon resonance (SPR) bands of the mixture. In the photothermal conversion experiment under simulated sunlight illumination, the dimer example exhibited an energy conversion efficiency about 1.4 times as high as that of the mixture.

Radiation chemistry of aromatic dimer radical cations

International Nuclear Information System (INIS)

Okamoto, Kazumasa; Tagawa, Seiichi

2009-01-01

π-π Interactions of aromatic molecules are paid attention much in many fields, especially biology, chemistry, and applied physics, represented as protein, DNA, electron donor-accepter complexes, charge transfers, and self assembly molecules. Aromatic molecules including benzene rings are the simplest case to study the π-π interactions. To interpret the charge resonance (CR) structure in the dimer radical cations, spectroscopic and ESR methods have been carried out. The spectroscopic study on the dimer radical ion of molecules with two chromophores would be profitable to identify the electronic and configurational properties. In this article, dynamics of the dimer radical cation of benzenes, polystyrenes, and resist polymers is described on the basis of direct observation of CR band by the nanosecond pulse radiolysis and low temperature γ-radiolysis methods. (author)

Analysis of hepatitis C virus RNA dimerization and core–RNA interactions

Science.gov (United States)

Ivanyi-Nagy, Roland; Kanevsky, Igor; Gabus, Caroline; Lavergne, Jean-Pierre; Ficheux, Damien; Penin, François; Fossé, Philippe; Darlix, Jean-Luc

2006-01-01

The core protein of hepatitis C virus (HCV) has been shown previously to act as a potent nucleic acid chaperone in vitro, promoting the dimerization of the 3′-untranslated region (3′-UTR) of the HCV genomic RNA, a process probably mediated by a small, highly conserved palindromic RNA motif, named DLS (dimer linkage sequence) [G. Cristofari, R. Ivanyi-Nagy, C. Gabus, S. Boulant, J. P. Lavergne, F. Penin and J. L. Darlix (2004) Nucleic Acids Res., 32, 2623–2631]. To investigate in depth HCV RNA dimerization, we generated a series of point mutations in the DLS region. We find that both the plus-strand 3′-UTR and the complementary minus-strand RNA can dimerize in the presence of core protein, while mutations in the DLS (among them a single point mutation that abolished RNA replication in a HCV subgenomic replicon system) completely abrogate dimerization. Structural probing of plus- and minus-strand RNAs, in their monomeric and dimeric forms, indicate that the DLS is the major if not the sole determinant of UTR RNA dimerization. Furthermore, the N-terminal basic amino acid clusters of core protein were found to be sufficient to induce dimerization, suggesting that they retain full RNA chaperone activity. These findings may have important consequences for understanding the HCV replicative cycle and the genetic variability of the virus. PMID:16707664

Analysis of hepatitis C virus RNA dimerization and core-RNA interactions.

Science.gov (United States)

Ivanyi-Nagy, Roland; Kanevsky, Igor; Gabus, Caroline; Lavergne, Jean-Pierre; Ficheux, Damien; Penin, François; Fossé, Philippe; Darlix, Jean-Luc

2006-01-01

The core protein of hepatitis C virus (HCV) has been shown previously to act as a potent nucleic acid chaperone in vitro, promoting the dimerization of the 3'-untranslated region (3'-UTR) of the HCV genomic RNA, a process probably mediated by a small, highly conserved palindromic RNA motif, named DLS (dimer linkage sequence) [G. Cristofari, R. Ivanyi-Nagy, C. Gabus, S. Boulant, J. P. Lavergne, F. Penin and J. L. Darlix (2004) Nucleic Acids Res., 32, 2623-2631]. To investigate in depth HCV RNA dimerization, we generated a series of point mutations in the DLS region. We find that both the plus-strand 3'-UTR and the complementary minus-strand RNA can dimerize in the presence of core protein, while mutations in the DLS (among them a single point mutation that abolished RNA replication in a HCV subgenomic replicon system) completely abrogate dimerization. Structural probing of plus- and minus-strand RNAs, in their monomeric and dimeric forms, indicate that the DLS is the major if not the sole determinant of UTR RNA dimerization. Furthermore, the N-terminal basic amino acid clusters of core protein were found to be sufficient to induce dimerization, suggesting that they retain full RNA chaperone activity. These findings may have important consequences for understanding the HCV replicative cycle and the genetic variability of the virus.

Quantum dissipative dynamics and decoherence of dimers on helium droplets

International Nuclear Information System (INIS)

Schlesinger, Martin

2011-01-01

In this thesis, quantum dynamical simulations are performed in order to describe the vibrational motion of diatomic molecules in a highly quantum environment, so-called helium droplets. We aim to reproduce and explain experimental findings which were obtained from dimers on helium droplets. Nanometer-sized helium droplets contain several thousands of 4 He atoms. They serve as a host for embedded atoms or molecules and provide an ultracold ''refrigerator'' for them. Spectroscopy of molecules in or on these droplets reveals information on both the molecule and the helium environment. The droplets are known to be in the superfluid He II phase. Superfluidity in nanoscale systems is a steadily growing field of research. Spectra obtained from full quantum simulations for the unperturbed dimer show deviations from measurements with dimers on helium droplets. These deviations result from the influence of the helium environment on the dimer dynamics. In this work, a well-established quantum optical master equation is used in order to describe the dimer dynamics effectively. The master equation allows to describe damping fully quantum mechanically. By employing that equation in the quantum dynamical simulation, one can study the role of dissipation and decoherence in dimers on helium droplets. The effective description allows to explain experiments with Rb 2 dimers on helium droplets. Here, we identify vibrational damping and associated decoherence as the main explanation for the experimental results. The relation between decoherence and dissipation in Morse-like systems at zero temperature is studied in more detail. The dissipative model is also used to investigate experiments with K 2 dimers on helium droplets. However, by comparing numerical simulations with experimental data, one finds that further mechanisms are active. Here, a good agreement is obtained through accounting for rapid desorption of dimers. We find that decoherence occurs in the electronic manifold of the

Photon Propagation through Linearly Active Dimers

Directory of Open Access Journals (Sweden)

José Delfino Huerta Morales

2017-06-01

Full Text Available We provide an analytic propagator for non-Hermitian dimers showing linear gain or losses in the quantum regime. In particular, we focus on experimentally feasible realizations of the PT -symmetric dimer and provide their mean photon number and second order two-point correlation. We study the propagation of vacuum, single photon spatially-separable, and two-photon spatially-entangled states. We show that each configuration produces a particular signature that might signal their possible uses as photon switches, semi-classical intensity-tunable sources, or spatially entangled sources to mention a few possible applications.

Mutability of bacteriophage M13 by ultraviolet light: role of pyrimidine dimers

International Nuclear Information System (INIS)

Schaaper, R.M.; Glickman, B.W.

1982-01-01

The role of pyrimidine dimers in mutagenesis by ultraviolet light was examined by measuring the UV-induced reversion of six different bacteriophage M13 amber mutants for which the neighboring DNA sequences are known. The mutational response at amber (TAG) codons preceded by a guanine or adenine (where no pyrimidine dimer can be formed) were compared with those preceded by thymine or cytosine (where dimer formation is possible). Equivalent levels of UV-induced mutagenesis were observed at both kinds of sites. This observation demonstrates that there is no requirement for a pyrimidine dimer directly at the site of UV-induced mutation in this single-stranded DNA phage. UV irradiation of the phage was also performed in the presence of Ag + ions, which specifically sensitize the DNA to dimer formation. The two methods of irradiation, when compared at equal survival levels (and presumably equal dimer frequencies), produced equivalent frequencies of reversion of the amber phage. We believe these results indicate that while the presence of pyrimidine dimers may be a prerequisite for UV mutagenesis, the actual mutagenic event can occur at a site some distance removed from a dimer. (orig.)

Fiber optic D dimer biosensor

Science.gov (United States)

Glass, Robert S.; Grant, Sheila A.

1999-01-01

A fiber optic sensor for D dimer (a fibrinolytic product) can be used in vivo (e.g., in catheter-based procedures) for the diagnosis and treatment of stroke-related conditions in humans. Stroke is the third leading cause of death in the United States. It has been estimated that strokes and stroke-related disorders cost Americans between $15-30 billion annually. Relatively recently, new medical procedures have been developed for the treatment of stroke. These endovascular procedures rely upon the use of microcatheters. These procedures could be facilitated with this sensor for D dimer integrated with a microcatheter for the diagnosis of clot type, and as an indicator of the effectiveness, or end-point of thrombolytic therapy.

Singlet fission in pentacene dimers

Science.gov (United States)

Zirzlmeier, Johannes; Lehnherr, Dan; Coto, Pedro B.; Chernick, Erin T.; Casillas, Rubén; Basel, Bettina S.; Thoss, Michael; Tykwinski, Rik R.; Guldi, Dirk M.

2015-01-01

Singlet fission (SF) has the potential to supersede the traditional solar energy conversion scheme by means of boosting the photon-to-current conversion efficiencies beyond the 30% Shockley–Queisser limit. Here, we show unambiguous and compelling evidence for unprecedented intramolecular SF within regioisomeric pentacene dimers in room-temperature solutions, with observed triplet quantum yields reaching as high as 156 ± 5%. Whereas previous studies have shown that the collision of a photoexcited chromophore with a ground-state chromophore can give rise to SF, here we demonstrate that the proximity and sufficient coupling through bond or space in pentacene dimers is enough to induce intramolecular SF where two triplets are generated on one molecule. PMID:25858954

Optical properties of electrically connected plasmonic nanoantenna dimer arrays

Science.gov (United States)

Zimmerman, Darin T.; Borst, Benjamin D.; Carrick, Cassandra J.; Lent, Joseph M.; Wambold, Raymond A.; Weisel, Gary J.; Willis, Brian G.

2018-02-01

We fabricate electrically connected gold nanoantenna arrays of homodimers and heterodimers on silica substrates and present a systematic study of their optical properties. Electrically connected arrays of plasmonic nanoantennas make possible the realization of novel photonic devices, including optical sensors and rectifiers. Although the plasmonic response of unconnected arrays has been studied extensively, the present study shows that the inclusion of nanowire connections modifies the device response significantly. After presenting experimental measurements of optical extinction for unconnected dimer arrays, we compare these to measurements of dimers that are interconnected by gold nanowire "busbars." The connected devices show the familiar dipole response associated with the unconnected dimers but also show a second localized surface plasmon resonance (LSPR) that we refer to as the "coupled-busbar mode." Our experimental study also demonstrates that the placement of the nanowire along the antenna modifies the LSPR. Using finite-difference time-domain simulations, we confirm the experimental results and investigate the variation of dimer gap and spacing. Changing the dimer gap in connected devices has a significantly smaller effect on the dipole response than it does in unconnected devices. On the other hand, both LSPR modes respond strongly to changing the spacing between devices in the direction along the interconnecting wires. We also give results for the variation of E-field strength in the dimer gap, which will be important for any working sensor or rectenna device.

Metal membrane with dimer slots as a universal polarizer

Science.gov (United States)

Zhukovsky, Sergej; Zalkovskij, Maksim; Malureanu, Radu; Kremers, Christian; Chigrin, Dmitry; Tang, Peter T.; Jepsen, Peter U.; Lavrinenko, Andrei V.

2014-03-01

In this work, we show theoretically and confirm experimentally that thin metal membranes patterned with an array of slot dimers (or their Babinet analogue with metal rods) can function as a versatile spectral and polarization filter. We present a detailed covariant multipole theory for the electromagnetic response of an arbitrary dimer based on the Green functions approach. The theory confirms that a great variety of polarization properties, such as birefringence, chirality and elliptical dichroism, can be achieved in a metal layer with such slot-dimer patterning (i.e. in a metasurface). Optical properties of the metasurface can be extensively tuned by varying the geometry (shape and dimensions) of the dimer, for example, by adjusting the sizes and mutual placement of the slots (e.g. inter-slot distance and alignment angle). Three basic shapes of dimers are analyzed: II-shaped (parallel slots), V-shaped, and T-shaped. These particular shapes of dimers are found to be sensitive to variations of the slots lengths and orientation of elements. Theoretical results are well supported by full-wave three-dimensional simulations. Our findings were verified experimentally on the metal membranes fabricated using UV lithography with subsequent Ni growth. Such metasurfaces were characterized using time-domain THz spectroscopy. The samples exhibit pronounced optical activity (500 degrees per wavelength) and high transmission: even though the slots cover only 4.3 % of the total membrane area the amplitude transmission reaches 0.67 at the resonance frequency 0.56 THz.

Analytical study of avian reticuloendotheliosis virus dimeric RNA generated in vivo and in vitro.

Science.gov (United States)

Darlix, J L; Gabus, C; Allain, B

1992-12-01

The retroviral genome consists of two identical RNA molecules associated at their 5' ends by a stable structure called the dimer linkage structure. The dimer linkage structure, while maintaining the dimer state of the retroviral genome, might also be involved in packaging and reverse transcription, as well as recombination during proviral DNA synthesis. To study the dimer structure of the retroviral genome and the mechanism of dimerization, we analyzed features of the dimeric genome of reticuloendotheliosis virus (REV) type A and identified elements required for its dimerization. Here we report that the REV dimeric genome extracted from virions and infected cells, as well as that synthesized in vitro, is more resistant to heat denaturation than avian sarcoma and leukemia virus, murine leukemia virus, or human immunodeficiency virus type 1 dimeric RNA. The minimal domain required to form a stable REV RNA dimer in vitro was found to map between positions 268 and 452 (KpnI and SalI sites), thus corresponding to the E encapsidation sequence (J. E. Embretson and H. M. Temin, J. Virol. 61:2675-2683, 1987). In addition, both the 5' and 3' halves of E are necessary in cis for RNA dimerization and the extent of RNA dimerization is influenced by viral sequences flanking E. Rapid and efficient dimerization of REV RNA containing gag sequences in addition to the E sequences and annealing of replication primer tRNA(Pro) to the primer-binding site necessitate the nucleocapsid protein.

Dimerization of human immunodeficiency virus (type 1) RNA: stimulation by cations and possible mechanism.

Science.gov (United States)

Marquet, R; Baudin, F; Gabus, C; Darlix, J L; Mougel, M; Ehresmann, C; Ehresmann, B

1991-05-11

The retroviral genome consists of two identical RNA molecules joined close to their 5' ends by the dimer linkage structure. Recent findings indicated that retroviral RNA dimerization and encapsidation are probably related events during virion assembly. We studied the cation-induced dimerization of HIV-1 RNA and results indicate that all in vitro generated HIV-1 RNAs containing a 100 nucleotide domain downstream from the 5' splice site are able to dimerize. RNA dimerization depends on the concentration of RNA, mono- and multivalent cations, the size of the monovalent cation, temperature, and pH. Up to 75% of HIV-1 RNA is dimeric in the presence of spermidine. HIV-1 RNA dimer is fairly resistant to denaturing agents and unaffected by intercalating drugs. Antisense HIV-1 RNA does not dimerize but heterodimers can be formed between HIV-1 RNA and either MoMuLV or RSV RNA. Therefore retroviral RNA dimerization probably does not simply proceed through mechanisms involving Watson-Crick base-pairing. Neither adenine and cytosine protonation, nor quartets containing only guanines appear to determine the stability of the HIV-1 RNA dimer, while quartets involving both adenine(s) and guanine(s) could account for our results. A consensus sequence PuGGAPuA found in the putative dimerization-encapsidation region of all retroviral genomes examined may participate in the dimerization process.

A Model for Dimerization of the SOX Group E Transcription Factor Family.

Directory of Open Access Journals (Sweden)

Sarah N Ramsook

Full Text Available Group E members of the SOX transcription factor family include SOX8, SOX9, and SOX10. Preceding the high mobility group (HMG domain in each of these proteins is a thirty-eight amino acid region that supports the formation of dimers on promoters containing tandemly inverted sites. The purpose of this study was to obtain new structural insights into how the dimerization region functions with the HMG domain. From a mutagenic scan of the dimerization region, the most essential amino acids of the dimerization region were clustered on the hydrophobic face of a single, predicted amphipathic helix. Consistent with our hypothesis that the dimerization region directly contacts the HMG domain, a peptide corresponding to the dimerization region bound a preassembled HMG-DNA complex. Sequence conservation among Group E members served as a basis to identify two surface exposed amino acids in the HMG domain of SOX9 that were necessary for dimerization. These data were combined to make a molecular model that places the dimerization region of one SOX9 protein onto the HMG domain of another SOX9 protein situated at the opposing site of a tandem promoter. The model provides a detailed foundation for assessing the impact of mutations on SOX Group E transcription factors.

Excitonic Behavior of Rhodamine Dimers: A Single-Molecule Study

NARCIS (Netherlands)

Hernando Campos, J.; van der Schaaf, Martijn; van Dijk, E.M.H.P.; Sauer, Markus; Garcia Parajo, M.F.; van Hulst, N.F.

2003-01-01

The optical behavior of a dimer of tetramethylrhodamine-5-isothiocyanate has been investigated by means of single-molecule measurements. Bulk absorption and fluorescence spectra show the existence of two populations of the dimer molecule that exhibit distinct excitonic interactions (strong and weak

2-Ethynylpyridine dimers: IR spectroscopic and computational study

Science.gov (United States)

Bakarić, Danijela; Spanget-Larsen, Jens

2018-04-01

2-ethynylpyridine (2-EP) presents a multifunctional system capable of participation in hydrogen-bonded complexes utilizing hydrogen bond donating (tbnd Csbnd H, Aryl-H) and hydrogen bond accepting functions (N-atom, Ctbnd C and pyridine π-systems). In this work, IR spectroscopy and theoretical calculations are used to study possible 2-EP dimer structures as well as their distribution in an inert solvent such as tetrachloroethene. Experimentally, the tbnd Csbnd H stretching vibration of the 2-EP monomer absorbs close to 3300 cm-1, whereas a broad band with maximum around 3215 cm-1 emerges as the concentration rises, indicating the formation of hydrogen-bonded complexes involving the tbnd Csbnd H moiety. The Ctbnd C stretching vibration of monomer 2-EP close to 2120 cm-1 is, using derivative spectroscopy, resolved from the signals of the dimer complexes with maximum around 2112 cm-1. Quantum chemical calculations using the B3LYP + D3 model with counterpoise correction predict that the two most stable dimers are of the π-stacked variety, closely followed by dimers with intermolecular tbnd Csbnd H⋯N hydrogen bonding; the predicted red shifts of the tbnd Csbnd H stretching wavenumbers due to hydrogen bonding are in the range 54-120 cm-1. No species with obvious hydrogen bonding involving the Ctbnd C or pyridine π-systems as acceptors are predicted. Dimerization constant at 25 °C is estimated to be K2 = 0.13 ± 0.01 mol-1 dm3.

Photoionization of helium dimers; Photoionisation von Heliumdimeren

Energy Technology Data Exchange (ETDEWEB)

Havermeier, Tilo

2010-06-09

The helium dimer is one of the most weakly bound systems in the universe. This makes it an interesting quantum mechanical object for investigation. These Van der Waals Clusters can be produced in an expansion of a cryogenic gas jet through a small nozzle into vacuum. In the present experiment we examine the interaction of He dimers with synchrotron radiation at an energy range from 64 to 78 eV. We observed different pathways leading to single ionization of both He atoms of the dimer compound. This two close standing ions begin now to dissociate in cause of their coulomb potential. All charged fragments were detected in coincidence with a COLTRIMS system. Especially Interatomic Coulombic Decay (ICD) and the two step process (TS1) were clearly identified. Furthermore a distribution of the internuclear distance was obtained from the measured Kinetic Energy Release (KER). (orig.)

Exact Solution of a Generalized Nonlinear Schrodinger Equation Dimer

DEFF Research Database (Denmark)

Christiansen, Peter Leth; Maniadis, P.; Tsironis, G.P.

1998-01-01

We present exact solutions for a nonlinear dimer system defined throught a discrete nonlinear Schrodinger equation that contains also an integrable Ablowitz-Ladik term. The solutions are obtained throught a transformation that maps the dimer into a double Sine-Gordon like ordinary nonlinear...... differential equation....

Quantum-statistical mechanics of an atom-dimer mixture: Lee-Yang cluster expansion approach

International Nuclear Information System (INIS)

Ohkuma, Takahiro; Ueda, Masahito

2006-01-01

We use the Lee-Yang cluster expansion method to study quantum-statistical properties of a mixture of interconvertible atoms and dimers, where the dimers form in a two-body bound state of the atoms. We point out an infinite series of cluster diagrams whose summation leads to the Bose-Einstein condensation of the dimers below a critical temperature. Our theory captures some important features of a cold atom-dimer mixture such as interconversion of atoms and dimers and properties of the mixture at the unitarity limit

Formation of thymine containing dimers in skin exposed to ultraviolet radiation

Energy Technology Data Exchange (ETDEWEB)

Johnson, B E [Dundee Univ. (UK)

1978-01-01

Nuclear DNA appears to be the major molecular target for the inhibitory, mutagenic and lethal effects of ultraviolet radiation on cells in culture. Cyclobutyl dimers between adjacent pyrimidine bases, the major photochemical lesions for these effects in prokaryotes, also play a part in UVR effects on eukaryotes cells. Pyrimidine dimers have been isolated from in vivo UV-irradiated guinea pig and mouse skin. The wavelength dependence for dimer induction is similar to that for acute skin reactions but no direct causal relationship has been established. Sunlight UVR may induce dimers in skin DNA. Excision of dimers from mouse skin in vivo is deficient as it is for most rodent cells in culture; human cell excision is efficient and the difficulties in interpretation of UV-carcinogenesis results with mice in terms of human skin cancer are therefore increased.

Artificial light harvesting by dimerized Möbius ring

Science.gov (United States)

Xu, Lei; Gong, Z. R.; Tao, Ming-Jie; Ai, Qing

2018-04-01

We theoretically study artificial light harvesting by a Möbius ring. When the donors in the ring are dimerized, the energies of the donor ring are split into two subbands. Because of the nontrivial Möbius boundary condition, both the photon and acceptor are coupled to all collective-excitation modes in the donor ring. Therefore, the quantum dynamics in the light harvesting is subtly influenced by dimerization in the Möbius ring. It is discovered that energy transfer is more efficient in a dimerized ring than that in an equally spaced ring. This discovery is also confirmed by a calculation with the perturbation theory, which is equivalent to the Wigner-Weisskopf approximation. Our findings may be beneficial to the optimal design of artificial light harvesting.

The induction and repair of cyclobutane thymidine dimers in human skin

International Nuclear Information System (INIS)

Roza, L.; Erasmus Univ., Rotterdam; Vermeulen, W.; Schans, G.P. van der; Lohman, P.H.M.

1987-01-01

The most important detrimental effect of ultraviolet radiation (UV) on the living cell, so far known, is the induction of damage in the DNA. The major photoproducts induced in DNA by UV-C (200-280 nm) and UV-B (280-315 nm) are the cyclobutane-type pyrimidine dimers, which have been implicated in UV-induced mutagenesis and carcinogenesis. Dimer lesions in DNA of cells may be repaired in the dark by a multi-enzyme process (excision repair), or via a light dependent enzymatic reaction known as photoreactivation (phr) which is specific for pyrimidine dimers. Although phr has been found to occur in a wide range of organisms, studies on the presence of phr in mammalian cells have yielded conflicting results. To investigate repair of pyrimidine dimers in human skin cells irradiated in vivo, a specific and sensitive detection method was developed based on a monoclonal antibody directed against thymidine dimers. Application together with a fluorescent immunostaining permits the direct detection of thymidine dimers in human skin cells. The method is used in studies aimed at a better understanding of the role of these lesions in the process of carcinogenesis. A report is given on the isolation and characterization of the antibodies, and their application in a study on the induction of pyrimidine dimers in human skin and on photorepair in cultured cells. 10 refs.; 2 figs

Effects of Dimerization of Serratia marcescens Endonuclease on Water Dynamics.

Energy Technology Data Exchange (ETDEWEB)

Chen, Chuanying; Beck, Brian W.; Krause, Kurt; Weksberg, Tiffany E.; Pettitt, Bernard M.

2007-02-15

The research described in this product was performed in part in the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory. The dynamics and structure of Serratia marcescens endonuclease and its neighboring solvent are investigated by molecular dynamics (MD). Comparisons are made with structural and biochemical experiments. The dimer form is physiologic and functions more processively than the monomer. We previously found a channel formed by connected clusters of waters from the active site to the dimer interface. Here, we show that dimerization clearly changes correlations in the water structure and dynamics in the active site not seen in the monomer. Our results indicate that water at the active sites of the dimer is less affected compared with bulk solvent than in the monomer where it has much slower characteristic relaxation times. Given that water is a required participant in the reaction, this gives a clear advantage to dimerization in the absence of an apparent ability to use both active sites simultaneously.

Quantitative Experimental Determination of Primer-Dimer Formation Risk by Free-Solution Conjugate Electrophoresis

Science.gov (United States)

Desmarais, Samantha M.; Leitner, Thomas; Barron, Annelise E.

2012-01-01

DNA barcodes are short, unique ssDNA primers that “mark” individual biomolecules. To gain better understanding of biophysical parameters constraining primer-dimer formation between primers that incorporate barcode sequences, we have developed a capillary electrophoresis method that utilizes drag-tag-DNA conjugates to quantify dimerization risk between primer-barcode pairs. Results obtained with this unique free-solution conjugate electrophoresis (FSCE) approach are useful as quantitatively precise input data to parameterize computation models of dimerization risk. A set of fluorescently labeled, model primer-barcode conjugates were designed with complementary regions of differing lengths to quantify heterodimerization as a function of temperature. Primer-dimer cases comprised two 30-mer primers, one of which was covalently conjugated to a lab-made, chemically synthesized poly-N-methoxyethylglycine drag-tag, which reduced electrophoretic mobility of ssDNA to distinguish it from ds primer-dimers. The drag-tags also provided a shift in mobility for the dsDNA species, which allowed us to quantitate primer-dimer formation. In the experimental studies, pairs of oligonucleotide primer-barcodes with fully or partially complementary sequences were annealed, and then separated by free-solution conjugate CE at different temperatures, to assess effects on primer-dimer formation. When less than 30 out of 30 basepairs were bonded, dimerization was inversely correlated to temperature. Dimerization occurred when more than 15 consecutive basepairs formed, yet non-consecutive basepairs did not create stable dimers even when 20 out of 30 possible basepairs bonded. The use of free-solution electrophoresis in combination with a peptoid drag-tag and different fluorophores enabled precise separation of short DNA fragments to establish a new mobility shift assay for detection of primer-dimer formation. PMID:22331820

Designer interface peptide grafts target estrogen receptor alpha dimerization

International Nuclear Information System (INIS)

Chakraborty, S.; Asare, B.K.; Biswas, P.K.; Rajnarayanan, R.V.

2016-01-01

The nuclear transcription factor estrogen receptor alpha (ERα), triggered by its cognate ligand estrogen, regulates a variety of cellular signaling events. ERα is expressed in 70% of breast cancers and is a widely validated target for anti-breast cancer drug discovery. Administration of anti-estrogen to block estrogen receptor activation is still a viable anti-breast cancer treatment option but anti-estrogen resistance has been a significant bottle-neck. Dimerization of estrogen receptor is required for ER activation. Blocking ERα dimerization is therefore a complementary and alternative strategy to combat anti-estrogen resistance. Dimer interface peptide “I-box” derived from ER residues 503–518 specifically blocks ER dimerization. Recently using a comprehensive molecular simulation we studied the interaction dynamics of ERα LBDs in a homo-dimer. Based on this study, we identified three interface recognition peptide motifs LDKITDT (ERα residues 479–485), LQQQHQRLAQ (residues 497–506), and LSHIRHMSNK (residues 511–520) and reported the suitability of using LQQQHQRLAQ (ER 497–506) as a template to design inhibitors of ERα dimerization. Stability and self-aggregation of peptide based therapeutics poses a significant bottle-neck to proceed further. In this study utilizing peptide grafted to preserve their pharmacophoric recognition motif and assessed their stability and potential to block ERα mediated activity in silico and in vitro. The Grafted peptides blocked ERα mediated cell proliferation and viability of breast cancer cells but did not alter their apoptotic fate. We believe the structural clues identified in this study can be used to identify novel peptidometics and small molecules that specifically target ER dimer interface generating a new breed of anti-cancer agents. - Highlights: • Designer peptide grafts retain core molecular recognition motif during MD simulations. • Designer peptide grafts with Poly-ALA helix form stable

Tricriticality for dimeric Coulomb molecular crystals in ground state

Science.gov (United States)

Travěnec, Igor; Šamaj, Ladislav

2017-12-01

We study the ground-state properties of a system of dimers. Each dimer consists in a pair of equivalent charges at a fixed distance, immersed in a neutralizing homogeneous background. All charges interact pairwisely by Coulomb potential. The dimer centers form a two-dimensional rectangular lattice with the aspect ratio α\\in [0, 1] and each dimer is allowed to rotate around its center. The previous numerical simulations, made for the more general Yukawa interaction, indicate that only two basic dimer configurations can appear: either all dimers are parallel or they have two different angle orientations within alternating (checkerboard) sublattices. As the dimer size increases, two second-order phase transitions, related to two kinds of the symmetry breaking in dimer’s orientations, were reported. In this paper, we use a recent analytic method based on an expansion of the interaction energy in Misra functions which converges quickly and provides an analytic derivation of the critical behaviour. Our main result is that there exists a specific aspect ratio of the rectangular lattice α^*=0.714 106 840 000 71\\ldots which divides the space of model’s phases onto two distinct regions. If the lattice aspect ratio α>α* , we recover both types of the second-order phase transitions and find that they are of mean-field type with the critical exponent β = 1/2 . If 0.711 535≤slantα<α* , the phase transition associated with the discontinuity of dimer’s angles on alternating sublattices becomes of first order. For α=α* , the first- and second-order phase transitions meet at the tricritical point, characterized by the different critical index β = 1/4 . Such phenomenon is known from literature about the Landau theory of one-component fields, but in our two-component version the scenario is more complicated: the component which is already in the symmetry-broken state at the tricritical point also interferes and exhibits unexpectedly the mean-field singular

Designer interface peptide grafts target estrogen receptor alpha dimerization

Energy Technology Data Exchange (ETDEWEB)

Chakraborty, S. [Laboratory of Computational Biophysics & Bioengineering, Department of Physics, Tougaloo College, Tougaloo, MS 39174 (United States); Asare, B.K. [Department of Pharmacology and Toxicology, University of Buffalo, Buffalo, NY 14214 (United States); Biswas, P.K., E-mail: pbiswas@tougaloo.edu [Laboratory of Computational Biophysics & Bioengineering, Department of Physics, Tougaloo College, Tougaloo, MS 39174 (United States); Rajnarayanan, R.V., E-mail: rajendra@buffalo.edu [Department of Pharmacology and Toxicology, University of Buffalo, Buffalo, NY 14214 (United States)

2016-09-09

The nuclear transcription factor estrogen receptor alpha (ERα), triggered by its cognate ligand estrogen, regulates a variety of cellular signaling events. ERα is expressed in 70% of breast cancers and is a widely validated target for anti-breast cancer drug discovery. Administration of anti-estrogen to block estrogen receptor activation is still a viable anti-breast cancer treatment option but anti-estrogen resistance has been a significant bottle-neck. Dimerization of estrogen receptor is required for ER activation. Blocking ERα dimerization is therefore a complementary and alternative strategy to combat anti-estrogen resistance. Dimer interface peptide “I-box” derived from ER residues 503–518 specifically blocks ER dimerization. Recently using a comprehensive molecular simulation we studied the interaction dynamics of ERα LBDs in a homo-dimer. Based on this study, we identified three interface recognition peptide motifs LDKITDT (ERα residues 479–485), LQQQHQRLAQ (residues 497–506), and LSHIRHMSNK (residues 511–520) and reported the suitability of using LQQQHQRLAQ (ER 497–506) as a template to design inhibitors of ERα dimerization. Stability and self-aggregation of peptide based therapeutics poses a significant bottle-neck to proceed further. In this study utilizing peptide grafted to preserve their pharmacophoric recognition motif and assessed their stability and potential to block ERα mediated activity in silico and in vitro. The Grafted peptides blocked ERα mediated cell proliferation and viability of breast cancer cells but did not alter their apoptotic fate. We believe the structural clues identified in this study can be used to identify novel peptidometics and small molecules that specifically target ER dimer interface generating a new breed of anti-cancer agents. - Highlights: • Designer peptide grafts retain core molecular recognition motif during MD simulations. • Designer peptide grafts with Poly-ALA helix form stable

Dimerization of the voltage-sensing phosphatase controls its voltage-sensing and catalytic activity.

Science.gov (United States)

Rayaprolu, Vamseedhar; Royal, Perrine; Stengel, Karen; Sandoz, Guillaume; Kohout, Susy C

2018-05-07

Multimerization is a key characteristic of most voltage-sensing proteins. The main exception was thought to be the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP). In this study, we show that multimerization is also critical for Ci-VSP function. Using coimmunoprecipitation and single-molecule pull-down, we find that Ci-VSP stoichiometry is flexible. It exists as both monomers and dimers, with dimers favored at higher concentrations. We show strong dimerization via the voltage-sensing domain (VSD) and weak dimerization via the phosphatase domain. Using voltage-clamp fluorometry, we also find that VSDs cooperate to lower the voltage dependence of activation, thus favoring the activation of Ci-VSP. Finally, using activity assays, we find that dimerization alters Ci-VSP substrate specificity such that only dimeric Ci-VSP is able to dephosphorylate the 3-phosphate from PI(3,4,5)P 3 or PI(3,4)P 2 Our results indicate that dimerization plays a significant role in Ci-VSP function. © 2018 Rayaprolu et al.

Changes in fibrin D-dimer, fibrinogen, and protein S during pregnancy

DEFF Research Database (Denmark)

Hansen, Anette Tarp; Andreasen, Birgitte Horst; Salvig, Jannie Dalby

2010-01-01

Background. Pregnancy is a hypercoagulable state with a 5- to 10- fold higher risk of venous thromboembolism. Existing reference intervals for fibrin D-dimer (D-dimer), functional fibrinogen (fibrinogen) and protein S, free antigen (protein S) are based on non-pregnant patients and reference...... intervals for pregnant patients are warranted. Objectives. The aim of the present study was to contribute to the establishment of reference intervals for D-dimer, fibrinogen and protein S during pregnancy and to discuss the use of the analyses during pregnancy. Methods. We included 55 healthy pregnant women...... in gestational week 11–17, with normal current pregnancy. Blood samples were collected in gestational weeks 11–17, 21–27 and 34–37. The three plasma parameters D-dimer, fibrinogen and protein S were analysed by STA-R Evolution®. Results. A significant rise in D-dimer was found from first to second trimester (p...

Radiation-induced tetramer-to-dimer transition of Escherichia coli lactose repressor

International Nuclear Information System (INIS)

Goffinont, S.; Davidkova, M.; Spotheim-Maurizot, M.

2009-01-01

The wild type lactose repressor of Escherichia coli is a tetrameric protein formed by two identical dimers. They are associated via a C-terminal 4-helix bundle (called tetramerization domain) whose stability is ensured by the interaction of leucine zipper motifs. Upon in vitro γ-irradiation the repressor losses its ability to bind the operator DNA sequence due to damage of its DNA-binding domains. Using an engineered dimeric repressor for comparison, we show here that irradiation induces also the change of repressor oligomerisation state from tetramer to dimer. The splitting of the tetramer into dimers can result from the oxidation of the leucine residues of the tetramerization domain.

D-dimer: a useful tool in gauging optimal duration of oral anticoagulant therapy?

Directory of Open Access Journals (Sweden)

M. Silingardi

2013-05-01

Full Text Available BACKGROUND AND AIM OF THE STUDY Optimal duration of oral anticoagulant therapy (OAT in idiopathic venous thromboembolism (VTE is unknown. Indefinite OAT carries an unacceptable risk of major bleeding and prospective studies have demonstrated that OAT is no longer protective after its withdrawal. How to identify the patients at risk for recurrence? D-dimer is a marker of thrombin activity. Early prospective studies showed that elevated D-dimer levels after anticoagulation had a highly predictive value for a recurrent episode. Does D-dimer assay have a role in gauging the appropriate duration of anticoagulant therapy? The PROLONG study tries to answer this question. METHOD D-dimer assay was performed one month after stopping anticoagulation. Patiens with normal D-dimer levels did not resume anticoagulation while patients with elevated D-dimer levels were randomized to discontinue or resume anticoagulation. Study end-points was the composite of recurrent VTE and major bleeding during an average follow-up of 1.4 years. RESULTS The rate of recurrence is significantly higher in patients with elevated D-dimer levels who discontinued anticoagulation. Resuming anticoagulation in this cohort of patients markedly reduces recurrent events without increasing major bleeding. DISCUSSION AND CONCLUSIONS PROLONG study is provocative, because D-dimer assay is simple, thus not requiring dedicated laboratory facilities. D-dimer test has otherwise high sensitivity but low specificity in VTE diagnosis. Aspecifically elevated D-dimer levels are available in the elderly and the majority of patients included in the study were > 65 years old, thus introducing a possible selection bias. Nonetheless the results of the study are useful for the clinician. Prolongation of vitamin K antagonists in patients with elevated D-dimer levels one month after discontinuation of OAT for a first unprovoked episode of VTE results in a favourable risk-benefit relationship. Probably this

Dimer and String Formation during Low Temperature Silicon Deposition on Si(100)

DEFF Research Database (Denmark)

Smith, A. P.; Jonsson, Hannes

1996-01-01

We present theoretical results based on density functional theory and kinetic Monte Carlo simulations of silicon deposition and address observations made in recently reported low temperature scanning tunneling microscopy studies. A mechanism is presented which explains dimer formation on top...... of the substrate's dimer rows at 160 K and up to room temperature, while between-row dimers and longer strings of adatoms (''diluted dimer rows'') form at higher temperature. A crossover occurs at around room temperature between two different mechanisms for adatom diffusion in our model....

A discotic triphenylene dimer as organic hole transporting material for electroluminescence devices

International Nuclear Information System (INIS)

Mao Huaxiang; He Zhiqun; Wang Junling; Zhang Chunxiu; Xie, Ping; Zhang Rongben

2007-01-01

A triphenylene dimer, an intermediate between a discotic triphenylene molecule and the macromolecule, had been prepared by linking together two triphenylene units via phenylene carbamate linkages, which was formed through a reaction between one 1,4-phenylene diisocyanate and two hydroxyl end groups on flexible substituents of triphenylenes. The dimer exhibited good film-forming property. Its temperature-dependent phase transitions were investigated using differential scanning calorimetry and polarized optical microscopy. Room temperature microstructure of the dimer was analyzed by X-ray diffraction. Charge mobility of the triphenylene dimer was also measured. Our preliminary result using the materials in a sandwich light-emitting device is reported here. It demonstrates that the triphenylene dimer is a promising candidate as a hole transporting material

D-dimer as marker for microcirculatory failure: correlation with LOD and APACHE II scores.

Science.gov (United States)

Angstwurm, Matthias W A; Reininger, Armin J; Spannagl, Michael

2004-01-01

The relevance of plasma d-dimer levels as marker for morbidity and organ dysfunction in severely ill patients is largely unknown. In a prospective study we determined d-dimer plasma levels of 800 unselected patients at admission to our intensive care unit. In 91% of the patients' samples d-dimer levels were elevated, in some patients up to several hundredfold as compared to normal values. The highest mean d-dimer values were present in the patient group with thromboembolic diseases, and particularly in non-survivors of pulmonary embolism. In patients with circulatory impairment (r=0.794) and in patients with infections (r=0.487) a statistically significant correlation was present between d-dimer levels and the APACHE II score (P<0.001). The logistic organ dysfunction score (LOD, P<0.001) correlated with d-dimer levels only in patients with circulatory impairment (r=0.474). On the contrary, patients without circulatory impairment demonstrated no correlation of d-dimer levels to the APACHE II or LOD score. Taking all patients together, no correlations of d-dimer levels with single organ failure or with indicators of infection could be detected. In conclusion, d-dimer plasma levels strongly correlated with the severity of the disease and organ dysfunction in patients with circulatory impairment or infections suggesting that elevated d-dimer levels may reflect the extent of microcirculatory failure. Thus, a therapeutic strategy to improve the microcirculation in such patients may be monitored using d-dimer plasma levels.

Dimerization of the Glucan Phosphatase Laforin Requires the Participation of Cysteine 329

Science.gov (United States)

Sánchez-Martín, Pablo; Raththagala, Madushi; Bridges, Travis M.; Husodo, Satrio; Gentry, Matthew S.; Sanz, Pascual; Romá-Mateo, Carlos

2013-01-01

Laforin, encoded by a gene that is mutated in Lafora Disease (LD, OMIM 254780), is a modular protein composed of a carbohydrate-binding module and a dual-specificity phosphatase domain. Laforin is the founding member of the glucan-phosphatase family and regulates the levels of phosphate present in glycogen. Multiple reports have described the capability of laforin to form dimers, although the function of these dimers and their relationship with LD remains unclear. Recent evidence suggests that laforin dimerization depends on redox conditions, suggesting that disulfide bonds are involved in laforin dimerization. Using site-directed mutagenesis we constructed laforin mutants in which individual cysteine residues were replaced by serine and then tested the ability of each protein to dimerize using recombinant protein as well as a mammalian cell culture assay. Laforin-Cys329Ser was the only Cys/Ser mutant unable to form dimers in both assays. We also generated a laforin truncation lacking the last three amino acids, laforin-Cys329X, and this truncation also failed to dimerize. Interestingly, laforin-Cys329Ser and laforin-Cys329X were able to bind glucans, and maintained wild type phosphatase activity against both exogenous and biologically relevant substrates. Furthermore, laforin-Cys329Ser was fully capable of participating in the ubiquitination process driven by a laforin-malin complex. These results suggest that dimerization is not required for laforin phosphatase activity, glucan binding, or for the formation of a functional laforin-malin complex. Cumulatively, these results suggest that cysteine 329 is specifically involved in the dimerization process of laforin. Therefore, the C329S mutant constitutes a valuable tool to analyze the physiological implications of laforin’s oligomerization. PMID:23922729

Dimer coverings on random multiple chains of planar honeycomb lattices

International Nuclear Information System (INIS)

Ren, Haizhen; Zhang, Fuji; Qian, Jianguo

2012-01-01

We study dimer coverings on random multiple chains. A multiple chain is a planar honeycomb lattice constructed by successively fusing copies of a ‘straight’ condensed hexagonal chain at the bottom of the previous one in two possible ways. A random multiple chain is then generated by admitting the Bernoulli distribution on the two types of fusing, which describes a zeroth-order Markov process. We determine the expectation of the number of the pure dimer coverings (perfect matchings) over the ensemble of random multiple chains by the transfer matrix approach. Our result shows that, with only two exceptions, the average of the logarithm of this expectation (i.e., the annealed entropy per dimer) is asymptotically nonzero when the fusing process goes to infinity and the length of the hexagonal chain is fixed, though it is zero when the fusing process and the length of the hexagonal chain go to infinity simultaneously. Some numerical results are provided to support our conclusion, from which we can see that the asymptotic behavior fits well to the theoretical results. We also apply the transfer matrix approach to the quenched entropy and reveal that the quenched entropy of random multiple chains has a close connection with the well-known Lyapunov exponent of random matrices. Using the theory of Lyapunov exponents we show that, for some random multiple chains, the quenched entropy per dimer is strictly smaller than the annealed one when the fusing process goes to infinity. Finally, we determine the expectation of the free energy per dimer over the ensemble of the random multiple chains in which the three types of dimers in different orientations are distinguished, and specify a series of non-random multiple chains whose free energy per dimer is asymptotically equal to this expectation. (paper)

A new D-dimer cutoff in bedridden hospitalized elderly patients.

Science.gov (United States)

Granziera, Serena; Rechichi, Alfonsina; De Rui, Marina; De Carlo, Paola; Bertozzo, Giulia; Marigo, Lucia; Nante, Giovanni; Manzato, Enzo

2013-03-01

Asymptomatic deep vein thrombosis (DVT) and pulmonary embolism are leading causes of morbidity following the hospitalization of elderly people. The diagnosis of DVT is supported by the D-dimer laboratory assay. The concentration of D-dimer increases in patients with DVT, but may be high in other conditions too (i.e. cancer, infections and inflammation). Old age coincides with a physiological increase in D-dimer values, and that is why D-dimer assay in the elderly is characteristically highly sensitive but scarcely specific. The aim of our study was to explore the reliability of different D-dimer cutoffs for the diagnosis of asymptomatic DVT in a population of bedridden hospitalized elderly patients. We studied 199 patients who were a mean 86.3 ± 6.7 years old. All participants underwent lower limb Doppler ultrasound (DUS) and D-dimer venous blood sampling on admission. In our cohort, the usual cutoff proved highly sensitive (100%), but its specificity was very poor (20.1%). To find a higher cutoff that could improve the method's specificity, we analyzed our data using a receiver operating characteristic curve analysis. The resulting D-dimer cutoff of 492 μg/l enabled us to retain the same sensitivity while improving the test's specificity to 39.1%, with a consequent improvement in its positive predictive value and accuracy. In addition to improving the method's reliability, this result may be helpful in clinical practice, in both medical wards and nursing homes. By adopting a cutoff of 492 μg/l, clinicians could significantly increase the proportion of older patients in whom DVT can be safely ruled out, reducing referrals for DUS and administration of heparin, with consequent clinical, practical and economic advantages.

Kinetics of the monomer-dimer reaction of yeast hexokinase PI.

Science.gov (United States)

Hoggett, J G; Kellett, G L

1992-10-15

Kinetic studies of the glucose-dependent monomer-dimer reaction of yeast hexokinase PI at pH 8.0 in the presence of 0.1 M-KCl have been carried out using the fluorescence temperature-jump technique. A slow-relaxation effect was observed which was attributed from its dependence on enzyme concentration to the monomer-dimer reaction; the reciprocal relaxation times tau-1 varied from 3 s-1 at low concentrations of glucose to 42 s-1 at saturating concentrations. Rate constants for association (kass.) and dissociation (kdiss.) were determined as a function of glucose concentration using values of the equilibrium association constant of the monomer-dimer reaction derived from sedimentation ultracentrifugation studies under similar conditions, and also from the dependence of tau-2 on enzyme concentration. kass. was almost independent of glucose concentration and its value (2 x 10(5) M-1.s-1) was close to that expected for a diffusion-controlled process. The influence of glucose on the monomer-dimer reaction is entirely due to effects on kdiss., which increases from 0.21 s-1 in the absence of glucose to 25 s-1 at saturating concentrations. The monomer and dimer forms of hexokinase have different affinities and Km values for glucose, and the results reported here imply that there may be a significant lag in the response of the monomer-dimer reaction to changes in glucose concentrations in vivo with consequent hysteretic effects on the hexokinase activity.

Structural features of the KPI domain control APP dimerization, trafficking, and processing.

Science.gov (United States)

Ben Khalifa, Naouel; Tyteca, Donatienne; Marinangeli, Claudia; Depuydt, Mathieu; Collet, Jean-François; Courtoy, Pierre J; Renauld, Jean-Christophe; Constantinescu, Stefan; Octave, Jean-Noël; Kienlen-Campard, Pascal

2012-02-01

The two major isoforms of human APP, APP695 and APP751, differ by the presence of a Kunitz-type protease inhibitor (KPI) domain in the extracellular region. APP processing and function is thought to be regulated by homodimerization. We used bimolecular fluorescence complementation (BiFC) to study dimerization of different APP isoforms and mutants. APP751 was found to form significantly more homodimers than APP695. Mutation of dimerization motifs in the TM domain did not affect fluorescence complementation, but native folding of KPI is critical for APP751 homodimerization. APP751 and APP695 dimers were mostly localized at steady state in the Golgi region, suggesting that most of the APP751 and 695 dimers are in the secretory pathway. Mutation of the KPI led to the retention of the APP homodimers in the endoplasmic reticulum. We finally showed that APP751 is more efficiently processed through the nonamyloidogenic pathway than APP695. These findings provide new insight on the particular role of KPI domain in APP dimerization. The correlation observed between dimerization, subcellular localization, and processing suggests that dimerization acts as an efficient regulator of APP trafficking in the secretory compartments that has major consequences on its processing.

On the asymptotics of dimers on tori

OpenAIRE

Kenyon, Richard W.; Sun, Nike; Wilson, David B.

2013-01-01

We study asymptotics of the dimer model on large toric graphs. Let $\\mathbb L$ be a weighted $\\mathbb{Z}^2$-periodic planar graph, and let $\\mathbb{Z}^2 E$ be a large-index sublattice of $\\mathbb{Z}^2$. For $\\mathbb L$ bipartite we show that the dimer partition function on the quotient $\\mathbb{L}/(\\mathbb{Z}^2 E)$ has the asymptotic expansion $\\exp[A f_0 + \\text{fsc} + o(1)]$, where $A$ is the area of $\\mathbb{L}/(\\mathbb{Z}^2 E)$, $f_0$ is the free energy density in the bulk, and $\\text{fsc...

On the diffusion and self-trapping of surface dimers

Science.gov (United States)

Kappus, W.

1982-03-01

The theory of elastic interactions between surface atoms which are caused by substrate strains is applied to the interaction of dimers on the (211) surface of tungsten. From the comparison of theoretical and experimental interactions which were derived from the diffusion behaviour of dimers, conclusions are drawn on the nature of the adatom-substrate bond.

Dislocations and vacancies in two-dimensional mixed crystals of spheres and dimers

KAUST Repository

Gerbode, Sharon J.

2010-10-15

In colloidal crystals of spheres, dislocation motion is unrestricted. On the other hand, recent studies of relaxation in crystals of colloidal dimer particles have demonstrated that the dislocation dynamics in such crystals are reminiscent of glassy systems. The observed glassy dynamics arise as a result of dislocation cages formed by certain dimer orientations. In the current study, we use experiments and simulations to investigate the transition that arises when a pure sphere crystal is doped with an increasing concentration of dimers. Specifically, we focus on both dislocation caging and vacancy motion. Interestingly, we find that any nonzero fraction of dimers introduces finite dislocation cages, suggesting that glassy dynamics are present for any mixed crystal. However, we have also identified a vacancy-mediated uncaging mechanism for releasing dislocations from their cages. This mechanism is dependent on vacancy diffusion, which slows by orders of magnitude as the dimer concentration is increased. We propose that in mixed crystals with low dimer concentrations vacancy diffusion is fast enough to uncage dislocations and delay the onset of glassy dislocation dynamics. © 2010 The American Physical Society.

Dislocations and vacancies in two-dimensional mixed crystals of spheres and dimers

KAUST Repository

Gerbode, Sharon J.; Ong, Desmond C.; Liddell, Chekesha M.; Cohen, Itai

2010-01-01

In colloidal crystals of spheres, dislocation motion is unrestricted. On the other hand, recent studies of relaxation in crystals of colloidal dimer particles have demonstrated that the dislocation dynamics in such crystals are reminiscent of glassy systems. The observed glassy dynamics arise as a result of dislocation cages formed by certain dimer orientations. In the current study, we use experiments and simulations to investigate the transition that arises when a pure sphere crystal is doped with an increasing concentration of dimers. Specifically, we focus on both dislocation caging and vacancy motion. Interestingly, we find that any nonzero fraction of dimers introduces finite dislocation cages, suggesting that glassy dynamics are present for any mixed crystal. However, we have also identified a vacancy-mediated uncaging mechanism for releasing dislocations from their cages. This mechanism is dependent on vacancy diffusion, which slows by orders of magnitude as the dimer concentration is increased. We propose that in mixed crystals with low dimer concentrations vacancy diffusion is fast enough to uncage dislocations and delay the onset of glassy dislocation dynamics. © 2010 The American Physical Society.

Asymmetric monometallic nanorod nanoparticle dimer and related compositions and methods

KAUST Repository

Han, Yu; Huang, Jianfeng; Zhu, Yihan

2016-01-01

and three-dimensional morphology of the dimer, as well as the growth pathway of the AuNP on the AuNR seed, was investigated for this example. The dimer exhibits an extraordinary broadband optical extinction spectrum spanning the UV, visible, and near

DFT Study of dimers of dimethyl sulfoxide in gas phase

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Reza Fazaeli

2014-10-01

Full Text Available Density functional (DFT calculations at M05-2x/aug-cc-pVDZ level were used to analyze the interactions between dimethyl sulfoxide (DMSO dimers. The structures obtained have been ana-lyzed with the Atoms in Molecules (AIMs and Natural Bond Orbital (NBO methodologies. Four minima were located on the potential energy surface of the dimers. Three types of interac-tions are observed, CH•••O, CH•••S hydrogen bonds and orthogonal interaction between the lone pair of the oxygen with the electron-deficient region of the sulfur atom. Stabilization energies of dimers including BSSE and ZPE are in the range 27–40 kJmol-1. The most stable conformers of dimers at DFT level is cyclic structure with antiparallel orientation of S=O groups pairing with three C–H∙∙∙O and a S∙∙∙O interactions.

Photoreactivation of pyrimidine dimers in the DNA of normal and xeroderma pigmentosum cells

International Nuclear Information System (INIS)

Sutherland, B.M.; Oliver, R.; Fuselier, C.O.; Sutherland, J.C.

1976-01-01

Photoproducts formed in the DNA of human cells irradiated with ultraviolet light (uv) were identified as cyclobutyl pyrimidine dimers by their chromatographic mobility, reversibility to monomers upon short wavelength uv irradiation, and comparison of the kinetics of this monomerization with that of authentic cis--syn thymine--thymine dimers prepared by irradiation of thymine in ice. The level of cellular photoreactivation of these dimers reflects the level of photoreactivating enzyme measured in cell extracts. Action spectra for cellular dimer photoreactivation in the xeroderma pigmentosum line XP12BE agree in range (300 nm to at least 577 nm) and maximum (near 400 nm) with that for photoreactivation by purified human photoreactivating enzyme. Normal human cells can also photoreactivate dimers in their DNA. The action spectrum for the cellular monomerization of dimers is similar to that for photoreactivation by the photoreactivating enzyme in extracts of normal human fibroblasts

Visualization of multipolar longitudinal and transversal surface plasmon modes in nanowire dimers.

Science.gov (United States)

Alber, Ina; Sigle, Wilfried; Müller, Sven; Neumann, Reinhard; Picht, Oliver; Rauber, Markus; van Aken, Peter A; Toimil-Molares, Maria Eugenia

2011-12-27

We study the transversal and longitudinal localized surface plasmon resonances in single nanowires and nanowire dimers excited by the fast traveling electron beam in a transmission electron microscope equipped with high-resolution electron energy-loss spectroscopy. Bright and dark longitudinal modes up to the fifth order are resolved on individual metallic nanowires. On nanowire dimers, mode splitting into bonding and antibonding is measured up to the third order for several dimers with various aspect ratio and controlled gap size. We observe that the electric field maxima of the bonding modes are shifted toward the gap, while the electric field maxima of the antibonding modes are shifted toward the dimer ends. Finally, we observe that the transversal mode is not detected in the region of the dimer gap and decays away from the rod more rapidly than the longitudinal modes.

Dimerization of 3He in 3He-4He mixture films

International Nuclear Information System (INIS)

Bashkin, E.

1994-01-01

3 He atoms dissolved in superfluid 4 He may form dimers ( 3 He) 2 in two-dimensional geometries. Dimer formation is studied in films of dilute 3 He- 4 He mixture. After designing a schematic 3 He- 3 He interaction potential, the dimer binding energy is calculated for various substrates. It is shown that 3 He impurity states localized near the substrate give rise to the highest magnitudes of the binding energy. (author). 32 refs., 6 figs.,; 1 tab

Glycine transporter dimers: evidence for occurrence in the plasma membrane.

Science.gov (United States)

Bartholomäus, Ingo; Milan-Lobo, Laura; Nicke, Annette; Dutertre, Sébastien; Hastrup, Hanne; Jha, Alok; Gether, Ulrik; Sitte, Harald H; Betz, Heinrich; Eulenburg, Volker

2008-04-18

Different Na(+)/Cl(-)-dependent neurotransmitter transporters of the SLC6a family have been shown to form dimers or oligomers in both intracellular compartments and at the cell surface. In contrast, the glycine transporters (GlyTs) GlyT1 and -2 have been reported to exist as monomers in the plasma membrane based on hydrodynamic and native gel electrophoretic studies. Here, we used cysteine substitution and oxidative cross-linking to show that of GlyT1 and GlyT2 also form dimeric complexes within the plasma membrane. GlyT oligomerization at the cell surface was confirmed for both GlyT1 and GlyT2 by fluorescence resonance energy transfer microscopy. Endoglycosidase treatment and surface biotinylation further revealed that complex-glycosylated GlyTs form dimers located at the cell surface. Furthermore, substitution of tryptophan 469 of GlyT2 by an arginine generated a transporter deficient in dimerization that was retained intracellulary. Based on these results and GlyT structures modeled by using the crystal structure of the bacterial homolog LeuT(Aa), as a template, residues located within the extracellular loop 3 and at the beginning of transmembrane domain 6 are proposed to contribute to the dimerization interface of GlyTs.

cis elements and trans-acting factors involved in dimer formation of murine leukemia virus RNA.

Science.gov (United States)

Prats, A C; Roy, C; Wang, P A; Erard, M; Housset, V; Gabus, C; Paoletti, C; Darlix, J L

1990-02-01

The genetic material of all retroviruses examined so far consists of two identical RNA molecules joined at their 5' ends by the dimer linkage structure (DLS). Since the precise location of the DLS as well as the mechanism and role(s) of RNA dimerization remain unclear, we analyzed the dimerization process of Moloney murine leukemia virus (MoMuLV) genomic RNA. For this purpose we derived an in vitro model for RNA dimerization. By using this model, murine leukemia virus RNA was shown to form dimeric molecules. Deletion mutagenesis in the 620-nucleotide leader of MoMuLV RNA showed that the dimer promoting sequences are located within the encapsidation element Psi between positions 215 and 420. Furthermore, hybridization assays in which DNA oligomers were used to probe monomer and dimer forms of MoMuLV RNA indicated that the DLS probably maps between positions 280 and 330 from the RNA 5' end. Also, retroviral nucleocapsid protein was shown to catalyze dimerization of MoMuLV RNA and to be tightly bound to genomic dimer RNA in virions. These results suggest that MoMuLV RNA dimerization and encapsidation are probably controlled by the same cis element, Psi, and trans-acting factor, nucleocapsid protein, and thus might be linked during virion formation.

Accuracy of D-Dimers to Rule Out Venous Thromboembolism Events across Age Categories

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G. Der Sahakian

2010-01-01

Full Text Available Background. Strategies combining pretest clinical assessment and D-dimers measurement efficiently and safely rule out venous thromboembolism events (VTE in low- and intermediate-risk patients. Objectives. As process of ageing is associated with altered concentrations of coagulation markers including an increase in D-dimers levels, we investigated whether D-dimers could reliably rule out VTE across age categories. Method. We prospectively assessed the test performance in 1,004 patients visiting the emergency department during the 6-month period with low or intermediate risk of VTE who also received additional diagnostic procedures. Results. 67 patients had VTE with D-dimers levels above the threshold, and 3 patients displayed D-dimers levels below the threshold. We observed that specificity of D-dimers test decreased in an age-dependent manner. However, sensitivity and negative predictive value remained at very high level in each age category including older patients. Conclusion. We conclude that, even though D-dimers level could provide numerous false positive results in elderly patients, its high sensitivity could reliably help physicians to exclude the diagnosis of VTE in every low- and intermediate-risk patient.

Analysis of pyrimidine dimer content of isolated DNA by nuclease digestion

International Nuclear Information System (INIS)

Farland, W.H.; Sutherland, B.M.

1980-01-01

Isolated DNA is highly susceptible to degradation by exogenous nucleases. Complete digestion is possible with a number of well-characterized enzymes from a variety of sources. Treatment of DNA with a battery of enzymes including both phosphodiesterase and phosphatase activities yields a mixture of nucleosides and inorganic phosphate (P/sub i/) as a final product. Unlike native DNA, ultraviolet-irradiated DNA is resistant to complete digestion. Setlow et al. demonstrated that the structural changes in the DNA responsible for the nuclease resistance were the formation of cyclobutyl pyrimidine dimers, the major photoproduct in UV-irradiated DNA. Using venom phosphodiesterase, they demonstrated that UV irradiation of DNA affected both the rate and extent of enzymatic hydrolysis. In addition, it was demonstrated that the major nuclease-resistant product of this hydrolysis was an oligonucleotide containing dimerized pyrimidines. Treatment of the DNA to split the dimers, either photochemically or photoenzymatically, rendered the polymer more susceptible to hydrolysis by the phosphodiesterase. The specificity of photoreactivating enzyme for pyrimidine dimers lends support to the role of these structures in conferring nuclease resistance to UV-irradiated DNA. The nuclease resistance of DNA containing dimers has been the basis of several assays for the measurement of these photoproducts. Sutherland and Chamberlin reported the development of a rapid and sensitive assay for dimers in 32 P-labeled DNA

Investigation of split-off dimers on the Si(001)2x1 surface

International Nuclear Information System (INIS)

Schofield, S.R.; O'Brien, J.L.; Curson, N.J.; Simmons, M.Y.; Clark, R.G.

2002-01-01

Full text: A detailed knowledge of the nature of crystalline defects on the Si(001)2x1 surface is becoming increasingly important as more research effort is dedicated to producing atomic-scale electronic devices. Here we present high-resolution scanning tunnelling microscopy (STM) images and ab initio pseudopotential calculations of an unusual defect of the silicon (001) surface called the split-off dimer. In high-resolution filled-state images, split-off dimers appear as a pair of protrusions, in contrast to the surrounding surface dimers that appear as 'bean-shaped' protrusions. We show that π-bonding does not exist between the atoms of the split-off dimer, but instead, the dimer atoms form π-bonds with two second layer atoms as part of a tetramer bonding arrangement. We discuss the strain associated with split-off dimer defects and describe how this strain significantly affects the bonding arrangements and local density of states around these defects

A short autocomplementary sequence plays an essential role in avian sarcoma-leukosis virus RNA dimerization.

Science.gov (United States)

Fossé, P; Motté, N; Roumier, A; Gabus, C; Muriaux, D; Darlix, J L; Paoletti, J

1996-12-24

Retroviral genomes consist of two identical RNA molecules joined noncovalently near their 5'-ends. Recently, two models have been proposed for RNA dimer formation on the basis of results obtained in vitro with human immunodeficiency virus type 1 RNA and Moloney murine leukemia virus RNA. It was first proposed that viral RNA dimerizes by forming an interstrand quadruple helix with purine tetrads. The second model postulates that RNA dimerization is initiated by a loop-loop interaction between the two RNA molecules. In order to better characterize the dimerization process of retroviral genomic RNA, we analyzed the in vitro dimerization of avian sarcoma-leukosis virus (ASLV) RNA using different transcripts. We determined the requirements for heterodimer formation, the thermal dissociation of RNA dimers, and the influence of antisense DNA oligonucleotides on dimer formation. Our results strongly suggest that purine tetrads are not involved in dimer formation. Data show that an autocomplementary sequence located upstream from the splice donor site and within a major packaging signal plays a crucial role in ASLV RNA dimer formation in vitro. This sequence is able to form a stem-loop structure, and phylogenetic analysis reveals that it is conserved in 28 different avian sarcoma and leukosis viruses. These results suggest that dimerization of ASLV RNA is initiated by a loop-loop interaction between two RNA molecules and provide an additional argument for the ubiquity of the dimerization process via loop-loop interaction.

Unphosphorylated rhabdoviridae phosphoproteins form elongated dimers in solution.

Science.gov (United States)

Gerard, Francine C A; Ribeiro, Euripedes de Almeida; Albertini, Aurélie A V; Gutsche, Irina; Zaccai, Guiseppe; Ruigrok, Rob W H; Jamin, Marc

2007-09-11

The phosphoprotein (P) is an essential component of the replication machinery of rabies virus (RV) and vesicular stomatitis virus (VSV), and the oligomerization of P, potentially controlled by phosphorylation, is required for its function. Up to now the stoichiometry of phosphoprotein oligomers has been controversial. Size exclusion chromatography combined with detection by multiangle laser light scattering shows that the recombinant unphosphorylated phosphoproteins from VSV and from RV exist as dimers in solution. Hydrodynamic analysis indicates that the dimers are highly asymmetric, with a Stokes radius of 4.8-5.3 nm and a frictional ratio larger than 1.7. Small-angle neutron scattering experiments confirm the dimeric state and the asymmetry of the structure and yield a radius of gyration of about 5.3 nm and a cross-sectional radius of gyration of about 1.6-1.8 nm. Similar hydrodynamic properties and molecular dimensions were obtained with a variant of VSV phosphoprotein in which Ser60 and Thr62 are substituted by Asp residues and which has been reported previously to mimic phosphorylation by inducing oligomerization and activating transcription. Here, we show that this mutant also forms a dimer with hydrodynamic properties and molecular dimensions similar to those of the wild type protein. However, incubation at 30 degrees C for several hours induced self-assembly of both wild type and mutant proteins, leading to the formation of irregular filamentous structures.

Covalent α-synuclein dimers: chemico-physical and aggregation properties.

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Micaela Pivato

Full Text Available The aggregation of α-synuclein into amyloid fibrils constitutes a key step in the onset of Parkinson's disease. Amyloid fibrils of α-synuclein are the major component of Lewy bodies, histological hallmarks of the disease. Little is known about the mechanism of aggregation of α-synuclein. During this process, α-synuclein forms transient intermediates that are considered to be toxic species. The dimerization of α-synuclein could represent a rate-limiting step in the aggregation of the protein. Here, we analyzed four covalent dimers of α-synuclein, obtained by covalent link of the N-terms, C-terms, tandem cloning of two sequences and tandem juxtaposition in one protein of the 1-104 and 29-140 sequences. Their biophysical properties in solution were determined by CD, FT-IR and NMR spectroscopies. SDS-induced folding was also studied. The fibrils formation was analyzed by ThT and polarization fluorescence assays. Their morphology was investigated by TEM and AFM-based quantitative morphometric analysis. All dimers were found to be devoid of ordered secondary structure under physiological conditions and undergo α-helical transition upon interaction with SDS. All protein species are able to form amyloid-like fibrils. The reciprocal orientation of the α-synuclein monomers in the dimeric constructs affects the kinetics of the aggregation process and a scale of relative amyloidogenic propensity was determined. Structural investigations by FT IR spectroscopy, and proteolytic mapping of the fibril core did not evidence remarkable difference among the species, whereas morphological analyses showed that fibrils formed by dimers display a lower and diversified level of organization in comparison with α-synuclein fibrils. This study demonstrates that although α-synuclein dimerization does not imply the acquisition of a preferred conformation by the participating monomers, it can strongly affect the aggregation properties of the molecules. The results

Pyrimidine dimer sites associated with the daughter DNA strands in uv-irradiated human fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Lehmann, A R; Kirk-Bell, S [Sussex Univ., Brighton (UK)

1978-03-01

Pyrimidine dimer sites associated with the newly-synthesized DNA were detected during post-replication repair of DNA in uv-irradiated human fibroblasts. These pyrimidine dimer sites were inferred from a decrease in the molecular weight of pulse-labelled DNA after treatment with an extract of Micrococcus luteus containing uv-specific endonuclease activity. In DNA synthesized immediately after irradiation, the frequency of these daughter strand dimer sites was 7 to 20% of that in the parental DNA. Such sites were found in fibroblasts from normal donors and from xeroderma pigmentosum patients (with defects in excision-repair or post-replication repair). They were excised from the DNA of normal cells. As the time between uv irradiation and pulse-labelling was increased, the frequency of dimer sites associated with the labelled DNA decreased. If the pulse-label was delivered 6 h after irradiation of normal cells or excision-defective xeroderma pigmentosum cells, no dimer sites were detected in the labelled DNA. It has usually been assumed that daughter-strand dimer sites were the result of recombinational exchanges. The assay procedure used in these experiments and in similar experiments of others did not distinguish between labelled DNA containing pyrimidine dimers within the labelled section, and labelled DNA which did not contain pyrimidine dimers but was attached to unlabelled DNA which did contain dimers. The latter structures would arise during normal replication immediately following uv irradiation of mammalian cells. Calculations are presented which suggest that a significant proportion and conceivably all of the dimer sites associated with the daughter strands may have arisen in this way, rather than from recombinational exchanges as has been generally assumed.

Pyrimidine dimer sites associated with the daughter DNA strands in UV-irradiated human fibroblasts

International Nuclear Information System (INIS)

Lehmann, A.R.; Kirk-Bell, S.

1978-01-01

Pyrimidine dimer sites associated with the newly-synthesized DNA were detected during post-replication repair of DNA in UV-irradiated human fibroblasts. These pyrimidine dimer sites were inferred from a decrease in the molecular weight of pulse-labelled DNA after treatment with an extract of Micrococcus luteus containing UV-specific endonuclease activity. In DNA synthesized immediately after irradiation the frequency of these daughter strand dimer sites was 7-20% of that in the parental DNA. Such sites were found in fibroblasts from normal donors and from xeroderma pigmentosum patients (with defects in excision-repair or post-replication repair). They were excised from the DNA of normal cells. As the time between UV-irradiation and pulse-labelling was increased, the frequency of dimer sites associated with the labelled DNA decreased. If the pulse-label was delivered 6 h after irradiation of normal cells or excision-defective xeroderma pigmentosum cells, no dimer sites were detected in the labelled DNA. It has usually been assumed that daughter-strand dimer sites were the result of recombinational exchanges. The assay procedure used in these experiments and in similar experiments of others did not distinguish between labelled DNA containing pyrimidine dimers within the labelled section, and labelled DNA which did not contain pyrimidine dimers but was attached to unlabelled DNA which did contain dimers. The latter structures would arise during normal replication immediately following UV-irradiation of mammalian cells. Calculations are presented which suggest that a significant proportion and conceivably all of the dimer sites associated with the daughter strands may have arisen in this way, rather than from recombinational exchanges as has been generally assumed. (author)

Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells

International Nuclear Information System (INIS)

Dietz, Marina S; Haße, Daniel; Ferraris, Davide M; Göhler, Antonia; Niemann, Hartmut H; Heilemann, Mike

2013-01-01

The human receptor tyrosine kinase MET and its ligand hepatocyte growth factor/scatter factor are essential during embryonic development and play an important role during cancer metastasis and tissue regeneration. In addition, it was found that MET is also relevant for infectious diseases and is the target of different bacteria, amongst them Listeria monocytogenes that induces bacterial uptake through the surface protein internalin B. Binding of ligand to the MET receptor is proposed to lead to receptor dimerization. However, it is also discussed whether preformed MET dimers exist on the cell membrane. To address these issues we used single-molecule fluorescence microscopy techniques. Our photobleaching experiments show that MET exists in dimers on the membrane of cells in the absence of ligand and that the proportion of MET dimers increases significantly upon ligand binding. Our results indicate that partially preformed MET dimers may play a role in ligand binding or MET signaling. The addition of the bacterial ligand internalin B leads to an increase of MET dimers which is in agreement with the model of ligand-induced dimerization of receptor tyrosine kinases.

Species A rotavirus NSP3 acquires its translation inhibitory function prior to stable dimer formation.

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Hugo I Contreras-Treviño

Full Text Available Species A rotavirus non-structural protein 3 (NSP3 is a translational regulator that inhibits or, under some conditions, enhances host cell translation. NSP3 binds to the translation initiation factor eIF4G1 and evicts poly-(A binding protein (PABP from eIF4G1, thus inhibiting translation of polyadenylated mRNAs, presumably by disrupting the effect of PABP bound to their 3'-ends. NSP3 has a long coiled-coil region involved in dimerization that includes a chaperone Hsp90-binding domain (HS90BD. We aimed to study the role in NSP3 dimerization of a segment of the coiled-coil region adjoining the HS90BD. We used a vaccinia virus system to express NSP3 with point mutations in conserved amino acids in the coiled-coil region and determined the effects of these mutations on translation by metabolic labeling of proteins as well as on accumulation of stable NSP3 dimers by non-dissociating Western blot, a method that separates stable NSP3 dimers from the monomer/dimerization intermediate forms of the protein. Four of five mutations reduced the total yield of NSP3 and the formation of stable dimers (W170A, K171E, R173E and R187E:K191E, whereas one mutation had the opposite effects (Y192A. Treatment with the proteasome inhibitor MG132 revealed that stable NSP3 dimers and monomers/dimerization intermediates are susceptible to proteasome degradation. Surprisingly, mutants severely impaired in the formation of stable dimers were still able to inhibit host cell translation, suggesting that NSP3 dimerization intermediates are functional. Our results demonstrate that rotavirus NSP3 acquires its function prior to stable dimer formation and remain as a proteasome target throughout dimerization.

Single-Molecule Rotational Switch on a Dangling Bond Dimer Bearing.

Science.gov (United States)

Godlewski, Szymon; Kawai, Hiroyo; Kolmer, Marek; Zuzak, Rafał; Echavarren, Antonio M; Joachim, Christian; Szymonski, Marek; Saeys, Mark

2016-09-27

One of the key challenges in the construction of atomic-scale circuits and molecular machines is to design molecular rotors and switches by controlling the linear or rotational movement of a molecule while preserving its intrinsic electronic properties. Here, we demonstrate both the continuous rotational switching and the controlled step-by-step single switching of a trinaphthylene molecule adsorbed on a dangling bond dimer created on a hydrogen-passivated Ge(001):H surface. The molecular switch is on-surface assembled when the covalent bonds between the molecule and the dangling bond dimer are controllably broken, and the molecule is attached to the dimer by long-range van der Waals interactions. In this configuration, the molecule retains its intrinsic electronic properties, as confirmed by combined scanning tunneling microscopy/spectroscopy (STM/STS) measurements, density functional theory calculations, and advanced STM image calculations. Continuous switching of the molecule is initiated by vibronic excitations when the electrons are tunneling through the lowest unoccupied molecular orbital state of the molecule. The switching path is a combination of a sliding and rotation motion over the dangling bond dimer pivot. By carefully selecting the STM conditions, control over discrete single switching events is also achieved. Combined with the ability to create dangling bond dimers with atomic precision, the controlled rotational molecular switch is expected to be a crucial building block for more complex surface atomic-scale devices.

Laser isotope separation using selective inhibition and encouragement of dimer formation

International Nuclear Information System (INIS)

Kivel, B.

1979-01-01

Method and apparatus for inhibiting dimer formation of molecules of a selected isotope type in a cooled flow of gas to enhance the effectiveness of mass difference isotope separation techniques are described. Molecules in the flow containing atoms of the selected isotope type are selectively excited by infrared radiation in order to inhibit the formation of dimers and larger clusters of such molecules, while the molecules not containing atoms of the selected, excited type are encouraged to form dimers and higher order aggregates by the cooling of the gaseous flow. The molecules with the excited isotope will predominate in monomers and will constitute the enriched product stream, while the aggregated group comprising molecules having the unexcited isotope will predominate in dimers and larger clusters of molecules, forming the tails stream. The difference in diffusion coefficientts between particles of the excited and unexcited isotopes is enhanced by the greater mass differences resulting from aggregation of unexcited particles into dimers and larger clusters. Prior art separation techniques which exploit differences in isotopic diffusion rates will consequently exhibit enhanced enrichment per stage by the utilization of the present invention

Spin Quantum Tunneling via Entangled States in a Dimer of Exchange-Coupled Single-Molecule Magnets

Science.gov (United States)

Tiron, R.; Wernsdorfer, W.; Foguet-Albiol, D.; Aliaga-Alcalde, N.; Christou, G.

2003-11-01

A new family of supramolecular, antiferromagnetically exchange-coupled dimers of single-molecule magnets (SMMs) has recently been reported. Each SMM acts as a bias on its neighbor, shifting the quantum tunneling resonances of the individual SMMs. Hysteresis loop measurements on a single crystal of SMM dimers have now established quantum tunneling of the magnetization via entangled states of the dimer. This shows that the dimer really does behave as a quantum mechanically coupled dimer, and also allows the measurement of the longitudinal and transverse superexchange coupling constants.

Light activation of the LOV protein vivid generates a rapidly exchanging dimer.

Science.gov (United States)

Zoltowski, Brian D; Crane, Brian R

2008-07-08

The fungal photoreceptor Vivid (VVD) plays an important role in the adaptation of blue-light responses in Neurospora crassa. VVD, an FAD-binding LOV (light, oxygen, voltage) protein, couples light-induced cysteinyl adduct formation at the flavin ring to conformational changes in the N-terminal cap (Ncap) of the VVD PAS domain. Size-exclusion chromatography (SEC), equilibrium ultracentrifugation, and static and dynamic light scattering show that these conformational changes generate a rapidly exchanging VVD dimer, with an expanded hydrodynamic radius. A three-residue N-terminal beta-turn that assumes two different conformations in a crystal structure of a VVD C71V variant is essential for light-state dimerization. Residue substitutions at a critical hinge between the Ncap and PAS core can inhibit or enhance dimerization, whereas a Tyr to Trp substitution at the Ncap-PAS interface stabilizes the light-state dimer. Cross-linking through engineered disulfides indicates that the light-state dimer differs considerably from the dark-state dimer found in VVD crystal structures. These results verify the role of Ncap conformational changes in gating the photic response of N. crassa and indicate that LOV-LOV homo- or heterodimerization may be a mechanism for regulating light-activated gene expression.

Structure of the dimeric form of CTP synthase from Sulfolobus solfataricus

DEFF Research Database (Denmark)

Lauritsen, Iben; Willemoës, Martin; Jensen, Kaj Frank

2011-01-01

CTP synthase catalyzes the last committed step in de novo pyrimidine-nucleotide biosynthesis. Active CTP synthase is a tetrameric enzyme composed of a dimer of dimers. The tetramer is favoured in the presence of the substrate nucleotides ATP and UTP; when saturated with nucleotide, the tetramer...... completely dominates the oligomeric state of the enzyme. Furthermore, phosphorylation has been shown to regulate the oligomeric states of the enzymes from yeast and human. The crystal structure of a dimeric form of CTP synthase from Sulfolobus solfataricus has been determined at 2.5 Å resolution...

Preparation of 177Lu-DOTA/DTPA-Bz-Cys-RGD dimer and biodistribution evaluation in normal mice

International Nuclear Information System (INIS)

Sheng Feng; Jia Bing; Wang Fan; He Weiwei; Liu Zhaofei; Zhao Huiyun

2008-01-01

177 Lu-DOTA-Bz-Cys-RGD dimer and 177 Lu-DTPA-Bz-Cys-RGD dimer were prepared, and the in vitro and in vivo properties were compared. TLC and HPLC show that the labeling yields of two radiolabeled compounds are more than 95% under optimal conditions (pH=5.0, reacting at 100 degree C for 15-20 min), and the two radiolabeled compounds show pretty good in vitro stability. HPLC analyses and lg P values reveal that lipophilicity of 177 Lu-DOTA-Bz-Cys- RGD dimer is higher than 177 Lu-DTPA-Bz-Cys-RGD dimer. The uptake of 177 Lu-DTPA-Bz-Cys- RGD dimer in other tissues is significantly higher than that of 177 Lu-DOTA-Bz-Cys-RGD dimer at 4 h postinjection, except for blood and spleen. The in vivo stability of 177 Lu-DOTA-Bz-Cys-RGD dimer is much better than 177 Lu-DTPA-Bz-Cys-RGD dimer. Bz-DOTA is an ideal bifunctional chelator for 177 Lu labeling of RGD dimer. (authors)

The Rate of Vitamin A Dimerization in Lipofuscinogenesis, Fundus Autofluorescence, Retinal Senescence and Degeneration.

Science.gov (United States)

Washington, Ilyas; Saad, Leonide

2016-01-01

One of the earliest events preceding several forms of retinal degeneration is the formation and accumulation of vitamin A dimers in the retinal pigment epithelium (RPE) and underlying Bruch's membrane (BM). Such degenerations include Stargardt disease, Best disease, forms of retinitis pigmentosa, and age-related macular degeneration (AMD). Since their discovery in the 1990's, dimers of vitamin A, have been postulated as chemical triggers driving retinal senescence and degeneration. There is evidence to suggest that the rate at which vitamin A dimerizes and the eye's response to the dimerization products may dictate the retina's lifespan. Here, we present outstanding questions, finding the answers to which may help to elucidate the role of vitamin A dimerization in retinal degeneration.

Gap solitons in a chain of split-ring resonator dimers

Energy Technology Data Exchange (ETDEWEB)

Cui, Wei-na, E-mail: cuiweinaa@163.com [Department of Applied Physics, Nanjing University of Science and Technology, Nanjing 210094 (China); Li, Hong-xia, E-mail: hxli@njust.edu.cn [Department of Applied Physics, Nanjing University of Science and Technology, Nanjing 210094 (China); Sun, Min [Department of Applied Physics, Nanjing University of Science and Technology, Nanjing 210094 (China); Bu, Ling-bing [Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters, Key Laboratory for Aerosol-Cloud-Precipitation of China Meteorological Administration, Key Laboratory of Meteorological Disaster of Ministry of Education, Nanjing University of Information Science and Technology, Nanjing 210044 (China)

2017-06-21

Dynamics of a chain of split-ring resonator dimers with Kerr nonlinear interaction are investigated. A dimer is built as a pair of coupled split-ring resonators with different size. It is shown that the gap solitons with frequency lying in the gap exist due to the interaction of the discreteness and nonlinearity. Such localized structures are studied in the phase plane and analytical and numerical expressions are also obtained. - Highlights: • The coupling of the two modes is studied in the chain of split-ring resonator dimers with Kerr nonlinear interaction. • The evolution of the localized structures is studied in the phase plane. • This system supports gap solitons with the frequencies lying in the gap.

Thermal entanglement in an orthogonal dimer-plaquette chain with alternating Ising–Heisenberg coupling

International Nuclear Information System (INIS)

Paulinelli, H G; De Souza, S M; Rojas, Onofre

2013-01-01

In this paper we explore the entanglement in an orthogonal dimer-plaquette Ising–Heisenberg chain, assembled between plaquette edges, also known as orthogonal dimer plaquettes. The quantum entanglement properties involving an infinite chain structure are quite important, not only because the mathematical calculation is cumbersome but also because real materials are well represented by infinite chains. Using the local gauge symmetry of this model, we are able to map onto a simple spin-1 like Ising and spin-1/2 Heisenberg dimer model with single effective ion anisotropy. Thereafter this model can be solved using the decoration transformation and transfer matrix approach. First, we discuss the phase diagram at zero temperature of this model, where we find five ground states, one ferromagnetic, one antiferromagnetic, one triplet–triplet disordered and one triplet–singlet disordered phase, beside a dimer ferromagnetic–antiferromagnetic phase. In addition, we discuss the thermodynamic properties such as entropy, where we display the residual entropy. Furthermore, using the nearest site correlation function it is possible also to analyze the pairwise thermal entanglement for both orthogonal dimers. Additionally, we discuss the threshold temperature of the entangled region as a function of Hamiltonian parameters. We find a quite interesting thin reentrance threshold temperature for one of the dimers, and we also discuss the differences and similarities for both dimers. (paper)

Synthesis and Diels–Alder cycloaddition reaction of norbornadiene and benzonorbornadiene dimers

Directory of Open Access Journals (Sweden)

Bilal Nişancı

2009-08-01

Full Text Available Dimeric forms of norbornadiene and benzonorbornadiene were synthesized starting with known monobromide derivatives. The Diels–Alder cycloaddition reaction of dimers with TCNE and PTAD was investigated and new norbornenoid polycyclics were obtained. All compounds were characterized properly using NMR spectroscopy.

Theoretical Insights into a CO Dimerization Mechanism in CO2 Electroreduction.

Science.gov (United States)

Montoya, Joseph H; Shi, Chuan; Chan, Karen; Nørskov, Jens K

2015-06-04

In this work, we present DFT simulations that demonstrate the ability of Cu to catalyze CO dimerization in CO2 and CO electroreduction. We describe a previously unreported CO dimer configuration that is uniquely stabilized by a charged water layer on both Cu(111) and Cu(100). Without this charged water layer at the metal surface, the formation of the CO dimer is prohibitively endergonic. Our calculations also demonstrate that dimerization should have a lower activation barrier on Cu(100) than Cu(111), which, along with a more exergonic adsorption energy and a corresponding higher coverage of *CO, is consistent with experimental observations that Cu(100) has a high activity for C-C coupling at low overpotentials. We also demonstrate that this effect is present with cations other than H(+), a finding that is consistent with the experimentally observed pH independence of C2 formation on Cu.

Conformational study of the protegrin-1 (PG-1 dimer interaction with lipid bilayers and its effect

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Nussinov Ruth

2007-04-01

Full Text Available Abstract Background Protegrin-1 (PG-1 is known as a potent antibiotic peptide; it prevents infection via an attack on the membrane surface of invading microorganisms. In the membrane, the peptide forms a pore/channel through oligomerization of multiple subunits. Recent experimental and computational studies have increasingly unraveled the molecular-level mechanisms underlying the interactions of the PG-1 β-sheet motifs with the membrane. The PG-1 dimer is important for the formation of oligomers, ordered aggregates, and for membrane damaging effects. Yet, experimentally, different dimeric behavior has been observed depending on the environment: antiparallel in the micelle environment, and parallel in the POPC bilayer. The experimental structure of the PG-1 dimer is currently unavailable. Results Although the β-sheet structures of the PG-1 dimer are less stable in the bulk water environment, the dimer interface is retained by two intermolecular hydrogen bonds. The formation of the dimer in the water environment implies that the pathway of the dimer invasion into the membrane can originate from the bulk region. In the initial contact with the membrane, both the antiparallel and parallel β-sheet conformations of the PG-1 dimer are well preserved at the amphipathic interface of the lipid bilayer. These β-sheet structures illustrate the conformations of PG-1 dimer in the early stage of the membrane attack. Here we observed that the activity of PG-1 β-sheets on the bilayer surface is strongly correlated with the dimer conformation. Our long-term goal is to provide a detailed mechanism of the membrane-disrupting effects by PG-1 β-sheets which are able to attack the membrane and eventually assemble into the ordered aggregates. Conclusion In order to understand the dimeric effects leading to membrane damage, extensive molecular dynamics (MD simulations were performed for the β-sheets of the PG-1 dimer in explicit water, salt, and lipid bilayers

How different is the borazine-acetylene dimer from the benzene-acetylene dimer? A matrix isolation infrared and ab initio quantum chemical study

Science.gov (United States)

Verma, Kanupriya; Viswanathan, K. S.; Majumder, Moumita; Sathyamurthy, N.

2017-11-01

The 1:1 dimer of borazine-acetylene has been studied for the first time, both experimentally and computationally. The borazine-acetylene dimer was trapped in Ar and N2 matrices, and studied using infrared spectroscopy. Our experiments clearly revealed two isomers of the borazine-acetylene complex, one in which the N-H of borazine interacted with the carbon of acetylene, and another in which the C-H of acetylene formed a hydrogen bond with a nitrogen atom of borazine. The formation of both isomers in the matrix was evidenced by shifts in the vibrational frequencies of the appropriate modes. Reassuringly, the experimental observations were corroborated by our computations using the second-order Møller-Plesset perturbation theoretic method and coupled-cluster singles, doubles and perturbative triples method in conjunction with different Dunning basis sets, which indicated both these isomers to be stable minima, with the N-HṡṡṡC complex being the global minimum. Atoms-in-molecules and energy decomposition analysis were also carried out for the different isomers of the dimer. These studies reveal that replacing the three C-C linkages in benzene with three B-N linkages in borazine modifies the interaction in the dimer sufficiently, to result in a different potential energy landscape for the borazine-acetylene system when compared with the benzene-acetylene system.

Alignment and Imaging of the CS2 Dimer Inside Helium Nanodroplets

Science.gov (United States)

Pickering, James D.; Shepperson, Benjamin; Hübschmann, Bjarke A. K.; Thorning, Frederik; Stapelfeldt, Henrik

2018-03-01

The carbon disulphide (CS2) dimer is formed inside He nanodroplets and identified using fs laser-induced Coulomb explosion, by observing the CS2+ ion recoil velocity. It is then shown that a 160 ps moderately intense laser pulse can align the dimer in advantageous spatial orientations which allow us to determine the cross-shaped structure of the dimer by analysis of the correlations between the emission angles of the nascent CS2+ and S+ ions, following the explosion process. Our method will enable fs time-resolved structural imaging of weakly bound molecular complexes during conformational isomerization, including formation of exciplexes.

Breaking symmetry in the structure determination of (large) symmetric protein dimers

Energy Technology Data Exchange (ETDEWEB)

Gaponenko, Vadim; Altieri, Amanda S.; Li, Jess; Byrd, R. Andrew [National Cancer Institute, Structural Biophysics Laboratory (United States)], E-mail: rabyrd@ncifcrf.gov

2002-10-15

We demonstrate a novel methodology to disrupt the symmetry in the NMR spectra of homodimers. A paramagnetic probe is introduced sub-stoichiometrically to create an asymmetric system with the paramagnetic probe residing on only one monomer within the dimer. This creates sufficient magnetic anisotropy for resolution of symmetry-related overlapped resonances and, consequently, detection of pseudocontact shifts and residual dipolar couplings specific to each monomeric component. These pseudocontact shifts can be readily incorporated into existing structure refinement calculations and enable determination of monomer orientation within the dimeric protein. This methodology can be widely used for solution structure determination of symmetric dimers.

Substrate-Induced Dimerization of Engineered Monomeric Variants of Triosephosphate Isomerase from Trichomonas vaginalis.

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Samuel Lara-Gonzalez

Full Text Available The dimeric nature of triosephosphate isomerases (TIMs is maintained by an extensive surface area interface of more than 1600 Å2. TIMs from Trichomonas vaginalis (TvTIM are held in their dimeric state by two mechanisms: a ball and socket interaction of residue 45 of one subunit that fits into the hydrophobic pocket of the complementary subunit and by swapping of loop 3 between subunits. TvTIMs differ from other TIMs in their unfolding energetics. In TvTIMs the energy necessary to unfold a monomer is greater than the energy necessary to dissociate the dimer. Herein we found that the character of residue I45 controls the dimer-monomer equilibrium in TvTIMs. Unfolding experiments employing monomeric and dimeric mutants led us to conclude that dimeric TvTIMs unfold following a four state model denaturation process whereas monomeric TvTIMs follow a three state model. In contrast to other monomeric TIMs, monomeric variants of TvTIM1 are stable and unexpectedly one of them (I45A is only 29-fold less active than wild-type TvTIM1. The high enzymatic activity of monomeric TvTIMs contrast with the marginal catalytic activity of diverse monomeric TIMs variants. The stability of the monomeric variants of TvTIM1 and the use of cross-linking and analytical ultracentrifugation experiments permit us to understand the differences between the catalytic activities of TvTIMs and other marginally active monomeric TIMs. As TvTIMs do not unfold upon dimer dissociation, herein we found that the high enzymatic activity of monomeric TvTIM variants is explained by the formation of catalytic dimeric competent species assisted by substrate binding.

Study of structural stability and damaging effect on membrane for four Aβ42 dimers.

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Wei Feng

Full Text Available Increasing evidence shows that Aβ oligomers are key pathogenic molecules in Alzheimer's disease. Among Aβ oligomers, dimer is the smallest aggregate and toxic unit. Therefore, understanding its structural and dynamic properties is quite useful to prevent the formation and toxicity of the Aβ oligomers. In this study, we performed molecular dynamic simulations on four Aβ42 dimers, 2NCb, CNNC, NCNC and NCCN, within the hydrated DPPC membrane. Four Aβ42 dimers differ in the arrangements of two Aβ42 peptides. This study aims to investigate the impact of aggregation pattern of two Aβ peptides on the structural stability of the Aβ42 dimer and its disruption to the biological membrane. The MD results demonstrate that the NCCN, CNNC and NCNC have the larger structural fluctuation at the N-terminus of Aβ42 peptide, where the β-strand structure converts into the coil structure. The loss of the N-terminal β-strand further impairs the aggregate ability of Aβ42 dimer. In addition, inserting Aβ42 dimer into the membrane can considerably decrease the average APL of DPPC membrane. Moreover this decrease effect is largely dependent on the distance to the location of Aβ42 dimer and its secondary structure forms. Based on the results, the 2NCb is considered as a stable dimeric unit for aggregating the larger Aβ42 oligomer, and has a potent ability to disrupt the membrane.

Alkane dimers interaction

DEFF Research Database (Denmark)

Ferrighi, Lara; Madsen, Georg Kent Hellerup; Hammer, Bjørk

2010-01-01

The interaction energies of a series of n-alkane dimers, from methane to decane, have been investigated with Density Functional Theory (DFT), using the MGGA-M06-L density functional. The results are compared both to the available wavefunction-based values as well as to dispersion corrected DFT...... values. The MGGA-M06-L density functional is a semi-local functional designed and has proven to provide accurate estimates of dispersion interactions for several systems at moderate computational cost. In the present application, it reproduces the trends obtained by the more expensive wavefunction...

Using dimers to measure biosignatures and atmospheric pressure for terrestrial exoplanets.

Science.gov (United States)

Misra, Amit; Meadows, Victoria; Claire, Mark; Crisp, Dave

2014-02-01

We present a new method to probe atmospheric pressure on Earth-like planets using (O2-O2) dimers in the near-infrared. We also show that dimer features could be the most readily detectable biosignatures for Earth-like atmospheres and may even be detectable in transit transmission with the James Webb Space Telescope (JWST). The absorption by dimers changes more rapidly with pressure and density than that of monomers and can therefore provide additional information about atmospheric pressures. By comparing the absorption strengths of rotational and vibrational features to the absorption strengths of dimer features, we show that in some cases it may be possible to estimate the pressure at the reflecting surface of a planet. This method is demonstrated by using the O2 A band and the 1.06 μm dimer feature, either in transmission or reflected spectra. It works best for planets around M dwarfs with atmospheric pressures between 0.1 and 10 bar and for O2 volume mixing ratios above 50% of Earth's present-day level. Furthermore, unlike observations of Rayleigh scattering, this method can be used at wavelengths longer than 0.6 μm and is therefore potentially applicable, although challenging, to near-term planet characterization missions such as JWST. We also performed detectability studies for JWST transit transmission spectroscopy and found that the 1.06 and 1.27 μm dimer features could be detectable (SNR>3) for an Earth analogue orbiting an M5V star at a distance of 5 pc. The detection of these features could provide a constraint on the atmospheric pressure of an exoplanet and serve as biosignatures for oxygenic photosynthesis. We calculated the required signal-to-noise ratios to detect and characterize O2 monomer and dimer features in direct imaging-reflected spectra and found that signal-to-noise ratios greater than 10 at a spectral resolving power of R=100 would be required.

Engineering of a novel Ca2+-regulated kinesin molecular motor using a calmodulin dimer linker

International Nuclear Information System (INIS)

Shishido, Hideki; Maruta, Shinsaku

2012-01-01

Highlights: ► Engineered kinesin–M13 and calmodulin involving single cysteine were prepared. ► CaM mutant was cross-linked to dimer by bifunctional thiol reactive reagent. ► Kinesin–M13 was dimerized via CaM dimer in the presence of calcium. ► Function of the engineered kinesin was regulated by a Ca 2+ -calmodulin dimer linker. -- Abstract: The kinesin–microtubule system holds great promise as a molecular shuttle device within biochips. However, one current barrier is that such shuttles do not have “on–off” control of their movement. Here we report the development of a novel molecular motor powered by an accelerator and brake system, using a kinesin monomer and a calmodulin (CaM) dimer. The kinesin monomer, K355, was fused with a CaM target peptide (M13 peptide) at the C-terminal part of the neck region (K355–M13). We also prepared CaM dimers using CaM mutants (Q3C), (R86C), or (A147C) and crosslinkers that react with cysteine residues. Following induction of K355–M13 dimerization with CaM dimers, we measured K355–M13 motility and found that it can be reversibly regulated in a Ca 2+ -dependent manner. We also found that velocities of K355–M13 varied depending on the type and crosslink position of the CaM dimer used; crosslink length also had a moderate effect on motility. These results suggest Ca 2+ -dependent dimerization of K355–M13 could be used as a novel molecular shuttle, equipped with an accelerator and brake system, for biochip applications.

Morphological and physiological retinal degeneration induced by intravenous delivery of vitamin A dimers in rabbits

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Jackie Penn

2015-02-01

Full Text Available The eye uses vitamin A as a cofactor to sense light and, during this process, some vitamin A molecules dimerize, forming vitamin A dimers. A striking chemical signature of retinas undergoing degeneration in major eye diseases such as age-related macular degeneration (AMD and Stargardt disease is the accumulation of these dimers in the retinal pigment epithelium (RPE and Bruch’s membrane (BM. However, it is not known whether dimers of vitamin A are secondary symptoms or primary insults that drive degeneration. Here, we present a chromatography-free method to prepare gram quantities of the vitamin A dimer, A2E, and show that intravenous administration of A2E to the rabbit results in retinal degeneration. A2E-damaged photoreceptors and RPE cells triggered inflammation, induced remolding of the choroidal vasculature and triggered a decline in the retina’s response to light. Data suggest that vitamin A dimers are not bystanders, but can be primary drivers of retinal degeneration. Thus, preventing dimer formation could be a preemptive strategy to address serious forms of blindness.

Dimerization inhibits the activity of receptor-like protein-tyrosine phosphatase-alpha

DEFF Research Database (Denmark)

Jiang, G; den Hertog, J; Su, J

1999-01-01

that dimerization can negatively regulate activity, through the interaction of an inhibitory 'wedge' on one monomer with the catalytic cleft of domain 1 in the other monomer. Here we show that dimerization inhibits the activity of a full-length RPTP in vivo. We generated stable disulphide-bonded full...

Detectability of H2-Ar and H2-Ne Dimers in Jovian Atmospheres

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Young-Key Minn

1997-12-01

Full Text Available The detection of jovian hydrogen-hydrogen dimers through the clear telluric 2-micron window(Kim et al. 1995, Trafton et al. 1997 suggests possibility to detect noble gases in the form of dimer with hydrogen in jovian atmospheres. Since noble gases do not have spectral structures in the infrared, it has been difficult to derive their abundances in the atmospheres of jovian planets. If there is a significant component of noble gases other than helium in the jovian atmospheres. it might be detected through its dimer spectrum with hydrogen molecule. The relatively sharp spectral structures of hydrogen-argon and hydrogen-neon dimers compared with those of hydrogen-hydrogen dimers are useful for the detection, if an adequate signal-to-noise (S/N is obtained. If we use a large telescope, such as the Keck telescope, with a long exposure time (>24 hours, then H2-Ar spectral structure may be detected.

Anion Photoelectron Spectroscopy of the Homogenous 2-Hydroxypyridine Dimer Electron Induced Proton Transfer System

Science.gov (United States)

Vlk, Alexandra; Stokes, Sarah; Wang, Yi; Hicks, Zachary; Zhang, Xinxing; Blando, Nicolas; Frock, Andrew; Marquez, Sara; Bowen, Kit; Bowen Lab JHU Team

Anion photoelectron spectroscopic (PES) and density functional theory (DFT) studies on the dimer anion of (2-hydroxypyridine)2-are reported. The experimentally measured vertical detachment energy (VDE) of 1.21eV compares well with the theoretically predicted values. The 2-hydroxypyridine anionic dimer system was investigated because of its resemblance to the nitrogenous heterocyclic pyrimidine nucleobases. Experimental and theoretical results show electron induced proton transfer (EIPT) in both the lactim and lactam homogeneous dimers. Upon electron attachment, the anion can serve as the intermediate between the two neutral dimers. A possible double proton transfer process can occur from the neutral (2-hydroxypyridine)2 to (2-pyridone)2 through the dimer anion. This potentially suggests an electron catalyzed double proton transfer mechanism of tautomerization. Research supported by the NSF Grant No. CHE-1360692.

Solution-dispersible Au nanocube dimers with greatly enhanced two-photon luminescence and SERS

Science.gov (United States)

Liu, Xiao-Li; Liang, Shan; Nan, Fan; Yang, Zhong-Jian; Yu, Xue-Feng; Zhou, Li; Hao, Zhong-Hua; Wang, Qu-Quan

2013-05-01

We report the synthesis of 43-nm diameter Au nanocube dimers by using Ag+ ions as competitive ligands to freeze l-cysteine-induced assembly process of the nanocubes to a desirable stage. Ascribed to the resonant interparticle coupling with an newly arising plasmon band at 710 nm and local field enhancement, the two-photon luminescence intensity of the Au nanocube dimers in solution was over 20 times stronger than that of the monomers in the wavelength range 555-620 nm. Furthermore, by coupling Raman tags onto the nanocube surface, a solution-based surface-enhanced Raman scattering (SERS) of the nanocube dimers had an enhancement factor of over 10 times compared to the isolated nanocubes. To sum up, with high stability in solution and attractive optical properties, the Au nanocube dimers have potential applications in in vivo bio-imaging and solution-based SERS.We report the synthesis of 43-nm diameter Au nanocube dimers by using Ag+ ions as competitive ligands to freeze l-cysteine-induced assembly process of the nanocubes to a desirable stage. Ascribed to the resonant interparticle coupling with an newly arising plasmon band at 710 nm and local field enhancement, the two-photon luminescence intensity of the Au nanocube dimers in solution was over 20 times stronger than that of the monomers in the wavelength range 555-620 nm. Furthermore, by coupling Raman tags onto the nanocube surface, a solution-based surface-enhanced Raman scattering (SERS) of the nanocube dimers had an enhancement factor of over 10 times compared to the isolated nanocubes. To sum up, with high stability in solution and attractive optical properties, the Au nanocube dimers have potential applications in in vivo bio-imaging and solution-based SERS. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr01170d

Synthesis and Dimerization Behavior of Five Metallophthalocyanines in Different Solvents

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Zhenhua Cheng

2014-01-01

Full Text Available Metallophthalocyanine (MPc has become one of the metal organic compounds with the largest production and the most widely application, because of its excellent performance in catalytic oxidation. However, aggregation of the MPc in solution, resulting in decreased solubility, greatly limits the performance of application. Studying the behavior of dimerization of MPcs can provide a theoretical basis for solving the problem of the low solubility. So five metallophthalocyanines (FePc, CoPc, NiPc, CuPc, and ZnPc were prepared with improved method and characterized. Dimerization of the five MPcs was measured by UV-Vis spectroscopy separately in N,N-dimethyl formamide (DMF and dimethylsulfoxide (DMSO. The red-shift of maximum absorption wavelength and deviations from Lambert-Beer law with increasing the concentration were observed for all the five MPcs. The dimerization equilibrium constants (K of the five MPcs in DMF were arranged in order of CoPc > ZnPc > CuPc > FePc > NiPc, while in DMSO they were arranged in order of ZnPc > CoPc > FePc > CuPc > NiPc. The type of the central metal and nature of the solvent affect the dimerization of the MPcs.

Fe65-PTB2 Dimerization Mimics Fe65-APP Interaction

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Lukas P. Feilen

2017-05-01

Full Text Available Physiological function and pathology of the Alzheimer’s disease causing amyloid precursor protein (APP are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs. The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD including the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2 opens an intra-molecular interaction causing a structural change and altering Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a homodimer in solution and determine its crystal structure at 2.6 Å resolution. Dimerization involves the unwinding of a C-terminal α-helix that mimics binding of the AICD internalization sequence, thus shielding the hydrophobic binding pocket. Specific dimer formation is validated by nuclear magnetic resonance (NMR techniques and cell-based analyses reveal that Fe65-PTB2 together with the WW domain are necessary and sufficient for dimerization. Together, our data demonstrate that Fe65 dimerizes via its APP interaction site, suggesting that besides intra- also intermolecular interactions between Fe65 molecules contribute to homeostatic regulation of APP mediated signaling.

Fe65-PTB2 Dimerization Mimics Fe65-APP Interaction.

Science.gov (United States)

Feilen, Lukas P; Haubrich, Kevin; Strecker, Paul; Probst, Sabine; Eggert, Simone; Stier, Gunter; Sinning, Irmgard; Konietzko, Uwe; Kins, Stefan; Simon, Bernd; Wild, Klemens

2017-01-01

Physiological function and pathology of the Alzheimer's disease causing amyloid precursor protein (APP) are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs). The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD) including the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2 opens an intra-molecular interaction causing a structural change and altering Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a homodimer in solution and determine its crystal structure at 2.6 Å resolution. Dimerization involves the unwinding of a C-terminal α-helix that mimics binding of the AICD internalization sequence, thus shielding the hydrophobic binding pocket. Specific dimer formation is validated by nuclear magnetic resonance (NMR) techniques and cell-based analyses reveal that Fe65-PTB2 together with the WW domain are necessary and sufficient for dimerization. Together, our data demonstrate that Fe65 dimerizes via its APP interaction site, suggesting that besides intra- also intermolecular interactions between Fe65 molecules contribute to homeostatic regulation of APP mediated signaling.

FAK dimerization controls its kinase-dependent functions at focal adhesions

KAUST Repository

Brami-Cherrier, Karen; Gervasi, Nicolas; Arsenieva, Diana A.; Walkiewicz, Katarzyna; Boutterin, Marie Claude; Ortega, Á lvaro Darí o; Leonard, Paul G.; Seantier, Bastien; Gasmi, Laï la; Bouceba, Tahar; Kadaré , Gress; Girault -, Jean Antoine; Arold, Stefan T.

2014-01-01

Focal adhesion kinase (FAK) controls adhesion-dependent cell motility, survival, and proliferation. FAK has kinase-dependent and kinase-independent functions, both of which play major roles in embryogenesis and tumor invasiveness. The precise mechanisms of FAK activation are not known. Using x-ray crystallography, small angle x-ray scattering, and biochemical and functional analyses, we show that the key step for activation of FAK's kinase-dependent functions-autophosphorylation of tyrosine-397-requires site-specific dimerization of FAK. The dimers form via the association of the N-terminal FERM domain of FAK and are stabilized by an interaction between FERM and the C-terminal FAT domain. FAT binds to a basic motif on FERM that regulates co-activation and nuclear localization. FAK dimerization requires local enrichment, which occurs specifically at focal adhesions. Paxillin plays a dual role, by recruiting FAK to focal adhesions and by reinforcing the FAT:FERM interaction. Our results provide a structural and mechanistic framework to explain how FAK combines multiple stimuli into a site-specific function. The dimer interfaces we describe are promising targets for blocking FAK activation. © 2014 The Authors.

Tautomerization and Dimerization of 6,13-Disubstituted Derivatives of Pentacene.

Science.gov (United States)

Garcia-Borràs, Marc; Konishi, Akihito; Waterloo, Andreas; Liang, Yong; Cao, Yang; Hetzer, Constantin; Lehnherr, Dan; Hampel, Frank; Houk, Kendall N; Tykwinski, Rik R

2017-05-02

Two new 6,13-disubstituted pentacene derivatives, 1 c and 1 d, with alkyl and triisopropylsilylethynyl substitution have been synthesized and characterized experimentally and computationally. The alkyl substituted 1 c and 1 d represent the first 6-alkyl-substituted pentacene derivative where the fully aromatic species dominates over the corresponding tautomer. Indeed, no tautomerization product is found for either 1 c or 1 d upon heating or in the presence of catalytic amounts of acid. On the other hand, an unexpected dimer (3 c) is formed from 1 c. A plausible mechanism for this new dimerization process of the 6-methyl-substituted pentacene derivative 1 c is proposed, which involves first a bimolecular hydrogen atom transfer followed by an intramolecular [4+2] Diels-Alder cycloaddition. In the case of 6-butyl substitution, neither tautomerization nor dimerization is observed. Computations support the proposed 1 c dehydrodimerization pathway, explain why 1 d does not dimerize, and show the importance of the nature of the group at C-13 in controlling the relative stability of 6-alkyl-substituted pentacene tautomers. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

FAK dimerization controls its kinase-dependent functions at focal adhesions

KAUST Repository

Brami-Cherrier, Karen

2014-01-30

Focal adhesion kinase (FAK) controls adhesion-dependent cell motility, survival, and proliferation. FAK has kinase-dependent and kinase-independent functions, both of which play major roles in embryogenesis and tumor invasiveness. The precise mechanisms of FAK activation are not known. Using x-ray crystallography, small angle x-ray scattering, and biochemical and functional analyses, we show that the key step for activation of FAK\\'s kinase-dependent functions-autophosphorylation of tyrosine-397-requires site-specific dimerization of FAK. The dimers form via the association of the N-terminal FERM domain of FAK and are stabilized by an interaction between FERM and the C-terminal FAT domain. FAT binds to a basic motif on FERM that regulates co-activation and nuclear localization. FAK dimerization requires local enrichment, which occurs specifically at focal adhesions. Paxillin plays a dual role, by recruiting FAK to focal adhesions and by reinforcing the FAT:FERM interaction. Our results provide a structural and mechanistic framework to explain how FAK combines multiple stimuli into a site-specific function. The dimer interfaces we describe are promising targets for blocking FAK activation. © 2014 The Authors.

Controlled Patterning of Plasmonic Dimers by Using an Ultrathin Nanoporous Alumina Membrane as a Shadow Mask.

Science.gov (United States)

Hao, Qi; Huang, Hao; Fan, Xingce; Yin, Yin; Wang, Jiawei; Li, Wan; Qiu, Teng; Ma, Libo; Chu, Paul K; Schmidt, Oliver G

2017-10-18

We report on design and fabrication of patterned plasmonic dimer arrays by using an ultrathin anodic aluminum oxide (AAO) membrane as a shadow mask. This strategy allows for controllable fabrication of plasmonic dimers where the location, size, and orientation of each particle in the dimer pairs can be independently tuned. Particularly, plasmonic dimers with ultrasmall nanogaps down to the sub-10 nm scale as well as a large dimer density up to 1.0 × 10 10 cm -2 are fabricated over a centimeter-sized area. The plasmonic dimers exhibit significant surface-enhanced Raman scattering (SERS) enhancement with a polarization-dependent behavior, which is well interpreted by finite-difference time-domain (FDTD) simulations. Our results reveal a facile approach for controllable fabrication of large-area dimer arrays, which is of fundamental interest for plasmon-based applications in surface-enhanced spectroscopy, biochemical sensing, and optoelectronics.

Plasma D-dimer concentration in patients with systemic sclerosis

Directory of Open Access Journals (Sweden)

Montagnana Martina

2006-01-01

Full Text Available Abstract Background Systemic sclerosis (SSc is an autoimmune disorder of the connective tissue characterized by widespread vascular lesions and fibrosis. Little is known so far on the activation of the hemostatic and fibrinolytic systems in SSc, and most preliminary evidences are discordant. Methods To verify whether SSc patients might display a prothrombotic condition, plasma D-dimer was assessed in 28 consecutive SSc patients and in 33 control subjects, matched for age, sex and environmental habit. Results and discussion When compared to healthy controls, geometric mean and 95% confidence interval (IC95% of plasma D-dimer were significantly increased in SSc patients (362 ng/mL, IC 95%: 361–363 ng/mL vs 229 ng/mL, IC95%: 228–231 ng/mL, p = 0.005. After stratifying SSc patients according to disease subset, no significant differences were observed between those with limited cutaneous pattern and controls, whereas patients with diffuse cutaneous pattern displayed substantially increased values. No correlation was found between plasma D-dimer concentration and age, sex, autoantibody pattern, serum creatinine, erythrosedimentation rate, nailfold videocapillaroscopic pattern and pulmonary involvement. Conclusion We demonstrated that SSc patients with diffuse subset are characterized by increased plasma D-dimer values, reflecting a potential activation of both the hemostatic and fibrinolytic cascades, which might finally predispose these patients to thrombotic complications.

The steady-state and time-resolved photophysical properties of a dimeric indium phthalocyanine complex

International Nuclear Information System (INIS)

Chen Yu; Araki, Yasuyuki; Dini, Danilo; Liu Ying; Ito, Osamu; Fujitsuka, Mamoru

2006-01-01

The steady-state and time-resolved photophysical properties and some molecular orbital calculation results of a dimeric indium phthalocyanine complex with an indium-indium bond, i.e., [tBu 4 PcIn] 2 .2tmed, have been described. The results regarding triplet excited state lifetimes can be ascribed to strong intramolecular interactions existing only in the excited state of this dimer because no significant difference in the absorption spectra of the tBu 4 PcInCl monomer and the [tBu 4 PcIn] 2 .2tmed dimer is observed, suggesting that no ground-state interaction can be assessed. The deactivation processes of the excited singlet state of [tBu 4 PcIn] 2 .2tmed are apparently faster than that of μ-oxo-bridged PcIn dimer [tBu 4 PcIn] 2 O. Molecular orbital calculation on the PcIn dimer shows no node between two indium atoms was found in the HOMO - 2 of the PcIn-InPc dimer, suggesting that bonding electrons distribute between two indium atoms

Quantitation of pyrimidine dimers in DNA from UVB-irradiated alfalfa (Medicago sativa L.) seedlings

International Nuclear Information System (INIS)

Quaite, F.E.; Sutherland, B.M.; Sutherland, J.C.

1991-01-01

Depletion of stratospheric ozone will increase the solar ultraviolet radiation in the range from 290-320 nm (UVB) that reaches the surface of the earth, placing an increased UV burden on exposed organisms. One consequence of increased UVB may be decreased productivity of crop plants. A principal lesion caused by UV in DNA is the cyclobutyl pyrimidine dimer. We have adapted a method for measuring these dimers in nanogram quantities of non-radioactive DNA for use in UV-irradiated plants. We find that biologically relevant doses of broad band UVB radiation induce easily detectable frequencies of pyrimidine dimers in the DNA of irradiated alfalfa sprout leaves and that the dose response for dimer formation is linear up to doses of at least 690 J/m 2 . We also find easily measurable frequencies of dimers in the leaves of seedlings grown in glass filtered sunlight but not exposed to additional UVB, suggesting that significant number of dimers are formed in plants exposed to normal sunlight. 27 refs., 3 figs., 1 tab

Complete Structure of an Epithelial Keratin Dimer: Implications for Intermediate Filament Assembly.

Directory of Open Access Journals (Sweden)

David J Bray

Full Text Available Keratins are cytoskeletal proteins that hierarchically arrange into filaments, starting with the dimer sub-unit. They are integral to the structural support of cells, in skin, hair and nails. In skin, keratin is thought to play a critical role in conferring the barrier properties and elasticity of skin. In general, the keratin dimer is broadly described by a tri-domain structure: a head, a central rod and a tail. As yet, no atomistic-scale picture of the entire dimer structure exists; this information is pivotal for establishing molecular-level connections between structure and function in intermediate filament proteins. The roles of the head and tail domains in facilitating keratin filament assembly and function remain as open questions. To address these, we report results of molecular dynamics simulations of the entire epithelial human K1/K10 keratin dimer. Our findings comprise: (1 the first three-dimensional structural models of the complete dimer unit, comprising of the head, rod and tail domains; (2 new insights into the chirality of the rod-domain twist gained from analysis of the full domain structure; (3 evidence for tri-subdomain partitioning in the head and tail domains; and, (4 identification of the residue characteristics that mediate non-covalent contact between the chains in the dimer. Our findings are immediately applicable to other epithelial keratins, such as K8/K18 and K5/K14, and to intermediate filament proteins in general.

Zak phase and band inversion in dimerized one-dimensional locally resonant metamaterials

Science.gov (United States)

Zhu, Weiwei; Ding, Ya-qiong; Ren, Jie; Sun, Yong; Li, Yunhui; Jiang, Haitao; Chen, Hong

2018-05-01

The Zak phase, which refers to Berry's phase picked up by a particle moving across the Brillouin zone, characterizes the topological properties of Bloch bands in a one-dimensional periodic system. Here the Zak phase in dimerized one-dimensional locally resonant metamaterials is investigated. It is found that there are some singular points in the bulk band across which the Bloch states contribute π to the Zak phase, whereas in the rest of the band the contribution is nearly zero. These singular points associated with zero reflection are caused by two different mechanisms: the dimerization-independent antiresonance of each branch and the dimerization-dependent destructive interference in multiple backscattering. The structure undergoes a topological phase-transition point in the band structure where the band inverts, and the Zak phase, which is determined by the numbers of singular points in the bulk band, changes following a shift in dimerization parameter. Finally, the interface state between two dimerized metamaterial structures with different topological properties in the first band gap is demonstrated experimentally. The quasi-one-dimensional configuration of the system allows one to explore topology-inspired new methods and applications on the subwavelength scale.

Modulation of BCR Signaling by the Induced Dimerization of Receptor-Associated SYK

Directory of Open Access Journals (Sweden)

Mark L. Westbroek

2017-12-01

Full Text Available Clustering of the B cell antigen receptor (BCR by polyvalent antigens is transmitted through the SYK tyrosine kinase to the activation of multiple intracellular pathways that determine the physiological consequences of receptor engagement. To explore factors that modulate the quantity and quality of signals sent by the crosslinked BCR, we developed a novel chemical mediator of dimerization to induce clustering of receptor-associated SYK. To accomplish this, we fused SYK with E. coli dihydrofolate reductase (eDHFR, which binds the small molecule trimethoprim (TMP with high affinity and selectivity and synthesized a dimer of TMP with a flexible linker. The TMP dimer is able to induce the aggregation of eDHFR-linked SYK in live cells. The induced dimerization of SYK bound to the BCR differentially regulates the activation of downstream transcription factors, promoting the activation of Nuclear Factor of Activated T cells (NFAT without affecting the activation of NFκB. The dimerization of SYK enhances the duration but not the amplitude of calcium mobilization by enhancing the extent and duration of its interaction with the crosslinked BCR at the plasma membrane.

Lifecourse social position and D-dimer; findings from the 1958 British birth cohort.

Science.gov (United States)

Tabassum, Faiza; Kumari, Meena; Rumley, Ann; Power, Chris; Strachan, David P; Lowe, Gordon

2014-01-01

The aim is to examine the association of lifecourse socioeconomic position (SEP) on circulating levels of D-dimer. Data from the 1958 British birth cohort were used, social class was determined at three stages of respondents' life: at birth, at 23 and at 42 years. A cumulative indicator score of SEP (CIS) was calculated ranging from 0 (always in the highest social class) to 9 (always in the lowest social class). In men and women, associations were observed between CIS and D-dimer (P<0.05). Thus, the respondents in more disadvantaged social classes had elevated levels of D-dimer compared to respondents in less disadvantaged social class. In multivariate analyses, the association of disadvantaged social position with D-dimer was largely explained by fibrinogen, C-reactive protein and von Willebrand Factor in women, and additionally by smoking, alcohol consumption and physical activity in men. Socioeconomic circumstances across the lifecourse at various stages also contribute independently to raised levels of D-dimer in middle age in women only. Risk exposure related to SEP accumulates across life and contributes to raised levels of D-dimer. The association of haemostatic markers and social differences in health may be mediated by inflammatory and other markers.

Nicotinamidase/pyrazinamidase of Mycobacterium tuberculosis forms homo-dimers stabilized by disulfide bonds.

Science.gov (United States)

Rueda, Daniel; Sheen, Patricia; Gilman, Robert H; Bueno, Carlos; Santos, Marco; Pando-Robles, Victoria; Batista, Cesar V; Zimic, Mirko

2014-12-01

Recombinant wild-pyrazinamidase from H37Rv Mycobacterium tuberculosis was analyzed by gel electrophoresis under differential reducing conditions to evaluate its quaternary structure. PZAse was fractionated by size exclusion chromatography under non-reducing conditions. PZAse activity was measured and mass spectrometry analysis was performed to determine the identity of proteins by de novo sequencing and to determine the presence of disulfide bonds. This study confirmed that M. tuberculosis wild type PZAse was able to form homo-dimers in vitro. Homo-dimers showed a slightly lower specific PZAse activity compared to monomeric PZAse. PZAse dimers were dissociated into monomers in response to reducing conditions. Mass spectrometry analysis confirmed the existence of disulfide bonds (C72-C138 and C138-C138) stabilizing the quaternary structure of the PZAse homo-dimer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dimer-flipping-assisted diffusion on a Si(001) surface

International Nuclear Information System (INIS)

Zi, J.; Min, B. J.; Lu, Y.; Wang, C. Z.; Ho, K. M.

2000-01-01

The binding sites and diffusion pathways of Si adatoms on a c(4x2) reconstructed Si(001) surface are investigated by a tight-binding method with an environment-dependent silicon potential in conjunction with ab initio calculations using the Car--Parrinello method. A new diffusion pathway along the trough edge driven by dimer flipping is found with a barrier of 0.74 eV, comparable to that of 0.68 eV along the top of the dimer rows

Solid-phase synthesis of 2{sup '}-O-methoxyethyl oligonucleotides using dimeric phosphoramidate blocks

Energy Technology Data Exchange (ETDEWEB)

Yu, Gi Weon; Kang, Yong Han [Dept. of Applied Chemistry, Hanyang University, Ansan (Korea, Republic of)

2016-11-15

This research focused on the method of using dimeric phosphoramidite blocks to synthesize oligonucleotides for development as oligonucleotide drugs. A 16-mer oligonucleotide with the randomly selected sequence of C*C*T*C*G*C *T*C*T*C*G*C*C* C*G*C was synthesized using CC, GC, and TC dimers, a combination of monomers and dimers, or only monomers as building blocks. Using dimer blocks in this synthetic method provided a significant decrease in critical impurities that had similar properties to the main product, which was confirmed by LC-MS and HPLC analysis.

Analysis of the dimerized Sb/Si(001)-(2x1) surface by x-ray standing waves

International Nuclear Information System (INIS)

Lyman, P.F.; Qian, Y.; Bedzyk, M.J.

1994-12-01

X-ray standing wave measurements were undertaken to study the bonding position of Sb adatoms on the Sb-saturated Si(001)-(2x1) surface. Using the (004) and (022) Bragg reflections, the authors find that the Sb atoms form dimers, and that the center of the Sb ad-dimers lies 1.64 angstrom above the bulk-like Si(004) surface atomic plane. These in-plane results are compared to two structural models consisting of dimers whose bonds are parallel to the surface plane and whose centers are either shifted or unshifted (parallel to the dimer bond direction) relative to the underlying substrate planes. The authors thus find two special cases consistent with these data: one with symmetric (unshifted) dimers having a dimer bond length of 2.81 angstrom, and the other with midpoint-shifted dimers, having a bond length of 2.88 angstrom and a lateral shift of 0.21 angstrom

Fano resonances in heterogeneous dimers of silicon and gold nanospheres

Science.gov (United States)

Zhao, Qian; Yang, Zhong-Jian; He, Jun

2018-06-01

We theoretically investigate the optical properties of dimers consisting of a gold nanosphere and a silicon nanosphere. The absorption spectrum of the gold sphere in the dimer can be significantly altered and exhibits a pronounced Fano profile. Analytical Mie theory and numerical simulations show that the Fano profile is induced by constructive and destructive interference between the incident electric field and the electric field of the magnetic dipole mode of the silicon sphere in a narrow wavelength range. The effects of the silicon sphere size, distance between the two spheres, and excitation configuration on the optical responses of the dimers are studied. Our study reveals the coherent feature of the electric fields of magnetic dipole modes in dielectric nanostructures and the strong interactions of the coherent fields with other nanophotonic structures.

The intrinsically disordered RNR inhibitor Sml1 is a dynamic dimer

DEFF Research Database (Denmark)

Danielsson, Jens; Liljedahl, Leena; Ba´ra´ny-Wallje, Elsa

2008-01-01

. Sml1 belongs to the class of intrinsically disordered proteins with a high degree of dynamics and very little stable structure. Earlier suggestions for a dimeric structure of Sml1 were confirmed, and from translation diffusion NMR measurements, a dimerization dissociation constant of 0.1 mM at 4...... natively disordered proteins....

Dimerization effect of sucrose octasulfate on rat FGF1

International Nuclear Information System (INIS)

Kulahin, N.; Kiselyov, V.; Kochoyan, A.; Kristensen, O.; Kastrup, Jette S.; Berezin, V.; Bock, E.; Gajhede, M.

2008-01-01

The work describes the sucrose octasulfate-mediated dimerization of rat FGF1 by gel-filtration experiments and crystal structure determination. Fibroblast growth factors (FGFs) constitute a family of at least 23 structurally related heparin-binding proteins that are involved in regulation of cell growth, survival, differentiation and migration. Sucrose octasulfate (SOS), a chemical analogue of heparin, has been demonstrated to activate FGF signalling pathways. The structure of rat FGF1 crystallized in the presence of SOS has been determined at 2.2 Å resolution. SOS-mediated dimerization of FGF1 was observed, which was further supported by gel-filtration experiments. The major contributors to the sulfate-binding sites in rat FGF1 are Lys113, Lys118, Arg122 and Lys128. An arginine at position 116 is a consensus residue in mammalian FGF molecules; however, it is a serine in rat FGF1. This difference may be important for SOS-mediated FGF1 dimerization in rat

Role of distonic dimer radical cations in the radiation-induced polymerisation of vinyl ethers

International Nuclear Information System (INIS)

Naumov, Sergej; Janovsky, Igor; Knolle, Wolfgang; Mehnert, Reiner

2005-01-01

The experimental low-temperature EPR results and the quantum chemical calculations suggest that dimer radical cations of cyclic and aliphatic vinyl ethers (VE) plays a key role in starting of radiation-induced polymerisation. The main species observed at high 2,3-dihydrofuran (DHF), 2,3-dihydropyran (DHP) and VE concentration is the dimer radical cation. In the case of cyclic VE the dimer radical cation transforms through H-abstraction from neutral molecule into a carbocation and radical, which could start both cationic and free-radical polymerisation. However, in the case of aliphatic VE no further reactive species, which could start polymerisation, were observed. This is caused (in agreement with experiment and quantum chemical calculations) by the very high stability of dimer radical cation and calculated endothermity of H-abstraction reaction by dimer radical cation from monomer

An introduction to the dimer model

International Nuclear Information System (INIS)

Kenyon, R.

2004-01-01

A perfect matching of a graph is a subset of edges which covers every vertex exactly once, that is, for every vertex there is exactly one edge in the set with that vertex as endpoint. The dimer model is the study of the set of perfect matchings of a (possibly infinite) graph. The most well-known example is when the graph is Z 2 , for which perfect matchings are equivalent (via a simple duality) to domino tilings, that is, tilings of the plane with 2 x 1 and 1 x 2 rectangles. In the first three sections we study domino tilings of the plane and of finite polygonal regions, or equivalently, perfect matchings on Z 2 and subgraphs of Z 2 . In the last two sections we study the FK-percolation model and the dimer model on a more general family of planar graphs

Neutral dipole-dipole dimers: A new field in science

Science.gov (United States)

Kosower, Edward M.; Borz, Galina

2018-03-01

Dimer formation with dipole neutralization produces species such as low polarity water (LPW) compatible with hydrophobic surfaces (Phys. Chem. Chem. Phys. 2015, 17, 24895-24900) Dimerization and dipole neutralization occurs for N-methylacetamide on polyethylene, a behavior drastically different from its contortions in acetonitrile on AgBr:AgCl planar crystals (AgX) (ChemPhysChem 2014, 15, 3598-3607). The weak infrared absorption of the amide dimer on polyethylene is shown experimentally. Dimerization of palmitic acid is shown along with some of the many ramifications for intracellular systems. Polyoligomers of water are present on polyethylene surfaces. Some high resolution spectra of three of the polyoligomers of water are shown along with a mechanistic scheme for polyoligomer formation and dissolution. The structures of some of the oligomers are known from spectroscopic studies of water on AgX. The scope of the article begins with PE, generally accepted as hydrophobic. The IR of PE revealed not only that water was present but that it appeared in two forms, oligomers (O) and polyoligomers (PO). How did we recognize what they were? These species had been observed as especially strong "marker" peaks in the spectra1 of water placed on planar AgX, a platform developed by Katzir and his coworkers [6]. But there was a problem: the proximity to PE of oligomers with substantial (calculated) dipole moments and thus polarity, including cyclic hexamers of water (chair and boat forms), the cyclic pentamer, the books I and II, and the cyclic trimer [7a]. Another link was needed, a role perfectly fit by the already cited low polarity water (LPW). The choice was experimentally supported by the detection of low intensity absorption in the bending region.Some important generalities flow from these results. What other dimers might be present in the biological or chemical world? Palmitic acid dimer (PAD) would be a candidate for decreasing the polarity of the acid (PA). Another

Probing Intermolecular Electron Delocalization in Dimer Radical Anions by Vibrational Spectroscopy

International Nuclear Information System (INIS)

Mani, Tomoyasu; Brookhaven National Laboratory; Grills, David C.

2017-01-01

Delocalization of charges is one of the factors controlling charge transport in conjugated molecules. It is considered to play an important role in the performance of a wide range of molecular technologies, including organic solar cells and organic electronics. Dimerization reactions are well-suited as a model to investigate intermolecular spatial delocalization of charges. And while dimerization reactions of radical cations are well investigated, studies on radical anions are still scarce. Upon dimerization of radical anions with neutral counterparts, an electron is considered to delocalize over the two molecules. By using time-resolved infrared (TRIR) detection coupled with pulse radiolysis, we show that radical anions of 4-n-hexyl-4'-cyanobiphenyl (6CB) undergo such dimerization reactions, with an electron equally delocalized over the two molecules. We have recently demonstrated that nitrile ν(C≡N) vibrations respond to the degree of electron localization of nitrile-substituted anions: we can quantify the changes in the electronic charges from the neutral to the anion states in the nitriles by monitoring the ν(C≡N) IR shifts. In the first part of this article, we show that the sensitivity of the ν(C≡N) IR shifts does not depend on solvent polarity. In the second part, we describe how probing the shifts of the nitrile IR vibrational band unambiguously confirms the formation of dimer radical anions, with K dim = 3 × 10 4 M –1 . IR findings are corroborated by electronic absorption spectroscopy and electronic structure calculations. We find that the presence of a hexyl chain and the formation of π–π interactions are both crucial for dimerization of radical anions of 6CB with neutral 6CB. Our study provides clear evidence of spatial delocalization of electrons over two molecular fragments.

Presence of the propeptide on recombinant lysosomal dipeptidase controls both activation and dimerization.

Science.gov (United States)

Dolenc, Iztok; Pain, Roger; Turk, Vito

2007-01-01

Lysosomal dipeptidase catalyzes the hydrolysis of dipeptides with unsubstituted terminals. It is a homodimer and binds zinc. Dimerization is an important issue in understanding the enzyme's function. In this study, we investigated the influence of the propeptide on the folding and dimerization of recombinant lysosomal dipeptidase. For this purpose, we separately cloned and overexpressed the mature protein and the proenzyme. The overexpressed proteins were localized exclusively to insoluble inclusion bodies. Refolding of the urea-solubilized inclusion bodies showed that only dipeptidase lacking the propeptide was dimeric. The soluble renatured proenzyme was a monomer, although circular dichroism and fluorescence spectra of the proenzyme indicated the formation of secondary and tertiary structure. The propeptide thus controls dimerization, as well as activation, of lysosomal dipeptidase.

Fibrin d-dimer concentration, deep vein thrombosis symptom duration, and venous thrombus volume.

Science.gov (United States)

Kurklinsky, Andrew K; Kalsi, Henna; Wysokinski, Waldemar E; Mauck, Karen F; Bhagra, Anjali; Havyer, Rachel D; Thompson, Carrie A; Hayes, Sharonne N; McBane, Robert D

2011-04-01

To determine the relationship between fibrin D-dimer levels, symptom duration, and thrombus volume, consecutive patients with incident deep venous thrombosis (DVT) were evaluated. In a cross-sectional study design, patient symptom onset was determined by careful patient questioning. Venous thrombosis was confirmed by compression duplex ultrasonography. Thrombus volume was estimated based on patient's femur length using a forensic anthropology method. Fibrin D-dimer was measured by latex immunoassay. 72 consecutive patients with confirmed leg DVT agreed to participate. The median symptom duration at the time of diagnosis was 10 days. The median D-dimer concentration was 1050 ng/dL. The median thrombus volume was 12.92 cm(3). D-Dimer levels correlated with estimated thrombus volume (P venous thrombosis and correlates with thrombus volume.

Fabrication and characterization of terahertz anisotropic anti-rod dimer planar metamaterials

DEFF Research Database (Denmark)

Zalkovskij, Maksim; Malureanu, Radu; Novitsky, Andrey

2012-01-01

In this work we describe the fabrication and characterization of free-standing membranes with thick anti-rod dimers metamaterials for terahertz waves. Two different designs with parallel and V-shape anti-rods were analysed. Even though both structures consists of simple elements, namely anti......-rod dimers, they reveal interesting birefringent and dichroic transmission properties....

Pyrimidine dimer excision in human cells and skin cancer

International Nuclear Information System (INIS)

Regan, J.D.; Carrier, W.L.; Smith, D.P.; Waters, R.

1977-01-01

We have compared three different methods for estimating the induction and removal of uv induced pyrimidine dimers from the DNA of human fibroblasts. Results indicate that after uv doses of 5-20 J/m 2 50% of the dimers are removed by 24 hours after irradiation. Almost complete excision can be observed if the cells are incubated for periods not less than 72 hours after 5 J/m 2 . After higher doses it probably takes even longer fr such complete removal to be seen

Photomonomerization of pyrimidine dimers by indoles and proteins

Energy Technology Data Exchange (ETDEWEB)

Chen, J.; Huang, C.W.; Hinman, L.; Gordon, M.P.; Deranleau, D.A.

1976-01-01

Model systems for the study of photoreactivation have been developed that utilize a variety of indole derivatives. These systems can split uracil cis-syn cyclobutadipyrimidine, either free or in RNA, when irradiated at wavelengths absorbed only by the indole moiety. The ability of indole compounds to split dimers is closely related to their electronic properties. Those of high electron-donor capacity such as indole, 3-methylindole, indole-3-acetic acid, 5-hydroxytryptophan and tryptophan are good photosensitizers, with efficacy in that order. Indoles with electron-withdrawing substituents such as indole-3-carboxylic acid, indole-3-aldehyde and oxindole are inactive in the monomerization reaction. These findings support the proposed mechanism that the photosensitized monomerization occurs as a result of electron transfer from the excited indole molecules to the pyrimidine bases. Proteins containing fully exposed tryptophan residues (chicken egg white lysozyme and bovine diisopropylphosphoryltrypsin) also cause the splitting of the /sup 14/C-labeled dimers under the same conditions. In the case of lysozyme the quantum yield of monomerization is similar to that of free tryptophan. Much of the monomerization ability of lysozyme was lost after the solvent-available tryptophan had been oxidized by treatment with N-bromosuccinimide. Bovine pancreatic ribonuclease A, a protein devoid of tryptophan, failed to exhibit photosensitized monomerization of uracil dimers. The biological implication of these reactions involving a protein with an exposed tryptophan residue is discussed. Although indoles are able to split the dimers in RNA, they fail to photoreactivate uv-damaged TMV-RNA. Indole-3-acetic acid, 3-methylindole and 5-hydroxytryptophan rapidly inactive viral RNA when irradiated at 313 nm, possibly because of side reactions.

Long-Lived Triplet Excited States of Bent-Shaped Pentacene Dimers by Intramolecular Singlet Fission.

Science.gov (United States)

Sakuma, Takao; Sakai, Hayato; Araki, Yasuyuki; Mori, Tadashi; Wada, Takehiko; Tkachenko, Nikolai V; Hasobe, Taku

2016-03-24

Intramolecular singlet fission (ISF) is a promising photophysical process to construct more efficient light energy conversion systems as one excited singlet state converts into two excited triplet states. Herein we synthesized and evaluated bent-shaped pentacene dimers as a prototype of ISF to reveal intrinsic characters of triplet states (e.g., lifetimes of triplet excited states). In this study, meta-phenylene-bridged TIPS-pentacene dimer (PcD-3Ph) and 2,2'-bipheynyl bridged TIPS-pentacene dimer (PcD-Biph) were newly synthesized as bent-shaped dimers. In the steady-state spectroscopy, absorption and emission bands of these dimers were fully characterized, suggesting the appropriate degree of electronic coupling between pentacene moieties in these dimers. In addition, the electrochemical measurements were also performed to check the electronic interaction between two pentacene moieties. Whereas the successive two oxidation peaks owing to the delocalization were observed in a directly linked-pentacene dimer (PcD) by a single bond, the cyclic voltammograms in PcD-Biph and PcD-3Ph implied the weaker interaction compared to that of p-phenylene-bridged TIPS-pentacene dimer (PcD-4Ph) and PcD. The femtosecond and nanosecond transient absorption spectra clearly revealed the slower ISF process in bent-shaped pentacene dimers (PcD-Biph and PcD-3Ph), more notably, the slower relaxation of the excited triplet states in PcD-Biph and PcD-3Ph. Namely, the quantum yields of triplet states (ΦT) by ISF approximately remain constant (ca. 180-200%) in all dimer systems, whereas the lifetimes of the triplet excited states became much longer (up to 360 ns) in PcD-Biph as compared to PcD-4Ph (15 ns). Additionally, the lifetimes of the corresponding triplet states in PcD-Biph and PcD-3Ph were sufficiently affected by solvent viscosity. In particular, the lifetimes of PcD-Biph triplet state in THF/paraffin (1.0 μs) increased up to approximately three times as compared to that in THF

DNA Origami Directed Au Nanostar Dimers for Single-Molecule Surface-Enhanced Raman Scattering.

Science.gov (United States)

Tanwar, Swati; Haldar, Krishna Kanta; Sen, Tapasi

2017-12-06

We demonstrate the synthesis of Au nanostar dimers with tunable interparticle gap and controlled stoichiometry assembled on DNA origami. Au nanostars with uniform and sharp tips were immobilized on rectangular DNA origami dimerized structures to create nanoantennas containing monomeric and dimeric Au nanostars. Single Texas red (TR) dye was specifically attached in the junction of the dimerized origami to act as a Raman reporter molecule. The SERS enhancement factors of single TR dye molecules located in the conjunction region in dimer structures having interparticle gaps of 7 and 13 nm are 2 × 10 10 and 8 × 10 9 , respectively, which are strong enough for single analyte detection. The highly enhanced electromagnetic field generated by the plasmon coupling between sharp tips and cores of two Au nanostars in the wide conjunction region allows the accommodation and specific detection of large biomolecules. Such DNA-directed assembled nanoantennas with controlled interparticle separation distance and stoichiometry, and well-defined geometry, can be used as excellent substrates in single-molecule SERS spectroscopy and will have potential applications as a reproducible platform in single-molecule sensing.

Structure of FGFR3 transmembrane domain dimer: implications for signaling and human pathologies.

Science.gov (United States)

Bocharov, Eduard V; Lesovoy, Dmitry M; Goncharuk, Sergey A; Goncharuk, Marina V; Hristova, Kalina; Arseniev, Alexander S

2013-11-05

Fibroblast growth factor receptor 3 (FGFR3) transduces biochemical signals via lateral dimerization in the plasma membrane, and plays an important role in human development and disease. Eight different pathogenic mutations, implicated in cancers and growth disorders, have been identified in the FGFR3 transmembrane segment. Here, we describe the dimerization of the FGFR3 transmembrane domain in membrane-mimicking DPC/SDS (9/1) micelles. In the solved NMR structure, the two transmembrane helices pack into a symmetric left-handed dimer, with intermolecular stacking interactions occurring in the dimer central region. Some pathogenic mutations fall within the helix-helix interface, whereas others are located within a putative alternative interface. This implies that although the observed dimer structure is important for FGFR3 signaling, the mechanism of FGFR3-mediated transduction across the membrane is complex. We propose an FGFR3 signaling mechanism that is based on the solved structure, available structures of isolated soluble FGFR domains, and published biochemical and biophysical data. Copyright © 2013 Elsevier Ltd. All rights reserved.

D-dimer assay for deep vein thrombosis: its role with colour Doppler sonography

Energy Technology Data Exchange (ETDEWEB)

Bradley, M.; Bladon, J.; Barker, H

2000-07-01

AIM: To evaluate the role of a negative D-dimer assay in the initial management of patients with clinically suspected deep venous thrombosis (DVT), using colour Doppler ultrasound as the primary diagnostic technique. MATERIALS AND METHODS: A double-blind prospective trial was performed on 143 patients with clinically suspected DVT. All patients underwent a D-dimer assay prior to anticoagulant therapy. DVT was confirmed or excluded by diagnostic colour Doppler ultrasound within 24 h of presentation. RESULTS: In nearly one-third of the cases (31.8%), Doppler ultrasound was positive. The D-dimer assay demonstrated a sensitivity of 97.7% with only one false-negative, but the specificity was low at 48.9% with 45 false-positive results. The positive predictive value for D-dimer assay was 48.8%, whilst the important negative predictive value was 98%. CONCLUSION: If D-dimer was used to screen for DVT, and patients with negative results were not imaged, then the imaging workload could be reduced by 35%. In this study one small calf vein thrombus would have been missed by adopting this practice. Bradley, M. (2000)

N-glycosylation of the β2 adrenergic receptor regulates receptor function by modulating dimerization.

Science.gov (United States)

Li, Xiaona; Zhou, Mang; Huang, Wei; Yang, Huaiyu

2017-07-01

N-glycosylation is a common post-translational modification of G-protein-coupled receptors (GPCRs). However, it remains unknown how N-glycosylation affects GPCR signaling. β 2 adrenergic receptor (β 2 AR) has three N-glycosylation sites: Asn6, Asn15 at the N-terminus, and Asn187 at the second extracellular loop (ECL2). Here, we show that deletion of the N-glycan did not affect receptor expression and ligand binding. Deletion of the N-glycan at the N-terminus rather than Asn187 showed decreased effects on isoproterenol-promoted G-protein-dependent signaling, β-arrestin2 recruitment, and receptor internalization. Both N6Q and N15Q showed decreased receptor dimerization, while N187Q did not influence receptor dimerization. As decreased β 2 AR homodimer accompanied with reduced efficiency for receptor function, we proposed that the N-glycosylation of β 2 AR regulated receptor function by influencing receptor dimerization. To verify this hypothesis, we further paid attention to the residues at the dimerization interface. Studies of Lys60 and Glu338, two residues at the receptor dimerization interface, exhibited that the K60A/E338A showed decreased β 2 AR dimerization and its effects on receptor signaling were similar to N6Q and N15Q, which further supported the importance of receptor dimerization for receptor function. This work provides new insights into the relationship among glycosylation, dimerization, and function of GPCRs. Peptide-N-glycosidase F (PNGase F, EC 3.2.2.11); endo-β-N-acetylglucosaminidase A (Endo-A, EC 3.2.1.96). © 2017 Federation of European Biochemical Societies.

The relative cytotoxicity and mutagenicity of cyclobutane pyrimidine dimers and photoproducts in Escherichia coli cells

International Nuclear Information System (INIS)

Tang, Moon-shong; Hrncir, J.; Mitchell, D.; Ross, J.; Clarkson, J.

1986-01-01

In order to calculate the relative cytotoxicity and mutagenicity of cyclobutane pyrimidine dimers and photoproducts, the authors have measured survival and mutation induction in UV-irradiated excision-deficient E. coli uvrA cells, with or without complete photoreactivation of the dimers. Radioimmunoassays with specificity for dimers or photoproducts have shown that maximum photoreactivation eliminates all of the dimers produce up to 10 Jm -2 254-nm light, while it has no effect on photoproducts. These results were confirmed by measuring the frequency of T4 endonuclease V-sensitive sites. Based on the best fit equations for survival and mutation induction, the authors have found that the calculated cytotoxicity of photoproducts is similar to that of dimers; however, the former is much more mutagenic than the latter. (Auth.)

Base Pair Opening in a Deoxynucleotide Duplex Containing a cis-syn Thymine Cyclobutane Dimer Lesion

Science.gov (United States)

Wenke, Belinda B.; Huiting, Leah N.; Frankel, Elisa B.; Lane, Benjamin F.; Núñez, Megan E.

2014-01-01

The cis-syn thymine cyclobutane dimer is a DNA photoproduct implicated in skin cancer. We compared the stability of individual base pairs in thymine dimer-containing duplexes to undamaged parent 10-mer duplexes. UV melting thermodynamic measurements, CD spectroscopy, and 2D NOESY NMR spectroscopy confirm that the thymine dimer lesion is locally and moderately destabilizing within an overall B-form duplex conformation. We measured the rates of exchange of individual imino protons by NMR using magnetization transfer from water and determined the equilibrium constant for the opening of each base pair Kop. In the normal duplex Kop decreases from the frayed ends of the duplex toward the center, such that the central TA pair is the most stable with a Kop of 8×10−7. In contrast, base pair opening at the 5’T of the thymine dimer is facile. The 5’T of the dimer has the largest equilibrium constant (Kop =3×10−4) in its duplex, considerably larger than even the frayed penultimate base pairs. Notably, base pairing by the 3’T of the dimer is much more stable than by the 5’T, indicating that the predominant opening mechanism for the thymine dimer lesion is not likely to be flipping out into solution as a single unit. The dimer asymmetrically affects the stability of the duplex in its vicinity, destabilizing base pairing on its 5’ side more than on the 3’ side. The striking differences in base pair opening between parent and dimer duplexes occur independently of the duplex-single strand melting transitions. PMID:24328089

Internal energy selection in vacuum ultraviolet photoionization of ethanol and ethanol dimers

Science.gov (United States)

Bodi, Andras

2013-10-01

Internal energy selected ethanol monomer and ethanol dimer ions were prepared by threshold photoionization of a supersonic molecular beam seeded with ethanol. The dissociative photoionization processes of the monomer, the lowest-energy CH3-loss channel of the dimer, and the fragmentation of larger clusters were found to be disjunct from the ionization onset to about 12 eV, which made it possible to determine the 0 K appearance energy of C-C bond breaking in the H-donor unit of the ethanol dimer cation as 9.719 ± 0.004 eV. This reaction energy is used together with ab initio calculations in a thermochemical cycle to determine the binding energy change from the neutral ethanol dimer to a protonated ethanol-formaldehyde adduct. The cycle also shows general agreement between experiment, theory, and previously published enthalpies of formation. The role of the initial ionization site, or rather the initial photoion state, is also discussed based on the dimer breakdown diagram and excited state calculations. There is no evidence for isolated state behavior, and the ethanol dimer dissociative photoionization processes appear to be governed by statistical theory and the ground electronic state of the ion. In the monomer breakdown diagram, the smoothly changing branching ratio between H and CH3 loss is at odds with rate theory predictions, and shows that none of the currently employed few-parameter rate models, appropriate for experimental rate curve fitting, yields a correct description for this process in the experimental energy range.

Performance Evaluation of Different d-Dimer Cutoffs in Bedridden Hospitalized Elderly Patients.

Science.gov (United States)

Kassim, Nevine A; Farid, Tamer M; Pessar, Shaimaa Abdelmalik; Shawkat, Salma A

2017-11-01

A rapid and accurate diagnosis of venous thromboembolism (VTE) in the elderly individuals represents a dilemma due to nonspecific clinical presentation, confusing laboratory results, and the hazards of radiological examination in this age-group. d-Dimer test is used mainly in combination with non-high clinical pretest probability (PTP) to exclude VTE. d-Dimer testing retains its sensitivity, however, its specificity decreases in the elderly individuals. Raising the cutoff level improves the specificity of the d-dimer test without compromising its sensitivity. The current study aimed to explore the reliability of higher d-dimer cutoff values for the diagnosis of asymptomatic VTE in a population of bedridden hospitalized elderly patients with non-high clinical PTP. This retrospective study included 252 bedridden hospitalized elderly patients (>65 years) who were admitted to the Ain shams University Specialized Hospital with non-high clinical probability and developed later reduced mobility; all underwent quantitation of d-dimer and Doppler examination. Considering the whole population (>65 years), the age-adjusted cutoff achieved the best performance in comparison with the conventional and receiver operating characteristic (ROC)-derived cutoffs. When stratified according to age, the age-adjusted cutoff showed the best performance in the age-group 65-70 and comparable performance with the ROC-derived cutoff in the age-group 71-80, however, its sensitivity compromised in those older than 80 years. In conclusion, it is recommended to use age-adjusted cutoff value of d-dimer together with the clinical probability score in elderly individuals (65-80 years).

Elucidation of cladofulvin biosynthesis reveals a cytochrome P450 monooxygenase required for anthraquinone dimerization.

Science.gov (United States)

Griffiths, Scott; Mesarich, Carl H; Saccomanno, Benedetta; Vaisberg, Abraham; De Wit, Pierre J G M; Cox, Russell; Collemare, Jérôme

2016-06-21

Anthraquinones are a large family of secondary metabolites (SMs) that are extensively studied for their diverse biological activities. These activities are determined by functional group decorations and the formation of dimers from anthraquinone monomers. Despite their numerous medicinal qualities, very few anthraquinone biosynthetic pathways have been elucidated so far, including the enzymatic dimerization steps. In this study, we report the elucidation of the biosynthesis of cladofulvin, an asymmetrical homodimer of nataloe-emodin produced by the fungus Cladosporium fulvum A gene cluster of 10 genes controls cladofulvin biosynthesis, which begins with the production of atrochrysone carboxylic acid by the polyketide synthase ClaG and the β-lactamase ClaF. This compound is decarboxylated by ClaH to yield emodin, which is then converted to chrysophanol hydroquinone by the reductase ClaC and the dehydratase ClaB. We show that the predicted cytochrome P450 ClaM catalyzes the dimerization of nataloe-emodin to cladofulvin. Remarkably, such dimerization dramatically increases nataloe-emodin cytotoxicity against mammalian cell lines. These findings shed light on the enzymatic mechanisms involved in anthraquinone dimerization. Future characterization of the ClaM enzyme should facilitate engineering the biosynthesis of novel, potent, dimeric anthraquinones and structurally related compound families.

21 CFR 176.120 - Alkyl ketene dimers.

Science.gov (United States)

2010-04-01

..., processing, preparing, treating, packaging, transporting, or holding food, subject to the provisions of this... paperboard. (c) The alkyl ketene dimers may be used in the form of an aqueous emulsion which may contain...

Dimerization of a flocculent protein from Moringa oleifera: experimental evidence and in silico interpretation.

Science.gov (United States)

Pavankumar, Asalapuram R; Kayathri, Rajarathinam; Murugan, Natarajan A; Zhang, Qiong; Srivastava, Vaibhav; Okoli, Chuka; Bulone, Vincent; Rajarao, Gunaratna K; Ågren, Hans

2014-01-01

Many proteins exist in dimeric and other oligomeric forms to gain stability and functional advantages. In this study, the dimerization property of a coagulant protein (MO2.1) from Moringa oleifera seeds was addressed through laboratory experiments, protein-protein docking studies and binding free energy calculations. The structure of MO2.1 was predicted by homology modelling, while binding free energy and residues-distance profile analyses provided insight into the energetics and structural factors for dimer formation. Since the coagulation activities of the monomeric and dimeric forms of MO2.1 were comparable, it was concluded that oligomerization does not affect the biological activity of the protein.

Structure of a rabbit muscle fructose-1, 6-bisphosphate aldolase A dimer variant

Energy Technology Data Exchange (ETDEWEB)

Sherawat, Manashi [Department of Physiology and Biophysics, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118-2394 (United States); Tolan, Dean R., E-mail: tolan@bu.edu [Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215 (United States); Allen, Karen N., E-mail: tolan@bu.edu [Department of Physiology and Biophysics, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118-2394 (United States)

2008-05-01

The X-ray crystallographic structure of a dimer variant of fructose-1, 6-bisphosphate aldolase demonstrates a stable oligomer that mirrors half of the native tetramer. The presence of product demonstrates that this is an active form. Fructose-1, 6-bisphosphate aldolase (aldolase) is an essential enzyme in glycolysis and gluconeogenesis. In addition to this primary function, aldolase is also known to bind to a variety of other proteins, a property that may allow it to perform ‘moonlighting’ roles in the cell. Although monomeric and dimeric aldolases possess full catalytic activity, the enzyme occurs as an unusually stable tetramer, suggesting a possible link between the oligomeric state and these noncatalytic cellular roles. Here, the first high-resolution X-ray crystal structure of rabbit muscle D128V aldolase, a dimeric form of aldolase mimicking the clinically important D128G mutation in humans associated with hemolytic anemia, is presented. The structure of the dimer was determined to 1.7 Å resolution with the product DHAP bound in the active site. The turnover of substrate to produce the product ligand demonstrates the retention of catalytic activity by the dimeric aldolase. The D128V mutation causes aldolase to lose intermolecular contacts with the neighboring subunit at one of the two interfaces of the tetramer. The tertiary structure of the dimer does not significantly differ from the structure of half of the tetramer. Analytical ultracentrifugation confirms the occurrence of the enzyme as a dimer in solution. The highly stable structure of aldolase with an independent active site is consistent with a model in which aldolase has evolved as a multimeric scaffold to perform other noncatalytic functions.

MONTE CARLO SIMULATIONS OF THE ADSORPTION OF DIMERS ON STRUCTURED HETEROGENEOUS SURFACES

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Abreu C.R.A.

2001-01-01

Full Text Available The effect of surface topography upon the adsorption of dimer molecules is analyzed by means of grand canonical ensemble Monte Carlo simulations. Heterogeneous surfaces were assumed to consist of a square lattice containing active sites with two different energies. These were distributed in three different configurations: a random distribution of isolated sites; a random distribution of grains with four high-energy sites; and a random distribution of grains with nine high-energy sites. For the random distribution of isolated sites, the results are in good agreement with the molecular simulations performed by Nitta et al. (1997. In general, the comparison with theoretical models shows that the Nitta et al. (1984 isotherm presents good predictions of dimer adsorption both on homogeneous and heterogeneous surfaces with sites having small differences in characteristic energies. The molecular simulation results also show that the energy topology of the solid surfaces plays an important role in the adsorption of dimers on solids with large differences in site energies. For these cases, the Nitta et al. model does not describe well the data on dimer adsorption on random heterogeneous surfaces (grains with one acid site, but does describe reasonably well the adsorption of dimers on more patchwise heterogeneous surfaces (grains with nine acid sites.

Theoretical analysis of bimetallic nanorod dimer biosensors for label-free molecule detection

Science.gov (United States)

Das, Avijit; Talukder, Muhammad Anisuzzaman

2018-02-01

In this work, we theoretically analyze a gold (Au) core within silver (Ag) shell (Au@Ag) nanorod dimer biosensor for label-free molecule detection. The incident light on an Au@Ag nanorod strongly couples to localized surface plasmon modes, especially around the tip region. The field enhancement around the tip of a nanorod or between the tips of two longitudinally aligned nanorods as in a dimer can be exploited for sensitive detection of biomolecules. We derive analytical expressions for the interactions of an Au@Ag nanorod dimer with the incident light. We also study the detail dynamics of an Au@Ag nanorod dimer with the incident light computationally using finite difference time domain (FDTD) technique when core-shell ratio, relative position of the nanorods, and angle of incidence of light change. We find that the results obtained using the developed analytical model match well with that obtained using FDTD simulations. Additionally, we investigate the sensitivity of the Au@Ag nanorod dimer, i.e., shift in the resonance wavelength, when a target biomolecule such as lysozyme (Lys), human serum albumin (HSA), anti-biotin (Abn), human catalase (CAT), and human fibrinogen (Fb) protein molecules are attached to the tips of the nanorods.

Metal membrane with dimer slots as a universal polarizer

DEFF Research Database (Denmark)

Zhukovsky, Sergei; Zalkovskij, Maksim; Malureanu, Radu

2014-01-01

In this work, we show theoretically and confirm experimentally that thin metal membranes patterned with an array of slot dimers (or their Babinet analogue with metal rods) can function as a versatile spectral and polarization filter. We present a detailed covariant multipole theory for the electr......In this work, we show theoretically and confirm experimentally that thin metal membranes patterned with an array of slot dimers (or their Babinet analogue with metal rods) can function as a versatile spectral and polarization filter. We present a detailed covariant multipole theory...

Revisiting the Optical PT-Symmetric Dimer

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José Delfino Huerta Morales

2016-08-01

Full Text Available Optics has proved a fertile ground for the experimental simulation of quantum mechanics. Most recently, optical realizations of PT -symmetric quantum mechanics have been shown, both theoretically and experimentally, opening the door to international efforts aiming at the design of practical optical devices exploiting this symmetry. Here, we focus on the optical PT -symmetric dimer, a two-waveguide coupler where the materials show symmetric effective gain and loss, and provide a review of the linear and nonlinear optical realizations from a symmetry-based point of view. We go beyond a simple review of the literature and show that the dimer is just the smallest of a class of planar N-waveguide couplers that are the optical realization of the Lorentz group in 2 + 1 dimensions. Furthermore, we provide a formulation to describe light propagation through waveguide couplers described by non-Hermitian mode coupling matrices based on a non-Hermitian generalization of the Ehrenfest theorem.

Electronic structure and optical absorption spectra of Y2 and Zr2 dimers

International Nuclear Information System (INIS)

Gutsev, G.L.

1989-01-01

The electron structure, ionization potentials from valent levels and energies of optic transitions of Y 2 and Zr 2 dimers are calculated within the framework of discrete-variatin X α -method. It is shown that the symmetry state 1 Σ g + is the main state of Y 2 and Zr 2 dimers, and the atoms in dimers have high-spin 4d n+1 5s 1 configuration. The chemical binding in Y 2 has the dominating 5s-5s nature which is revealed in a considerable interatomic distance; binding of 4d-electrons brings about a significant decrease in the bond length in Zr 2 dimer. The theoretical spectrum of optical absorption of Zr 2 agrees well with the obtained experimental spectrum of this molecule isolated in the organ matrix

Serum Potassium Levels Inversely Correlate with D-Dimer In Patients with Acute-Onset Atrial Fibrillation

International Nuclear Information System (INIS)

Cervellin, Gianfranco; Bonfanti, Laura; Picanza, Alessandra; Lippi, Giuseppe

2015-01-01

D-dimer values are frequently increased in patients with atrial fibrillation (AF) compared to subjects in sinus rhythm. Hypokalemia plays a role in several cardiovascular diseases, but little is known about the association with AF. D-dimer values are frequently increased in patients with atrial fibrillation (AF) compared with subjects in sinus rhythm. Hypokalemia plays a role in several cardiovascular diseases, but little is known about the association with AF. The aim of this study was to investigate correlations between D-dimer and serum potassium in acute-onset AF (AAF). To investigate the potential correlation between the values of serum potassium and D-dimer in patients with AAF, we retrospectively reviewed clinical and laboratory data of all emergency department visits for AAF in 2013. Among 271 consecutive AAF patients with D-dimer assessments, those with hypokalemia (n = 98) had significantly higher D-dimer values than normokalemic patients (139 versus 114 ng/mL, p = 0.004). The rate of patients with D-dimer values exceeding the diagnostic cut-off was higher in the group of patients with hypokalemia than in those with normal serum potassium (26.5% versus 16.2%; p = 0.029). An inverse and highly significant correlation was found between serum potassium and D-dimer (r = −0.21; p < 0.001), even after adjustments for age and sex (beta coefficient −94.8; p = 0.001). The relative risk for a positive D-dimer value attributed to hypokalemia was 1.64 (95% CI, 1.02 to 2.63; p = 0.040). The correlation remained statistically significant in patients free from antihypertensive drugs (r = −0.25; p = 0.018), but not in those taking angiotensin-receptor blockers, angiotensin-converting enzyme inhibitors, or diuretics. The inverse correlation between values of potassium and D-dimer in patients with AAF provides important and complementary information about the thromboembolic risk of these patients

Serum Potassium Levels Inversely Correlate with D-Dimer In Patients with Acute-Onset Atrial Fibrillation

Energy Technology Data Exchange (ETDEWEB)

Cervellin, Gianfranco, E-mail: gcervellin@ao.pr.it; Bonfanti, Laura; Picanza, Alessandra; Lippi, Giuseppe [1Academic Hospital of Parma (Italy)

2015-03-15

D-dimer values are frequently increased in patients with atrial fibrillation (AF) compared to subjects in sinus rhythm. Hypokalemia plays a role in several cardiovascular diseases, but little is known about the association with AF. D-dimer values are frequently increased in patients with atrial fibrillation (AF) compared with subjects in sinus rhythm. Hypokalemia plays a role in several cardiovascular diseases, but little is known about the association with AF. The aim of this study was to investigate correlations between D-dimer and serum potassium in acute-onset AF (AAF). To investigate the potential correlation between the values of serum potassium and D-dimer in patients with AAF, we retrospectively reviewed clinical and laboratory data of all emergency department visits for AAF in 2013. Among 271 consecutive AAF patients with D-dimer assessments, those with hypokalemia (n = 98) had significantly higher D-dimer values than normokalemic patients (139 versus 114 ng/mL, p = 0.004). The rate of patients with D-dimer values exceeding the diagnostic cut-off was higher in the group of patients with hypokalemia than in those with normal serum potassium (26.5% versus 16.2%; p = 0.029). An inverse and highly significant correlation was found between serum potassium and D-dimer (r = −0.21; p < 0.001), even after adjustments for age and sex (beta coefficient −94.8; p = 0.001). The relative risk for a positive D-dimer value attributed to hypokalemia was 1.64 (95% CI, 1.02 to 2.63; p = 0.040). The correlation remained statistically significant in patients free from antihypertensive drugs (r = −0.25; p = 0.018), but not in those taking angiotensin-receptor blockers, angiotensin-converting enzyme inhibitors, or diuretics. The inverse correlation between values of potassium and D-dimer in patients with AAF provides important and complementary information about the thromboembolic risk of these patients.

Theoretical Research on the Mechanism of the Dimerization Reactions of Alkyl Ketene

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Zhiguo Zhang

2013-01-01

Full Text Available A quantum chemical method was employed to investigate the mechanism of dimerization reactions of alkyl ketene. All the geometric configurations of the stationary points on the reactions path were optimized with Gaussian03 employing density functional theory at the B3LYP/6-311G++(d, p level by energy gradient technique. The transition states were also investigated through synchronous transit method, and its reasonability was confirmed by using frequency analysis and intrinsic reaction coordinate analysis. The results can be summed up as follows: according to the frontier orbital theory, the dimerization reaction (3 to generate four-membered carbon cyclic product P3 is forbidden. Two different dimerization processes of alkyl ketene are all concerted but nonsynchronous, taking place through twisted four-membered cyclic transition states. The activation energies were calculated to be 34.54 and 61.73 kJ/mol, respectively for the two ketene dimerization processes. Calculation results satisfactorily explained the experimental facts.

Jellium-model calculation for monomer and dimer decays of some potassium clusters

International Nuclear Information System (INIS)

Saito, Susumu; Cohen, M.L.; Lawrence Berkeley Lab., CA

1989-01-01

We have studied several decay processes of potassium clusters and found that a dimer-decay mechanism can explain the observed lowest abundance of K 10 in the K n mass spectra. Total-energy curves for decay processes are calculated using a jellium-background model for positive-ion cores and the local-spin-density-functional approximation for valence electrons. The energy-barrier height for a dimer decay of K 10 from the energy-minimum point is found to be 0.18 eV, which is a reasonable magnitude for the decay to take place thermally in the experiment. The monomer decay of K 9 and the dimer decay of K 11 , which are expected to be the most favorable decays of K 9 and K 11 , are found to have high barriers. Monomer and dimer decays of K 8 are also studied and the monomer decay is found to be more favorable, in accord with the high-nozzle-temperature mass spectrum. (orig.)

Antiviral activity of α-helical stapled peptides designed from the HIV-1 capsid dimerization domain

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Cowburn David

2011-05-01

Full Text Available Abstract Background The C-terminal domain (CTD of HIV-1 capsid (CA, like full-length CA, forms dimers in solution and CTD dimerization is a major driving force in Gag assembly and maturation. Mutations of the residues at the CTD dimer interface impair virus assembly and render the virus non-infectious. Therefore, the CTD represents a potential target for designing anti-HIV-1 drugs. Results Due to the pivotal role of the dimer interface, we reasoned that peptides from the α-helical region of the dimer interface might be effective as decoys to prevent CTD dimer formation. However, these small peptides do not have any structure in solution and they do not penetrate cells. Therefore, we used the hydrocarbon stapling technique to stabilize the α-helical structure and confirmed by confocal microscopy that this modification also made these peptides cell-penetrating. We also confirmed by using isothermal titration calorimetry (ITC, sedimentation equilibrium and NMR that these peptides indeed disrupt dimer formation. In in vitro assembly assays, the peptides inhibited mature-like virus particle formation and specifically inhibited HIV-1 production in cell-based assays. These peptides also showed potent antiviral activity against a large panel of laboratory-adapted and primary isolates, including viral strains resistant to inhibitors of reverse transcriptase and protease. Conclusions These preliminary data serve as the foundation for designing small, stable, α-helical peptides and small-molecule inhibitors targeted against the CTD dimer interface. The observation that relatively weak CA binders, such as NYAD-201 and NYAD-202, showed specificity and are able to disrupt the CTD dimer is encouraging for further exploration of a much broader class of antiviral compounds targeting CA. We cannot exclude the possibility that the CA-based peptides described here could elicit additional effects on virus replication not directly linked to their ability to bind

Relative stabilities and the spectral signatures of stacked and hydrogen-bonded dimers of serotonin

Science.gov (United States)

Dev, S.; Giri, K.; Majumder, M.; Sathyamurthy, N.

2015-10-01

The O-HṡṡṡN hydrogen-bonded dimer of serotonin is shown to be more stable than the stacked dimer in its ground electronic state, by using the Møller-Plesset second-order perturbation theory (MP2) and the 6-31g** basis set. The vertical excitation energy for the lowest π → π* transition for the monomer as well as the dimer is predicted by time-dependent density functional theory. The experimentally observed red shift of excitation wavelength on oligomerisation is explained in terms of the change in the HOMO-LUMO energy gap due to complex formation. The impact of dimer formation on the proton magnetic resonance spectrum of serotonin monomer is also examined.

Numerical investigation of radiative properties and surface plasmon resonance of silver nanorod dimers on a substrate

International Nuclear Information System (INIS)

An, Wei; Zhu, Tong; Zhu, QunZhi

2014-01-01

When the distance between two silver nanoparticles is small enough, interparticle surface plasmon coupling has a great impact on their radiative properties. It is becoming a promising technique to use in the sensing and imaging. A model based on finite difference time domain method is developed to investigate the effect of the assembled parameters on the radiative properties and the field-enhancement effect of silver nanorod dimer. The numerical results indicate that the radiative properties of silver nanorod dimer are very sensitive to the assembled angle and the polarization orientation of incident wave. There is great difference on the intensity and location of field-enhancement effect for the cases of different assembled angle and polarization. The most intensive field-enhancement effect occurs in the middle of two nanorods when two nanorods is assembled head to head and the polarization orientation parallels to the length axis of nanorods. Moreover, compared with the single nanorod, the wavelength of extinction peak of dimer has a red-shift, and the intensity of field-enhancement effect on the dimer is more intensive than that of single particle. With the increasing of particle length, extinction cross-section of silver nanorod dimer rises, while extinction efficiency and scattering efficiency firstly increase then drop down gradually. In addition, the extinction peaks of silver nanorod dimer on the substrate are smaller than that without the substrate, and their extinction peaks has a red-shift compared with that without the substrate. -- Highlights: ► Radiative properties of silver nanorod dimer are very sensitive to the assembled angle. ► The projective length of nanorod dimer on the polarization orientation is crucial. ► Compared with single nanorod, wavelength of extinction peak of dimer has a red-shift. ► Extinction peaks of dimer on the substrate are smaller than that without the substrate

Is a positive L-dimer result a sufficient indication for performing a V/Q lung scan?

International Nuclear Information System (INIS)

Salanitri, G.C.; Kelly, M.J.; O'Donnell, M.; Kalff, V.

2002-01-01

Full text: At our institution there has developed a practice of referring some patients for assessment of pulmonary embolism (PE) because of a positive L-dimer test but without standard clinical indications. Therefore this study aimed to determine whether a positive L-dimer test result by itself is a sufficient indication to perform a ventilation/perfusion V/Q study. V/Q lung scan results, L-dimer test results and appropriate radiology results of 949 consecutive patients from August 2000 to October 2001 were retrospectively reviewed. Prediction of V/Q results by L-dimer results was compared with that of clinical risk factors for PE (Risk factor + or -) These factors were dyspnoea, current deep vein thrombosis (DVT), recent orthopaedic procedure or a past history of PE/DVT, Of the 949 patients in the study population, 254 patients had an L-dimer study, with 206 positive and 48 negative L-dimer results. Helical CT was performed in 8 patients with an equivocal V/Q - 4 showed PE and 4 did not. In the 27 patients with a positive L-dimer result and PE on either V-Q scan or CT, 25 (92.6%) had additional recognised major risk factors for PE. A positive L-dimer test is a poor predictor of a positive V/Q scan compared to conventional clinical indications. Thus, a positive L-dimer test result in isolation does not constitute an appropriate indication to perform a V/Q scan. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

Comprehensive prediction in 78 human cell lines reveals rigidity and compactness of transcription factor dimers

Science.gov (United States)

Jankowski, Aleksander; Szczurek, Ewa; Jauch, Ralf; Tiuryn, Jerzy; Prabhakar, Shyam

2013-01-01

The binding of transcription factors (TFs) to their specific motifs in genomic regulatory regions is commonly studied in isolation. However, in order to elucidate the mechanisms of transcriptional regulation, it is essential to determine which TFs bind DNA cooperatively as dimers and to infer the precise nature of these interactions. So far, only a small number of such dimeric complexes are known. Here, we present an algorithm for predicting cell-type–specific TF–TF dimerization on DNA on a large scale, using DNase I hypersensitivity data from 78 human cell lines. We represented the universe of possible TF complexes by their corresponding motif complexes, and analyzed their occurrence at cell-type–specific DNase I hypersensitive sites. Based on ∼1.4 billion tests for motif complex enrichment, we predicted 603 highly significant cell-type–specific TF dimers, the vast majority of which are novel. Our predictions included 76% (19/25) of the known dimeric complexes and showed significant overlap with an experimental database of protein–protein interactions. They were also independently supported by evolutionary conservation, as well as quantitative variation in DNase I digestion patterns. Notably, the known and predicted TF dimers were almost always highly compact and rigidly spaced, suggesting that TFs dimerize in close proximity to their partners, which results in strict constraints on the structure of the DNA-bound complex. Overall, our results indicate that chromatin openness profiles are highly predictive of cell-type–specific TF–TF interactions. Moreover, cooperative TF dimerization seems to be a widespread phenomenon, with multiple TF complexes predicted in most cell types. PMID:23554463

Investigation of the hydrated 7-hydroxy-4-methylcoumarin dimer by combined IR/UV spectroscopy

International Nuclear Information System (INIS)

Stamm, A.; Schwing, K.; Gerhards, M.

2014-01-01

The first molecular beam investigations on a coumarin dimer and clusters of a coumarin dimer with water both in the neutral (S 0 ) and cationic (D 0 ) electronic ground state are performed. The structure and structural changes due to ionization of the isolated 7-hydroxy-4-methylcoumarin dimer (7H4MC) 2 as well as its mono- and dihydrate (7H4MC) 2 (H 2 O) 1-2 are analyzed by applying combined IR/UV spectroscopy compared with density functional theory calculations. In case of the neutral dimer of 7H4MC a doubly hydrogen-bonded structure is formed. This doubly hydrogen-bonded arrangement opens to a singly hydrogen-bonded structure in the ion presenting a rearrangement reaction within an isolated dimer. By attaching one or two water molecules to the neutral 7H4MC dimer water is inserted into the hydrogen bonds. In contrast to the non-hydrated species this general binding motif with water in a bridging function does not change via ionization but especially for the dihydrate the spatial arrangement of the two 7H4MC units changes strengthening the interaction between the aromatic chromophores. The presented analyses illustrate the strong dependence of binding motifs as a function of successive hydration and charge including a rearrangement reaction

Photoreactivation of ultraviolet radiation-induced pyrimidine dimers in neonatal BALB/c mouse skin

International Nuclear Information System (INIS)

Ananthaswamy, H.N.; Fisher, M.S.

1981-01-01

The numbers of ultraviolet light (uv)-induced pyrimidine dimers in the DNA of neonatal BALB/c mouse skin were measured by assessing the sensitivity of the DNA to Micrococcus luteus uv endonuclease. Irradiation of neonatal BALB/c mice with FS40 sunlamps caused a dose-dependent induction of endonuclease-sensitive sites (pyrimidine dimers) in DNA extracted from back skin. Exposure of these uv-irradiated neonatal mice to photoreactivating (PR) light (cool white fluorescent lamp and incandescent lamp) caused a reduction in the number of pyrimidine dimers in the DNA, as revealed by a shift in low-molecular-weight DNA to high-molecular-weight DNA. In contrast, DNA profiles of the skin of either uv-irradiated mice or uv-irradiated mice kept in the dark for the same duration as those exposed to PR light did not show a loss of uv-induced endonuclease-sensitive sites. Furthermore, reversing the order of treatment, i.e., administering PR light first and then uv, did not produce a reduction in pyrimidine dimers. These results demonstrate that PR or uv-induced pyrimidine dimers occurs in neonatal BALB/c mouse skin. The optimal wavelength range for in vivo PR appears to be in the visible region of the spectrum (greater than 400 nm). Although dimer formation could be detected in both dermis and epidermis, PR occurred only in the dermis. Furthermore, the PR phenomenon could not be detected in the skin of adult mice from the same inbred strain

Dimerization effects on coacervation property of an elastin-derived synthetic peptide (FPGVG)5.

Science.gov (United States)

Suyama, Keitaro; Taniguchi, Suguru; Tatsubo, Daiki; Maeda, Iori; Nose, Takeru

2016-04-01

Elastin, a core protein of the elastic fibers, exhibits the coacervation (temperature-dependent reversible association/dissociation) under physiological conditions. Because of this characteristic, elastin and elastin-derived peptides have been considered to be useful as base materials for developing various biomedical products, skin substitutes, synthetic vascular grafts, and drug delivery systems. Although elastin-derived polypeptide (Val-Pro-Gly-Val-Gly)n also has been known to demonstrate coacervation property, a sufficiently high (VPGVG)n repetition number (n>40) is required for coacervation. In the present study, a series of elastin-derived peptide (Phe-Pro-Gly-Val-Gly)5 dimers possessing high coacervation potential were newly developed. These novel dimeric peptides exhibited coacervation at significantly lower concentrations and temperatures than the commonly used elastin-derived peptide analogs; this result suggests that the coacervation ability of the peptides is enhanced by dimerization. Circular dichroism (CD) measurements indicate that the dimers undergo similar temperature-dependent and reversible conformational changes when coacervation occurs. The molecular dynamics calculation results reveal that the sheet-turn-sheet motif involving a type II β-turn-like structure commonly observed among the dimers and caused formation of globular conformation of them. These synthesized peptide dimers may be useful not only as model peptides for structural analysis of elastin and elastin-derived peptides, but also as base materials for developing various temperature-sensitive biomedical and industrial products. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Mass spectrometric characterization of human serum albumin dimer: A new potential biomarker in chronic liver diseases.

Science.gov (United States)

Naldi, Marina; Baldassarre, Maurizio; Nati, Marina; Laggetta, Maristella; Giannone, Ferdinando Antonino; Domenicali, Marco; Bernardi, Mauro; Caraceni, Paolo; Bertucci, Carlo

2015-08-10

Human serum albumin (HSA) undergoes several structural alterations affecting its properties in pro-oxidant and pro-inflammatory environments, as it occurs during liver cirrhosis. These modifications include the formation of albumin dimers. Although HSA dimers were reported to be an oxidative stress biomarker, to date nothing is known about their role in liver cirrhosis and related complications. Additionally, no high sensitive analytical method was available for HSA dimers assessment in clinical settings. Thus the HSA dimeric form in human plasma was characterized by mass spectrometry using liquid chromatography tandem mass spectrometry (LC-ESI-Q-TOF) and matrix assisted laser desorption time of flight (MALDI-TOF) techniques. N-terminal and C-terminal truncated HSA, as well as the native HSA, undergo dimerization by binding another HSA molecule. This study demonstrated the presence of both homo- and hetero-dimeric forms of HSA. The dimerization site was proved to be at Cys-34, forming a disulphide bridge between two albumin molecules, as determined by LC-MS analysis after tryptic digestion. Interestingly, when plasma samples from cirrhotic subjects were analysed, the dimer/monomer ratio resulted significantly increased when compared to that of healthy subjects. These isoforms could represent promising biomarkers for liver disease. Additionally, this analytical approach leads to the relative quantification of the residual native HSA, with fully preserved structural integrity. Copyright © 2014 Elsevier B.V. All rights reserved.

Stabilization of sulfuric acid dimers by ammonia, methylamine, dimethylamine, and trimethylamine

Science.gov (United States)

Jen, Coty N.; McMurry, Peter H.; Hanson, David R.

2014-06-01

This study experimentally explores how ammonia (NH3), methylamine (MA), dimethylamine (DMA), and trimethylamine (TMA) affect the chemical formation mechanisms of electrically neutral clusters that contain two sulfuric acid molecules (dimers). Dimers may also contain undetectable compounds, such as water or bases, that evaporate upon ionization and sampling. Measurements were conducted using a glass flow reactor which contained a steady flow of humidified nitrogen with sulfuric acid concentrations of 107 to 109 cm-3. A known molar flow rate of a basic gas was injected into the flow reactor. The University of Minnesota Cluster Chemical Ionization Mass Spectrometer was used to measure the resulting sulfuric acid vapor and cluster concentrations. It was found that, for a given concentration of sulfuric acid vapor, the dimer concentration increases with increasing concentration of the basic gas, eventually reaching a plateau. The base concentrations at which the dimer concentrations saturate suggest NH3 heuristic models for cluster formation by acid-base reactions are developed to interpret the data. The models provide ranges of evaporation rate constants that are consistent with observations and leads to an analytic expression for nucleation rates that is consistent with atmospheric observations.

Model-Based Comparison of Antibody Dimerization in Continuous and Batch-Wise Downstream Processing

Directory of Open Access Journals (Sweden)

Anton Sellberg

2015-07-01

Full Text Available Monoclonal antibodies are generally produced using a generic platform approach in which several chromatographic separations assure high purity of the product. Dimerization can occur during the fermentation stage and may occur also during the downstream processing. We present here simulations in which a traditional platform approach that consist of protein A capture, followed by cation-exchange and anion-exchange chromatography for polishing is compared to a continuous platform in which dimer removal and virus inactivation are carried out on a size-exclusion column. A dimerization model that takes pH, salt concentration and the concentration of antibodies into account is combined with chromatographic models, to be able to predicted both the separation and the degree to which dimers are formed. Purification of a feed composition that contained 1% by weight of dimer and a total antibody concentration of 1 g/L was modeled using both approaches, and the amount of antibodies in the continuous platform was at least 4 times lower than in the traditional platform. The total processing time was also lower, as the cation-exchange polish could be omitted.

TACO: a general-purpose tool for predicting cell-type-specific transcription factor dimers.

Science.gov (United States)

Jankowski, Aleksander; Prabhakar, Shyam; Tiuryn, Jerzy

2014-03-19

Cooperative binding of transcription factor (TF) dimers to DNA is increasingly recognized as a major contributor to binding specificity. However, it is likely that the set of known TF dimers is highly incomplete, given that they were discovered using ad hoc approaches, or through computational analyses of limited datasets. Here, we present TACO (Transcription factor Association from Complex Overrepresentation), a general-purpose standalone software tool that takes as input any genome-wide set of regulatory elements and predicts cell-type-specific TF dimers based on enrichment of motif complexes. TACO is the first tool that can accommodate motif complexes composed of overlapping motifs, a characteristic feature of many known TF dimers. Our method comprehensively outperforms existing tools when benchmarked on a reference set of 29 known dimers. We demonstrate the utility and consistency of TACO by applying it to 152 DNase-seq datasets and 94 ChIP-seq datasets. Based on these results, we uncover a general principle governing the structure of TF-TF-DNA ternary complexes, namely that the flexibility of the complex is correlated with, and most likely a consequence of, inter-motif spacing.

Characterization of topological phases of dimerized Kitaev chain via edge correlation functions

Science.gov (United States)

Wang, Yucheng; Miao, Jian-Jian; Jin, Hui-Ke; Chen, Shu

2017-11-01

We study analytically topological properties of a noninteracting modified dimerized Kitaev chain and an exactly solvable interacting dimerized Kitaev chain under open boundary conditions by analyzing two introduced edge correlation functions. The interacting dimerized Kitaev chain at the symmetry point Δ =t and the chemical potential μ =0 can be exactly solved by applying two Jordan-Wigner transformations and a spin rotation, which permits us to calculate the edge correlation functions analytically. We demonstrate that the two edge correlation functions can be used to characterize the trivial, Su-Schrieffer-Heeger-like topological and topological superconductor phases of both the noninteracting and interacting systems and give their phase diagrams.

Analytical expressions for the correlation function of a hard sphere dimer fluid

Science.gov (United States)

Kim, Soonho; Chang, Jaeeon; Kim, Hwayong

A closed form expression is given for the correlation function of a hard sphere dimer fluid. A set of integral equations is obtained from Wertheim's multidensity Ornstein-Zernike integral equation theory with Percus-Yevick approximation. Applying the Laplace transformation method to the integral equations and then solving the resulting equations algebraically, the Laplace transforms of the individual correlation functions are obtained. By the inverse Laplace transformation, the radial distribution function (RDF) is obtained in closed form out to 3D (D is the segment diameter). The analytical expression for the RDF of the hard dimer should be useful in developing the perturbation theory of dimer fluids.

Field-based scanning tunneling microscope manipulation of antimony dimers on Si(001)

NARCIS (Netherlands)

Rogge, S.; Timmerman, R.H.; Scholte, P.M.L.O.; Geerligs, L.J.; Salemink, H.W.M.

2001-01-01

The manipulation of antimony dimers, Sb2, on the silicon (001) surface by means of a scanning tunneling microscope (STM) has been experimentally investigated. Directed hopping of the Sb2 dimers due the STM tip can dominate over the thermal motion at temperatures between 300 and 500 K. Statistics on

Spin quantum tunneling via entangled states in a dimer of exchange coupled single-molecule magnets

Science.gov (United States)

Tiron, R.; Wernsdorfer, W.; Aliaga-Alcalde, N.; Foguet-Albiol, D.; Christou, G.

2004-03-01

A new family of supramolecular, antiferromagnetically exchange-coupled dimers of single-molecule magnets (SMMs) has recently been reported [W. Wernsdorfer, N. Aliaga-Alcalde, D.N. Hendrickson, and G. Christou, Nature 416, 406 (2002)]. Each SMM acts as a bias on its neighbor, shifting the quantum tunneling resonances of the individual SMMs. Hysteresis loop measurements on a single crystal of SMM-dimers have now established quantum tunneling of the magnetization via entangled states of the dimer. This shows that the dimer really does behave as a quantum-mechanically coupled dimer. The transitions are well separated, suggesting long coherence times compared to the time scale of the energy splitting. This result is of great importance if such systems are to be used for quantum computing. It also allows the measurement of the longitudinal and transverse superexchange coupling constants [Phys. Rev. Lett. 91, 227203 (2003)].

The hyperfine spectrum of hydrogen dimers

International Nuclear Information System (INIS)

Verberne, J.F.C.

1979-01-01

The authors' aim was to obtain the level scheme for the hydrogen dimers and to investigate the angle dependent interactions by analyzing the zero magnetic field hyperfine spectrum of the ortho-ortho and ortho-para species. The results were tested by several recent semi-empirical and ab initio potentials. (Auth.)

UV light-induced cyclobutane pyrimidine dimers are mutagenic in mammalian cells

International Nuclear Information System (INIS)

Protic-Sabljic, M.; Tuteja, N.; Munson, P.J.; Hauser, J.; Kraemer, K.H.; Dixon, K.

1986-01-01

We used a simian virus 40-based shuttle vector plasmid, pZ189, to determine the role of pyrimidine cyclobutane dimers in UV light-induced mutagenesis in monkey cells. The vector DNA was UV irradiated and then introduced into monkey cells by transfection. After replication, vector DNA was recovered from the cells and tested for mutations in its supF suppressor tRNA marker gene by transformation of Escherichia coli carrying a nonsense mutation in the beta-galactosidase gene. When the irradiated vector was treated with E. coli photolyase prior to transfection, pyrimidine cyclobutane dimers were removed selectively. Removal of approximately 90% of the pyrimidine cyclobutane dimers increased the biological activity of the vector by 75% and reduced its mutation frequency by 80%. Sequence analysis of 72 mutants recovered indicated that there were significantly fewer tandem double-base changes and G X C----A X T transitions (particularly at CC sites) after photoreactivation of the DNA. UV-induced photoproducts remained (although at greatly reduced levels) at all pyr-pyr sites after photoreactivation, but there was a relative increase in photoproducts at CC and TC sites and a relative decrease at TT and CT sites, presumably due to a persistence of (6-4) photoproducts at some CC and TC sites. These observations are consistent with the fact that mutations were found after photoreactivation at many sites at which only cyclobutane dimers would be expected to occur. From these results we conclude that UV-induced pyrimidine cyclobutane dimers are mutagenic in DNA replicated in monkey cells

Elevation in D-dimer concentrations is positively correlated with gestation in normal uncomplicated pregnancy

Directory of Open Access Journals (Sweden)

Jeremiah ZA

2012-08-01

Full Text Available Zaccheaus A Jeremiah,1 Teddy C Adias,2 Margaret Opiah,3 Siyeoforiye P George,4 Osaro Mgbere,5 Ekere J Essien61Department of Medical Laboratory Sciences, Niger Delta University, Wilberforce Island, Nigeria; 2Bayelsa State College of Health Technology, Ogbia-Town, Nigeria; 3Department of Maternal and Child Health, Faculty of Nursing, Niger Delta University, Wilberforce Island, Nigeria; 4Postgraduate Hematology Unit, Rivers State University of Science and Technology, Port Harcourt, Nigeria; 5Houston Department of Health and Human Services, Houston, TX, USA; 6Institute of Community Health, University of Houston, Houston, TX, USABackground: D-dimer levels have been reported to increase progressively during pregnancy, but how this affects Nigerian women is not well known.Objective: This study aims to determine the D-dimer concentration and its relationship to other coagulation parameters among pregnant women in Port Harcourt, Nigeria.Method: In a cross-sectional observational study conducted in Port Harcourt, Nigeria, 120 pregnant women and 60 nonpregnant controls, drawn from a tertiary health institution in the Niger Delta, Nigeria, were assessed, using the standard procedures, for the following parameters: D-dimer concentration, prothrombin time, activated partial thromboplastin time, platelet count, hemoglobin, and packed cell volume.Results: The median D-dimer concentration of 153.1 ng/mL in the pregnant group was found to be significantly elevated when compared with the control value of 118.5 ng/mL (t = 2.348, P = 0.021. Conversely, there was a marked depression in the platelet count among pregnant women (193.5 × 109/L when compared with 229.0 × 109/L in the control group (t = 3.424; P = 0.001. There was no statistically significant difference in the values for the prothrombin time and the activated partial thromboplastin time between pregnant and nonpregnant women. D-dimer values correlated positively and significantly with gestation (r = 0

Dimerization Efficiency of Canine Distemper Virus Matrix Protein Regulates Membrane-Budding Activity.

Science.gov (United States)

Bringolf, Fanny; Herren, Michael; Wyss, Marianne; Vidondo, Beatriz; Langedijk, Johannes P; Zurbriggen, Andreas; Plattet, Philippe

2017-08-15

Paramyxoviruses rely on the matrix (M) protein to orchestrate viral assembly and budding at the plasma membrane. Although the mechanistic details remain largely unknown, structural data suggested that M dimers and/or higher-order oligomers may facilitate membrane budding. To gain functional insights, we employed a structure-guided mutagenesis approach to investigate the role of canine distemper virus (CDV) M protein self-assembly in membrane-budding activity. Three six-alanine-block (6A-block) mutants with mutations located at strategic oligomeric positions were initially designed. While the first one includes residues potentially residing at the protomer-protomer interface, the other two display amino acids located within two distal surface-exposed α-helices proposed to be involved in dimer-dimer contacts. We further focused on the core of the dimeric interface by mutating asparagine 138 (N138) to several nonconservative amino acids. Cellular localization combined with dimerization and coimmunopurification assays, performed under various denaturing conditions, revealed that all 6A-block mutants were impaired in self-assembly and cell periphery accumulation. These phenotypes correlated with deficiencies in relocating CDV nucleocapsid proteins to the cell periphery and in virus-like particle (VLP) production. Conversely, all M-N138 mutants remained capable of self-assembly, though to various extents, which correlated with proper accumulation and redistribution of nucleocapsid proteins at the plasma membrane. However, membrane deformation and VLP assays indicated that the M-N138 variants exhibiting the most reduced dimerization propensity were also defective in triggering membrane remodeling and budding, despite proper plasma membrane accumulation. Overall, our data provide mechanistic evidence that the efficiency of CDV M dimerization/oligomerization governs both cell periphery localization and membrane-budding activity. IMPORTANCE Despite the availability of

Disintegration and dimerization of δ-tocopherol under radiation effect

International Nuclear Information System (INIS)

Jasinska-Stepniak, A.; Gogolewski, M.; Zabielski, J.

1996-01-01

The goal of the work was to recognize scala changes of δ-tocopherol in model system (diluted in benzene, ethanol and ''in substantia'') after 2.5, 5, 10 and 20 kGy dose irradiation. δ-tocopherol and its mild oxidation products (dimers) after TLC separation were quantitatively determined with Emmerie-Engel method. Relations dose-effect have been defined and radiation capacity has been calculated. The results show that disintegration of δ-tocopherol diluted in ethanol is about ten times stronger the diluted in benzene. δ-tocopherol in benzene was dimerized. The most stable after irradiation was δ-tocopherol ''in substantia''. (author)

Serum Potassium Levels Inversely Correlate with D-Dimer In Patients with Acute-Onset Atrial Fibrillation.

Science.gov (United States)

Cervellin, Gianfranco; Bonfanti, Laura; Picanza, Alessandra; Lippi, Giuseppe

2014-12-09

Background: D-dimer values are frequently increased in patients with atrial fibrillation (AF) compared to subjects in sinus rhythm. Hypokalemia plays a role in several cardiovascular diseases, but little is known about the association with AF. Objective: D-dimer values are frequently increased in patients with atrial fibrillation (AF) compared with subjects in sinus rhythm. Hypokalemia plays a role in several cardiovascular diseases, but little is known about the association with AF. The aim of this study was to investigate correlations between D-dimer and serum potassium in acute-onset AF (AAF). Methods: To investigate the potential correlation between the values of serum potassium and D-dimer in patients with AAF, we retrospectively reviewed clinical and laboratory data of all emergency department visits for AAF in 2013. Results: Among 271 consecutive AAF patients with D-dimer assessments, those with hypokalemia (n = 98) had significantly higher D-dimer values than normokalemic patients (139 versus 114 ng/mL, p = 0.004). The rate of patients with D-dimer values exceeding the diagnostic cut-off was higher in the group of patients with hypokalemia than in those with normal serum potassium (26.5% versus 16.2%; p = 0.029). An inverse and highly significant correlation was found between serum potassium and D-dimer (r = -0.21; p enzima conversora de angiotensina e diuréticos. Conclusões: A correlação inversa existente entre os níveis séricos de potássio e D-dímero em pacientes com FAA fornece informações importantes sobre o risco de tromboembolismo nestes pacientes.

Antimicrobial peptide protegrin-3 adopt an antiparallel dimer in the presence of DPC micelles: a high-resolution NMR study

Energy Technology Data Exchange (ETDEWEB)

Usachev, K. S., E-mail: k.usachev@kpfu.ru; Efimov, S. V.; Kolosova, O. A.; Klochkova, E. A.; Aganov, A. V.; Klochkov, V. V. [Kazan Federal University, NMR Laboratory, Institute of Physics (Russian Federation)

2015-05-15

A tendency to dimerize in the presence of lipids was found for the protegrin. The dimer formation by the protegrin-1 (PG-1) is the first step for further oligomeric membrane pore formation. Generally there are two distinct model of PG-1 dimerization in either a parallel or antiparallel β-sheet. But despite the wealth of data available today, protegrin dimer structure and pore formation is still not completely understood. In order to investigate a more detailed dimerization process of PG-1 and if it will be the same for another type of protegrins, in this work we used a high-resolution NMR spectroscopy for structure determination of protegrin-3 (RGGGL-CYCRR-RFCVC-VGR) in the presence of perdeuterated DPC micelles and demonstrate that PG-3 forms an antiparallel NCCN dimer with a possible association of these dimers. This structural study complements previously published solution, solid state and computational studies of PG-1 in various environments and validate the potential of mean force simulations of PG-1 dimers and association of dimers to form octameric or decameric β-barrels.

Dimers of nineteen-electron sandwich compounds: Crystal and electronic structures, and comparison of reducing strengths

KAUST Repository

Mohapatra, Swagat Kumar

2014-10-03

The dimers of some Group 8 metal cyclopentadienyl/ arene complexes and Group 9 metallocenes can be handled in air, yet are strongly reducing, making them useful n-dopants in organic electronics. In this work, the Xray molecular structures are shown to resemble those of Group 8 metal cyclopentadienyl/pentadienyl or Group 9 metal cyclopentadienyl/diene model compounds. Compared to those of the model compounds, the DFT HOMOs of the dimers are significantly destabilized by interactions between the metal and the central C-C σ-bonding orbital, accounting for the facile oxidation of the dimers. The lengths of these C-C bonds (X-ray or DFT) do not correlate with DFT dissociation energies, the latter depending strongly on the monomer stabilities. Ru and Ir monomers are more reducing than their Fe and Rh analogues, but the corresponding dimers also exhibit much higher dissociation energies, so the estimated monomer cation/neutral dimer potentials are, with the exception of that of [RhCp2]2, rather similar (-1.97 to-2.15 V vs. FeCp2 +/0 in THF). The consequences of the variations in bond strength and redox potentials for the reactivity of the dimers are discussed.

Comparison of FDTD numerical computations and analytical multipole expansion method for plasmonics-active nanosphere dimers.

Science.gov (United States)

Dhawan, Anuj; Norton, Stephen J; Gerhold, Michael D; Vo-Dinh, Tuan

2009-06-08

This paper describes a comparative study of finite-difference time-domain (FDTD) and analytical evaluations of electromagnetic fields in the vicinity of dimers of metallic nanospheres of plasmonics-active metals. The results of these two computational methods, to determine electromagnetic field enhancement in the region often referred to as "hot spots" between the two nanospheres forming the dimer, were compared and a strong correlation observed for gold dimers. The analytical evaluation involved the use of the spherical-harmonic addition theorem to relate the multipole expansion coefficients between the two nanospheres. In these evaluations, the spacing between two nanospheres forming the dimer was varied to obtain the effect of nanoparticle spacing on the electromagnetic fields in the regions between the nanostructures. Gold and silver were the metals investigated in our work as they exhibit substantial plasmon resonance properties in the ultraviolet, visible, and near-infrared spectral regimes. The results indicate excellent correlation between the two computational methods, especially for gold nanosphere dimers with only a 5-10% difference between the two methods. The effect of varying the diameters of the nanospheres forming the dimer, on the electromagnetic field enhancement, was also studied.

Dimers of nineteen-electron sandwich compounds: Crystal and electronic structures, and comparison of reducing strengths

KAUST Repository

Mohapatra, Swagat Kumar; Fonari, Alexandr; Risko, Chad; Yesudas, Kada; Moudgil, Karttikay; Delcamp, Jared Heath; Timofeeva, Tatiana V.; Bredas, Jean-Luc; Marder, Seth R.; Barlow, Stephen J.

2014-01-01

The dimers of some Group 8 metal cyclopentadienyl/ arene complexes and Group 9 metallocenes can be handled in air, yet are strongly reducing, making them useful n-dopants in organic electronics. In this work, the Xray molecular structures are shown to resemble those of Group 8 metal cyclopentadienyl/pentadienyl or Group 9 metal cyclopentadienyl/diene model compounds. Compared to those of the model compounds, the DFT HOMOs of the dimers are significantly destabilized by interactions between the metal and the central C-C σ-bonding orbital, accounting for the facile oxidation of the dimers. The lengths of these C-C bonds (X-ray or DFT) do not correlate with DFT dissociation energies, the latter depending strongly on the monomer stabilities. Ru and Ir monomers are more reducing than their Fe and Rh analogues, but the corresponding dimers also exhibit much higher dissociation energies, so the estimated monomer cation/neutral dimer potentials are, with the exception of that of [RhCp2]2, rather similar (-1.97 to-2.15 V vs. FeCp2 +/0 in THF). The consequences of the variations in bond strength and redox potentials for the reactivity of the dimers are discussed.

Pyrimidine dimers in Drosophila chromatin become increasingly accessible after irradiation

International Nuclear Information System (INIS)

Harris, P.V.; Boyd, J.B.

1987-01-01

A prokaryotic DNA-repair enzyme has been utilized as a probe for changes in the accessibility of pyrimidine dimers in Drosophila chromatin following UV irradiation. The results demonstrate a rapid cellular response to physiologically relevant doses of radiation which results in at least a 40% increase in accessible dimers. This increase occurs in two incision-deficient mutants which indicates that the excision-repair process, at or beyond the incision step, is not required or responsible for the increase. In the absence of excision the increase in accessibility persists for a least 2 days following irradiation. The observed increase in accessibility is inhibited by both novobiocin and coumermycin. These inhibitors do not inhibit the initial rate of incision, but do reduce dimer excision measured over more extended periods. A pre-incision process is proposed which actively exposes DNA lesions to excision repair. A fraction of the genome is postulated to be accessible without the intervention of that process. (Auth.)

Biosynthesis of intestinal microvillar proteins. Dimerization of aminopeptidase N and lactase-phlorizin hydrolase

DEFF Research Database (Denmark)

Danielsen, E M

1990-01-01

of dimers of this enzyme therefore occurs prior to the Golgi-associated processing, and the slow rate of dimerization may be the rate-limiting step in the transport from the endoplasmic reticulum to the Golgi complex. For lactase-phlorizin hydrolase, the posttranslational processing includes a proteolytic......The pig intestinal brush border enzymes aminopeptidase N (EC 3.4.11.2) and lactase-phlorizin hydrolase (EC 3.2.1.23-62) are present in the microvillar membrane as homodimers. Dimethyl adipimidate was used to cross-link the two [35S]methionine-labeled brush border enzymes from cultured mucosal...... explants. For aminopeptidase N, dimerization did not begin until 5-10 min after synthesis, and maximal dimerization by cross-linking of the transient form of the enzyme required 1 h, whereas the mature form of aminopeptidase N cross-linked with unchanged efficiency from 45 min to 3 h of labeling. Formation...

Possibilities of the observation of the discrete spectrum of the water dimer at equilibrium in millimeter-wave band

International Nuclear Information System (INIS)

Krupnov, A.F.; Tretyakov, M.Yu.; Leforestier, C.

2009-01-01

Attempts of experimental observations of the water dimer spectrum at equilibrium conditions have lasted for more than 40 years since the dimeric hypothesis for extra absorption, but have not yielded any positive confirmed result. In the present paper a new approach is considered: using a high-resolution millimeter-wave spectrum of the water dimer at equilibrium, calculated by a rigorous fully quantum method, we show the potential existence of discernible spectral series of discrete features of the water dimer, which correspond to J+1 1 symmetry, already observed in cold molecular beam experiments and having, therefore, well-defined positions. The intensity of spectral series and contrast to the remaining continuum-like spectrum of the dimer are calculated and compared with the monomer absorption. The suitability of two types of microwave spectrometers for observing these series is considered. The collisional line-width of millimeter lines of the dimer at equilibrium is estimated and the width of IR dimer bands is discussed. It is pointed out that the large width of IR dimer bands may pose difficulties for their reliable observation and conclusive separation from the rest of absorption in water vapor. This situation contrasts with the suggested approach of dimer detection in millimeter-waves.

Mutation of Asn28 Disrupts the Dimerization and Enzymatic Activity of SARS 3CL

Energy Technology Data Exchange (ETDEWEB)

Barrila, J.; Gabelli, S; Bacha, U; Amzel, M; Freire, E

2010-01-01

Coronaviruses are responsible for a significant proportion of annual respiratory and enteric infections in humans and other mammals. The most prominent of these viruses is the severe acute respiratory syndrome coronavirus (SARS-CoV) which causes acute respiratory and gastrointestinal infection in humans. The coronavirus main protease, 3CL{sup pro}, is a key target for broad-spectrum antiviral development because of its critical role in viral maturation and high degree of structural conservation among coronaviruses. Dimerization is an indispensable requirement for the function of SARS 3CL{sup pro} and is regulated through mechanisms involving both direct and long-range interactions in the enzyme. While many of the binding interactions at the dimerization interface have been extensively studied, those that are important for long-range control are not well-understood. Characterization of these dimerization mechanisms is important for the structure-based design of new treatments targeting coronavirus-based infections. Here we report that Asn28, a residue 11 {angstrom} from the closest residue in the opposing monomer, is essential for the enzymatic activity and dimerization of SARS 3CLpro. Mutation of this residue to alanine almost completely inactivates the enzyme and results in a 19.2-fold decrease in the dimerization K{sub d}. The crystallographic structure of the N28A mutant determined at 2.35 {angstrom} resolution reveals the critical role of Asn28 in maintaining the structural integrity of the active site and in orienting key residues involved in binding at the dimer interface and substrate catalysis. These findings provide deeper insight into complex mechanisms regulating the activity and dimerization of SARS 3CL{sup pro}.

Chloroplast Preproteins Bind to the Dimer Interface of the Toc159 Receptor during Import1[OPEN

Science.gov (United States)

Chen, Lih-Jen; Yeh, Yi-Hung; Hsiao, Chwan-Deng

2017-01-01

Most chloroplast proteins are synthesized in the cytosol as higher molecular weight preproteins and imported via the translocons in the outer (TOC) and inner (TIC) envelope membranes of chloroplasts. Toc159 functions as a primary receptor and directly binds preproteins through its dimeric GTPase domain. As a first step toward a molecular understanding of how Toc159 mediates preprotein import, we mapped the preprotein-binding regions on the Toc159 GTPase domain (Toc159G) of pea (Pisum sativum) using cleavage by bound preproteins conjugated with the artificial protease FeBABE and cysteine-cysteine cross-linking. Our results show that residues at the dimer interface and the switch II region of Toc159G are in close proximity to preproteins. The mature portion of preproteins was observed preferentially at the dimer interface, whereas the transit peptide was found at both regions equally. Chloroplasts from transgenic plants expressing engineered Toc159 with a cysteine placed at the dimer interface showed increased cross-linking to bound preproteins. Our data suggest that, during preprotein import, the Toc159G dimer disengages and the dimer interface contacts translocating preproteins, which is consistent with a model in which conformational changes induced by dimer-monomer conversion in Toc159 play a direct role in facilitating preprotein import. PMID:28250068

A first principles study of fluorescence quenching in rhodamine B dimers : how can quenching occur in dimeric species?

NARCIS (Netherlands)

Setiawan, Dani; Kazaryan, Andranik; Martoprawiro, Muhamad Abdulkadir; Filatov, Michael

2010-01-01

Rhodamine B (RhB) is widely used in chemistry and biology due to its high fluorescence quantum yield. In high concentrations, the quantum yield of fluorescence decreases considerably which is attributed to the formation of RhB dimers. In the present work, a possible mechanism of fluorescence

The dimerization domain in DapE enzymes is required for catalysis.

Directory of Open Access Journals (Sweden)

Boguslaw Nocek

Full Text Available The emergence of antibiotic-resistant bacterial strains underscores the importance of identifying new drug targets and developing new antimicrobial compounds. Lysine and meso-diaminopimelic acid are essential for protein production and bacterial peptidoglycan cell wall remodeling and are synthesized in bacteria by enzymes encoded within dap operon. Therefore dap enzymes may serve as excellent targets for developing a new class of antimicrobial agents. The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE converts N-succinyl-L,L-diaminopimelic acid to L,L-diaminopimelic acid and succinate. The enzyme is composed of catalytic and dimerization domains, and belongs to the M20 peptidase family. To understand the specific role of each domain of the enzyme we engineered dimerization domain deletion mutants of DapEs from Haemophilus influenzae and Vibrio cholerae, and characterized these proteins structurally and biochemically. No activity was observed for all deletion mutants. Structural comparisons of wild-type, inactive monomeric DapE enzymes with other M20 peptidases suggest that the dimerization domain is essential for DapE enzymatic activity. Structural analysis and molecular dynamics simulations indicate that removal of the dimerization domain increased the flexibility of a conserved active site loop that may provide critical interactions with the substrate.

The dimerization domain in DapE enzymes is required for catalysis.

Science.gov (United States)

Nocek, Boguslaw; Starus, Anna; Makowska-Grzyska, Magdalena; Gutierrez, Blanca; Sanchez, Stephen; Jedrzejczak, Robert; Mack, Jamey C; Olsen, Kenneth W; Joachimiak, Andrzej; Holz, Richard C

2014-01-01

The emergence of antibiotic-resistant bacterial strains underscores the importance of identifying new drug targets and developing new antimicrobial compounds. Lysine and meso-diaminopimelic acid are essential for protein production and bacterial peptidoglycan cell wall remodeling and are synthesized in bacteria by enzymes encoded within dap operon. Therefore dap enzymes may serve as excellent targets for developing a new class of antimicrobial agents. The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) converts N-succinyl-L,L-diaminopimelic acid to L,L-diaminopimelic acid and succinate. The enzyme is composed of catalytic and dimerization domains, and belongs to the M20 peptidase family. To understand the specific role of each domain of the enzyme we engineered dimerization domain deletion mutants of DapEs from Haemophilus influenzae and Vibrio cholerae, and characterized these proteins structurally and biochemically. No activity was observed for all deletion mutants. Structural comparisons of wild-type, inactive monomeric DapE enzymes with other M20 peptidases suggest that the dimerization domain is essential for DapE enzymatic activity. Structural analysis and molecular dynamics simulations indicate that removal of the dimerization domain increased the flexibility of a conserved active site loop that may provide critical interactions with the substrate.

Combinatorial Synthesis of Structurally Diverse Triazole-Bridged Flavonoid Dimers and Trimers

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Tze Han Sum

2016-09-01

Full Text Available Flavonoids are a large family of compounds associated with a broad range of biologically useful properties. In recent years, synthetic compounds that contain two flavonoid units linked together have attracted attention in drug discovery and development projects. Numerous flavonoid dimer systems, incorporating a range of monomers attached via different linkers, have been reported to exhibit interesting bioactivities. From a medicinal chemistry perspective, the 1,2,3-triazole ring system has been identified as a particularly attractive linker moiety in dimeric derivatives (owing to several favourable attributes including proven biological relevance and metabolic stability and triazole-bridged flavonoid dimers possessing anticancer and antimalarial activities have recently been reported. However, there are relatively few examples of libraries of triazole-bridged flavonoid dimers and the diversity of flavonoid subunits present within these is typically limited. Thus, this compound type arguably remains underexplored within drug discovery. Herein, we report a modular strategy for the synthesis of novel and biologically interesting triazole-bridged flavonoid heterodimers and also very rare heterotrimers from readily available starting materials. Application of this strategy has enabled step-efficient and systematic access to a library of structurally diverse compounds of this sort, with a variety of monomer units belonging to six different structural subclasses of flavonoid successfully incorporated.

High-resolution Crystal Structure of Dimeric VP40 From Sudan ebolavirus.

Science.gov (United States)

Clifton, Matthew C; Bruhn, Jessica F; Atkins, Kateri; Webb, Terry L; Baydo, Ruth O; Raymond, Amy; Lorimer, Donald D; Edwards, Thomas E; Myler, Peter J; Saphire, Erica Ollmann

2015-10-01

Ebolaviruses cause severe hemorrhagic fever. Central to the Ebola life cycle is the matrix protein VP40, which oligomerizes and drives viral budding. Here we present the crystal structure of the Sudan virus (SUDV) matrix protein. This structure is higher resolution (1.6 Å) than previously achievable. Despite differences in the protein purification, we find that it still forms a stable dimer in solution, as was noted for other Ebola VP40s. Although the N-terminal domain interface by which VP40 dimerizes is conserved between Ebola virus and SUDV, the C-terminal domain interface by which VP40 dimers may further assemble is significantly smaller in this SUDV assembly. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Dimerization of BTas is required for the transactivational activity of bovine foamy virus

International Nuclear Information System (INIS)

Tan Juan; Qiao Wentao; Xu Fengwen; Han Hongqi; Chen Qimin; Geng Yunqi

2008-01-01

The BTas protein of bovine foamy virus (BFV) is a 249-amino-acid nuclear regulatory protein which transactivates viral gene expression directed by the long terminal repeat promoter (LTR) and the internal promoter (IP). Here, we demonstrate the BTas protein forms a dimeric complex in mammalian cells by using mammalian two hybrid systems and cross-linking assay. Functional analyses with deletion mutants reveal that the region of 46-62aa is essential for dimer formation. Furthermore, our results show that deleting the dimerization region of BTas did not affect the localization of BTas, but that it did result in the loss of its transactivational activity on the LTR and IP. Furthermore, BTas (Δ46-62aa) retained binding ability to the LTR and IP similar to that of the wild-type BTas. These data suggest the dimerization region is necessary for the transactivational function of BTas and is crucial to the replication of BFV

Dimers of nineteen-electron sandwich compounds: crystal and electronic structures, and comparison of reducing strengths.

Science.gov (United States)

Mohapatra, Swagat K; Fonari, Alexandr; Risko, Chad; Yesudas, Kada; Moudgil, Karttikay; Delcamp, Jared H; Timofeeva, Tatiana V; Brédas, Jean-Luc; Marder, Seth R; Barlow, Stephen

2014-11-17

The dimers of some Group 8 metal cyclopentadienyl/arene complexes and Group 9 metallocenes can be handled in air, yet are strongly reducing, making them useful n-dopants in organic electronics. In this work, the X-ray molecular structures are shown to resemble those of Group 8 metal cyclopentadienyl/pentadienyl or Group 9 metal cyclopentadienyl/diene model compounds. Compared to those of the model compounds, the DFT HOMOs of the dimers are significantly destabilized by interactions between the metal and the central CC σ-bonding orbital, accounting for the facile oxidation of the dimers. The lengths of these CC bonds (X-ray or DFT) do not correlate with DFT dissociation energies, the latter depending strongly on the monomer stabilities. Ru and Ir monomers are more reducing than their Fe and Rh analogues, but the corresponding dimers also exhibit much higher dissociation energies, so the estimated monomer cation/neutral dimer potentials are, with the exception of that of [RhCp2 ]2 , rather similar (-1.97 to -2.15 V vs. FeCp2 (+/0) in THF). The consequences of the variations in bond strength and redox potentials for the reactivity of the dimers are discussed. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The dimer interface of the membrane type 1 matrix metalloproteinase hemopexin domain: crystal structure and biological functions.

Science.gov (United States)

Tochowicz, Anna; Goettig, Peter; Evans, Richard; Visse, Robert; Shitomi, Yasuyuki; Palmisano, Ralf; Ito, Noriko; Richter, Klaus; Maskos, Klaus; Franke, Daniel; Svergun, Dmitri; Nagase, Hideaki; Bode, Wolfram; Itoh, Yoshifumi

2011-03-04

Homodimerization is an essential step for membrane type 1 matrix metalloproteinase (MT1-MMP) to activate proMMP-2 and to degrade collagen on the cell surface. To uncover the molecular basis of the hemopexin (Hpx) domain-driven dimerization of MT1-MMP, a crystal structure of the Hpx domain was solved at 1.7 Å resolution. Two interactions were identified as potential biological dimer interfaces in the crystal structure, and mutagenesis studies revealed that the biological dimer possesses a symmetrical interaction where blades II and III of molecule A interact with blades III and II of molecule B. The mutations of amino acids involved in the interaction weakened the dimer interaction of Hpx domains in solution, and incorporation of these mutations into the full-length enzyme significantly inhibited dimer-dependent functions on the cell surface, including proMMP-2 activation, collagen degradation, and invasion into the three-dimensional collagen matrix, whereas dimer-independent functions, including gelatin film degradation and two-dimensional cell migration, were not affected. These results shed light on the structural basis of MT1-MMP dimerization that is crucial to promote cellular invasion.

Spectroscopic features of dimer and dangling bond E' centres in amorphous silica

International Nuclear Information System (INIS)

Mukhopadhyay, Sanghamitra; Sushko, Peter V; Mashkov, Vladimir A; Shluger, Alexander L

2005-01-01

We performed first-principle embedded cluster calculations of the hyperfine parameters, g-tensors and optical excitation energies for the dimer and back-projected configurations of the E' centre in amorphous silica. The optical transition energies of these defects are calculated for the first time. We predict a strong optical transition at about 6.3 eV for the dimer configuration and a relatively weak transition at 5.6 eV for the back-projected configuration of the E' centre. These predictions could be used for further experimental identification of these centres. Our results support the dimer model of the E' δ centre, and for the first time provide a full range of spectroscopic parameters for the back-projected configuration of the E' centre in amorphous silica

Covalent dimers of 1,3-diphenylisobenzofuran for singlet fission: synthesis and electrochemistry.

Science.gov (United States)

Akdag, Akin; Wahab, Abdul; Beran, Pavel; Rulíšek, Lubomír; Dron, Paul I; Ludvík, Jiří; Michl, Josef

2015-01-02

The synthesis of covalent dimers in which two 1,3-diphenylisobenzofuran units are connected through one phenyl substituent on each is reported. In three of the dimers, the subunits are linked directly, and in three others, they are linked via an alkane chain. A seventh new compound in which two 1,3-diphenylisobenzofuran units share a phenyl substituent is also described. These materials are needed for investigations of the singlet fission process, which promises to increase the efficiency of solar cells. The electrochemical oxidation and reduction of the monomer, two previously known dimers, and the seven new compounds have been examined, and reversible redox potentials have been compared with results obtained from density functional theory. Although the overall agreement is satisfactory, some discrepancies are noted and discussed.

Diffusion and adsorption of dimers on reconstructed Pt(1 1 0) surfaces: First principle and EAM studies

Science.gov (United States)

Matrane, I.; Mazroui, M.; Sbiaai, K.

2018-03-01

We present a density functional theory (DFT) and embedded atom method (EAM) studies of Pt2 , Au2 and AuPt dimers adsorption and diffusion on the clean Pt (1 1 0) (1 × 1) surface and (1 × 2) (1 × 3) and (1 × 4) missing row reconstructed geometries. As a first step, adsorption energies are calculated for all considered dimers, and their stability is checked by computing the binding energies. Furthermore, the energy barriers for the elementary diffusion mechanisms (concerted jump, dissociation-reassociation and leapfrog) are calculated for dimers diffusion on all considered geometries. The potential energy profile for the leapfrog mechanism is provided for dimers diffusion on the (1 × 2) (1 × 3) and (1 × 4) missing row reconstructed geometries. Our results show that each of the three dimers exhibits a qualitatively different behaviours. In addition, the obtained results provide interesting atomistic information about dimers stability and mobility, which is required for understanding the macroscopic kinetics of crystal growth.

Human cystatin C forms an inactive dimer during intracellular trafficking in transfected CHO cells

DEFF Research Database (Denmark)

Merz, G S; Benedikz, Eirikur; Schwenk, V

1997-01-01

To define the cellular processing of human cystatin C as well as to lay the groundwork for investigating its contribution to lcelandic Hereditary Cerebral Hemorrhage with Amyloidosis (HCHWA-I), we have characterized the trafficking, secretion, and extracellular fate of human cystatin C...... that the cystatin C dimer, formed during intracellular trafficking, is converted to monomer at or before secretion. Cells in which exit from the endoplasmic reticulum (ER) was blocked with brefeldin A contained the 33 kDa species, indicating that cystatin C dimerization occurs in the ER. After removal of brefeldin......, presumably as a consequence of the low pH of late endosome/lysosomes. As a dimer, cystatin C would be prevented from inhibiting the lysosomal cysteine proteases. These results reveal a novel mechanism, transient dimerization, by which cystatin C is inactivated during the early part of its trafficking through...

Giant magnetic anisotropy of rare-earth adatoms and dimers adsorbed by graphene oxide.

Science.gov (United States)

Zhang, Kai-Cheng; Li, Yong-Feng; Liu, Yong; Zhu, Yan; Shi, Li-Bin

2017-05-24

Nowadays, transition-metal adatoms and dimers with giant magnetic anisotropy have attracted much attention due to their potential applications in data storage, spintronics and quantum computations. Using density-functional calculations, we investigated the magnetic anisotropy of the rare-earth adatoms and dimers adsorbed by graphene oxide. Our calculations reveal that the adatoms of Tm, Er and Sm possess giant magnetic anisotropy, typically larger than 40 meV. When the dimers of (Tm,Er,Sm)-Ir are adsorbed onto graphene oxide, the magnetic anisotropy even exceeds 200 meV. The magnetic anisotropy can be tuned by the external electric field as well as the environment.

Data on dimer formation between importin α subtypes

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Yoichi Miyamoto

2016-06-01

Full Text Available This article describes data related to the research article titled “Functional characterization of importin α8 as a classical nuclear localization signal receptor” [1]. A GST pull-down assay showed that both importin α1 and α8, which are classical nuclear localization signal (cNLS receptors, can form a dimer with importin α6, α7, or α8. Importin α8 has higher dimer-forming ability than importin α1. In addition, our data show that either importin α1 or importin α8 can form a heterodimer with importin α3, which exists in a preformed complex with cNLS substrates such as the conventional SV40TNLS or the p53 protein, resulting in the release of the cNLS substrates from importin α3.

International survey on D-dimer test reporting: a call for standardization.

Science.gov (United States)

Lippi, Giuseppe; Tripodi, Armando; Simundic, Ana-Maria; Favaloro, Emmanuel J

2015-04-01

D-dimer is the biochemical gold standard for diagnosing a variety of thrombotic disorders, but result reporting is heterogeneous in clinical laboratories. A specific five-item questionnaire was developed to gain a clear picture of the current standardization of D-dimer test results. The questionnaire was opened online (December 24, 2014-February 10, 2015) on the platform "Google Drive (Google Inc., Mountain View; CA)," and widely disseminated worldwide by newsletters and alerts. A total of 409 responses were obtained during the period of data capture, the largest of which were from Italy (136; 33%), Australia (55; 22%), Croatia (29; 7%), Serbia (26; 6%), and the United States (21; 5%). Most respondents belonged to laboratories in general hospitals (208; 51%), followed by laboratories in university hospitals (104; 26%), and the private sector (94; 23%). The majority of respondents (i.e., 246; 60%) indicated the use of fibrinogen equivalent unit for expressing D-dimer results, with significant heterogeneities across countries and health care settings. The highest prevalence of laboratories indicated they were using "ng/mL" (139; 34%), followed by "mg/L" (136; 33%), and "µg/L" (73; 18%), with significant heterogeneity across countries but not among different health care settings. Expectedly, the vast majority of laboratories (379; 93%) declared to be using a fixed cutoff rather than an age-adjusted threshold, with no significant heterogeneity across countries and health care settings. The results of this survey attest that at least 28 different combinations of measurement units are currently used to report D-dimer results worldwide, and this evidence underscores the urgent need for more effective international joined efforts aimed to promote a worldwide standardization of D-dimer results reporting. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A nanolens-type enhancement in the linear and second harmonic response of a metallic dimer

International Nuclear Information System (INIS)

Pustovit, Vitaliy; Biswas, Sushmita; Vaia, Richard; Urbas, Augustine

2014-01-01

In this paper we explore the linear and second-order nonlinear response of gold nanoparticle pairs (dimers). Despite that even-order nonlinear processes are forbidden in bulk centrosymmetric media like metals, second order nonlinear response exhibits a high degree of sensitivity for spherical nanoparticles where inversion symmetry is broken at the surface. Recent experiments demonstrate significant dependence of linear response and second-harmonic surface nonlinear response arising from the local fundamental field distribution in a dimer configuration. Our calculations are carried out taking into account high order multipolar interactions between metal nanoparticles, and demonstrate that linear and nonlinear optical responses of the dimer exhibit periodic behavior dependent on the separation distance between nanoparticles. This response increases for dimers with a large difference between particle sizes. (paper)

Fibrillar dimer formation of islet amyloid polypeptides

Energy Technology Data Exchange (ETDEWEB)

Chiu, Chi-cheng [Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States); de Pablo, Juan J. [Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States)

2015-05-08

Amyloid deposits of human islet amyloid polypeptide (hIAPP), a 37-residue hormone co-produced with insulin, have been implicated in the development of type 2 diabetes. Residues 20 – 29 of hIAPP have been proposed to constitute the amyloidogenic core for the aggregation process, yet the segment is mostly unstructured in the mature fibril, according to solid-state NMR data. Here we use molecular simulations combined with bias-exchange metadynamics to characterize the conformational free energies of hIAPP fibrillar dimer and its derivative, pramlintide. We show that residues 20 – 29 are involved in an intermediate that exhibits transient β-sheets, consistent with recent experimental and simulation results. By comparing the aggregation of hIAPP and pramlintide, we illustrate the effects of proline residues on inhibition of the dimerization of IAPP. The mechanistic insights presented here could be useful for development of therapeutic inhibitors of hIAPP amyloid formation.

Fibrillar dimer formation of islet amyloid polypeptides

Directory of Open Access Journals (Sweden)

Chi-cheng Chiu

2015-09-01

Full Text Available Amyloid deposits of human islet amyloid polypeptide (hIAPP, a 37-residue hormone co-produced with insulin, have been implicated in the development of type 2 diabetes. Residues 20 – 29 of hIAPP have been proposed to constitute the amyloidogenic core for the aggregation process, yet the segment is mostly unstructured in the mature fibril, according to solid-state NMR data. Here we use molecular simulations combined with bias-exchange metadynamics to characterize the conformational free energies of hIAPP fibrillar dimer and its derivative, pramlintide. We show that residues 20 – 29 are involved in an intermediate that exhibits transient β-sheets, consistent with recent experimental and simulation results. By comparing the aggregation of hIAPP and pramlintide, we illustrate the effects of proline residues on inhibition of the dimerization of IAPP. The mechanistic insights presented here could be useful for development of therapeutic inhibitors of hIAPP amyloid formation.

Structures of closed and open conformations of dimeric human ATM

Science.gov (United States)

Baretić, Domagoj; Pollard, Hannah K.; Fisher, David I.; Johnson, Christopher M.; Santhanam, Balaji; Truman, Caroline M.; Kouba, Tomas; Fersht, Alan R.; Phillips, Christopher; Williams, Roger L.

2017-01-01

ATM (ataxia-telangiectasia mutated) is a phosphatidylinositol 3-kinase–related protein kinase (PIKK) best known for its role in DNA damage response. ATM also functions in oxidative stress response, insulin signaling, and neurogenesis. Our electron cryomicroscopy (cryo-EM) suggests that human ATM is in a dynamic equilibrium between closed and open dimers. In the closed state, the PIKK regulatory domain blocks the peptide substrate–binding site, suggesting that this conformation may represent an inactive or basally active enzyme. The active site is held in this closed conformation by interaction with a long helical hairpin in the TRD3 (tetratricopeptide repeats domain 3) domain of the symmetry-related molecule. The open dimer has two protomers with only a limited contact interface, and it lacks the intermolecular interactions that block the peptide-binding site in the closed dimer. This suggests that the open conformation may be more active. The ATM structure shows the detailed topology of the regulator-interacting N-terminal helical solenoid. The ATM conformational dynamics shown by the structures represent an important step in understanding the enzyme regulation. PMID:28508083

Magnetic anisotropy of heteronuclear dimers in the gas phase and supported on graphene: relativistic density-functional calculations.

Science.gov (United States)

Błoński, Piotr; Hafner, Jürgen

2014-04-09

The structural and magnetic properties of mixed PtCo, PtFe, and IrCo dimers in the gas phase and supported on a free-standing graphene layer have been calculated using density-functional theory, both in the scalar-relativistic limit and self-consistently including spin-orbit coupling. The influence of the strong magnetic moments of the 3d atoms on the spin and orbital moments of the 5d atoms, and the influence of the strong spin-orbit coupling contributed by the 5d atom on the orbital moments of the 3d atoms have been studied in detail. The magnetic anisotropy energy is found to depend very sensitively on the nature of the eigenstates in the vicinity of the Fermi level, as determined by band filling, exchange splitting and spin-orbit coupling. The large magnetic anisotropy energy of free PtCo and IrCo dimers relative to the easy direction parallel to the dimer axis is coupled to a strong anisotropy of the orbital magnetic moments of the Co atom for both dimers, and also on the Ir atom in IrCo. In contrast the PtFe dimer shows a weak perpendicular anisotropy and only small spin and orbital anisotropies of opposite sign on the two atoms. For dimers supported on graphene, the strong binding within the dimer and the stronger interaction of the 3d atom with the substrate stabilizes an upright geometry. Spin and orbital moments on the 3d atom are strongly quenched, but due to the weaker binding within the dimer the properties of the 5d atom are more free-atom-like with increased spin and orbital moments. The changes in the magnetic moment are reflected in the structure of the electronic eigenstates near the Fermi level, for all three dimers the easy magnetic direction is now parallel to the dimer axis and perpendicular to the graphene layer. The already very large magnetic anisotropy energy (MAE) of IrCo is further enhanced by the interaction with the support, the MAE of PtFe changes sign, and that of the PtCo dimer is reduced. These changes are discussed in relation to

Control activity of yeast geranylgeranyl diphosphate synthase from dimer interface through H-bonds and hydrophobic interaction.

Science.gov (United States)

Chang, Chih-Kang; Teng, Kuo-Hsun; Lin, Sheng-Wei; Chang, Tao-Hsin; Liang, Po-Huang

2013-04-23

Previously we showed that yeast geranylgeranyl diphosphate synthase (GGPPS) becomes an inactive monomer when the first N-terminal helix involved in dimerization is deleted. This raises questions regarding why dimerization is required for GGPPS activity and which amino acids in the dimer interface are essential for dimerization-mediated activity. According to the GGPPS crystal structure, three amino acids (N101, N104, and Y105) located in the helix F of one subunit are near the active site of the other subunit. As presented here, when these residues were replaced individually with Ala caused insignificant activity changes, N101A/Y105A and N101A/N104A but not N104A/Y105A showed remarkably decreased k(cat) values (200-250-fold). The triple mutant N101A/N104A/Y105A displayed no detectable activity, although dimer was retained in these mutants. Because N101 and Y105 form H-bonds with H139 and R140 in the other subunit, respectively, we generated H139A/R140A double mutant and found it was inactive and became monomeric. Therefore, the multiple mutations apparently influence the integrity of the catalytic site due to the missing H-bonding network. Moreover, Met111, also on the highly conserved helix F, was necessary for dimer formation and enzyme activity. When Met111 was replaced with Glu, the negative-charged repulsion converted half of the dimer into a monomer. In conclusion, the H-bonds mainly through N101 for maintaining substrate binding stability and the hydrophobic interaction of M111 in dimer interface are essential for activity of yeast GGPPS.

Nitrobenzene anti-parallel dimer formation in non-polar solvents

Directory of Open Access Journals (Sweden)

Toshiyuki Shikata

2014-06-01

Full Text Available We investigated the dielectric and depolarized Rayleigh scattering behaviors of nitrobenzene (NO2-Bz, which is a benzene mono-substituted with a planar molecular frame bearing the large electric dipole moment 4.0 D, in non-polar solvents solutions, such as tetrachloromethane and benzene, at up to 3 THz for the dielectric measurements and 8 THz for the scattering experiments at 20 °C. The dielectric relaxation strength of the system was substantially smaller than the proportionality to the concentration in a concentrated regime and showed a Kirkwood correlation factor markedly lower than unity; gK ∼ 0.65. This observation revealed that NO2-Bz has a tendency to form dimers, (NO2-Bz2, in anti-parallel configurations for the dipole moment with increasing concentration of the two solvents. Both the dielectric and scattering data exhibited fast and slow Debye-type relaxation modes with the characteristic time constants ∼7 and ∼50 ps in a concentrated regime (∼15 and ∼30 ps in a dilute regime, respectively. The fast mode was simply attributed to the rotational motion of the (monomeric NO2-Bz. However, the magnitude of the slow mode was proportional to the square of the concentration in the dilute regime; thus, the mode was assigned to the anti-parallel dimer, (NO2-Bz2, dissociation process, and the slow relaxation time was attributed to the anti-parallel dimer lifetime. The concentration dependencies of both the dielectric and scattering data show that the NO2-Bz molecular processes are controlled through a chemical equilibrium between monomers and anti-parallel dimers, 2NO2-Bz ↔ (NO2-Bz2, due to a strong dipole-dipole interaction between nitro groups.

Metal-porphyrin interactions. V. Kinetics of cyanide addition to a water soluble iron porphyrin dimer(1)

Energy Technology Data Exchange (ETDEWEB)

Hambright, P; Rishnamurthy, M K

1975-01-01

The kinetics of cyanide addition to the water-soluble oxybridged iron dimer of tetra (p-sulophenyl) porphin indicate that HCN is the reactant. The rate law is of the form: Rate = (3.8 +- 0.2) x 10/sup 4/ (Fe dimer) (HCN)/(1 + (3.1 +- 0.3) x 10/sup 10/ (H/sup +/)) at 25/sup 0/ ..mu.. = 0.7 (NaNO/sub 3/). The cyano iron dimer dissociates into dicyano iron monomers by two pathways, one first order in (H/sup +/), and one proportional to (H/sup +/)(CN/sup -/)/sup 2/. The mechanism of this dimer reaction is compared to iron porphyrin monomer systems.

Structures and energetics of lithium adatom and its dimer on graphene–a DFT study

International Nuclear Information System (INIS)

Kaur, Gagandeep; Gupta, Shuchi; Dharamvir, Keya

2015-01-01

Highlights: • For single Li adatom adsorption on graphene, it prefers H-site followed by B-site. • By the examination of the calculated cohesive energies, it is possible to conclude that both Li/Li 2 binds strongly to graphene which corroborate previous results. • The calculations showed that the interaction between Li and graphene has minimal effects on the electronic states of the graphene sheet, in agreement with previous calculations. • Charge transfer (0.338e)upon adsorption also induces significant electric dipole moments and affect total magnetic moment at B-site and T-site. • For the Li dimer adsorption, we found that horizontal orientation is favored over the vertical. • Adsorption of lithium dimer to the HH-site alters graphene sheet only by small amount ∼0.0022 Å–0.0034 Å. • The methodology demonstrated in this paper maybe applied to larger lithium clusters on graphene sheet. - Abstract: We performed a systematic density functional theory (DFT) study of the adsorption of Lithium adatom and its dimer on graphene using SIESTA package [1], in the generalized gradient approximation (GGA). The adsorption energy, geometry, charge transfer and density of states of adatom/dimer-graphene system are calculated. The calculations showed that the interaction between Li adatom and graphene is strong (∼1.07 eV) and it prefers to adsorb on H-site. Further calculations of both horizontally and vertically aligned dimers show that the adsorption is also weak for the latter orientation. The preferred orientation of each dimer was found to be parallel to graphene sheet with the two atoms of the dimer occupying adjacent H-sites on the graphene. Significant charge transfer (∼0.388e) from Li adatom to graphene will induce electric dipole moments in the adatom/graphene system. We also calculated DOS for the stable Li -graphene system. The Fermi energy is seen to lie above the Dirac point inside the conduction band indicating that appreciable electrons

Live cell imaging unveils multiple domain requirements for in vivo dimerization of the glucocorticoid receptor.

Directory of Open Access Journals (Sweden)

Diego M Presman

2014-03-01

Full Text Available Glucocorticoids are essential for life, but are also implicated in disease pathogenesis and may produce unwanted effects when given in high doses. Glucocorticoid receptor (GR transcriptional activity and clinical outcome have been linked to its oligomerization state. Although a point mutation within the GR DNA-binding domain (GRdim mutant has been reported as crucial for receptor dimerization and DNA binding, this assumption has recently been challenged. Here we have analyzed the GR oligomerization state in vivo using the number and brightness assay. Our results suggest a complete, reversible, and DNA-independent ligand-induced model for GR dimerization. We demonstrate that the GRdim forms dimers in vivo whereas adding another mutation in the ligand-binding domain (I634A severely compromises homodimer formation. Contrary to dogma, no correlation between the GR monomeric/dimeric state and transcriptional activity was observed. Finally, the state of dimerization affected DNA binding only to a subset of GR binding sites. These results have major implications on future searches for therapeutic glucocorticoids with reduced side effects.

Periodic table of 3d-metal dimers and their ions.

Science.gov (United States)

Gutsev, G L; Mochena, M D; Jena, P; Bauschlicher, C W; Partridge, H

2004-10-08

The ground states of the mixed 3d-metal dimers TiV, TiCr, TiMn, TiFe, TiCo, TiNi, TiCu, TiZn, VCr, VMn, VFe, VCo, VNi, VCu, VZn, CrMn, CrFe, CrCo, CrNi, CrCu, CrZn, MnFe, MnCo, MnNi, MnCu, MnZn, FeCo, FeNi, FeCu, FeZn, CoNi, CoCu, CoZn, NiCu, NiZn, and CuZn along with their singly negatively and positively charged ions are assigned based on the results of computations using density functional theory with generalized gradient approximation for the exchange-correlation functional. Except for TiCo and CrMn, our assignment agrees with experiment. Computed spectroscopic constants (r(e),omega(e),D(o)) are in fair agreement with experiment. The ground-state spin multiplicities of all the ions are found to differ from the spin multiplicities of the corresponding neutral parents by +/-1. Except for TiV, MnFe, and MnCu, the number of unpaired electrons, N, in a neutral ground-state dimer is either N(1)+N(2) or mid R:N(1)-N(2)mid R:, where N(1) and N(2) are the numbers of unpaired 3d electrons in the 3d(n)4s(1) occupation of the constituent atoms. Combining the present and previous results obtained at the same level of theory for homonuclear 3d-metal and ScX (X=Ti-Zn) dimers allows one to construct "periodic" tables of all 3d-metal dimers along with their singly charged ions.

GLYCOLALDEHYDE FORMATION VIA THE DIMERIZATION OF THE FORMYL RADICAL

Energy Technology Data Exchange (ETDEWEB)

Woods, Paul M.; Viti, Serena [Department of Physics and Astronomy, University College London, Gower Street, London WC1E 6BT (United Kingdom); Slater, Ben; Raza, Zamaan; Brown, Wendy A.; Burke, Daren J., E-mail: p.woods@qub.ac.uk [Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ (United Kingdom)

2013-11-10

Glycolaldehyde, the simplest monosaccharide sugar, has recently been detected in low- and high-mass star-forming cores. Following our previous investigation into glycolaldehyde formation, we now consider a further mechanism for the formation of glycolaldehyde that involves the dimerization of the formyl radical, HCO. Quantum mechanical investigation of the HCO dimerization process upon an ice surface is predicted to be barrierless and therefore fast. In an astrophysical context, we show that this mechanism can be very efficient in star-forming cores. It is limited by the availability of the formyl radical, but models suggest that only very small amounts of CO are required to be converted to HCO to meet the observational constraints.

GLYCOLALDEHYDE FORMATION VIA THE DIMERIZATION OF THE FORMYL RADICAL

International Nuclear Information System (INIS)

Woods, Paul M.; Viti, Serena; Slater, Ben; Raza, Zamaan; Brown, Wendy A.; Burke, Daren J.

2013-01-01

Glycolaldehyde, the simplest monosaccharide sugar, has recently been detected in low- and high-mass star-forming cores. Following our previous investigation into glycolaldehyde formation, we now consider a further mechanism for the formation of glycolaldehyde that involves the dimerization of the formyl radical, HCO. Quantum mechanical investigation of the HCO dimerization process upon an ice surface is predicted to be barrierless and therefore fast. In an astrophysical context, we show that this mechanism can be very efficient in star-forming cores. It is limited by the availability of the formyl radical, but models suggest that only very small amounts of CO are required to be converted to HCO to meet the observational constraints

Stability of gold atoms and dimers adsorbed on graphene

International Nuclear Information System (INIS)

Varns, R; Strange, P

2008-01-01

We report density functional theory (DFT) calculations for gold atoms and dimers on the surface of graphene. The calculations were performed using the plane wave pseudopotential method. Calculations were performed for a variety of geometries, and both the graphene surface and gold atoms were allowed to fully relax. In agreement with experiment, our results show that the gold-gold interaction is considerably stronger than the gold-graphene interaction, implying that uniform coverage could not be attained. The minimum energy configuration for a single gold atom is found to be directly above a carbon atom, while for the dimer it is perpendicular to the surface and directly above a carbon-carbon bond. Our results are consistent with previous similar calculations

Van der Waals potential and vibrational energy levels of the ground state radon dimer

Science.gov (United States)

Sheng, Xiaowei; Qian, Shifeng; Hu, Fengfei

2017-08-01

In the present paper, the ground state van der Waals potential of the Radon dimer is described by the Tang-Toennies potential model, which requires five essential parameters. Among them, the two dispersion coefficients C6 and C8 are estimated from the well determined dispersion coefficients C6 and C8 of Xe2. C10 is estimated by using the approximation equation that C6C10/C82 has an average value of 1.221 for all the rare gas dimers. With these estimated dispersion coefficients and the well determined well depth De and Re the Born-Mayer parameters A and b are derived. Then the vibrational energy levels of the ground state radon dimer are calculated. 40 vibrational energy levels are observed in the ground state of Rn2 dimer. The last vibrational energy level is bound by only 0.0012 cm-1.

Non-Ligand-Induced Dimerization is Sufficient to Initiate the Signalling and Endocytosis of EGF Receptor

Directory of Open Access Journals (Sweden)

George Kourouniotis

2016-07-01

Full Text Available The binding of epidermal growth factor (EGF to EGF receptor (EGFR stimulates cell mitogenesis and survival through various signalling cascades. EGF also stimulates rapid EGFR endocytosis and its eventual degradation in lysosomes. The immediate events induced by ligand binding include receptor dimerization, activation of intrinsic tyrosine kinase and autophosphorylation. However, in spite of intensified efforts, the results regarding the roles of these events in EGFR signalling and internalization is still very controversial. In this study, we constructed a chimeric EGFR by replacing its extracellular domain with leucine zipper (LZ and tagged a green fluorescent protein (GFP at its C-terminus. We showed that the chimeric LZ-EGFR-GFP was constitutively dimerized. The LZ-EGFR-GFP dimer autophosphorylated each of its five well-defined C-terminal tyrosine residues as the ligand-induced EGFR dimer does. Phosphorylated LZ-EGFR-GFP was localized to both the plasma membrane and endosomes, suggesting it is capable of endocytosis. We also showed that LZ-EGFR-GFP activated major signalling proteins including Src homology collagen-like (Shc, extracellular signal-regulated kinase (ERK and Akt. Moreover, LZ-EGFR-GFP was able to stimulate cell proliferation. These results indicate that non-ligand induced dimerization is sufficient to activate EGFR and initiate cell signalling and EGFR endocytosis. We conclude that receptor dimerization is a critical event in EGF-induced cell signalling and EGFR endocytosis.

Structure of an RNA dimer of a regulatory element from human thymidylate synthase mRNA

OpenAIRE

Dibrov, Sergey; McLean, Jaime; Hermann, Thomas

2011-01-01

An oligonucleotide representing a regulatory element of human thymidylate synthase mRNA has been crystallized as a dimer. The structure of the asymmetric dimer has been determined at 1.97 Å resolution.

Predictive value of elevated D-dimer in patients undergoing primary angioplasty for ST elevation myocardial infarction.

Science.gov (United States)

Akgul, Ozgur; Uyarel, Huseyin; Pusuroglu, Hamdi; Gul, Mehmet; Isiksacan, Nilgun; Turen, Selahattin; Erturk, Mehmet; Surgit, Ozgur; Cetin, Mustafa; Bulut, Umit; Baycan, Omer F; Uslu, Nevzat

2013-10-01

The aim of this study was to evaluate the prognostic value of D-dimer in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). The prognostic value of D-dimer has been documented in patients with acute coronary syndrome without ST-segment elevation. However, its value in acute ST-segment elevation myocardial infarction (STEMI) remains unclear. We prospectively enrolled 453 consecutive STEMI patients (mean age 55.6 ± 12.4 years, 364 male, 89 female) undergoing primary PCI. The study population was divided into tertiles based on admission D-dimer values. The high D-dimer group (n = 151) was defined as a value in the third tertile [>0.72 ug/ml fibrinogen equivalent units (FEU)], and the low D-dimer group (n = 302) included those patients with a value in the lower two tertiles (≤0.72 ug/ml FEU). Clinical characteristics, in-hospital and 6-month outcomes of primary PCI were analyzed. The patients of the high D-dimer group were older (mean age 60.1 ± 13.5 versus 52.4 ± 10.6, P 0.72 ug/ml FEU) was found to be a powerful independent predictor of 6-month all-cause mortality (odds ratio: 10.1, 95% confidence interval: 1.24-42.73, P = 0.03). These results suggest that a high admission D-dimer, level was associated with increased in-hospital cardiovascular mortality and 6-month all-cause mortality in patients with STEMI undergoing primary PCI.

Effect of pigment on photomediated production of thymine dimers in cultured melanoma cells

International Nuclear Information System (INIS)

London, D.A.; Carter, D.M.; Condit, E.S.

1976-01-01

It was the aim of these studies to determine whether the presence of intracellular melanin quantitatively alters the rate of production of thymine dimers in DNA of irradiated cells in culture. Pigmented and nonpigmented Cloudman mouse melanoma cells were selected assuming that the two cell lines differ primarily in their content of melanin pigment. Cells were cultivated in tritiated thymine in order to label their DNA and were then exposed to ultraviolet (uv) irradiation (260 nm, 500-2000 ergs/mm 2 ). Neither cell line survived these doses of irradiation. DNA was extracted immediately following irradiation and was subjected to acid hydrolysis. The presence of thymine dimers was determined by two-dimensional paper chromatography. The percent of labeled thymine recovered as thymine dimer was calculated and was found to be a linear function of uv dose for both cell lines. The rate of formation of dimers in the nonpigmented cells was nearly twice that in the pigmented cells. These data demonstrate the photoprotective property of intracellular melanin in shielding isolated cells from one type of photomediated injury to DNA

Construction of covalently coupled, concatameric dimers of 7TM receptors

DEFF Research Database (Denmark)

Terpager, Marie; Scholl, D Jason; Kubale, Valentina

2009-01-01

-Ala repeats flanked by flexible spacers and positively charged residues to ensure correct inside-out orientation plus an extracellular HA-tag to construct covalently coupled dimers of 7TM receptors. Such 15 TM concatameric homo- and heterodimers of the beta(2)-adrenergic and the NK(1) receptors, which...... for either of the protomers, which was not observed upon simple coexpression of the two receptors. It is concluded that covalently joined 7TM receptor dimers with surprisingly normal receptor properties can be constructed with use of an artificial transmembrane connector, which perhaps can be used to fuse...

On the photophysics and photochemistry of the water dimer

Energy Technology Data Exchange (ETDEWEB)

Segarra-Marti, Javier; Merchan, Manuela [Instituto de Ciencia Molecular, Universitat de Valencia, P.O. Box 22085, 46071 Valencia (Spain); Roca-Sanjuan, Daniel; Lindh, Roland [Department of Chemistry - Angstroem, Theoretical Chemistry Program, Uppsala University, Box 518, 75120 Uppsala (Sweden)

2012-12-28

The photochemistry of the water dimer irradiated by UV light is studied by means of the complete active space perturbation theory//complete active space self-consistent field (CASPT2//CASSCF) method and accurate computational approaches like as minimum energy paths. Both electronic structure computations and ab initio molecular dynamics simulations are carried out. The results obtained show small shifts relative to a single water molecule on the vertical excitation energies of the dimer due to the hydrogen bond placed between the water donor (W{sub D}) and the water acceptor (W{sub A}). A red-shift and a blue-shift are predicted for the W{sub D} and W{sub A}, respectively, supporting previous theoretical and experimental results. The photoinduced chemistry of the water dimer is described as a process occurring between two single water molecules in which the effect of the hydrogen bond plays a minor role. Thus, the photoinduced decay routes correspond to two photodissociation processes, one for each water molecule. The proposed mechanism for the decay channels of the lowest-lying excited states of the system is established as the photochemical production of a hydrogen-bonded H{sub 2}O Horizontal-Ellipsis HO species plus a hydrogen H atom.

99mTc-labeling of HYNIC-conjugated cyclic RGDfK dimer and tetramer using EDDA as coligand.

Science.gov (United States)

Wang, Jianjun; Kim, Young-Seung; Liu, Shuang

2008-03-01

In this study, EDDA (ethylenediamine- N, N'-diacetic acid) was used as the coligand for 99mTc-labeling of cyclic RGDfK conjugates: HYNIC-dimer (HYNIC = 6-hydrazinonicotinamide; dimer = E[c(RGDfK)]2) and HYNIC-tetramer (tetramer = E{E[c(RGDfK)]2}2). First, HYNIC-dimer was allowed to react with 99mTcO4 (-) in the presence of excess tricine and stannous chloride to form the intermediate complex [99mTc(HYNIC-dimer)(tricine)2], which was then allowed to react with EDDA to afford [99mTc(HYNIC-dimer)(EDDA)] with high yield (>90%) and high specific activity ( approximately 8.0 Ci/micromol). Under the same radiolabeling conditions, the yield for [99mTc(HYNIC-tetramer)(EDDA)] was always EDDA bonding to the 99mTc-HYNIC core in [99mTc(HYNIC-dimer)(EDDA)]. The athymic nude mice bearing subcutaneous U87MG human glioma xenografts were used to evaluate the impact of EDDA coligand on the biodistribution characteristics and excretion kinetics of the 99mTc-labeled HYNIC-dimer and HYNIC-tetramer. Surprisingly, [99mTc(HYNIC-dimer)(EDDA)] and [99mTc(HYNIC-tetramer)(EDDA)] had almost identical tumor uptake over the 2 h period. The use of EDDA as coligand to replace tricine/TPPTS (TPPTS = trisodium triphenylphosphine-3,3',3''-trisulfonate) did not significantly change the uptake of the 99mTc-labeled HYNIC-dimer in noncancerous organs, such as the liver, kidneys, and lungs; but it did result in a significantly lower kidney uptake for the 99mTc-labeled HYNIC-tetramer due to faster renal excretion. It was also found that the radiotracer tumor uptake decreases in a linear fashion as the tumor size increases. The smaller the tumors are, the higher the tumor uptake is regardless of the identity of radiotracer.

New developments in porphyrin-like macrocyclic chemistry: a novel family of dibenzotetraaza[14]annulene-based cofacial dimers.

Science.gov (United States)

Zwoliński, K M; Eilmes, J

2016-03-14

The first known homoleptic cofacial dimers, based on covalently linked dibenzotetraaza[14]annulenes, were synthesized in reasonable 35-40% yields, without recourse to high-dilution techniques. Dinuclear zinc(ii) dimer showed strong binding affinity toward DABCO. Site-selective monometallation of the dimer, triggered by the linkers' structure, was observed, allowing access to heterobimetallic co-receptors.

Arm-in-Arm Response Regulator Dimers Promote Intermolecular Signal Transduction

Energy Technology Data Exchange (ETDEWEB)

Baker, Anna W.; Satyshur, Kenneth A.; Morales, Neydis Moreno; Forest, Katrina T. (UW)

2016-02-01

Bacteriophytochrome photoreceptors (BphPs) and their cognate response regulators make up two-component signal transduction systems which direct bacteria to mount phenotypic responses to changes in environmental light quality. Most of these systems utilize single-domain response regulators to transduce signals through unknown pathways and mechanisms. Here we describe the photocycle and autophosphorylation kinetics of RtBphP1, a red light-regulated histidine kinase from the desert bacteriumRamlibacter tataouinensis. RtBphP1 undergoes red to far-red photoconversion with rapid thermal reversion to the dark state. RtBphP1 is autophosphorylated in the dark; this activity is inhibited under red light. The RtBphP1 cognate response regulator, theR. tataouinensisbacteriophytochrome response regulator (RtBRR), and a homolog, AtBRR fromAgrobacterium tumefaciens, crystallize unexpectedly as arm-in-arm dimers, reliant on a conserved hydrophobic motif, hFWAhL (where h is a hydrophobic M, V, L, or I residue). RtBRR and AtBRR dimerize distinctly from four structurally characterized phytochrome response regulators found in photosynthetic organisms and from all other receiver domain homodimers in the Protein Data Bank. A unique cacodylate-zinc-histidine tag metal organic framework yielded single-wavelength anomalous diffraction phases and may be of general interest. Examination of the effect of the BRR stoichiometry on signal transduction showed that phosphorylated RtBRR is accumulated more efficiently than the engineered monomeric RtBRR (RtBRR_mon) in phosphotransfer reactions. Thus, we conclude that arm-in-arm dimers are a relevant signaling intermediate in this class of two-component regulatory systems.

D-dimer as an applicable test for detection of posttraumatic deep vein thrombosis in lower limb fracture.

Science.gov (United States)

Bakhshi, Hooman; Alavi-Moghaddam, Mostafa; Wu, Karin C; Imami, Mohammad; Banasiri, Mohammad

2012-06-01

Measuring the plasma levels of D-dimer is an accurate and easy modality to detect deep vein thrombosis (DVT) in nontraumatic settings. However, the diagnostic reliability of D-dimer assays in detecting posttraumatic DVT among patients with lower limb fracture undergoing orthopedic surgery is not validated. In this study, 141 patients with lower limb fracture admitted through the emergency department and undergoing orthopedic surgery were enrolled. Postoperative venous blood samples for D-dimer assay were taken on the 1st, 7th, and 28th postoperative days. Color Doppler sonography examination of both lower limbs was performed at the same time as a standard test. Eight out of the 141 patients (6%) had acute DVT based on Color Doppler sonography. Mean D-dimer was 2160 ng/mL in DVT positive patients and 864 in DVT negative patients. D-dimer levels greater than 1000 ng/mL were 100% sensitive and 71% specific for detecting postoperative DVT. D-dimer assay is a useful and sensitive test for detecting posttraumatic DVT.

Cis elements and trans-acting factors involved in the RNA dimerization of the human immunodeficiency virus HIV-1.

Science.gov (United States)

Darlix, J L; Gabus, C; Nugeyre, M T; Clavel, F; Barré-Sinoussi, F

1990-12-05

The retroviral genome consists of two identical RNA molecules joined at their 5' ends by the Dimer Linkage Structure (DLS). To study the mechanism of dimerization and the DLS of HIV-1 RNA, large amounts of bona fide HIV-1 RNA and of mutants have been synthesized in vitro. We report that HIV-1 RNA forms dimeric molecules and that viral nucleocapsid (NC) protein NCp15 greatly activates dimerization. Deletion mutagenesis in the RNA 5' 1333 nucleotides indicated that a small domain of 100 nucleotides, located between positions 311 to 415 from the 5' end, is necessary and sufficient to promote HIV-1 RNA dimerization. This dimerization domain encompasses an encapsidation element located between the 5' splice donor site and initiator AUG of gag and shows little sequence variations in different strains of HIV-1. Furthermore, cross-linking analysis of the interactions between NC and HIV-1 RNA (311 to 415) locates a major contact site in the encapsidation element of HIV-1 RNA. The genomic RNA dimer is tightly associated with nucleocapsid protein molecules in avian and murine retroviruses, and this ribonucleoprotein structure is believed to be the template for reverse transcription. Genomic RNA-protein interactions have been analyzed in human immunodeficiency virus (HIV) virions and results showed that NC protein molecules are tightly bound to the genomic RNA dimer. Since retroviral RNA dimerization and packaging appear to be under the control of the same cis element, the encapsidation sequences, and trans-acting factor, the NC protein, they are probably related events in the course of virion assembly.

Rational Organization of Lanthanide-Based SMM Dimers into Three-Dimensional Networks.

Science.gov (United States)

Yi, Xiaohui; Calvez, Guillaume; Daiguebonne, Carole; Guillou, Olivier; Bernot, Kevin

2015-06-01

Optimization of the reaction of [Ln(hfac)3]·2H2O and pyridine-N-oxide (PyNO), which is known to afford double-bridged dimers, leads to triple-bridged dimers of formula [(Ln(hfac)3)2(PyNO)3] (Ln = Gd (1), Dy (2)) from which the Dy derivative (2) behaves as a single-molecule magnet (SMM). The pseudo threefold axis symmetry of this zero-dimensional building block makes possible its extension into a tridimensional network. By changing PyNO for 4,4'-bipyridine N,N'-dioxide (4,4'BipyNO) a tridimensional compound of formula {[Ln(hfac)3]2(4,4'BipyNO)2]} (Ln = Eu (3), Gd (4), and Dy (5)) is then rationally obtained. This covalent three-dimensional (3D) network has a remarkably high cell volume (V = 24 419 A(3)) and is an arrangement of interpenetrated 3D subnetworks whose triple-bridged dimers still behave as SMMs.

D-dimer in the diagnosis of thromboembolic disease after spinal surgery

International Nuclear Information System (INIS)

Oyama, Motohiko; Saita, Kazuo; Iijima, Yuki; Ueda, Yusuke; Endo, Teruaki

2010-01-01

The plasma D-dimer levels of 136 patients (80 men and 56 women, mean age 63.9 years) who underwent spinal surgery in our hospital were measured on pod 3 and pod 7, as a method of screening for thromboembolic disease. A D-dimer cut off value of 10 μg/dl was used and only the patients with higher values were examined by CT. No patients had symptomatic thromboembolic disease. On pod 7 the D-dimer levels of 14 patients was above 10 μg/dl, but only 2 of them were detected in asymptomatic pulmonary embolism. Both of them had undergone anterior fusion surgery, and no deep venous thrombosis was detected in the lower extremities. Anticoagulation therapy with heparin and warfarin was started immediately, and the patients were discharged symptom-free. Another methods of thromboprophylaxis in addition to traditional mechanical thromboprophylaxis, such as by wearing compression stockings and foot pumps, may be necessary after anterior spinal surgery. (author)

A strategy for complex dimer formation when biomimicry fails: total synthesis of ten coccinellid alkaloids.

Science.gov (United States)

Sherwood, Trevor C; Trotta, Adam H; Snyder, Scott A

2014-07-09

Although dimeric natural products can often be synthesized in the laboratory by directly merging advanced monomers, these approaches sometimes fail, leading instead to non-natural architectures via incorrect unions. Such a situation arose during our studies of the coccinellid alkaloids, when attempts to directly dimerize Nature's presumed monomeric precursors in a putative biomimetic sequence afforded only a non-natural analogue through improper regiocontrol. Herein, we outline a unique strategy for dimer formation that obviates these difficulties, one which rapidly constructs the coccinellid dimers psylloborine A and isopsylloborine A through a terminating sequence of two reaction cascades that generate five bonds, five rings, and four stereocenters. In addition, a common synthetic intermediate is identified which allows for the rapid, asymmetric formal or complete total syntheses of eight monomeric members of the class.

The immunity-related GTPase Irga6 dimerizes in a parallel head-to-head fashion.

Science.gov (United States)

Schulte, Kathrin; Pawlowski, Nikolaus; Faelber, Katja; Fröhlich, Chris; Howard, Jonathan; Daumke, Oliver

2016-03-02

The immunity-related GTPases (IRGs) constitute a powerful cell-autonomous resistance system against several intracellular pathogens. Irga6 is a dynamin-like protein that oligomerizes at the parasitophorous vacuolar membrane (PVM) of Toxoplasma gondii leading to its vesiculation. Based on a previous biochemical analysis, it has been proposed that the GTPase domains of Irga6 dimerize in an antiparallel fashion during oligomerization. We determined the crystal structure of an oligomerization-impaired Irga6 mutant bound to a non-hydrolyzable GTP analog. Contrary to the previous model, the structure shows that the GTPase domains dimerize in a parallel fashion. The nucleotides in the center of the interface participate in dimerization by forming symmetric contacts with each other and with the switch I region of the opposing Irga6 molecule. The latter contact appears to activate GTP hydrolysis by stabilizing the position of the catalytic glutamate 106 in switch I close to the active site. Further dimerization contacts involve switch II, the G4 helix and the trans stabilizing loop. The Irga6 structure features a parallel GTPase domain dimer, which appears to be a unifying feature of all dynamin and septin superfamily members. This study contributes important insights into the assembly and catalytic mechanisms of IRG proteins as prerequisite to understand their anti-microbial action.

Differences in pyrimidine dimer removal between rat skin cells in vitro and in vivo

International Nuclear Information System (INIS)

Mullaart, E.; Lohman, P.H.; Vijg, J.

1988-01-01

Pyrimidine dimers, the most abundant type of DNA lesions induced by ultraviolet light (UV), are rapidly repaired in human skin fibroblasts in vitro. In the same cell type from rats, however, there is hardly any removal of such dimers. To investigate whether this low capacity of rat skin cells to repair lesions in their DNA is an inherent characteristic of this species or an artifact due to cell culturing, we measured the removal of UV-induced pyrimidine dimers from rat epidermal keratinocytes both in vitro and in vivo. Epidermal keratinocytes in vitro were unable to remove any dimers over the first 3 h after UV-irradiation, while only about 20% was removed during a repair period of 24 h. In this respect, these cells were not different from cultured rat fibroblasts. In contrast to the results obtained with keratinocytes in vitro, we observed a rapid repair of pyrimidine dimers in UV-irradiated keratinocytes in vivo over the first 3 h; this rapid repair phase was followed by a much slower repair phase between 3 and 24 h. These results are discussed in terms of the possibility that mammalian cells are able to switch from one DNA repair pathway to another

Energetics and dynamics of Pt dimers on Pt(110)-(1x2)

International Nuclear Information System (INIS)

Linderoth, T.R.; Horch, S.; Petersen, L.; Helveg, S.; Schoenning, M.; Laegsgaard, E.; Stensgaard, I.; Besenbacher, F.

2000-01-01

The stability and dynamics of Pt dimers on Pt(110)-(1x2) are studied using fast-scanning, variable-temperature STM. The kinetics of both dissociation and association of dimers have been quantified from a direct analysis of time-lapse STM movies. The extracted barriers are at variance with results from ab initio calculations, and we speculate that the discrepancies are due to trace amounts of gas impurities such as CO

Core-to-core dimers forming switchable mesophase

Czech Academy of Sciences Publication Activity Database

Horčic, M.; Svoboda, J.; Novotná, Vladimíra; Pociecha, D.; Gorecka, E.

2017-01-01

Roč. 53, č. 18 (2017), s. 2721-2724 ISSN 1359-7345 R&D Projects: GA ČR GA15-02843S Institutional support: RVO:68378271 Keywords : liquid crystals * bent- core mesogens * dimers Subject RIV: JJ - Other Materials OBOR OECD: Nano-materials (production and properties) Impact factor: 6.319, year: 2016

Synthesis and characterization of monomeric and dimeric ...

African Journals Online (AJOL)

The two complexes are isostructural, with the central metal atom lying on a crystallographic 2-fold axis. Both complexes are approximately octahedral, the coordination being provided by two trans pyridine nitrogen atoms and two cis amine nitrogen atoms from the oxime ligands, and by two cis chlorides. The dimeric ...

A study of the dimer formation of Rous sarcoma virus RNA and of its effect on viral protein synthesis in vitro.

Science.gov (United States)

Bieth, E; Gabus, C; Darlix, J L

1990-01-11

The genetic material of all retroviruses examined so far is an RNA dimer where two identical RNA subunits are joined at their 5' ends by a structure named dimer linkage structure (DLS). Since the precise location and structure of the DLS as well as the mechanism and role(s) of RNA dimerization remain unclear, we analysed the dimerization process of Rous sarcoma virus (RSV) RNA. For this purpose we set up an in vitro model for RSV RNA dimerization. Using this model RSV RNA was shown to form dimeric molecules and this dimerization process was greatly activated by nucleocapsid protein (NCp12) of RSV. Furthermore, RSV RNA dimerization was performed in the presence of complementary 5'32P-DNA oligomers in order to probe the monomer and dimer forms of RSV RNA. Data indicated that the DLS of RSV RNA probably maps between positions 544-564 from the 5' end. In an attempt to define sequences needed for the dimerization of RSV RNA, deletion mutageneses were generated in the 5' 600 nt. The results showed that the dimer promoting sequences probably are located within positions 208-270 and 400-600 from the 5' end and hence possibly encompassing the cis-acting elements needed for the specific encapsidation of RSV genomic RNA. Also it is reported that synthesis of the polyprotein precursor Pr76gag is inhibited upon dimerization of RSV RNA. These results suggest that dimerization and encapsidation of genome length RSV RNA might be linked in the course of virion formation since they appear to be under the control of the same cis elements, E and DLS, and the trans-acting factor nucleocapsid protein NCp12.

CtBP1/BARS Gly172 → Glu mutant structure: Impairing NAD(H)-binding and dimerization

International Nuclear Information System (INIS)

Nardini, Marco; Valente, Carmen; Ricagno, Stefano; Luini, Alberto; Corda, Daniela; Bolognesi, Martino

2009-01-01

C-terminal binding proteins (CtBPs) are multi-functional proteins involved in nuclear transcriptional co-repression, Golgi membrane fission, and synaptic ribbon formation. Binding of NAD(H) to CtBPs promotes dimerization. CtBP dimers act as a scaffold for multimeric protein complex formation, thus bridging transcriptional repressors and their targets in the nucleus. Based on size-exclusion chromatography experiments and on the crystal structure of the NAD(H)-free G172E CtBP mutant, we show here that absence of NAD(H) induces flexibility/backbone conformational changes at the dimerization interface and at the CtBP interdomain region. The results presented shed first light on the correlation between NAD(H)-binding and functional CtBP dimerization.

A riboswitch regulates RNA dimerization and packaging in human immunodeficiency virus type 1 virions

NARCIS (Netherlands)

Ooms, Marcel; Huthoff, Hendrik; Russell, Rodney; Liang, Chen; Berkhout, Ben

2004-01-01

The genome of retroviruses, including human immunodeficiency virus type I (HIV-1), consists of two identical RNA strands that are packaged as noncovalently linked dimers. The core packaging and dimerization signals are located in the downstream part of the untranslated leader of HIV-1 RNA-the Psi

Experimental Observation of Strongly Bound Dimers of Sulfuric Acid: Application to Nucleation in the Atmosphere

DEFF Research Database (Denmark)

Petaja, Tuukka; Sipila, Mikko; Paasonen, Pauli

2011-01-01

rate was clearly higher than the measured new particle formation rate at similar to 1.5 nmsuggesting that the rate limiting step for the nucleation takes place after the dimerization step. The quantum chemical calculations suggested that even in the ultraclean conditions there exist (a) stabilizing...... compound(s) with (a) concentration(s) high enough to prevent the dimer evaporation. Such a stabilizing compound should be abundant enough in any natural environment and would therefore not limit the formation of sulfuric acid dimers in the atmosphere....

Impaired thromboxane receptor dimerization reduces signaling efficiency: A potential mechanism for reduced platelet function in vivo.

Science.gov (United States)

Capra, Valérie; Mauri, Mario; Guzzi, Francesca; Busnelli, Marta; Accomazzo, Maria Rosa; Gaussem, Pascale; Nisar, Shaista P; Mundell, Stuart J; Parenti, Marco; Rovati, G Enrico

2017-01-15

Thromboxane A 2 is a potent mediator of inflammation and platelet aggregation exerting its effects through the activation of a G protein-coupled receptor (GPCR), termed TP. Although the existence of dimers/oligomers in Class A GPCRs is widely accepted, their functional significance still remains controversial. Recently, we have shown that TPα and TPβ homo-/hetero-dimers interact through an interface of residues in transmembrane domain 1 (TM1) whose disruption impairs dimer formation. Here, biochemical and pharmacological characterization of this dimer deficient mutant (DDM) in living cells indicates a significant impairment in its response to agonists. Interestingly, two single loss-of-function TPα variants, namely W29C and N42S recently identified in two heterozygous patients affected by bleeding disorders, match some of the residues mutated in our DDM. These two naturally occurring variants display a reduced potency to TP agonists and are characterized by impaired dimer formation in transfected HEK-293T cells. These findings provide proofs that lack of homo-dimer formation is a crucial process for reduced TPα function in vivo, and might represent one molecular mechanism through which platelet TPα receptor dysfunction affects the patient(s) carrying these mutations. Copyright © 2016 Elsevier Inc. All rights reserved.

Embolus location affects the sensitivity of a rapid quantitative D-dimer assay in the diagnosis of pulmonary embolism

NARCIS (Netherlands)

de Monyé, Wouter; Sanson, Bernd-Jan; Mac Gillavry, Melvin R.; Pattynama, Peter M. T.; Büller, Harry R.; van den Berg-Huysmans, Annette A.; Huisman, Menno V.

2002-01-01

D-dimer blood tests have been suggested to rule out pulmonary embolism. Despite evidence of the safety of withholding anticoagulant treatment in patients with suspected pulmonary embolism and a normal D-dimer assay result, clinicians remain reluctant to use a D-dimer assay as a sole diagnostic test.

Study of plasmonics in hybrids made from a quantum emitter and double metallic nanoshell dimer

Science.gov (United States)

Guo, Jiaohan; Black, Kevin; Hu, Jiawen; Singh, Mahi

2018-05-01

We developed a theory for the fluorescence (FL) for quantum emitter and double metallic nanoshell dimer hybrids using the density matrix method. The dimer is made from two identical double metallic nanoshells, which are made of a dielectric core, a gold metallic shell and a dielectric spacer layer. The quantum emitters are deposited on the surface of the spacer layers of the dimers due to the electrostatic absorptions. We consider that dimer hybrids are surrounded by biological cells. This can be achieved by injecting them into human or animal cells. The surface plasmon polaritons (SPP) are calculated for the dimer using Maxwell’s equations in the static wave approximation. The calculated SPP energy agrees with experimental data from Zhai et al (2017 Plasmonics 12 263) for the dimer made from a silica core, a gold metallic nanoshell and a silica spacer layer. We have also obtained an analytical expression of the FL using the density matrix method. We compare our theory with FL experimental data from Zhai et al (2017 Plasmonics 12 263) where the FL spectrum was measured by varying the thickness of the spacer layer from 9 nm to 40 nm. A good agreement between theory and experiment is found. We have shown that the enhancement of the FL increases as the thickness of the spacer layer decreases. We have also found that the enhancement of the FL increases as the distance between the double metallic nanoshells in the dimer decreases. These are interesting findings which are consistent with the experiments of Zhai et al (2017 Plasmonics 12 263) and can be used to control the FL enhancement in the FL-based biomedical imaging and cancer treatment. These interesting findings may also be useful in the fabrication of nanosensors and nanoswitches for applications in medicine.

Variations in the heterogeneity of the decay of the fluorescence in six procyanidin dimers

Science.gov (United States)

Donghwan Cho; Rujiang Tian; Lawrence J. Porter; Richard W. Hemingway; Wayne L. Mattice

1990-01-01

The decay of the fluorescence has been measured in 1,4-dioxane for six dimers of (2R,3R)-(-)-epicatechin and (2R,3S)-(+)-catechin, hereafter denoted simply epicatechin and catechin. The dimers are epicatechin-(4β→8)-catechin, epicatechin-(4β→8)-epicatechin...

Dimerization interface of 3-hydroxyacyl-CoA dehydrogenase tunes the formation of its catalytic intermediate.

Directory of Open Access Journals (Sweden)

Yingzhi Xu

Full Text Available 3-Hydroxyacyl-CoA dehydrogenase (HAD, EC 1.1.1.35 is a homodimeric enzyme localized in the mitochondrial matrix, which catalyzes the third step in fatty acid β-oxidation. The crystal structures of human HAD and subsequent complexes with cofactor/substrate enabled better understanding of HAD catalytic mechanism. However, numerous human diseases were found related to mutations at HAD dimerization interface that is away from the catalytic pocket. The role of HAD dimerization in its catalytic activity needs to be elucidated. Here, we solved the crystal structure of Caenorhabditis elegans HAD (cHAD that is highly conserved to human HAD. Even though the cHAD mutants (R204A, Y209A and R204A/Y209A with attenuated interactions on the dimerization interface still maintain a dimerization form, their enzymatic activities significantly decrease compared to that of the wild type. Such reduced activities are in consistency with the reduced ratios of the catalytic intermediate formation. Further molecular dynamics simulations results reveal that the alteration of the dimerization interface will increase the fluctuation of a distal region (a.a. 60-80 that plays an important role in the substrate binding. The increased fluctuation decreases the stability of the catalytic intermediate formation, and therefore the enzymatic activity is attenuated. Our study reveals the molecular mechanism about the essential role of the HAD dimerization interface in its catalytic activity via allosteric effects.

Repair of closely opposed cyclobutyl pyrimidine dimers in UV-sensitive human diploid fibroblasts

International Nuclear Information System (INIS)

Lam, L.H.; Reynolds, R.J.

1986-01-01

An enzyme-sensitive site assay has been used to examine the fate of closely opposed pyrimidine dimers in fibroblasts from individuals afflicted with various genetic disorders that confer increased cellular sensitivity to UV radiation. The disappearance of bifilar enzyme-sensitive sites was found to be normal in cells from individuals with Fanconi's anemia, Cockayne's syndrome, dyskeratosis congenita and the variant form of xeroderma pigmentosum. The rate of bifilar enzyme-sensitive site removal in XP cells assigned to complementation group C was reduced by an amount similar to that observed for the repair of isolated dimers. Our results indicate that the initiation of repair at closely opposed dimers is slow in XP-C cells but normal in all other cells examined. (Auth.)

Glycine transporter dimers: evidence for occurrence in the plasma membrane

DEFF Research Database (Denmark)

Bartholomäus, Ingo; Milan-Lobo, Laura; Nicke, Annette

2008-01-01

membrane based on hydrodynamic and native gel electrophoretic studies. Here, we used cysteine substitution and oxidative cross-linking to show that of GlyT1 and GlyT2 also form dimeric complexes within the plasma membrane. GlyT oligomerization at the cell surface was confirmed for both GlyT1 and GlyT2......Different Na(+)/Cl(-)-dependent neurotransmitter transporters of the SLC6a family have been shown to form dimers or oligomers in both intracellular compartments and at the cell surface. In contrast, the glycine transporters (GlyTs) GlyT1 and -2 have been reported to exist as monomers in the plasma...

Fabrication and characterization of Au dimer antennas on glass pillars with enhanced plasmonic response

DEFF Research Database (Denmark)

Sadeghi, Pedram; Wu, Kaiyu; Rindzevicius, Tomas

2017-01-01

We report on the fabrication and dark-field spectroscopy characterization of Au dimer nanoantennas placed on top of SiO2 nanopillars. The reported process enables the fabrication of nanopillar dimers with gaps down to 15 nm and heights up to 1 μm. A clear dependence of the plasmonic resonance...

Correlative SEM SERS for quantitative analysis of dimer nanoparticles.

Science.gov (United States)

Timmermans, F J; Lenferink, A T M; van Wolferen, H A G M; Otto, C

2016-11-14

A Raman microscope integrated with a scanning electron microscope was used to investigate plasmonic structures by correlative SEM-SERS analysis. The integrated Raman-SEM microscope combines high-resolution electron microscopy information with SERS signal enhancement from selected nanostructures with adsorbed Raman reporter molecules. Correlative analysis is performed for dimers of two gold nanospheres. Dimers were selected on the basis of SEM images from multi aggregate samples. The effect of the orientation of the dimer with respect to the polarization state of the laser light and the effect of the particle gap size on the Raman signal intensity is observed. Additionally, calculations are performed to simulate the electric near field enhancement. These simulations are based on the morphologies observed by electron microscopy. In this way the experiments are compared with the enhancement factor calculated with near field simulations and are subsequently used to quantify the SERS enhancement factor. Large differences between experimentally observed and calculated enhancement factors are regularly detected, a phenomenon caused by nanoscale differences between the real and 'simplified' simulated structures. Quantitative SERS experiments reveal the structure induced enhancement factor, ranging from ∼200 to ∼20 000, averaged over the full nanostructure surface. The results demonstrate correlative Raman-SEM microscopy for the quantitative analysis of plasmonic particles and structures, thus enabling a new analytical method in the field of SERS and plasmonics.

Aromatic C-Nitroso Compounds and Their Dimers: A Model for Probing the Reaction Mechanisms in Crystalline Molecular Solids

Directory of Open Access Journals (Sweden)

Ivana Biljan

2017-12-01

Full Text Available This review is focused on the dimerization and dissociation of aromatic C-nitroso compounds and their dimers, the reactions that could be used as a convenient model for studying the thermal organic solid-state reaction mechanisms. This molecular model is simple because it includes formation or breaking of only one covalent bond between two nitrogen atoms. The crystalline molecular solids of nitroso dimers (azodioxides dissociate by photolysis under the cryogenic conditions, and re-dimerize by slow warming. The thermal re-dimerization reaction is examined under the different topotactic conditions in crystals: disordering, surface defects, and phase transformations. Depending on the conditions, and on the molecular structure, aromatic C-nitroso compounds can associate to form one-dimensional polymeric structures and are able to self-assemble on gold surfaces.

Preparation and characterization of dimeric and tetrameric clusters of molybdenum and tungsten

Energy Technology Data Exchange (ETDEWEB)

Ryan, T.R.

1981-10-01

The cyclo-addition of two Mo/sub 2/Cl/sub 4/(P(C/sub 6/H/sub 5/)/sub 3/)/sub 2/(CH/sub 3/OH)/sub 2/ molecules has produced a new type of tetrameric molybdenum cluster, Mo/sub 4/Cl/sub 8/L/sub 4/. Structural characterization of this dimer revealed weak molybdenum-methanol bonding which was consistent with the observed reactivity of the compound. New synthetic methods were devised for the preparation of Mo/sub 4/X/sub 8/L/sub 4/ clusters where X = Cl, Br, I and L = PR/sub 3/, Po/sub 3/, RCN, CH/sub 3/OH. A scheme for the metal-metal bonding in these clusters was presented which was in agreement with the known structural features of Mo/sub 4/Cl/sub 8/(PR/sub 3/)/sub 4/, R = C/sub 2/H/sub 5/, n-C/sub 4/H/sub 9/. The preparation of the analogous W/sub 4/Cl/sub 8/(PR/sub 3/)/sub 4/ cluster from WCl/sub 4/ was accomplished by application of techniques used in the molybdenum syntheses. The single crystal x-ray structure revealed slight differences from the molybdenum analog which were rationalized in terms of the known behavior in dimeric tungsten and molybdenum species. The attempted preparation of a tetrameric tungsten cluster from W/sub 2/(mhp)/sub 4/ was unsuccessful (mhp = anion of 2-methyl-6-hydroxypyridine). Instead, the new tungsten dimer, W/sub 2/Cl/sub 2/(mhp)/sub 3/, was isolated which possessed a metal-metal bond order of 3.5. The x-ray crystal structure of the dimer revealed that the chlorine atoms were situated cis, one bound to each tungsten. Cyclic voltammetry showed that the compound could be reversibly reduced, presumably to a W/sub 2//sup 4 +/ dimer containing a quadruple metal-metal bond.

Elevation of serum CA 125 and D-dimer levels associated with rupture of ovarian endometrioma.

Science.gov (United States)

Uharcek, P; Mlyncek, M; Ravinger, J

2007-01-01

Patients with endometriosis rarely have a serum CA 125 concentration >100 IU/mL. A raised plasma level of D-dimer indicates active fibrinolysis, either secondary to clot formation or primarily activated. This condition is seldom diagnosed in patients with endometriosis. A 53-year-old woman was referred to our institution for acute abdominal pain. Laparoscopic surgery revealed a large ovarian cyst with rupture on the left side. Preoperative laboratory tests detected high serum CA 125 and D-dimer levels. Adnexectomy was performed, resulting in a sharp decrease in serum CA 125 and D-dimer concentration. We describe the clinical course of the patient. Rupture of a large ovarian endometrioma can lead to a high serum concentration of CA 125, a condition which, in addition to the detected pelvic mass, may mimic a malignant process. The increased D-dimer plasma level indicated that a ruptured endometriotic cyst can induce coagulation reactions.

Imaging of 99Tcm-labeled new cyclic RGDfK Dimer in nude mice bearing U87MG human glioma xenografts

International Nuclear Information System (INIS)

Jin Xiao'an; Shi Jiyun; Liu Yan; Zhu Zhaohui; Jia Bing; Liu Zhaofei; Shi Ximin; Wang Fan; Li Fang

2010-01-01

Objective: (1) To evaluate the effect of insertion of two 15-amino-4, 7, 10, 13-tetraoxapentadecanoic (2 PEG 4 ) linkers into cyclic Arg-Gly-Asp (RGD) Dimer E [c(RGDfK)] 2 on receptor binding in vitro, (2) to assess its biodistribution in vivo and (3) to investigate the value of 99 Tc m labeled 2PEG 4 -Dimer for integrin α v β 3 -positive tumors imaging. Methods: The expression of U87 human glioma cells and integrin α v β 3 was determined by immunofluorescence staining. The half-inhibition concentrations (IC 50 ) for 125 I-cyclo (Arg-Gly-Asp-D-Tyr-Lys) (c(RGDyK)) of c (RGDyK), hydrazinonictinamide (HYNIC)-Dimer and HYNIC-2PEG 4 -Dimer binding to integrin α v β 3 were measured. 99 Tc m -HYNIC-Dimer and 99 Tc m -HYNIC-2PEG 4 -Dimer were synthesized using non-SnCl 2 formulation. Biodistribution and imaging studies were performed in nude mice bearing human glioma xenografts. The unpaired t test was used for statistical analysis. Results: The labeling yield of the two radiotracers was more than 95%, and the radiochemical purity was more than 99% through Sep-Pek C18 cartridge. HYNIC-2PEG 4 -Dimer had significantly higher binding affinity of integrin α v β 3 than c(RGDyK) and HYNIC-Dimer (IC 50 =0.8 nmol/L, 27 nmol/L and 2.4 nmol/L, respectively). Biodistribution study showed that 99 Tc m -HYNIC-2PEG 4 -Dimer was mainly excreted via the kidney. The tumor uptake of 99 Tc m -HYNIC-2PEG 4 -Dimer was higher than that of 99 Tc m -HYNIC-Dimer at 2 h post injection ((5.71±0.96) and (2.10±0.50) % ID/g, t =4.80, P 99 Tc m -HYNIC-2PEG 4 -Dimer is a promising radiotracer for integrin α v β 3 -positive tumor imaging. (authors)

What factors control dimerization of coniferyl alcohol?

Science.gov (United States)

Carl J. Houtman

1999-01-01

Data suggest that the dimerization of coniferyl alcohol is not under thermodynamic control. In this study, molecular dynamics calculations were used to estimate the effect of the solvent environment. In water, the coniferyl alcohol radicals were forced to associate by the formation of a solvent cage. In glycerol, the solvent cage effect appeared to be absent. These...

pi-Dimers of end-capped oligopyrrole cation radicals

NARCIS (Netherlands)

Haare, van J.A.E.H.; Groenendaal, L.; Havinga, E.E.; Janssen, R.A.J.; Meijer, E.W.

1996-01-01

In two consecutive one-electron oxidations, oligopyrroles substituted with phenyl capping groups (PhPynPh, n = 2–4) can be oxidized reversibly to give stable cation radicals and dications. Spectroelectrochemical studies give direct evidence that diamagnetic p-dimers of cation radicals are formed in

Importance of dimer formation of myocardin family members in the regulation of their nuclear export.

Science.gov (United States)

Hayashi, Ken'ichiro; Morita, Tsuyoshi

2013-01-01

Myocardin (Mycd) family members function as a transcriptional cofactor for serum response factor (SRF). Dimer formation is necessary to exhibit their function, and the coiled-coil domain (CC) plays a critical role in their dimerization. We have recently revealed a detailed molecular mechanism for their Crm1 (exportin1)-mediated nuclear export. Here, we found other unique significances of the dimerization of Mycd family members. Introduction of mutations in the CC of myocardin-related transcription factor A (MRTF-A) and truncated Mycd resulted in significant decreases in their cytoplasmic localization and increases in their nuclear localization. In accordance with such subcellular localization changes, their binding to Crm1 were reduced. These results indicate that the dimerization of Mycd family members is necessary for their Crm1-mediated nuclear export. We have recently found that the N-terminal region of Mycd consisting of 128 amino acids (Mycd N128) self-associates to Mycd via the central basic domain (CB), resulting in masking the Crm1-binding site. Such self-association of MRTF-A would be unlikely. In this study, we also revealed that the dimerization of Mycd was also necessary for this self-association. Wild-type Mycd activated SRF-mediated transcription more potently than Mycd lacking the Mycd N128 (Mycd ΔN128) did. These results suggest two possible functions of the Mycd N128: 1) stabilization of Mycd dimer to enhance SRF-mediated transcription and 2) positive regulation of the transactivation ability of Mycd. These findings provide a new insight into the functional regulation of Mycd family members.

Topological edge states and impurities: Manifestation in the local static and dynamical characteristics of dimerized quantum chains

Science.gov (United States)

Zvyagin, A. A.

2018-04-01

Based on the results of exact analytic calculations, we show that topological edge states and impurities in quantum dimerized chains manifest themselves in various local static and dynamical characteristics, which can be measured in experiments. In particular, topological edge states can be observed in the magnetic field behavior of the local magnetization or magnetic susceptibility of dimerized spin chains as jumps (for the magnetization) and features (for the static susceptibility) at zero field. In contrast, impurities reveal themselves in similar jumps and features, however, at nonzero values of the critical field. We also show that dynamical characteristics of dimerized quantum chains also manifest the features, related to the topological edge states and impurities. Those features, as a rule, can be seen more sharply than the manifestation of bulk extended states in, e.g., the dynamical local susceptibility. Such peculiarities can be observed in one-dimensional dimerized spin chains, e.g., in NMR experiments, or in various realizations of quantum dimerized chains in optical experiments.

Formation of pyrimidine dimers in Simian virus 40 chromosomes and DNA in vitro: effects of salt

International Nuclear Information System (INIS)

Edenberg, H.J.

1984-01-01

Simian virus 40 chromosomes were used to determine whether packaging of DNA into chromatin affected the yield of cylcobutane pyrimidine dimers introduced by ultraviolet light (254 nm). SV40 chromatin and purified SV40 DNA (radioactively labeled with different isotopes) were mixed and irradiated in vitro. The proteins were extracted and pyrimidine dimers detected as sites sensitive to the UV-endonuclease encoded by bacteriophage T4. When irradiation was carried out in the presence of at least 0.05 M NaCl the same number of dimers were formed in chromatin as in free DNA. Irradiation in the absence of NaCl, however, reduced the relative yield of dimers in chromatin to 89% of that in free DNA. Different methods of chromatin preparation did not influence these results. (author)

Dissociative recombination of the weakly bound NO-dimer cation: Cross sections and three-body dynamics

NARCIS (Netherlands)

Petrignani, A.; Andersson, P.U.; Pettersson, J.B.C.; Thomas, R.; Hellberg, F.; Ehlerding, A.; Larsson, M.; Zande, W.J. van der

2005-01-01

Dissociative recombination (DR) of the dimer ion (NO)(2)(+) has been studied at the heavy-ion storage ring CRYRING at the Manne Siegbahn Laboratory, Stockholm. The experiments were aimed at determining details on the strongly enhanced thermal rate coefficient for the dimer, interpreting the

Antagonizing STAT3 dimerization with a rhodium(III) complex.

Science.gov (United States)

Ma, Dik-Lung; Liu, Li-Juan; Leung, Ka-Ho; Chen, Yen-Ting; Zhong, Hai-Jing; Chan, Daniel Shiu-Hin; Wang, Hui-Min David; Leung, Chung-Hang

2014-08-25

Kinetically inert metal complexes have arisen as promising alternatives to existing platinum and ruthenium chemotherapeutics. Reported herein, to our knowledge, is the first example of a substitutionally inert, Group 9 organometallic compound as a direct inhibitor of signal transducer and activator of transcription 3 (STAT3) dimerization. From a series of cyclometalated rhodium(III) and iridium(III) complexes, a rhodium(III) complex emerged as a potent inhibitor of STAT3 that targeted the SH2 domain and inhibited STAT3 phosphorylation and dimerization. Significantly, the complex exhibited potent anti-tumor activities in an in vivo mouse xenograft model of melanoma. This study demonstrates that rhodium complexes may be developed as effective STAT3 inhibitors with potent anti-tumor activity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Scaling of the Surface Plasmon Resonance in Gold and Silver Dimers Probed by EELS

DEFF Research Database (Denmark)

Kadkhodazadeh, Shima; de Lasson, Jakob Rosenkrantz; Beleggia, Marco

2014-01-01

The dependence of surface plasmon coupling on the distance between two nanoparticles (dimer) is the basis of nanometrology tools such as plasmon rulers. Application of these nanometric rulers requires an accurate description of the scaling of the surface plasmon resonance (SPR) wavelength...... with distance. Here, we have applied electron energy-loss spectroscopy (EELS) and scanning transmission electron microscopy (STEM) imaging to investigate the relationship between the SPR wavelength of gold and silver nanosphere dimers (radius R) and interparticle distance (d) in the range 0.1R .... Instead, within the range 0.1R gold and silver dimers. Despite this common power dependence, consistently larger SPR wavelength shifts are registered for silver for a given change in d, implying...

CT Findings of Disease with Elevated Serum D-Dimer Levels in an Emergency Room Setting

International Nuclear Information System (INIS)

Choi, Ji Youn; Kwon, Woo Cheol; Kim, Young Ju

2012-01-01

Pulmonary embolism and deep vein thrombosis are the leading causes of elevated serum D-dimer levels in the emergency room. Although D-dimer is a useful screening test because of its high sensitivity and negative predictive value, it has a low specificity. In addition, D-dimer can be elevated in various diseases. Therefore, information on the various diseases with elevated D-dimer levels and their radiologic findings may allow for accurate diagnosis and proper management. Herein, we report the CT findings of various diseases with elevated D-dimer levels in an emergency room setting, including an intravascular contrast filling defect with associated findings in a venous thromboembolism, fracture with soft tissue swelling and hematoma formation in a trauma patient, enlargement with contrast enhancement in the infected organ of a patient, coronary artery stenosis with a perfusion defect of the myocardium in a patient with acute myocardial infarction, high density of acute thrombus in a cerebral vessel with a low density of affected brain parenchyma in an acute cerebral infarction, intimal flap with two separated lumens in a case of aortic dissection, organ involvement of malignancy in a cancer patient, and atrophy of a liver with a dilated portal vein and associated findings.

CT Findings of Disease with Elevated Serum D-Dimer Levels in an Emergency Room Setting

Energy Technology Data Exchange (ETDEWEB)

Choi, Ji Youn; Kwon, Woo Cheol; Kim, Young Ju [Dept. of Radiology, Wonju Christian Hospital, Yensei University Wonju College of Medicine, Wonju (Korea, Republic of)

2012-01-15

Pulmonary embolism and deep vein thrombosis are the leading causes of elevated serum D-dimer levels in the emergency room. Although D-dimer is a useful screening test because of its high sensitivity and negative predictive value, it has a low specificity. In addition, D-dimer can be elevated in various diseases. Therefore, information on the various diseases with elevated D-dimer levels and their radiologic findings may allow for accurate diagnosis and proper management. Herein, we report the CT findings of various diseases with elevated D-dimer levels in an emergency room setting, including an intravascular contrast filling defect with associated findings in a venous thromboembolism, fracture with soft tissue swelling and hematoma formation in a trauma patient, enlargement with contrast enhancement in the infected organ of a patient, coronary artery stenosis with a perfusion defect of the myocardium in a patient with acute myocardial infarction, high density of acute thrombus in a cerebral vessel with a low density of affected brain parenchyma in an acute cerebral infarction, intimal flap with two separated lumens in a case of aortic dissection, organ involvement of malignancy in a cancer patient, and atrophy of a liver with a dilated portal vein and associated findings.

DNA repair in B. subtilis: an inducible dimer-specific W-reactivation system

International Nuclear Information System (INIS)

Fields, P.I.; Yasbin, R.E.

1982-01-01

The W-reactivation system of Bacillus subtilis can repair pyrimidine dimers in bacteriophage DNA. This inducible repair system can be activated by treatment of the bacteria with uv, alkylating agents, cross-linking agents and gamma irradiation. However, bacteriophage treated with agents other than those that cause pyrimidine dimers to be produced was not repaired by this unique form of W-reactivation. In contrast, the W-reactivation system of Escherichia coli can repair a variety of damages placed in the bacteriophage DNA

Alanine substitutions in the GXXXG motif alter C99 cleavage by γ-secretase but not its dimerization.

Science.gov (United States)

Higashide, Hidekazu; Ishihara, Seiko; Nobuhara, Mika; Ihara, Yasuo; Funamoto, Satoru

2017-03-01

The amyloid β (Aβ) protein is a major component of senile plaques, one of the neuropathological hallmarks of Alzheimer's disease. Amyloidogenic processing of amyloid precursor protein (APP) by β- and γ-secretases leads to production of Aβ. APP contains tandem triple repeats of the GXXXG motif in its extracellular juxtamembrane and transmembrane regions. It is reported that the GXXXG motif is related to protein-protein interactions, but it remains controversial whether the GXXXG motif in APP is involved in substrate dimerization and whether dimerization affects γ-secretase-dependent cleavage. Therefore, the relationship between the GXXXG motifs, substrate dimerization, and γ-secretase-dependent cleavage sites remains unclear. Here, we applied blue native poly acrylamide gel electrophoresis to examine the effect of alanine substitutions within the GXXXG motifs of APP carboxyl terminal fragment (C99) on its dimerization and Aβ production. Surprisingly, alanine substitutions in the motif failed to alter C99 dimerization in detergent soluble state. Cell-based and solubilized γ-secretase assays demonstrated that increasing alanine substitutions in the motif tended to decrease long Aβ species such as Aβ42 and Aβ43 and to increase in short Aβ species concomitantly. Our data suggest that the GXXXG motif is crucial for Aβ production, but not for C99 dimerization. © 2016 International Society for Neurochemistry.

Small molecule and peptide-mediated inhibition of Epstein-Barr virus nuclear antigen 1 dimerization

International Nuclear Information System (INIS)

Kim, Sun Young; Song, Kyung-A; Kieff, Elliott; Kang, Myung-Soo

2012-01-01

Highlights: ► Evidence that targeting EBNA1 dimer, an EBV onco-antigen, can be achievable. ► A small molecule and a peptide as EBNA1 dimerization inhibitors identified. ► Both inhibitors associated with EBNA1 and blocked EBNA1 DNA binding activity. ► Also, prevented its dimerization, and repressed viral gene transcription. -- Abstract: Latent Epstein-Barr virus (EBV) infection is associated with human B cell lymphomas and certain carcinomas. EBV episome persistence, replication, and gene expression are dependent on EBV-encoded nuclear antigen 1 (EBNA1)’s DNA binding domain (DBD)/dimerization domain (DD)-mediated sequence-specific DNA binding activity. Homodimerization of EBNA1 is essential for EBNA1 DNA binding and transactivation. In this study, we characterized a novel small molecule EBNA1 inhibitor EiK1, screened from the previous high throughput screening (HTS). The EiK1 compound specifically inhibited the EBNA1-dependent, OriP-enhanced transcription, but not EBNA1-independent transcription. A Surface Plasmon Resonance Biacore assay revealed that EiK1 associates with EBNA1 amino acid 459–607 DBD/DD. Consistent with the SPR data, in vitro gel shift assays showed that EiK1 suppressed the activity of EBNA1 binding to the cognate familial repeats (FR) sequence, but not control RBP-Jκ binding to the Jκ site. Subsequently, a cross-linker-mediated in vitro multimerization assay and EBNA1 homodimerization-dependent yeast two-hybrid assay showed that EiK1 significantly inhibited EBNA1 dimerization. In an attempt to identify more highly specific peptide inhibitors, small peptides encompassing the EBNA1 DBD/DD were screened for inhibition of EBNA1 DBD-mediated DNA binding function. The small peptide P85, covering EBNA1 a.a. 560–574, significantly blocked EBNA1 DNA binding activity in vitro, prevented dimerization in vitro and in vivo, associated with EBNA1 in vitro, and repressed EBNA1-dependent transcription in vivo. Collectively, this study describes two

Small molecule and peptide-mediated inhibition of Epstein-Barr virus nuclear antigen 1 dimerization

Energy Technology Data Exchange (ETDEWEB)

Kim, Sun Young; Song, Kyung-A [Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Samsung Biomedical Research Institute (SBRI), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kieff, Elliott [Department of Medicine, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States); Kang, Myung-Soo, E-mail: mkang@skku.edu [Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Samsung Biomedical Research Institute (SBRI), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Department of Medicine, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States)

2012-07-27

Highlights: Black-Right-Pointing-Pointer Evidence that targeting EBNA1 dimer, an EBV onco-antigen, can be achievable. Black-Right-Pointing-Pointer A small molecule and a peptide as EBNA1 dimerization inhibitors identified. Black-Right-Pointing-Pointer Both inhibitors associated with EBNA1 and blocked EBNA1 DNA binding activity. Black-Right-Pointing-Pointer Also, prevented its dimerization, and repressed viral gene transcription. -- Abstract: Latent Epstein-Barr virus (EBV) infection is associated with human B cell lymphomas and certain carcinomas. EBV episome persistence, replication, and gene expression are dependent on EBV-encoded nuclear antigen 1 (EBNA1)'s DNA binding domain (DBD)/dimerization domain (DD)-mediated sequence-specific DNA binding activity. Homodimerization of EBNA1 is essential for EBNA1 DNA binding and transactivation. In this study, we characterized a novel small molecule EBNA1 inhibitor EiK1, screened from the previous high throughput screening (HTS). The EiK1 compound specifically inhibited the EBNA1-dependent, OriP-enhanced transcription, but not EBNA1-independent transcription. A Surface Plasmon Resonance Biacore assay revealed that EiK1 associates with EBNA1 amino acid 459-607 DBD/DD. Consistent with the SPR data, in vitro gel shift assays showed that EiK1 suppressed the activity of EBNA1 binding to the cognate familial repeats (FR) sequence, but not control RBP-J{kappa} binding to the J{kappa} site. Subsequently, a cross-linker-mediated in vitro multimerization assay and EBNA1 homodimerization-dependent yeast two-hybrid assay showed that EiK1 significantly inhibited EBNA1 dimerization. In an attempt to identify more highly specific peptide inhibitors, small peptides encompassing the EBNA1 DBD/DD were screened for inhibition of EBNA1 DBD-mediated DNA binding function. The small peptide P85, covering EBNA1 a.a. 560-574, significantly blocked EBNA1 DNA binding activity in vitro, prevented dimerization in vitro and in vivo, associated

The influence of inhibitors on dimer removal and repair of single-strand breaks in normal and bromodeoxyuridine substituted DNA of HeLa cells

International Nuclear Information System (INIS)

Cornelis, J.J.

1978-01-01

The elimination of cyclobutane pyrimidine dimers from the nuclear DNA of ultraviolet irradiated HeLa cells has been examined by means of chromatography and immunoautoradiography. The extent and duration of the process was similar when dimers were assayed by both methods, proving that the antisera recognized pyrimidine dimers. The rate of dimer excision did not differ through the cell cycle with the exception of mitosis during which no dimers were removed. Dimer excision is a relatively fast process which is terminated within a few hours, but it leaves many dimers in the DNA. Excision is depressed by inhibitors of semiconservative DNA synthesis that affect the DNA precursor pool or DNA polymerases. Cells whose DNA is partly substituted with bromodeoxyuridine instead of thymidine, repair single-strand breaks and remove dimers at the same rate but to different extents. On the other hand, inhibitors limit repair of breaks and removal of dimers to the same degree suggesting that the repair of the two types of lesion is coordinated. (Auth.)

Dimerization of inositol monophosphatase Mycobacterium tuberculosis SuhB is not constitutive, but induced by binding of the activator Mg2+

Directory of Open Access Journals (Sweden)

Nigou Jérôme

2007-08-01

Full Text Available Abstract Background The cell wall of Mycobacterium tuberculosis contains a wide range of phosphatidyl inositol-based glycolipids that play critical structural roles and, in part, govern pathogen-host interactions. Synthesis of phosphatidyl inositol is dependent on free myo-inositol, generated through dephosphorylation of myo-inositol-1-phosphate by inositol monophosphatase (IMPase. Human IMPase, the putative target of lithium therapy, has been studied extensively, but the function of four IMPase-like genes in M. tuberculosis is unclear. Results We determined the crystal structure, to 2.6 Å resolution, of the IMPase M. tuberculosis SuhB in the apo form, and analysed self-assembly by analytical ultracentrifugation. Contrary to the paradigm of constitutive dimerization of IMPases, SuhB is predominantly monomeric in the absence of the physiological activator Mg2+, in spite of a conserved fold and apparent dimerization in the crystal. However, Mg2+ concentrations that result in enzymatic activation of SuhB decisively promote dimerization, with the inhibitor Li+ amplifying the effect of Mg2+, but failing to induce dimerization on its own. Conclusion The correlation of Mg2+-driven enzymatic activity with dimerization suggests that catalytic activity is linked to the dimer form. Current models of lithium inhibition of IMPases posit that Li+ competes for one of three catalytic Mg2+ sites in the active site, stabilized by a mobile loop at the dimer interface. Our data suggest that Mg2+/Li+-induced ordering of this loop may promote dimerization by expanding the dimer interface of SuhB. The dynamic nature of the monomer-dimer equilibrium may also explain the extended concentration range over which Mg2+ maintains SuhB activity.

Acylphenols and dimeric acylphenols from Myristica maxima Warb.

Science.gov (United States)

Othman, Muhamad Aqmal; Sivasothy, Yasodha; Looi, Chung Yeng; Ablat, Abdulwali; Mohamad, Jamaludin; Litaudon, Marc; Awang, Khalijah

2016-06-01

Giganteone E (1), a new dimeric acylphenol was isolated as a minor constituent from the bark of Myristica maxima Warb. The structure of 1 was established on the basis of 1D and 2D NMR techniques and LCMS-IT-TOF analysis. Malabaricones A-C (2-4), giganteones A and C (5 and 6), maingayones A and B (7 and 8), maingayic acid B (9) and β-sitosteryl oleate (10) were also characterized in this plant for the first time. Compound 10 was identified for the first time in the Myristicaceae. Compounds 2 and 5 were active against human prostate cancer cell-lines, thus making this the first report on the prostate cancer inhibiting potential of acylphenols and dimeric acylphenols. Compounds 1, 4, 5, 7 and 8 exhibited potent DPPH free radical scavenging activity. This is the first report on their free radical scavenging capacity. Copyright © 2016. Published by Elsevier B.V.

Monomer-dimer problem on random planar honeycomb lattice

Energy Technology Data Exchange (ETDEWEB)

Ren, Haizhen [School of Mathematical Sciences, Xiamen University, Xiamen 361005, Fujian (China); Department of Mathematics, Qinghai Normal University, Xining 810008, Qinghai (China); Zhang, Fuji; Qian, Jianguo, E-mail: jqqian@xmu.edu.cn [School of Mathematical Sciences, Xiamen University, Xiamen 361005, Fujian (China)

2014-02-15

We consider the monomer-dimer (MD) problem on a random planar honeycomb lattice model, namely, the random multiple chain. This is a lattice system with non-periodic boundary condition, whose generating process is inspired by the growth of single walled zigzag carbon nanotubes. By applying algebraic and combinatorial techniques we establish a calculating expression of the MD partition function for bipartite graphs, which corresponds to the permanent of a matrix. Further, by using the transfer matrix argument we show that the computing problem of the permanent of high order matrix can be converted into some lower order matrices for this family of lattices, based on which we derive an explicit recurrence formula for evaluating the MD partition function of multiple chains and random multiple chains. Finally, we analyze the expectation of the number of monomer-dimer arrangements on a random multiple chain and the asymptotic behavior of the annealed MD entropy when the multiple chain becomes infinite in width and length, respectively.

Image storage in coumarin-based copolymer thin films by photoinduced dimerization.

Science.gov (United States)

Gindre, Denis; Iliopoulos, Konstantinos; Krupka, Oksana; Champigny, Emilie; Morille, Yohann; Sallé, Marc

2013-11-15

We report a technique to encode grayscale digital images in thin films composed of copolymers containing coumarins. A nonlinear microscopy setup was implemented and two nonlinear optical processes were used to store and read information. A third-order process (two-photon absorption) was used to photoinduce a controlled dimer-to-monomer ratio within a defined tiny volume in the material, which corresponds to each recorded bit of data. Moreover, a second-order process (second-harmonic generation) was used to read the stored information, which has been found to be highly dependent upon the monomer-to-dimer ratio.

Dichroism, chirality, and polarization eigenstates in Babinet nanoslot-dimer membrane metamaterials

Science.gov (United States)

Zhukovsky, Sergei V.; Chigrin, Dmitry N.; Kremers, Christian; Lavrinenko, Andrei V.

2013-11-01

We present a detailed theoretical description of the optical properties of planar metamaterials comprising a metal membrane patterned with openings (microslots) arranged in closely located couples (dimers). Using the covariant coupled-dipole approach, the effective material tensors of such a metamaterial are recovered, and contributions responsible for elliptical dichroism and optical activity are identified. Polarization conversion properties of II-shaped and V-shaped dimers are determined and explained in terms of elliptically polarized eigenmodes of the metamaterial. Good agreement with direct numerical simulations is demonstrated. The results obtained are promising for the design of thin-film frequency selective polarization shapers for terahertz waves.

Gold dimer nanoantenna with slanted gap for tunable LSPR and improved SERS

KAUST Repository

Kessentini, Sameh

2014-02-13

We focus on improving the surface-enhanced Raman scattering (SERS) of dimer nanoantenna by tailoring the shape of the coupled nanoantennas extremities from rounded to straight or slanted ones. A numerical model based on the discrete dipole approximation method-taking into account periodicity, adhesion layer, and roughness-is first validated by comparison with localized surface plasmon resonance (LSPR) and SERS experiments on round-edged dimer nanoantennas and then used to investigate the effect of the straight or slanted gap in the dimer antenna. Simulations show that both LSPR and SERS can be tuned by changing the gap slanting angle. The SERS enhancement factor can also be improved by 2 orders of magnitude compared to the one reached using a rounded gap. Therefore, the slanting angle can be used as a new control parameter in the design of SERS substrates to guarantee stronger field confinement and higher sensitivity, especially as its feasibility is demonstrated. © 2014 American Chemical Society.

Gold dimer nanoantenna with slanted gap for tunable LSPR and improved SERS

KAUST Repository

Kessentini, Sameh; Barchiesi, Dominique; D'Andrea, Cristiano; Toma, Andrea; Guillot, Nicolas; Di Fabrizio, Enzo M.; Fazio, Barbara; Maragó , Onofrio M.; Gucciardi, Pietro Giuseppe; Lamy De La Chapelle, Marc L.

2014-01-01

We focus on improving the surface-enhanced Raman scattering (SERS) of dimer nanoantenna by tailoring the shape of the coupled nanoantennas extremities from rounded to straight or slanted ones. A numerical model based on the discrete dipole approximation method-taking into account periodicity, adhesion layer, and roughness-is first validated by comparison with localized surface plasmon resonance (LSPR) and SERS experiments on round-edged dimer nanoantennas and then used to investigate the effect of the straight or slanted gap in the dimer antenna. Simulations show that both LSPR and SERS can be tuned by changing the gap slanting angle. The SERS enhancement factor can also be improved by 2 orders of magnitude compared to the one reached using a rounded gap. Therefore, the slanting angle can be used as a new control parameter in the design of SERS substrates to guarantee stronger field confinement and higher sensitivity, especially as its feasibility is demonstrated. © 2014 American Chemical Society.

D-dimer levels and stroke progression in patients with acute ischemic stroke and atrial fibrillation

DEFF Research Database (Denmark)

Krarup, L-H; Sandset, E C; Sandset, P M

2011-01-01

Krarup L-H, Sandset EC, Sandset PM, Berge E. D-dimer levels and stroke progression in patients with acute ischemic stroke and atrial fibrillation. Acta Neurol Scand: 2011: 124: 40-44. © 2010 John Wiley & Sons A/S. Background -  Patients with acute ischemic stroke and atrial fibrillation are at in......Krarup L-H, Sandset EC, Sandset PM, Berge E. D-dimer levels and stroke progression in patients with acute ischemic stroke and atrial fibrillation. Acta Neurol Scand: 2011: 124: 40-44. © 2010 John Wiley & Sons A/S. Background -  Patients with acute ischemic stroke and atrial fibrillation.......96), and the combined endpoint of stroke progression, recurrent stroke, and death (D-dimer: 991 ng/ml vs 970 ng/ml, P = 0.91). Multivariable analyses did not alter the results. Conclusion -  D-dimer and other markers of hemostatic activation were not associated with stroke progression, recurrent stroke, or death...

Fabrication and characterization of Au dimer antennas on glass pillars with enhanced plasmonic response

Directory of Open Access Journals (Sweden)

Sadeghi Pedram

2017-06-01

Full Text Available We report on the fabrication and dark-field spectroscopy characterization of Au dimer nanoantennas placed on top of SiO2 nanopillars. The reported process enables the fabrication of nanopillar dimers with gaps down to 15 nm and heights up to 1 μm. A clear dependence of the plasmonic resonance position on the dimer gap is observed for smaller pillar heights, showing the high uniformity and reproducibility of the process. It is shown how increasing the height of nanopillars significantly affects the recorded elastic scattering spectra from Au nanoantennas. The results are compared to finite-difference time-domain (FDTD and finite-element method (FEM simulations. Additionally, measured spectra are accompanied by dark-field microscopy images of the dimers, showing the pronounced change in color. Placing nanoantennas on nanopillars with a height comparable to the in-plane dimer dimensions results in an enhancement of the scattering response, which can be understood through reduced interaction of the near-fields with the substrate. When increasing the pillar height further, scattering by the pillars themselves manifests itself as a strong tail at lower wavelengths. Additionally, strong directional scattering is expected as a result of the interface between the nanoantennas and nanopillars, which is taken into account in simulations. For pillars of height close to the plasmonic resonance wavelength, the scattering spectra become more complex due to additional scattering peaks as a result of larger geometrical nonuniformities.

Role of quaternary structure in muscle creatine kinase stability: tryptophan 210 is important for dimer cohesion.

Science.gov (United States)

Perraut, C; Clottes, E; Leydier, C; Vial, C; Marcillat, O

1998-07-01

A mutant of the dimeric rabbit muscle creatine kinase (MM-CK) in which tryptophan 210 was replaced has been studied to assess the role of this residue in dimer cohesion and the importance of the dimeric state for the native enzyme stability. Wild-type protein equilibrium unfolding induced by guanidine hydrochloride occurs through intermediate states with formation of a molten globule and a premolten globule. Unlike the wild-type enzyme, the mutant inactivates at lower denaturant concentration and the loss of enzymatic activity is accompanied by the dissociation of the dimer into two apparently compact monomers. However, the Stokes radius of the monomer increases with denaturant concentration as determined by size exclusion chromatography, indicating that, upon monomerization, the protein structure is destabilized. Binding of 8-anilinonaphthalene-1-sulfonate shows that the dissociated monomer exposes hydrophobic patches at its surface, suggesting that it could be a molten globule. At higher denaturant concentrations, both wild-type and mutant follow similar denaturation pathways with formation of a premolten globule around 1.5-M guanidine, indicating that tryptophan 210 does not contribute to a large extent to the monomer conformational stability, which may be ensured in the dimeric state through quaternary interactions.

Temperature-dependent conformations of exciton-coupled Cy3 dimers in double-stranded DNA

Science.gov (United States)

Kringle, Loni; Sawaya, Nicolas P. D.; Widom, Julia; Adams, Carson; Raymer, Michael G.; Aspuru-Guzik, Alán; Marcus, Andrew H.

2018-02-01

Understanding the properties of electronically interacting molecular chromophores, which involve internally coupled electronic-vibrational motions, is important to the spectroscopy of many biologically relevant systems. Here we apply linear absorption, circular dichroism, and two-dimensional fluorescence spectroscopy to study the polarized collective excitations of excitonically coupled cyanine dimers (Cy3)2 that are rigidly positioned within the opposing sugar-phosphate backbones of the double-stranded region of a double-stranded (ds)-single-stranded (ss) DNA fork construct. We show that the exciton-coupling strength of the (Cy3)2-DNA construct can be systematically varied with temperature below the ds-ss DNA denaturation transition. We interpret spectroscopic measurements in terms of the Holstein vibronic dimer model, from which we obtain information about the local conformation of the (Cy3)2 dimer, as well as the degree of static disorder experienced by the Cy3 monomer and the (Cy3)2 dimer probe locally within their respective DNA duplex environments. The properties of the (Cy3)2-DNA construct we determine suggest that it may be employed as a useful model system to test fundamental concepts of protein-DNA interactions and the role of electronic-vibrational coherence in electronic energy migration within exciton-coupled bio-molecular arrays.

The dynamics of a polariton dimer in a disordered coupled array of cavities

Science.gov (United States)

Aiyejina, Abuenameh; Andrews, Roger

2018-03-01

We investigate the effect of disorder in the laser intensity on the dynamics of dark-state polaritons in an array of 20 cavities, each containing an ensemble of four-level atoms that is described by a Bose-Hubbard Hamiltonian. We examine the evolution of the polariton number in the cavities starting from a state with either one or two polaritons in one of the cavities. For the case of a single polariton without disorder in the laser intensity, we calculate the wavefunction of the polariton and find that it disperses away from the initial cavity with time. The addition of disorder results in minimal suppression of the dispersal of the wavefunction. In the case of two polaritons with an on-site repulsion to hopping strength ratio of 20, we find that the polaritons form a repulsively bound state or dimer. Without disorder the dimer wavefunction disperses similarly to the single polariton wavefunction but over a longer time period. The addition of sufficiently strong disorder results in localization of the polariton dimer. The localization length is found to be described by a power law with exponent - 1.31. We also find that we can localise the dimer at any given time by switching on the disorder.

Involvement of UV-inducible repair in pyrimidine dimer excision in Escherichia coli

International Nuclear Information System (INIS)

Masek, F.; Sedliakova, M.

1978-01-01

The influence of UV radiation on pyrimidine dimer excision in the cells of three excision-proficient E.coli strains was studied. For this purpose cells were irradiated with a first fluence of 300 ergs/mm 2 and at different time intervals with a second fluence of 500 ergs/mm 2 . After the second fluence dimer excision was found to be partly inhibited in E.coli B/r Hcr + and E.coli 15 555-7, but not in E.coli K12 SR20. (author)

Involvement of UV-inducible repair in pyrimidine dimer excision in Escherichia coli

Energy Technology Data Exchange (ETDEWEB)

Masek, F; Sedliakova, M [Slovenska Akademia Vied, Bratislava (Czechoslovakia)

1978-11-15

The influence of UV radiation on pyrimidine dimer excision in the cells of three excision-proficient E.coli strains was studied. For this purpose cells were irradiated with a first fluence of 300 ergs/mm/sup 2/ and at different time intervals with a second fluence of 500 ergs/mm/sup 2/. After the second fluence dimer excision was found to be partly inhibited in E.coli B/r Hcr/sup +/ and E.coli 15 555-7, but not in E.coli K12 SR20.

Photoreactivation of UV-induced pyrimidine dimers and erythema in the marsupial Monodelphis domestica

International Nuclear Information System (INIS)

Ley, R.D.

1985-01-01

Post-UV treatment of the gray, short-tailed opossum Monodelphis domestica with photoreactivating light (320-400 nm) suppressed the appearance of UV-induced erythema as evidenced by an increase in the dose of UV required to elicit an erythemal response. Pre-UV exposure to photoreactivating light had no effect on the UV induction of erythema. The dose-response for the photoreversal of pyrimidine dimers in epidermal DNA of M. domestica was similar to that for the photoreactivation of erythema induction. These data not only support the notion that DNA is the primary chromophore involved in the induction of erythema but also identify pyrimidine dimers as the major DNA change responsible for its induction. These results also identify M. domestica as a useful whole-animal system with which to determine the role of pyrimidine dimers in other photobiological responses of mammalian skin

Micrococcus radiodurans surface exonuclease. Dimer to monomer conversion by ionizing radiation-generated aqueous free radicals

Energy Technology Data Exchange (ETDEWEB)

Mitchel, R E.J.

1980-01-01

Micrococcus radiodurans possesses an exonuclease firmly bound to a middle cell wall membrane layer. Aqueous OH/sup -/ radicals generated chemically or by ionizing radiation cause the immediate release of this enzyme into the surrounding medium. The enzyme is located in a hydrophobic site and can also be released by aqueous n-butanol. When extracted by this solvent it is a non-covalently linked dimer and has a molecular weight of 260,000 as determined by gel filtration. When released by radiation generated OH/sup -/ radicals, the enzyme initially appears in solution as the dimer but is rapidly split by further aqueous radical attack into two 130,000 molecular weight subunits. Hydroxyl radicals are most effective but reducing radicals are also able to monomerize the enzyme. Only the released dimer enzyme is subject to free radical monomerization. Bound dimer enzyme is not split prior to release. No detectable loss of activity or change in catalytic properties accompanies the free radical cleavage of the enzyme. Both subunits of the dimer enzyme possess a tightly bound metal ion (probably Ca/sup 2 +/) required for activity. The monomer but not the dimer enzyme will bind to an anion exchanger. The monomer is susceptible to loss of its metal ion, and consequent inactivation, when exposed to the exchanger in the absence of Ca/sup 2 +/. Besides providing information on some of the immediate non-lethal effects of ionizing radiation, the behavior of this enzyme system demonstrates a potential cellular mechanism by which internally or externally generated free radicals could be utilized by the cell to control various enzymic reactions.

Experimental and Theoretical Study of the Rotation of Si Ad-dimers on the Si(100) Surface

DEFF Research Database (Denmark)

Swartzentruber, B. S.; Smith, A. P.; Jonsson, Hannes

1996-01-01

Scanning tunneling microscopy measurements and first principles density functional theory calculations are used to study the rate of the rotational transition of Si ad-dimers on top of the surface dimer rows of Si(100). The rotation rate and the relative population of the two stable orientations ...... of the ad-dimers are measured as a function of the applied electric field to extract the zero-field behavior. The measured relative stability of the two configurations is used to test the accuracy of various functionals for density functional theory calculations....

On the dimerization of linear polymers

International Nuclear Information System (INIS)

Aragao Carvalho, C. de.

1988-08-01

We use the continuum limit of the Su-Schrieffer-Heeger model for linear polymers to construct its effective potential (Gibbs free energy) both at zero and finite temperature. We study both trans and cis-polymers. Our results show that, depending on a renormalization condition to be extracted from experiment, there are several possibilities for the minima of the dimerized ground state of cis-polymers. All calculations are done in the one-loop approximation. (author). 16 refs, 3 figs

Pd(OAc)2/Ph3P-catalyzed dimerization of isoprene and synthesis of monoterpenic heterocycles.

Science.gov (United States)

Kellner, Dominik; Weger, Maximilian; Gini, Andrea; Mancheño, Olga García

2017-01-01

The palladium-catalyzed dimerization of isoprene is a practical approach of synthesizing monoterpenes. Though several highly selective methods have been reported, most of them still required pressure or costly ligands for attaining the active system and desired selectivity. Herein, we present a simple and economical procedure towards the tail-to-tail dimer using readily available Pd(OAc) 2 and inexpensive triphenylphosphine as ligand. Furthermore, simple screw cap vials are employed, allowing carrying out the reaction at low pressure. In addition, the potential of the dimer as a chemical platform for the preparation of heterocyclic terpenes by subsequent (hetero)-Diels-Alder or [4 + 1]-cycloadditions with nitrenes is also depicted.

The diagnostic value of ventilation-perfusion scintigraphy combined with plasma D-dimer assay in diagnosis of pulmonary embolism

International Nuclear Information System (INIS)

Wang Qian; Huang Lili; Qin Shuling; Yue Minggang; Wang Yu; Nie Yuxin; Liang Tiejun

2005-01-01

Objective: To investigate the clinical diagnostic value of ventilation-perfusion scintigraphy combined with plasma D-dimer assay in diagnosis of pulmonary embolism (PE). Methods: One hundred and four patients with clinically suspected PE underwent both pulmonary ventilation-perfusion scintigraphy and plasma D-dimer assay. According to the criteria of prospective investigation of the pulmonary embolism diagnosis (PIOPED), ventilation-perfusion scintigraphy was interpreted as normal, very low or low probability of PE, intermediate probability of PE and high probability of PE. High probability was considered as positive; normal and very low or low probability as negative and intermediate probability as non-diagnostic. Plasma D-dimer levels were measured using a quantitative immunoturbidimetric method, and a cut-off value of 500 mg/L was used in the diagnosis of PE. Clinical diagnostic value of ventilation-perfusion scintigraphy, D-dimer assay and combined use of ventilation-perfusion scintigraphy and D-dimer assay for diagnosing PE was evaluated, respectively, comparing with the final clinical diagnosis that was based on the clinical findings. Results: Among the 104 patients, 44 were diagnosed with PE and 60 were excluded. Ventilation-perfusion scintigraphy provided diagnostic interpretations for 86 (82.7%) patients, and non-diagnostic interpretations for 18 (17.3%) patients. For diagnosing PE, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of ventilation-perfusion scintigraphy was 84.1%, 75.0%, 78.8%, 71.2% and 86.5%, respectively, and with D-dimer assay was 93.2%, 60.0%, 74.0%, 63.1% and 92.3%, respectively. If a plasma D-dimer level of < 500 mg/L was taken as a criterion to exclude PE for those intermediate probability of ventilation-perfusion scintigraphy, the diagnostic specificity and accuracy would be raised to 85.0% and 84.6%, respectively. Conclusions: When a non-diagnostic interpretation was occurred on

Dimeric MHC-peptides inserted into an immunoglobulin scaffold as new immunotherapeutic agents

Science.gov (United States)

Goldberg, Burt; Bona, Constantin

2011-01-01

Abstract The interactions of the T cell receptor (TCR) with cognate MHC-peptide and co-stimulatory molecules expressed at surface of antigen presenting cells (APC) leads to activation or tolerance of T cells. The development of molecular biological tools allowed for the preparation of soluble MHC-peptide molecules as surrogate for the APC. A decade ago a monomeric class II MHC molecule in which the peptide was covalently linked to β-chain of class II molecule was generated. This type of molecule had a low-binding affinity and did not cause the multimerization of TCR. The requirement of multimerization of TCR led to development of a new class of reagents, chimeric peptides covalently linked to MHC that was dimerized via Fc fragment of an immunoglobulin and linked to 3′ end of the β-chain of MHC class II molecule. These soluble dimerized MHC-peptide chimeric molecules display high affinity for the TCR and caused multimerization of TCR without processing by an APC. Because dimeric molecules are devoid of co-stimulatory molecules interacting with CD28, a second signal, they induce anergy rather the activation of T cells. In this review, we compare the human and murine dimerized MHC class II-peptides and their effect on CD4+ T cells, particularly the generation of T regulatory cells, which make these chimeric molecules an appealing approach for the treatment of autoimmune diseases. PMID:21435177

Hsa-miR-1587 G-quadruplex formation and dimerization induced by NH4+, molecular crowding environment and jatrorrhizine derivatives.

Science.gov (United States)

Tan, Wei; Yi, Long; Zhu, Zhentao; Zhang, Lulu; Zhou, Jiang; Yuan, Gu

2018-03-01

A guanine-rich human mature microRNA, miR-1587, was discovered to form stable intramolecular G-quadruplexes in the presence of K + , Na + and low concentration of NH 4 + (25mM) by electrospray ionization mass spectrometry (ESI-MS) combined with circular dichroism (CD) spectroscopy. Furthermore, under high concentration of NH 4 + (100mM) or molecular crowding environments, miR-1587 formed a dimeric G-quadruplex through 3'-to-3' stacking of two monomeric G-quadruplex subunits with one ammonium ion sandwiched between the interfaces. Specifically, two synthesized jatrorrhizine derivatives with terminal amine groups could also induce the dimerization of miR-1587 G-quadruplex and formed 1:1 and 2:1 complexes with the dimeric G-quadruplex. In contrast, jatrorrhizine could bind with the dimeric miR-1587 G-quadruplex, but could not induce dimerization of miR-1587 G-quadruplex. These results provide a new strategy to regulate the functions of miR-1587 through induction of G-quadruplex formation and dimerization. Copyright © 2017 Elsevier B.V. All rights reserved.

Viscosity and sedimentation behaviors of the magnetorheological suspensions with oleic acid/dimer acid as surfactants

Science.gov (United States)

Yang, Jianjian; Yan, Hua; Hu, Zhide; Ding, Ding

2016-11-01

This work deals with the role of polar interactions on the viscosity and sedimentation behaviors of magnetorheological suspensions with micro-sized magnetic particles dispersed in oil carriers. The oleic acid and dimer acid were employed to make an adjustment of the hydrophobicity of iron particles, in the interest of performing a comparative evaluation of the contributions of the surface polarity. The viscosity tests show that the adsorbed surfactant layer may impose a hindrance to the movement of iron particles in the oil medium. The polar attractions between dimer acid covered particles gave rise to a considerable increase in viscosity, indicating flocculation structure developed in the suspensions. The observed plateau-like region in the vicinity of 0.1 s-1 for MRF containing dimer acid is possibly due to the flocculation provoked by the carboxylic polar attraction, in which the structure is stable against fragmentation. Moreover, a quick recovery of the viscosity and a higher viscosity-temperature index also suggest the existence of particle-particle polar interaction in the suspensions containing dimer acid. The sedimentation measurements reveal that the steric repulsion of oleic acid plays a limited role in the stability of suspensions only if a large quantity of surfactant was used. The sedimentation results observed in the dimer acid covered particles confirm that loose and open flocculation was formed and enhanced sedimentation stability.

Ab initio and matrix isolation study of the acetylene-furan dimer

International Nuclear Information System (INIS)

Sanchez-Garcia, Elsa; Mardyukov, Artur; Tekin, Adem; Crespo-Otero, Rachel; Montero, Luis A.; Sander, Wolfram; Jansen, Georg

2008-01-01

Five acetylene-furan dimer structures are identified using ab initio calculations at the second-order Moller-Plesset (MP2) level of theory. The structures are stabilized by two basic types of intermolecular interactions: the CH...O and the CH...π interaction. The CH...π interaction appears in two variants, depending on which molecule provides the hydrogen atom and which molecule the π system. The MP2 results indicate that the CH...π interaction between one of the hydrogen atoms of acetylene and the π system of furan as found in structure A is the strongest interaction, followed by the in-plane CH...O interaction in the second most stable acetylene-furan dimer structure B. A matrix isolation study shows the acetylene-furan dimer to exist in an argon matrix, but likely rather as structure B than as A. High level coupled cluster calculations with up to triple excitations (CCSD(T)) yield the interaction energy of structure A as about -2.4 kcal/mol in the complete basis set limit and find structure B to be nearly isoenergetic with -2.3 kcal/mol. This is confirmed in calculations employing the density functional theory combined with symmetry adapted intermolecular perturbation theory (DFT-SAPT) approach yielding interaction energies of -2.3 and -2.0 kcal/mol for A and B, respectively. DFT-SAPT also helps to understand the importance of the electrostatic, induction and dispersion interaction energies and their respective exchange counterparts for the stability of the various acetylene-furan dimer structures. The CH...O and CH...π interactions are furthermore analyzed with the help of the atoms in molecules (AIM) theory

Fragment-Based Protein-Protein Interaction Antagonists of a Viral Dimeric Protease.

Science.gov (United States)

Gable, Jonathan E; Lee, Gregory M; Acker, Timothy M; Hulce, Kaitlin R; Gonzalez, Eric R; Schweigler, Patrick; Melkko, Samu; Farady, Christopher J; Craik, Charles S

2016-04-19

Fragment-based drug discovery has shown promise as an approach for challenging targets such as protein-protein interfaces. We developed and applied an activity-based fragment screen against dimeric Kaposi's sarcoma-associated herpesvirus protease (KSHV Pr) using an optimized fluorogenic substrate. Dose-response determination was performed as a confirmation screen, and NMR spectroscopy was used to map fragment inhibitor binding to KSHV Pr. Kinetic assays demonstrated that several initial hits also inhibit human cytomegalovirus protease (HCMV Pr). Binding of these hits to HCMV Pr was also confirmed by NMR spectroscopy. Despite the use of a target-agnostic fragment library, more than 80 % of confirmed hits disrupted dimerization and bound to a previously reported pocket at the dimer interface of KSHV Pr, not to the active site. One class of fragments, an aminothiazole scaffold, was further explored using commercially available analogues. These compounds demonstrated greater than 100-fold improvement of inhibition. This study illustrates the power of fragment-based screening for these challenging enzymatic targets and provides an example of the potential druggability of pockets at protein-protein interfaces. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quenching points of dimeric single-molecule magnets: Exchange interaction effects

International Nuclear Information System (INIS)

Florez, J.M.; Nunez, Alvaro S.; Vargas, P.

2010-01-01

We study the quenched energy-splitting (Δ E ) of a single-molecule magnet (SMM) conformed by two exchange coupled giant-spins. An assessment of two nontrivial characteristics of this quenching is presented: (i) The quenching-points of a strongly exchange-coupled dimer differ from the ones of their respective giant-spin modeled SMM and such a difference can be well described by using the Solari-Kochetov extra phase; (ii) the dependence on the exchange coupling of the magnetic field values at the quenching-points when Δ E passes from monomeric to dimeric behavior. The physics behind these exchange-modified points, their relation with the Δ E -oscillations experimentally obtained by the Landau-Zener method and with the diabolical-plane of a SMM, is discussed.

Quenching points of dimeric single-molecule magnets: Exchange interaction effects

Energy Technology Data Exchange (ETDEWEB)

Florez, J.M., E-mail: juanmanuel.florez@alumnos.usm.c [Departamento de Fisica, Universidad Tecnica Federico Santa Maria, P.O. Box 110-V, Valparaiso (Chile); Nunez, Alvaro S., E-mail: alnunez@dfi.uchile.c [Departamento de Fisica, Facultad de Ciencias Fisicas y Matematicas, Universidad de Chile, Casilla 487-3, Santiago (Chile); Vargas, P., E-mail: patricio.vargas@usm.c [Departamento de Fisica, Universidad Tecnica Federico Santa Maria, P.O. Box 110-V, Valparaiso (Chile)

2010-11-15

We study the quenched energy-splitting ({Delta}{sub E}) of a single-molecule magnet (SMM) conformed by two exchange coupled giant-spins. An assessment of two nontrivial characteristics of this quenching is presented: (i) The quenching-points of a strongly exchange-coupled dimer differ from the ones of their respective giant-spin modeled SMM and such a difference can be well described by using the Solari-Kochetov extra phase; (ii) the dependence on the exchange coupling of the magnetic field values at the quenching-points when {Delta}{sub E} passes from monomeric to dimeric behavior. The physics behind these exchange-modified points, their relation with the {Delta}{sub E}-oscillations experimentally obtained by the Landau-Zener method and with the diabolical-plane of a SMM, is discussed.

In vitro production of thymine dimer by ultroviolet irradiation of DNA from mesophilic and thermophilic bacteria

International Nuclear Information System (INIS)

Yein, F.S.; Stenesh, J.

1989-01-01

Thymine dimer was produced in vitro by ultraviolet irradiation of DNA, isolated from the mesophile Bacillus licheniformis and the thermophile B. stearothermophilus. Irradiation was performed at three different temperaturs (35, 45 and 55 C) and the thymine dimer was isolated and determined. An HPLC procedure was developed that permitted temperature was greater for the thermophile than for the mesophile. Formation of thymine dimer increased with temperature for both organisms but more so for the thermophile; over the temperature range of 35-55 C, the average increase in thymine dimer production for the themrophile was about 4-times that for the mesophile. The melting out temperature, as a function of increasing irradiation temperature, was essentially unchanged for the mesophilic DNA, but decreased progressively for the thermophilic DNA. These results are discussed in terms of the macromolecular theory of to the macromolecular theory of the thermophily. (author). 31 refs.; 4 figs.; 3 tabs

High-speed atomic force microscopy reveals structural dynamics of α -synuclein monomers and dimers

Science.gov (United States)

Zhang, Yuliang; Hashemi, Mohtadin; Lv, Zhengjian; Williams, Benfeard; Popov, Konstantin I.; Dokholyan, Nikolay V.; Lyubchenko, Yuri L.

2018-03-01

α-Synuclein (α-syn) is the major component of the intraneuronal inclusions called Lewy bodies, which are the pathological hallmark of Parkinson's disease. α-Syn is capable of self-assembly into many different species, such as soluble oligomers and fibrils. Even though attempts to resolve the structures of the protein have been made, detailed understanding about the structures and their relationship with the different aggregation steps is lacking, which is of interest to provide insights into the pathogenic mechanism of Parkinson's disease. Here we report the structural flexibility of α-syn monomers and dimers in an aqueous solution environment as probed by single-molecule time-lapse high-speed AFM. In addition, we present the molecular basis for the structural transitions using discrete molecular dynamics (DMD) simulations. α-Syn monomers assume a globular conformation, which is capable of forming tail-like protrusions over dozens of seconds. Importantly, a globular monomer can adopt fully extended conformations. Dimers, on the other hand, are less dynamic and show a dumbbell conformation that experiences morphological changes over time. DMD simulations revealed that the α-syn monomer consists of several tightly packed small helices. The tail-like protrusions are also helical with a small β-sheet, acting as a "hinge". Monomers within dimers have a large interfacial interaction area and are stabilized by interactions in the non-amyloid central (NAC) regions. Furthermore, the dimer NAC-region of each α-syn monomer forms a β-rich segment. Moreover, NAC-regions are located in the hydrophobic core of the dimer.

In situ control of As dimer orientation on Ge(100) surfaces

International Nuclear Information System (INIS)

Brückner, Sebastian; Döscher, Henning; Supplie, Oliver; Luczak, Johannes; Barrigón, Enrique; Rey-Stolle, Ignacio; Kleinschmidt, Peter; Hannappel, Thomas

2012-01-01

We investigated the preparation of single domain Ge(100):As surfaces in a metal-organic vapor phase epitaxy reactor. In situ reflection anisotropy spectra (RAS) of vicinal substrates change when arsenic is supplied either by tertiarybutylarsine or by background As 4 during annealing. Low energy electron diffraction shows mutually perpendicular orientations of dimers, scanning tunneling microscopy reveals distinct differences in the step structure, and x-ray photoelectron spectroscopy confirms differences in the As coverage of the Ge(100):As samples. Their RAS signals consist of contributions related to As dimer orientation and to step structure, enabling precise in situ control over preparation of single domain Ge(100):As surfaces.

In situ control of As dimer orientation on Ge(100) surfaces

Energy Technology Data Exchange (ETDEWEB)

Brueckner, Sebastian; Doescher, Henning [Helmholtz-Zentrum Berlin, Hahn-Meitner-Platz 1, 14109 Berlin (Germany); Technische Universitaet Ilmenau, Institut fuer Physik, Postfach 10 05 65, 98684 Ilmenau (Germany); Supplie, Oliver; Luczak, Johannes [Helmholtz-Zentrum Berlin, Hahn-Meitner-Platz 1, 14109 Berlin (Germany); Barrigon, Enrique; Rey-Stolle, Ignacio [Instituto de Energia Solar, Universidad Politecnica de Madrid, Avda. Complutense s/n, 28040 Madrid (Spain); Kleinschmidt, Peter [Helmholtz-Zentrum Berlin, Hahn-Meitner-Platz 1, 14109 Berlin (Germany); CiS Forschungsinstitut fuer Mikrosensorik und Photovoltaik GmbH, Konrad-Zuse-Strasse 14, 99099 Erfurt (Germany); Hannappel, Thomas [Helmholtz-Zentrum Berlin, Hahn-Meitner-Platz 1, 14109 Berlin (Germany); Technische Universitaet Ilmenau, Institut fuer Physik, Postfach 10 05 65, 98684 Ilmenau (Germany); CiS Forschungsinstitut fuer Mikrosensorik und Photovoltaik GmbH, Konrad-Zuse-Strasse 14, 99099 Erfurt (Germany)

2012-09-17

We investigated the preparation of single domain Ge(100):As surfaces in a metal-organic vapor phase epitaxy reactor. In situ reflection anisotropy spectra (RAS) of vicinal substrates change when arsenic is supplied either by tertiarybutylarsine or by background As{sub 4} during annealing. Low energy electron diffraction shows mutually perpendicular orientations of dimers, scanning tunneling microscopy reveals distinct differences in the step structure, and x-ray photoelectron spectroscopy confirms differences in the As coverage of the Ge(100):As samples. Their RAS signals consist of contributions related to As dimer orientation and to step structure, enabling precise in situ control over preparation of single domain Ge(100):As surfaces.

Different β-alanine dimeric forms in trifluoromethanesulfonic acid salts. XRD and vibrational studies

Science.gov (United States)

Wołoszyn, Łukasz; Ilczyszyn, Maria M.

2018-03-01

Two new crystalline salts: β-alaninium trifluoromethanesulfonate (β-AlaOTf) and bis(β-alanine) trifluoromethanesulfonate (β-2AlaOTf) were obtained. The former one contains diprotonated β-alanine dimer, the latter one monoprotonated β-alanine dimer. Both compounds were studied by single crystal XRD, vibrational (IR and Raman) spectroscopy and calorimetric method. The quantum-mechanical calculations (DFT/B3LYP/6-311 ++G(2d,2p)) for the diprotonated dimer were carried out. The β-AlaOTf salt crystallizes in the P 1 bar space group of triclinic system (Z = 2), the β-2AlaOTf in the P21/m space group of monoclinic system (Z = 2). The vibrational data for the studied compounds are discussed in relation to their crystal structure, and provide insight into the character of hydrogen bonds and β-alanine protonation. The studied crystals do not exhibit phase transitions in the solid state.

Dimerization of translationally controlled tumor protein is essential for its cytokine-like activity.

Directory of Open Access Journals (Sweden)

Miyoung Kim

Full Text Available BACKGROUND: Translationally Controlled Tumor Protein (TCTP found in nasal lavage fluids of allergic patients was named IgE-dependent histamine-releasing factor (HRF. Human recombinant HRF (HrHRF has been recently reported to be much less effective than HRF produced from activated mononuclear cells (HRFmn. METHODS AND FINDINGS: We found that only NH(2-terminal truncated, but not C-terminal truncated, TCTP shows cytokine releasing activity compared to full-length TCTP. Interestingly, only NH(2-terminal truncated TCTP, unlike full-length TCTP, forms dimers through intermolecular disulfide bonds. We tested the activity of dimerized full-length TCTP generated by fusing it to rabbit Fc region. The untruncated-full length protein (Fc-HrTCTP was more active than HrTCTP in BEAS-2B cells, suggesting that dimerization of TCTP, rather than truncation, is essential for the activation of TCTP in allergic responses. We used confocal microscopy to evaluate the affinity of TCTPs to its putative receptor. We detected stronger fluorescence in the plasma membrane of BEAS-2B cells incubated with Del-N11TCTP than those incubated with rat recombinant TCTP (RrTCTP. Allergenic activity of Del-N11TCTP prompted us to see whether the NH(2-terminal truncated TCTP can induce allergic airway inflammation in vivo. While RrTCTP had no influence on airway inflammation, Del-N11TCTP increased goblet cell hyperplasia in both lung and rhinal cavity. The dimerized protein was found in sera from allergic patients, and bronchoalveolar lavage fluids from airway inflamed mice. CONCLUSIONS: Dimerization of TCTP seems to be essential for its cytokine-like activity. Our study has potential to enhance the understanding of pathogenesis of allergic disease and provide a target for allergic drug development.

How to prevent dimerization of laser dyes in water? Simulation and organic synthesis

International Nuclear Information System (INIS)

Dare-Doyen, S.

2000-01-01

Xanthenes are widely used as laser dyes in ethanol medium because their photophysical properties there are excellent. On the other hand, when they are dissolved in water, their fluorescence is almost zero on account of the dimerization phenomenon (aggregation of two molecules) which is specific in water although the interaction between the two molecules (these dyes are mainly cations) be repulsive. The first part of this work deals with the dimerization study of two dyes, the 6G rhodamine and the 6G pyronine. Molecular dynamics simulation results (AMBER software) have been compared with those of the NMR; thus it has been possible to describe the geometry of the 6G rhodamine dimer and to identify two structures present in equal quantities for the 6G pyronine dimer. It has been demonstrated that the role of water is essential in the aggregation mechanism; this role can be understood as resulting of the hydrophobic effect. The second part of this work concerns the synthesis of rhodamines which are soluble but not able to dimerize in water at the running concentrations of the laser dyes. At first, aminophenol precursors having hydrophilic ionic groups on modifiable sites have been synthesized without changing their photophysical properties. The synthesis sequence of the 3-(2-alkylamino-4-hydroxyphenyl)propionic acids has not given the waited products but N-(3'-hydroxyphenyl)amino-alkylsulfonic acids have been obtained. Their condensation with the phthalic anhydride has led to dyes of a charge -2 at a pH of 5 in water and which have photophysical properties similar to those of the rhodamine 575 in ethanol and laser emission properties in the emission spectral range of the rhodamine 6G in ethanol. This synthesis work has then led to the preparation of two laser dyes usable in water. (author) [fr

Cyclodextrin dimers as receptor molecules for steroid sensors

NARCIS (Netherlands)

de Jong, M.R.; Engbersen, Johannes F.J.; Huskens, Jurriaan; Reinhoudt, David

2000-01-01

The dansyl-modified dimer 9 complexes strongly with the steroidal bile salts. Relative to native -cyclodextrin, the binding of cholate (1 a) and deoxycholate (1 b) salts is especially enhanced. These steroids bind exclusively in a 1:1 fashion. For other bile salts (1 c-1 e) both 1:1 and 1:2

Role of the EHD2 unstructured loop in dimerization, protein binding and subcellular localization.

Directory of Open Access Journals (Sweden)

Kriti Bahl

Full Text Available The C-terminal Eps 15 Homology Domain proteins (EHD1-4 play important roles in regulating endocytic trafficking. EHD2 is the only family member whose crystal structure has been solved, and it contains an unstructured loop consisting of two proline-phenylalanine (PF motifs: KPFRKLNPF. In contrast, despite EHD2 having nearly 70% amino acid identity with its paralogs, EHD1, EHD3 and EHD4, the latter proteins contain a single KPF or RPF motif, but no NPF motif. In this study, we sought to define the precise role of each PF motif in EHD2's homo-dimerization, binding with the protein partners, and subcellular localization. To test the role of the NPF motif, we generated an EHD2 NPF-to-NAF mutant to mimic the homologous sequences of EHD1 and EHD3. We demonstrated that this mutant lost both its ability to dimerize and bind to Syndapin2. However, it continued to localize primarily to the cytosolic face of the plasma membrane. On the other hand, EHD2 NPF-to-APA mutants displayed normal dimerization and Syndapin2 binding, but exhibited markedly increased nuclear localization and reduced association with the plasma membrane. We then hypothesized that the single PF motif of EHD1 (that aligns with the KPF of EHD2 might be responsible for both binding and localization functions of EHD1. Indeed, the EHD1 RPF motif was required for dimerization, interaction with MICAL-L1 and Syndapin2, as well as localization to tubular recycling endosomes. Moreover, recycling assays demonstrated that EHD1 RPF-to-APA was incapable of supporting normal receptor recycling. Overall, our data suggest that the EHD2 NPF phenylalanine residue is crucial for EHD2 localization to the plasma membrane, whereas the proline residue is essential for EHD2 dimerization and binding. These studies support the recently proposed model in which the EHD2 N-terminal region may regulate the availability of the unstructured loop for interactions with neighboring EHD2 dimers, thus promoting

Dimerization in the Grb7 Protein

OpenAIRE

Peterson, Tabitha A.; Benallie, Renee L.; Bradford, Andrew M.; Pias, Sally C.; Yazzie, Jaron.; Lor, Siamee N.; Haulsee, Zachary M.; Park, Chad K.; Johnson, Dennis L.; Rohrschneider, Larry R.; Spuches, Anne.; Lyons, Barbara A.

2012-01-01

In previous studies, we showed that the tyrosine phosphorylation state of growth factor receptor–bound protein 7 (Grb7) affects its ability to bind to the transcription regulator FHL2 and the cortactin-interacting protein, human HS-1-associated protein-1. Here, we present results describing the importance of dimerization in the Grb7–Src homology 2 (SH2) domain in terms of its structural integrity and the ability to bind phosphorylated tyrosine peptide ligands. A tyrosine phosphorylation-mimic...

Non-Covalent Interactions and Impact of Charge Penetration Effects in Linear Oligoacene Dimers and Single Crystals

KAUST Repository

Ryno, Sean; Risko, Chad; Bredas, Jean-Luc

2016-01-01

of charge penetration, which is shown to account for up to 50% of the total interaction energy in dimers extracted from the experimental single crystals; in the case of the most stable co-facial model dimers, this contribution is even larger than the total

Sensitive SERS detection at the single-particle level based on nanometer-separated mushroom-shaped plasmonic dimers

Science.gov (United States)

Xiang, Quan; Li, Zhiqin; Zheng, Mengjie; Liu, Qing; Chen, Yiqin; Yang, Lan; Jiang, Tian; Duan, Huigao

2018-03-01

Elevated metallic nanostructures with nanogaps (film deposition. By controlling the initial size of nanogaps in resist structures and the following deposited film thickness, metallic nanogaps could be tuned at the sub-10 nm scale with single-digit nanometer precision. Both experimental and simulated results revealed that gold dimer on mushroom-shaped pillars have the capability to achieve higher SERS enhancement factor comparing to those plasmonic dimers on cylindrical pillars or on a common SiO2/Si substrate, implying that the nanometer-gapped elevated dimer is an ideal platform to achieve the highest possible field enhancement for various plasmonic applications.

Direct Assessment of the Effect of the Gly380Arg Achondroplasia Mutation on FGFR3 Dimerization Using Quantitative Imaging FRET

Science.gov (United States)

Placone, Jesse; Hristova, Kalina

2012-01-01

The Gly380Arg mutation in FGFR3 is the genetic cause for achondroplasia (ACH), the most common form of human dwarfism. The mutation has been proposed to increase FGFR3 dimerization, but the dimerization propensities of wild-type and mutant FGFR3 have not been compared. Here we use quantitative imaging FRET to characterize the dimerization of wild-type FGFR3 and the ACH mutant in plasma membrane-derived vesicles from HEK293T cells. We demonstrate a small, but statistically significant increase in FGFR3 dimerization due to the ACH mutation. The data are consistent with the idea that the ACH mutation causes a structural change which affects both the stability and the activity of FGFR3 dimers in the absence of ligand. PMID:23056398

1 / n Expansion for the Number of Matchings on Regular Graphs and Monomer-Dimer Entropy

Science.gov (United States)

Pernici, Mario

2017-08-01

Using a 1 / n expansion, that is an expansion in descending powers of n, for the number of matchings in regular graphs with 2 n vertices, we study the monomer-dimer entropy for two classes of graphs. We study the difference between the extensive monomer-dimer entropy of a random r-regular graph G (bipartite or not) with 2 n vertices and the average extensive entropy of r-regular graphs with 2 n vertices, in the limit n → ∞. We find a series expansion for it in the numbers of cycles; with probability 1 it converges for dimer density p diverges as |ln(1-p)| for p → 1. In the case of regular lattices, we similarly expand the difference between the specific monomer-dimer entropy on a lattice and the one on the Bethe lattice; we write down its Taylor expansion in powers of p through the order 10, expressed in terms of the number of totally reducible walks which are not tree-like. We prove through order 6 that its expansion coefficients in powers of p are non-negative.

Pd(OAc2/Ph3P-catalyzed dimerization of isoprene and synthesis of monoterpenic heterocycles

Directory of Open Access Journals (Sweden)

Dominik Kellner

2017-08-01

Full Text Available The palladium-catalyzed dimerization of isoprene is a practical approach of synthesizing monoterpenes. Though several highly selective methods have been reported, most of them still required pressure or costly ligands for attaining the active system and desired selectivity. Herein, we present a simple and economical procedure towards the tail-to-tail dimer using readily available Pd(OAc2 and inexpensive triphenylphosphine as ligand. Furthermore, simple screw cap vials are employed, allowing carrying out the reaction at low pressure. In addition, the potential of the dimer as a chemical platform for the preparation of heterocyclic terpenes by subsequent (hetero-Diels–Alder or [4 + 1]-cycloadditions with nitrenes is also depicted.

Stepwise "Dark Photoswitching" of Photochromic Dimers in a Junction

DEFF Research Database (Denmark)

Olsen, Stine Tetzschner; Hansen, Thorsten; Nielsen, Mogens Brøndsted

2017-01-01

-induced switching) has been termed dark photoswitching and was observed for the dihydroazulene–vinylheptafulvene couple in a junction. In this theoretical study, we expand this concept to dimeric structures containing two dihydroazulene units linked through meta- or para-phenylene bridges and anchored...

Dimer formation and transcription activation in the sporulation response regulator Spo0A.

Science.gov (United States)

Lewis, Richard J; Scott, David J; Brannigan, James A; Ladds, Joanne C; Cervin, Marguerite A; Spiegelman, George B; Hoggett, James G; Barák, Imrich; Wilkinson, Anthony J

2002-02-15

The response regulator Spo0A is the master control element in the initiation of sporulation in Bacillus subtilis. Like many other multi-domain response regulators, the latent activity of the effector, C-terminal domain is stimulated by phosphorylation on a conserved aspartic acid residue in the regulatory, N-terminal domain. If a threshold concentration of phosphorylated Spo0A is achieved, the transcription of genes required for sporulation is activated, whereas the genes encoding stationary phase sentinels are repressed, and sporulation proceeds. Despite detailed genetic, biochemical and structural characterisation, it is not understood how the phosphorylation signal in the receiver domain is transduced into DNA binding and transcription activation in the distal effector domain. An obstacle to our understanding of Spo0A function is the uncertainty concerning changes in quaternary structure that accompany phosphorylation. Here we have revisited this question and shown unequivocally that Spo0A forms dimers upon phosphorylation and that the subunit interactions in the dimer are mediated principally by the receiver domain. Purified dimers of two mutants of Spo0A, in which the phosphorylatable aspartic acid residue has been substituted, activate transcription from the spoIIG promoter in vitro, whereas monomers do not. This suggests that dimers represent the activated form of Spo0A. Copyright 2002 Elsevier Science Ltd.

Dimeric Structure of the Blue Light Sensor Protein Photozipper in the Active State.

Science.gov (United States)

Ozeki, Kohei; Tsukuno, Hiroyuki; Nagashima, Hiroki; Hisatomi, Osamu; Mino, Hiroyuki

2018-02-06

The light oxygen voltage-sensing (LOV) domain plays a crucial role in blue light (BL) sensing in plants and microorganisms. LOV domains are usually associated with the effector domains and regulate the activities of effector domains in a BL-dependent manner. Photozipper (PZ) is monomeric in the dark state. BL induces reversible dimerization of PZ and subsequently increases its affinity for the target DNA sequence. In this study, we report the analyses of PZ by pulsed electron-electron double resonance (PELDOR). The neutral flavin radical was formed by BL illumination in the presence of dithiothreitol in the LOV-C254S (without the bZIP domain) and PZ-C254S mutants, where the cysteine residue responsible for adduct formation was replaced with serine. The magnetic dipole interactions of 3 MHz between the neutral radicals were detected in both LOV-C254S and PZ-C254S, indicating that these mutants are dimeric in the radical state. The PELDOR simulation showed that the distance between the radical pair is close to that estimated from the dimeric crystal structure in the "light state" [Heintz, U., and Schlichting, I. (2016) eLife 5, e11860], suggesting that in the radical state, LOV domains in PZ-C254S form a dimer similar to that of LOV-C254S, which lacks the bZIP domain.

Theory and simulations of adhesion receptor dimerization on membrane surfaces.

Science.gov (United States)

Wu, Yinghao; Honig, Barry; Ben-Shaul, Avinoam

2013-03-19

The equilibrium constants of trans and cis dimerization of membrane bound (2D) and freely moving (3D) adhesion receptors are expressed and compared using elementary statistical-thermodynamics. Both processes are mediated by the binding of extracellular subdomains whose range of motion in the 2D environment is reduced upon dimerization, defining a thin reaction shell where dimer formation and dissociation take place. We show that the ratio between the 2D and 3D equilibrium constants can be expressed as a product of individual factors describing, respectively, the spatial ranges of motions of the adhesive domains, and their rotational freedom within the reaction shell. The results predicted by the theory are compared to those obtained from a novel, to our knowledge, dynamical simulations methodology, whereby pairs of receptors perform realistic translational, internal, and rotational motions in 2D and 3D. We use cadherins as our model system. The theory and simulations explain how the strength of cis and trans interactions of adhesive receptors are affected both by their presence in the constrained intermembrane space and by the 2D environment of membrane surfaces. Our work provides fundamental insights as to the mechanism of lateral clustering of adhesion receptors after cell-cell contact and, more generally, to the formation of lateral microclusters of proteins on cell surfaces. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Cardiac Calcium ATPase Dimerization Measured by Cross-Linking and Fluorescence Energy Transfer.

Science.gov (United States)

Blackwell, Daniel J; Zak, Taylor J; Robia, Seth L

2016-09-20

The cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA) establishes the intracellular calcium gradient across the sarcoplasmic reticulum membrane. It has been proposed that SERCA forms homooligomers that increase the catalytic rate of calcium transport. We investigated SERCA dimerization in rabbit left ventricular myocytes using a photoactivatable cross-linker. Western blotting of cross-linked SERCA revealed higher-molecular-weight species consistent with SERCA oligomerization. Fluorescence resonance energy transfer measurements in cells transiently transfected with fluorescently labeled SERCA2a revealed that SERCA readily forms homodimers. These dimers formed in the absence or presence of the SERCA regulatory partner, phospholamban (PLB) and were unaltered by PLB phosphorylation or changes in calcium or ATP. Fluorescence lifetime data are compatible with a model in which PLB interacts with a SERCA homodimer in a stoichiometry of 1:2. Together, these results suggest that SERCA forms constitutive homodimers in live cells and that dimer formation is not modulated by SERCA conformational poise, PLB binding, or PLB phosphorylation. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Direct demonstration of NCAM cis-dimerization and inhibitory effect of palmitoylation using the BRET2 technique

DEFF Research Database (Denmark)

Kulahin, Nikolaj; Grunnet, Lars Groth; Lundh, Morten

2011-01-01

, cis-dimerization in living cells has not been shown directly and the role of the cytoplasmic part in NCAM dimerization is poorly understood. Here, we used the bioluminescence resonance energy transfer (BRET(2)) technique to directly demonstrate that full-length NCAM cis-homodimerizes in living cells...

Structural basis of RNA recognition and dimerization by the STAR proteins T-STAR and Sam68

Science.gov (United States)

Feracci, Mikael; Foot, Jaelle N.; Grellscheid, Sushma N.; Danilenko, Marina; Stehle, Ralf; Gonchar, Oksana; Kang, Hyun-Seo; Dalgliesh, Caroline; Meyer, N. Helge; Liu, Yilei; Lahat, Albert; Sattler, Michael; Eperon, Ian C.; Elliott, David J.; Dominguez, Cyril

2016-01-01

Sam68 and T-STAR are members of the STAR family of proteins that directly link signal transduction with post-transcriptional gene regulation. Sam68 controls the alternative splicing of many oncogenic proteins. T-STAR is a tissue-specific paralogue that regulates the alternative splicing of neuronal pre-mRNAs. STAR proteins differ from most splicing factors, in that they contain a single RNA-binding domain. Their specificity of RNA recognition is thought to arise from their property to homodimerize, but how dimerization influences their function remains unknown. Here, we establish at atomic resolution how T-STAR and Sam68 bind to RNA, revealing an unexpected mode of dimerization different from other members of the STAR family. We further demonstrate that this unique dimerization interface is crucial for their biological activity in splicing regulation, and suggest that the increased RNA affinity through dimer formation is a crucial parameter enabling these proteins to select their functional targets within the transcriptome. PMID:26758068

The EBNA-2 N-Terminal Transactivation Domain Folds into a Dimeric Structure Required for Target Gene Activation.

Directory of Open Access Journals (Sweden)

Anders Friberg

2015-05-01

Full Text Available Epstein-Barr virus (EBV is a γ-herpesvirus that may cause infectious mononucleosis in young adults. In addition, epidemiological and molecular evidence links EBV to the pathogenesis of lymphoid and epithelial malignancies. EBV has the unique ability to transform resting B cells into permanently proliferating, latently infected lymphoblastoid cell lines. Epstein-Barr virus nuclear antigen 2 (EBNA-2 is a key regulator of viral and cellular gene expression for this transformation process. The N-terminal region of EBNA-2 comprising residues 1-58 appears to mediate multiple molecular functions including self-association and transactivation. However, it remains to be determined if the N-terminus of EBNA-2 directly provides these functions or if these activities merely depend on the dimerization involving the N-terminal domain. To address this issue, we determined the three-dimensional structure of the EBNA-2 N-terminal dimerization (END domain by heteronuclear NMR-spectroscopy. The END domain monomer comprises a small fold of four β-strands and an α-helix which form a parallel dimer by interaction of two β-strands from each protomer. A structure-guided mutational analysis showed that hydrophobic residues in the dimer interface are required for self-association in vitro. Importantly, these interface mutants also displayed severely impaired self-association and transactivation in vivo. Moreover, mutations of solvent-exposed residues or deletion of the α-helix do not impair dimerization but strongly affect the functional activity, suggesting that the EBNA-2 dimer presents a surface that mediates functionally important intra- and/or intermolecular interactions. Our study shows that the END domain is a novel dimerization fold that is essential for functional activity. Since this specific fold is a unique feature of EBNA-2 it might provide a novel target for anti-viral therapeutics.

The polar 2e/12c bond in phenalenyl-azaphenalenyl hetero-dimers: Stronger stacking interaction and fascinating interlayer charge transfer

Energy Technology Data Exchange (ETDEWEB)

Zhong, Rong-Lin; Li, Zhi-Ru, E-mail: hlxu@nenu.edu.cn, E-mail: lzr@jlu.edu.cn [Institute of Theoretical Chemistry, Jilin University, Changchun 130023 (China); Xu, Hong-Liang, E-mail: hlxu@nenu.edu.cn, E-mail: lzr@jlu.edu.cn [Institute of Functional Material Chemistry, Faculty of Chemistry, Northeast Normal University, Changchun, Jilin 130024 (China)

2016-08-07

An increasing number of chemists have focused on the two-electron/multicenter bond (2e/mc) that was first introduced to interpret the bonding mechanism of radical dimers. Herein, we report the polar two-electron/twelve center (2e/12c) bonding character in a series of phenalenyl-azaphenalenyl radical hetero-dimers. Interestingly, the bonding energy of weaker polar hetero-dimer (P-TAP) is dominated by the overlap of the two different singly occupied molecular orbital of radicals, while that of stronger polar hetero-dimer (P-HAP) is dominated by the electrostatic attraction. Results show that the difference between the electronegativity of the monomers plays a prominent role in the essential attribution of the polar 2e/12c bond. Correspondingly, a stronger stacking interaction in the hetero-dimer could be effectively achieved by increasing the difference of nitrogen atoms number between the monomers. It is worthy of note that an interesting interlayer charge transfer character is induced in the polar hetero-dimers, which is dependent on the difference between the electronegativity of the monomers. It is our expectation that the new knowledge about the bonding nature of radical hetero-dimers might provide important information for designing radical based functional materials with various applications.

Pyrimidine dimers are not the principal pre-mutagenic lesions induced in lambda phage DNA by ultraviolet light

International Nuclear Information System (INIS)

Wood, R.D.

1985-01-01

Experiments were performed to examine the role of cyclobutyl pyrimidine dimers in the process of mutagenesis by ultraviolet light. Lambda phage DNA was irradiated with u.v. and then incubated with an Escherichia coli photoreactivating enzyme, which monomerizes cyclobutyl pyrimidine dimers upon exposure to visible light. The photoreactivated DNA was packaged into lambda phage particles, which were used to infect E. coli uvr - host cells that had been induced for SOS functions by ultraviolet irradiation. Photoreactivation removed most toxic lesions from irradiated phage, but did not change the frequency of induction of mutations to the clear-plaque phenotype. This implies that cyclobutyl pyrimidine dimers can be lethal, but usually do not serve as sites of mutations in the phage. The DNA sequences of mutants, derived from photoreactivated DNA showed that almost two-thirds (16/28) were transitions, the same fraction found for u.v. mutagenesis without photoreactivation. Thus the lesion inducing transitions is not the cyclobutyl pyrimidine dimer. Photoreactivation of SOS-induced host cells before infection with u.v.-irradiated phage reduced mutagenesis substantially. In this case, photoreversal of cyclobutyl dimers serves to reduce expression of the SOS functions that are required in targeted u.v. mutagenesis. (author)

L-Cysteine halogenides: A new family of salts with an L-cysteine⋯L-cysteinium dimeric cation

Science.gov (United States)

Ghazaryan, V. V.; Minkov, V. S.; Boldyreva, E. V.; Petrosyan, A. M.

2016-10-01

Two L-cysteinium-halogenides with (L-cysteine···L-cysteinium) dimeric cations have been obtained, (L-Cys⋯L-Cys+)·Cl-, and (L-Cys⋯L-Cys+)·Br-. Both salts crystallize in monoclinic space group P21. Although these salts have the same dimeric cations and isotypical halogen anions, crystal packing is different. The main difference between the two salts rests in the conformation of (L-Cys⋯L-Cys+) dimeric cation, which also differs from that of the dimeric cation in the previously reported compound L-Cys+(L-Cys⋯L-Cys+)·F-·(F-⋯HF). The dimeric cation is formed by a very short O-H⋯O hydrogen bond with d(O···O) of 2.449(2) Å and 2.435(11) Å in the chloride and bromide, respectively. In addition to crystal structure analysis, Infrared and Raman spectra have been registered and discussed with a particular focus on intermolecular interactions. The L-Cys+·Br-·H2O salt with a simple L-cysteinium cation was also obtained and the crystal structure solved. It resembles its chloride analogue, L-Cys+·Cl-·H2O.

Resistance of 3T3 mouse cells to UV light in relation to excision and transfer of dimers to daughter strands

Energy Technology Data Exchange (ETDEWEB)

Menck, C F.M.; Meneghini, R [Sao Paulo Univ. (Brazil). Inst. de Quimica

1982-04-01

Mouse cells (3T3 line) and human fibroblasts are equally sensitive to UV light. At fluences of 2.0-2.5 J/m/sup 2/ mouse cells excise only 20% of the pyrimidine dimers as compared to 80% excised by human fibroblasts. This fluence allows 37% survival in both cases. Hence, mouse cells are more resistant to the same burden of unexcised dimers. The reason for this increased tolerance to dimers does not seem to be due to a recombinational mechanism, as judged by the fact that only ca. 5% of the dimers are transferred from parental to daughter strands. The transfer of dimers was measured by the Micrococcus luteus UV endonuclease assay, irradiating cells at G/sub 1/ to avoid artifacts arising from introduction of dimers in nascent strands. The possibility of other mechanisms being involved in the process of tolerance to DNA lesions is discussed.

Effects of gold based dimers on structural and electronic properties of MoS{sub 2}

Energy Technology Data Exchange (ETDEWEB)

Kadioglu, Yelda [Department of Physics, Adnan Menderes University, 09100 Aydın (Turkey); Gökoğlu, Gökhan [Department of Physics, Karabük University, 78050 Karabük (Turkey); Aktürk, Olcay Üzengi, E-mail: ouzengi@adu.edu.tr [Department of Electrical & Electronics Engineering, Adnan Menderes University, 09100 Aydın (Turkey); Nanotechnology Application and Research Center, Adnan Menderes University, 09100 Aydın (Turkey)

2017-02-28

Highlights: • Semiconductor MoS{sub 2} shows metallic character by AuPt and AuPd adsorption. • MoS{sub 2} maintains its semiconductor characteristics with a decrease in the band gap values after AuAg, AuCu, and AuAl adsorption. • AuPt adsorbed system is the most stable structure energetically. • AuAl exhibits the weakest adsorption to MoS{sub 2} among the considered dimers. - Abstract: In view of first principles calculations, we investigate the electronic structure redecoration of monolayer MoS{sub 2} upon adsorptions of AuAg, AuPt, AuPd, AuCu, and AuAl bimetallic dimers. Geometrical structure, band structures, electronic density of states, charge density differences of dimer adsorbed MoS{sub 2} systems are presented and discussed. All the systems studied have non-magnetic ground states. Charge transfers occur from dimer to surface except for AuPt adsorption. Our results indicate that the semiconductor MoS{sub 2} maintains its semiconductor character with decreased band gaps upon AuAg, AuCu, and AuAl adsorptions. However, MoS{sub 2} shows metallic behaviour by AuPt and AuPd adsorptions, so Pt-d and Pd-d states cross Fermi level yielding metallic character. AuPt adsorbed system has the highest E{sub ads} value of 3.15 eV indicating the most stable structure energetically among the dimer adsorbed MoS{sub 2} systems considered.

Even-odd alternation of the formation of dimer isomers in irradiated polycrystalline alkanes: evidence from product analysis

International Nuclear Information System (INIS)

Baudson, T.; Tilquin, B.

1984-01-01

Recent ESR studies on n-alkanes from n-C 11 to n-C 25 have shown that a prominent chain end (-CH 2 -CH 2 ) alkyl radical is formed in odd members of the series. In this preliminary discussion of our study, we shall report the capillary chromatogram in the dimer isomers range for n-alkanes ranging from n-C 11 to n-C 17 irradiated at 80 kGy. Dimer isomers, produced in part by the combination of chain end radicals, are eluted at the end chromatogram. The combination of two chain end radicals gives the dimer (D 11 ) isomer eluted at the last place. It is shown that dimers produced by the combination of chain end alkyl radicals are more important for the odd members of the series than for the even members. (author)

Direct assessment of the effect of the Gly380Arg achondroplasia mutation on FGFR3 dimerization using quantitative imaging FRET.

Directory of Open Access Journals (Sweden)

Jesse Placone

Full Text Available The Gly380Arg mutation in FGFR3 is the genetic cause for achondroplasia (ACH, the most common form of human dwarfism. The mutation has been proposed to increase FGFR3 dimerization, but the dimerization propensities of wild-type and mutant FGFR3 have not been compared. Here we use quantitative imaging FRET to characterize the dimerization of wild-type FGFR3 and the ACH mutant in plasma membrane-derived vesicles from HEK293T cells. We demonstrate a small, but statistically significant increase in FGFR3 dimerization due to the ACH mutation. The data are consistent with the idea that the ACH mutation causes a structural change which affects both the stability and the activity of FGFR3 dimers in the absence of ligand.

Different β-alanine dimeric forms in trifluoromethanesulfonic acid salts. XRD and vibrational studies.

Science.gov (United States)

Wołoszyn, Łukasz; Ilczyszyn, Maria M

2018-03-15

Two new crystalline salts: β-alaninium trifluoromethanesulfonate (β-AlaOTf) and bis(β-alanine) trifluoromethanesulfonate (β-2AlaOTf) were obtained. The former one contains diprotonated β-alanine dimer, the latter one monoprotonated β-alanine dimer. Both compounds were studied by single crystal XRD, vibrational (IR and Raman) spectroscopy and calorimetric method. The quantum-mechanical calculations (DFT/B3LYP/6-311++G(2d,2p)) for the diprotonated dimer were carried out. The β-AlaOTf salt crystallizes in the P1¯ space group of triclinic system (Z=2), the β-2AlaOTf in the P2 1 /m space group of monoclinic system (Z=2). The vibrational data for the studied compounds are discussed in relation to their crystal structure, and provide insight into the character of hydrogen bonds and β-alanine protonation. The studied crystals do not exhibit phase transitions in the solid state. Copyright © 2017 Elsevier B.V. All rights reserved.

Cytotoxic bibenzyl dimers from the stems of Dendrobium fimbriatum Hook.

Science.gov (United States)

Xu, Feng-Qing; Xu, Fang-Cheng; Hou, Bo; Fan, Wei-Wei; Zi, Cheng-Ting; Li, Yan; Dong, Fa-Wu; Liu, Yu-Qing; Sheng, Jun; Zuo, Zhi-Li; Hu, Jiang-Miao

2014-11-15

The bioassay-guided chemical investigation of the stems of Dendrobium fimbriatum Hook led to the isolation of seven first reported bibenzyl dimers with a linkage of a methylene moiety, fimbriadimerbibenzyls A-G (1-7), together with a new dihydrophenanthrene derivative (S)-2,4,5,9-tetrahydroxy-9,10-dihydrophenanthrene (8) and thirteen known compounds (9-21). The structure of the new compound was established by spectroscopic analysis. Biological evaluation of bibenzyl derivatives against five human cell lines indicated that seven of those compounds exhibited broad-spectrum and cytotoxic activities with IC50 values ranging from 2.2 to 21.2 μM. Those rare bibenzyl dimers exhibited cytotoxic activities in vitro and the cytotoxicity decreased as the number of oxygen-containing groups in the structure decreases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Oncogenic TPM3-ALK activation requires dimerization through the coiled-coil structure of TPM3

International Nuclear Information System (INIS)

Amano, Yosuke; Ishikawa, Rie; Sakatani, Toshio; Ichinose, Junji; Sunohara, Mitsuhiro; Watanabe, Kousuke; Kage, Hidenori; Nakajima, Jun; Nagase, Takahide; Ohishi, Nobuya; Takai, Daiya

2015-01-01

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal tumor that can arise from anywhere in the body. Anaplastic lymphoma kinase (ALK) gene rearrangements, most often resulting in the tropomyosin 3 (TPM3)-ALK fusion gene, are the main causes of IMT. However, the mechanism of malignant transformation in IMT has yet to be elucidated. The purpose of this study was to clarify the role of the TPM3 region in the transformation of IMT via TPM3-ALK. Lentivirus vectors containing a TPM3-ALK fusion gene lacking various lengths of TPM3 were constructed and expressed in HEK293T and NIH3T3 cell lines. Focus formation assay revealed loss of contact inhibition in NIH3T3 cells transfected with full-length TPM3-ALK, but not with ALK alone. Blue-native polyacrylamide gel electrophoresis (BN-PAGE) revealed that TPM3-ALK dimerization increased in proportion to the length of TPM3. Western blot showed phosphorylation of ALK, ERK1/2, and STAT3 in HEK293T cells transfected with TPM3-ALK. Thus, the coiled-coil structure of TPM3 contributes to the transforming ability of the TPM3-ALK fusion protein, and longer TPM3 region leads to higher dimer formation. - Highlights: • TPM3-ALK fusion protein dimerizes through the coiled-coil structure of TPM3. • Longer coiled-coil structure of TPM3 leads to higher TPM3-ALK dimer formation. • Presence of TPM3-ALK dimer leads to ALK, STAT3, and ERK1/2 phosphorylation. • Presence of TPM3-ALK leads to loss of contact inhibition. • BN-PAGE is a simple technique for visualizing oncogenic dimerization

Oncogenic TPM3-ALK activation requires dimerization through the coiled-coil structure of TPM3

Energy Technology Data Exchange (ETDEWEB)

Amano, Yosuke; Ishikawa, Rie; Sakatani, Toshio [Department of Respiratory Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Ichinose, Junji [Department of Cardiothoracic Surgery, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Sunohara, Mitsuhiro; Watanabe, Kousuke; Kage, Hidenori [Department of Respiratory Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Nakajima, Jun [Department of Cardiothoracic Surgery, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Nagase, Takahide; Ohishi, Nobuya [Department of Respiratory Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Takai, Daiya, E-mail: dtakai-ind@umin.ac.jp [Department of Respiratory Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Department of Clinical Laboratory, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan)

2015-02-13

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal tumor that can arise from anywhere in the body. Anaplastic lymphoma kinase (ALK) gene rearrangements, most often resulting in the tropomyosin 3 (TPM3)-ALK fusion gene, are the main causes of IMT. However, the mechanism of malignant transformation in IMT has yet to be elucidated. The purpose of this study was to clarify the role of the TPM3 region in the transformation of IMT via TPM3-ALK. Lentivirus vectors containing a TPM3-ALK fusion gene lacking various lengths of TPM3 were constructed and expressed in HEK293T and NIH3T3 cell lines. Focus formation assay revealed loss of contact inhibition in NIH3T3 cells transfected with full-length TPM3-ALK, but not with ALK alone. Blue-native polyacrylamide gel electrophoresis (BN-PAGE) revealed that TPM3-ALK dimerization increased in proportion to the length of TPM3. Western blot showed phosphorylation of ALK, ERK1/2, and STAT3 in HEK293T cells transfected with TPM3-ALK. Thus, the coiled-coil structure of TPM3 contributes to the transforming ability of the TPM3-ALK fusion protein, and longer TPM3 region leads to higher dimer formation. - Highlights: • TPM3-ALK fusion protein dimerizes through the coiled-coil structure of TPM3. • Longer coiled-coil structure of TPM3 leads to higher TPM3-ALK dimer formation. • Presence of TPM3-ALK dimer leads to ALK, STAT3, and ERK1/2 phosphorylation. • Presence of TPM3-ALK leads to loss of contact inhibition. • BN-PAGE is a simple technique for visualizing oncogenic dimerization.

Intermolecular interaction potentials of the methane dimer from the local density approximation

International Nuclear Information System (INIS)

Chen Xiangrong; Bai Yulin; Zhu Jun; Yang Xiangdong

2004-01-01

The intermolecular interaction potentials of methane (CH 4 ) dimer are calculated within the density functional theory in the local density approximation (LDA). It is found that the calculated potentials have minima when the intermolecular distance of CH 4 dimer is about 7.0 a.u., which is in good agreement with the experiment. The depth of the potential is 0.017 eV. The results obtained by our LDA calculations seem to agree well with those obtained by MP2, MP3, and CCSD from the Moeller-Plesset and coupled cluster methods by Tsuzuki et al. and with the experimental data

Heterologous Secretory Expression and Characterization of Dimerized Bone Morphogenetic Protein 2 in Bacillus subtilis

Directory of Open Access Journals (Sweden)

Muhammad Umair Hanif

2017-01-01

Full Text Available Recombinant human Bone Morphogenetic Protein 2 (rhBMP2 has important applications in the spine fusion and ortho/maxillofacial surgeries. Here we first report the secretory expression of biological active dimerized rhBMP2 from Bacillus subtilis system. The mature domain of BMP2 gene was amplified from pTz57R/BMP2 plasmid. By using pHT43 expression vector two constructs, pHT43-BMP2-M (single BMP2 gene and pHT43-BMP2-D (two BMP2 genes coupled with a linker to produce a dimer, were designed. After primary cloning (DH5α strain and sequence analysis, constructs were transformed into Bacillus subtilis for secretory expression. Expression conditions like media (2xYT and temperature (30°C were optimized. Maximum 35% and 25% secretory expression of monomer (~13 kDa and dimer (~25 kDa, respectively, were observed on SDS-PAGE in SCK6 strain. The expression and dimeric nature of rhBMP2 were confirmed by western blot and native PAGE analysis. For rhBMP2 purification, 200 ml culture supernatant was freeze dried to 10 ml and dialyzed (Tris-Cl, pH 8.5 and Fast Protein Liquid Chromatography (6 ml, Resource Q column was performed. The rhBMP2 monomer and dimer were eluted at 0.9 M and 0.6 M NaCl, respectively. The alkaline phosphatase assay of rhBMP2 (0, 50, 100, 200, and 400 ng/ml was analyzed on C2C12 cells and maximum 200 ng/ml activity was observed in dose dependent manner.

Antioxidant and membrane effects of procyanidin dimers and trimers isolated from peanut and cocoa.

Science.gov (United States)

Verstraeten, Sandra V; Hammerstone, John F; Keen, Carl L; Fraga, César G; Oteiza, Patricia I

2005-06-15

The antioxidant and membrane effects of dimer (Dim) and trimer (Trim) procyanidins isolated from cocoa (Theobroma cacao) (B- and C-bonded) and peanut (Arachis hypogea L.) skin (A-bonded) were evaluated in phosphatidyl choline liposomes. When liposomes were oxidized with a steady source of oxidants, the above dimers and trimers inhibited to a similar extent lipid oxidation in a concentration (0.33-5 microM)-dependent manner. With respect to membrane effects, Dim A1, Dim B, Trim A, and Trim C increased (Dim A1 = Dim B and Trim A = Trim C), while Dim A2 decreased, membrane surface potential. All of the procyanidins tested decreased membrane fluidity as determined by fluorescent probes at the water-lipid interface, an effect that extended into the hydrophobic region of the bilayer. Both dimers and trimers protected the lipid bilayer from disruption by Triton X-100. The magnitude of the protection was Dim A1 > Dim A2 > Dim B and Trim C > Trim A. Thus, dimers and trimers can interact with membrane phospholipids, presumably with their polar headgroup. As a consequence of this interaction, they can provide protection against the attack of oxidants and other molecules that challenge the integrity of the bilayer.

Theory of the orthogonal dimer Heisenberg spin model for SrCu sub 2 (BO sub 3) sub 2

CERN Document Server

Miyahara, S

2003-01-01

The magnetic properties of SrCu sub 2 (BO sub 3) sub 2 are reviewed from a theoretical point of view. SrCu sub 2 (BO sub 3) sub 2 is a new two-dimensional spin gap system and its magnetic properties are well described by a spin-1/2 antiferromagnetic Heisenberg model of the orthogonal dimer lattice. The model has a dimer singlet ground state whose exactness was proven by Shastry and Sutherland for a topologically equivalent model more than 20 years ago. The exactness of the ground state is maintained even if interlayer couplings are introduced for SrCu sub 2 (BO sub 3) sub 2. In the two-dimensional model, quantum phase transitions take place between different ground states for which three phases are expected: a gapped dimer singlet state, a plaquette resonating valence bond state and a gapless magnetic ordered state. Analysis of the experimental data shows that the dimer singlet ground state is realized in SrCu sub 2 (BO sub 3) sub 2. The orthogonality of the dimer bonds, which is the underlying symmetry of th...

Dissociation of nucleosomal particles by chemical modification. Equivalence of the two binding sites for H2A.H2B dimers

International Nuclear Information System (INIS)

Jordano, J.; Nieto, M.A.; Palacian, E.

1985-01-01

Treatment of nucleosomal particles with dimethylmaleic anhydride, a reagent for protein amino groups, is accompanied by a biphasic release of histones H2A plus H2B; one H2A.H2B dimer is more easily released than the other. This behavior allows the preparation of nucleosomal particles containing only one H2A.H2B dimer, which were complemented with 125 I-labeled H2A.H2B. These reconstituted particles, which contain one labeled and one unlabeled H2A.H2B dimer, were treated with the amount of reagent needed to release one of the two H2A.H2B dimers. Radioactivity was equally distributed between residual particles and released proteins, which is consistent with equivalent binding sites in the nucleosomal particle for H2A.H2B dimers, rather than with intrinsically different sites. The asymmetric release of H2A.H2B dimers would be caused by a change in the binding site of one dimer following the release of the other. This behavior might be related to the structural dynamics of nucleosomes

Repair of pyrimidine dimers in radiation-sensitive mutants rad3, rad4, rad6, and rad9 of Saccharomyces cerevisiae. [nicking

Energy Technology Data Exchange (ETDEWEB)

Prakash, L [Rochester Univ., N.Y. (USA). Dept. of Radiation Biology and Biophysics; Rochester Univ., N.Y. (USA). School of Medicine and Dentistry)

1977-10-01

The ability to remove ultraviolet-induced pyrimidine dimers was examined in four radiation-sensitive mutants of Saccharomyces cerevisiae. The susceptibility of DNA from irradiated cells to nicking by either the T4 uv-endonuclease or an endonuclease activity found in crude extracts of Micrococcus luteus was used to measure the presence of dimers in DNA. The rad3 and rad4 mutants are shown to be defective in dimer excision whereas the rad6 and rad9 mutants are proficient in dimer excision.

Synthesis of the iron phthalocyaninate radical cation μ-nitrido dimer and its interaction with hydrogen peroxide

Science.gov (United States)

Grishina, E. S.; Makarova, A. S.; Kudrik, E. V.; Makarov, S. V.; Koifman, O. I.

2016-03-01

The iron phthalocyaninate μ-nitrido dimer radical cation, as well as the μ-nitrido dimer complexes of iron phthalocyaninate, was found to have high catalytic activity in the oxidation of organic compounds. It was concluded that this compound is of interest as a model of active intermediates—catalase and oxidase enzymes.

The Structure of the Poxvirus A33 Protein Reveals a Dimer of Unique C-Type Lectin-Like Domains

Energy Technology Data Exchange (ETDEWEB)

Su, Hua-Poo; Singh, Kavita; Gittis, Apostolos G.; Garboczi, David N. (NIH)

2010-11-03

The current vaccine against smallpox is an infectious form of vaccinia virus that has significant side effects. Alternative vaccine approaches using recombinant viral proteins are being developed. A target of subunit vaccine strategies is the poxvirus protein A33, a conserved protein in the Chordopoxvirinae subfamily of Poxviridae that is expressed on the outer viral envelope. Here we have determined the structure of the A33 ectodomain of vaccinia virus. The structure revealed C-type lectin-like domains (CTLDs) that occur as dimers in A33 crystals with five different crystal lattices. Comparison of the A33 dimer models shows that the A33 monomers have a degree of flexibility in position within the dimer. Structural comparisons show that the A33 monomer is a close match to the Link module class of CTLDs but that the A33 dimer is most similar to the natural killer (NK)-cell receptor class of CTLDs. Structural data on Link modules and NK-cell receptor-ligand complexes suggest a surface of A33 that could interact with viral or host ligands. The dimer interface is well conserved in all known A33 sequences, indicating an important role for the A33 dimer. The structure indicates how previously described A33 mutations disrupt protein folding and locates the positions of N-linked glycosylations and the epitope of a protective antibody.

A Dimeric Mutant of Human Pancreatic Ribonuclease with Selective Cytotoxicity toward Malignant Cells

Science.gov (United States)

Piccoli, Renata; di Gaetano, Sonia; de Lorenzo, Claudia; Grauso, Michela; Monaco, Carmen; Spalletti-Cernia, Daniela; Laccetti, Paolo; Cinatl, Jaroslav; Matousek, Josef; D'Alessio, Giuseppe

1999-07-01

Monomeric human pancreatic RNase, devoid of any biological activity other than its RNA degrading ability, was engineered into a dimeric protein with a cytotoxic action on mouse and human tumor cells, but lacking any appreciable toxicity on mouse and human normal cells. This dimeric variant of human pancreas RNase selectively sensitizes to apoptotic death cells derived from a human thyroid tumor. Because of its selectivity for tumor cells, and because of its human origin, this protein represents a potentially very attractive, novel tool for anticancer therapy.

Building-up novel coordination polymer with Zn(II) porphyrin dimer ...

Indian Academy of Sciences (India)

mer with porphyrin dimer. Solution structures of the complexes along with binding studies in solution between ... porphyrin polymers by self-assembly is fascinating ..... ture determination. ..... J K M 2000 In The Porphyrin Handbook Kadish K M,.

Computed Tomography Angiography in Patients Evaluated for Acute Pulmonary Embolism with Low Serum D-dimer Levels: A Prospective Study.

Science.gov (United States)

Gimber, Lana Hirai; Travis, R Ing; Takahashi, Jayme M; Goodman, Torrey L; Yoon, Hyo-Chun

2009-01-01

Pulmonary computed tomography angiography (CTA) and the Wells criteria both have interobserver variability in the assessment of pulmonary embolism (PE). Quantitative D-dimer assay findings have been shown to have a high negative predictive value in patients with low pretest probability of PE. Evaluate roles for clinical probability and CTA in Emergency Department (ED) patients suspected of acute PE but having a low serum D-dimer level. Prospective observational study of ED patients with possible PE who underwent pulmonary CTA and had D-dimer levels tiebreaker. Pulmonary CTA findings positive for acute embolism should be viewed with caution, especially if the suspected PE is in a distal segmental or subsegmental artery in a patient with a serum D-dimer level of dimer levels because most will have low or intermediate clinical probability of PE.

Dimerization of Carboxylic Acids: An Equation of State Approach

DEFF Research Database (Denmark)

Tsivintzelis, Ioannis; Kontogeorgis, Georgios; Panayiotou, Costas

2017-01-01

The association term of the nonrandom hydrogen bonding theory, which is an equation of state model, is extended to describe the dimerization of carboxylic acids in binary mixtures with inert solvents and in systems of two different acids. Subsequently, the model is applied to describe the excess...

Inhibition of cyclobutane pyrimidine dimer formation in epidermal p53 gene of UV-irradiated mice by alpha-tocopherol

International Nuclear Information System (INIS)

Chen, W.; Barthelman, M.; Martinez, J.; Alberts, D.; Gensler, H.L.

1997-01-01

Mutations or alterations in the p53 gene have been observed in 50-100% of ultraviolet light (UV)-induced squamous cell carcinoma in humans and animals. Most of the mutations occurred at dipyrimidine sequences, suggesting that pyrimidine dimers in the p53 gene play a role in the pathogenesis of cutaneous squamous cell carcinoma. We previously showed that topical alpha-tocopherol prevents UV-induced skin carcinogenesis in the mouse. In the present study we asked whether topical alpha-tocopherol reduces the level of UV-induced cyclobutane pyrimidine dimers in the murine epidermal p53 gene. Mice received six dorsal applications of 25 mg each of alpha-tocopherol, on alternate days, before exposure to 500 J/m2 of UV-B irradiation. Mice were killed at selected times after irradiation. The level of dimers in the epidermal p53 gene was measured using the T4 endonuclease V assay with quantitative Southern hybridization. Topical alpha-tocopherol caused a 55% reduction in the formation of cyclobutane pyrimidine dimers in the epidermal p53 gene. The rate of reduction of pyrimidine dimers between 1 and 10 hours after irradiation was similar in UV-irradiated mice, regardless of alpha-tocopherol treatment. Therefore, the lower level of cyclobutane pyrimidine dimers in UV-irradiated mice treated with alpha-tocopherol than in control UV-irradiated mice resulted from the prevention of formation of the dimers, and not from enhanced repair of these lesions. Our results indicate that alpha-tocopherol acts as an effective sunscreen in vivo, preventing the formation of premutagenic DNA lesions in a gene known to be important in skin carcinogenesis

Structural basis of genomic RNA (gRNA) dimerization and packaging determinants of mouse mammary tumor virus (MMTV).

Science.gov (United States)

Aktar, Suriya J; Vivet-Boudou, Valérie; Ali, Lizna M; Jabeen, Ayesha; Kalloush, Rawan M; Richer, Delphine; Mustafa, Farah; Marquet, Roland; Rizvi, Tahir A

2014-11-14

One of the hallmarks of retroviral life cycle is the efficient and specific packaging of two copies of retroviral gRNA in the form of a non-covalent RNA dimer by the assembling virions. It is becoming increasingly clear that the process of dimerization is closely linked with gRNA packaging, and in some retroviruses, the latter depends on the former. Earlier mutational analysis of the 5' end of the MMTV genome indicated that MMTV gRNA packaging determinants comprise sequences both within the 5' untranslated region (5' UTR) and the beginning of gag. The RNA secondary structure of MMTV gRNA packaging sequences was elucidated employing selective 2'hydroxyl acylation analyzed by primer extension (SHAPE). SHAPE analyses revealed the presence of a U5/Gag long-range interaction (U5/Gag LRI), not predicted by minimum free-energy structure predictions that potentially stabilizes the global structure of this region. Structure conservation along with base-pair covariations between different strains of MMTV further supported the SHAPE-validated model. The 5' region of the MMTV gRNA contains multiple palindromic (pal) sequences that could initiate intermolecular interaction during RNA dimerization. In vitro RNA dimerization, SHAPE analysis, and structure prediction approaches on a series of pal mutants revealed that MMTV RNA utilizes a palindromic point of contact to initiate intermolecular interactions between two gRNAs, leading to dimerization. This contact point resides within pal II (5' CGGCCG 3') at the 5' UTR and contains a canonical "GC" dyad and therefore likely constitutes the MMTV RNA dimerization initiation site (DIS). Further analyses of these pal mutants employing in vivo genetic approaches indicate that pal II, as well as pal sequences located in the primer binding site (PBS) are both required for efficient MMTV gRNA packaging. Employing structural prediction, biochemical, and genetic approaches, we show that pal II functions as a primary point of contact between

Values of the Wells and Revised Geneva Scores Combined with D-dimer in Diagnosing Elderly Pulmonary Embolism Patients

Directory of Open Access Journals (Sweden)

Dan-Jie Guo

2015-01-01

Full Text Available Background: Pulmonary embolism (PE can be difficult to diagnose in elderly patients because of the coexistent diseases and the combination of drugs that they have taken. We aimed to compare the clinical diagnostic values of the Wells score, the revised Geneva score and each of them combined with D-dimer for suspected PE in elderly patients. Methods: Three hundred and thirty-six patients who were admitted for suspected PE were enrolled retrospectively and divided into two groups based on age (≥65 or <65 years old. The Wells and revised Geneva scores were applied to evaluate the clinical probability of PE, and the positive predictive values of both scores were calculated using computed tomography pulmonary arteriography as a gold standard; overall accuracy was evaluated by the area under the curve (AUC of receiver operator characteristic curve; the negative predictive values of D-dimer, the Wells score combined with D-dimer, and the revised Geneva score combined with D-dimer were calculated. Results: Ninety-six cases (28.6% were definitely diagnosed as PE among 336 cases, among them 56 cases (58.3% were ≥65 years old. The positive predictive values of Wells and revised Geneva scores were 65.8% and 32.4%, respectively (P < 0.05 in the elderly patients; the AUC for the Wells score and the revised Geneva score in elderly was 0.682 (95% confidence interval [CI]: 0.612-0.746 and 0.655 (95% CI: 0.584-0.722, respectively (P = 0.389. The negative predictive values of D-dimer, the Wells score combined with D-dimer, and the revised Geneva score combined with D-dimer were 93.7%, 100%, and 100% in the elderly, respectively. Conclusions: The diagnostic value of the Wells score was higher than the revised Geneva score for the elderly cases with suspected PE. The combination of either the Wells score or the revised Geneva score with a normal D-dimer concentration is a safe strategy to rule out PE.

A multistep single-crystal-to-single-crystal bromodiacetylene dimerization

Science.gov (United States)

Hoheisel, Tobias N.; Schrettl, Stephen; Marty, Roman; Todorova, Tanya K.; Corminboeuf, Clémence; Sienkiewicz, Andrzej; Scopelliti, Rosario; Schweizer, W. Bernd; Frauenrath, Holger

2013-04-01

Packing constraints and precise placement of functional groups are the reason that organic molecules in the crystalline state often display unusual physical or chemical properties not observed in solution. Here we report a single-crystal-to-single-crystal dimerization of a bromodiacetylene that involves unusually large atom displacements as well as the cleavage and formation of several bonds. Density functional theory computations support a mechanism in which the dimerization is initiated by a [2 + 1] photocycloaddition favoured by the nature of carbon-carbon short contacts in the crystal structure. The reaction proceeded up to the theoretical degree of conversion without loss of crystallinity, and it was also performed on a preparative scale with good yield. Moreover, it represents the first synthetic pathway to (E)-1,2-dibromo-1,2-diethynylethenes, which could serve as synthetic intermediates for the preparation of molecular carbon scaffolds. Our findings both extend the scope of single-crystal-to-single-crystal reactions and highlight their potential as a synthetic tool for complex transformations.

Dimerization deficiency of enigmatic retinitis pigmentosa-linked rhodopsin mutants

Science.gov (United States)

Ploier, Birgit; Caro, Lydia N.; Morizumi, Takefumi; Pandey, Kalpana; Pearring, Jillian N.; Goren, Michael A.; Finnemann, Silvia C.; Graumann, Johannes; Arshavsky, Vadim Y.; Dittman, Jeremy S.; Ernst, Oliver P.; Menon, Anant K.

2016-10-01

Retinitis pigmentosa (RP) is a blinding disease often associated with mutations in rhodopsin, a light-sensing G protein-coupled receptor and phospholipid scramblase. Most RP-associated mutations affect rhodopsin's activity or transport to disc membranes. Intriguingly, some mutations produce apparently normal rhodopsins that nevertheless cause disease. Here we show that three such enigmatic mutations--F45L, V209M and F220C--yield fully functional visual pigments that bind the 11-cis retinal chromophore, activate the G protein transducin, traffic to the light-sensitive photoreceptor compartment and scramble phospholipids. However, tests of scramblase activity show that unlike wild-type rhodopsin that functionally reconstitutes into liposomes as dimers or multimers, F45L, V209M and F220C rhodopsins behave as monomers. This result was confirmed in pull-down experiments. Our data suggest that the photoreceptor pathology associated with expression of these enigmatic RP-associated pigments arises from their unexpected inability to dimerize via transmembrane helices 1 and 5.

Theoretical analysis of the domain-swapped dimerization of cytochrome c: An MD and 3D-RISM approach

Science.gov (United States)

Yoshida, Norio; Higashi, Masahiro; Motoki, Hideyoshi; Hirota, Shun

2018-01-01

The structural stability of a cytochrome c domain-swapped dimer compared with that of the monomer was investigated by molecular dynamics (MD) simulations and by three-dimensional reference interaction site model (3D-RISM) theory. The structural fluctuation and structural energy of cytochrome c were treated by MD simulations, and the solvation thermodynamics was treated by 3D-RISM theory. The domain-swapped dimer state is slightly less stable than the monomer state, which is consistent with experimental observations; the total free energy difference is calculated as 25 kcal mol-1. The conformational change and translational/rotational entropy change contribute to the destabilization of the dimer, whereas the hydration and vibrational entropy contribute to the stabilization. Further analyses on the residues located at the hinge loop for swapping were conducted, and the results reveal details at the molecular level of the structural and interaction changes upon dimerization.

Laser desorption single-conformation UV and IR spectroscopy of the sulfonamide drug sulfanilamide, the sulfanilamide-water complex, and the sulfanilamide dimer.

Science.gov (United States)

Uhlemann, Thomas; Seidel, Sebastian; Müller, Christian W

2017-06-07

We have studied the conformational preferences of the sulfonamide drug sulfanilamide, its dimer, and its monohydrated complex through laser desorption single-conformation UV and IR spectroscopy in a molecular beam. Based on potential energy curves for the inversion of the anilinic and the sulfonamide NH 2 groups calculated at DFT level, we suggest that the zero-point level wave function of the sulfanilamide monomer is appreciably delocalized over all four conformer wells. The sulfanilamide dimer, and the monohydrated complex each exhibit a single isomer in the molecular beam. The isomeric structures of the sulfanilamide dimer and the monohydrated sulfanilamide complex were assigned based on their conformer-specific IR spectra in the NH and OH stretch region. Quantum Theory of Atoms in Molecules (QTAIM) analysis of the calculated electron density in the water complex suggests that the water molecule is bound side-on in a hydrogen bonding pocket, donating one O-HO[double bond, length as m-dash]S hydrogen bond and accepting two hydrogen bonds, a NHO and a CHO hydrogen bond. QTAIM analysis of the dimer electron density suggests that the C i symmetry dimer structure exhibits two dominating N-HO[double bond, length as m-dash]S hydrogen bonds, and three weaker types of interactions: two CHO bonds, two CHN bonds, and a chalcogen OO interaction. Most interestingly, the molecular beam dimer structure closely resembles the R dimer unit - the dimer unit with the greatest interaction energy - of the α, γ, and δ crystal polymorphs. Interacting Quantum Atoms analysis provides evidence that the total intermolecular interaction in the dimer is dominated by the short-range exchange-correlation contribution.

Photo-physical properties of dimers formed by tri-aryl pyrylium salts: experimental and theoretical study

International Nuclear Information System (INIS)

Lampre, Isabelle

1996-01-01

This research thesis reports the study of dimers formed in solution by aggregation of tri-aryl pyrylium salts, in order to establish a direct correlation between properties and electronic structure of components, on the one hand, and molecular pattern, on the other hand. The author adopted a multidisciplinary approach by using experimental techniques and calculations based on the excitonic theory and methods of quantum chemistry. First, the properties of the first excited states of cationic chromophores have been studied (characterisation of electronic transitions, relaxation at the singlet excited state, formation of triplet state). Then, the author analysed dimerisation processes and showed that each dimer is formed by two pairs of ions. She discusses some original optical properties of dimers. The geometry of dimers is theoretically determined by minimising the system interaction potential energy. Electronic transitions are then determined as linear combinations of transitions of two monomers. Properties are thus calculated and are in agreement with those deduced from spectral analysis. The experimentally noticed polarisation change and large Stokes displacement are then explained in terms of emission for a localised state on a chromophore [fr

Entanglement in a Dimerized Antiferromagnetic Heisenberg Chain

OpenAIRE

Hao, Xiang; Zhu, Shiqun

2008-01-01

The entanglement properties in an antiferromagnetic dimerized Heisenberg spin-1/2 chain are investigated. The entanglement gap, which is the difference between the ground-state energy and the minimal energy that any separable state can attain, is calculated to detect the entanglement. It is found that the entanglement gap can be increased by varying the alternation parameter. Through thermal energy, the witness of the entanglement can determine a characteristic temperature below that an entan...

Physical and chemical transformations of μ-oxo dimers and alkoxy complexes of Fe-octaethylporphyrins in solids and in solutions

Science.gov (United States)

Ivashin, N. V.; Shulga, A. M.; Terekhov, S. N.; Dzilinski, K.

1996-11-01

It has been found that relatively small changes in conditions of crystallization in the synthesis process of μ-oxo dimers can lead to quite different products with dimeric or monomeric structures. Molecular structures of these products, discussed on the basis of Fe-octaethylporphyrin (FeOEP) complexes, have been studied using IR, NMR, EPR, resonance Raman (RR), mass and Mössbauer spectroscopies. The use of chloroform with admixture of alcohols (methanol, deuteromethanol and ethanol) in place of pure chloroform for crystallization of the eluate obtained during synthesis of μ-oxo dimers leads to the formation of alkoxy complexes instead of the μ-oxo dimers. It has been also established that dissolution of the μ-oxo dimers in chloroform-ethanol or chloroform-methanol mixtures leads to conversion of the μ-oxo dimers into the alkoxy complexes after evaporation of the solvents. Methoxy and ethoxy ligands in Fe(OEP)OCH 3 and Fe(OEP)OC 2H 5 complexes can exchange the positions during addition of ethanol to the former and methanol to the latter complex in solution. The possibility of generation of doubly bridged structures of the type: OEP Fe< RRFe OEP where R is OCH 3 or OC 2H 5 is discussed.

40 CFR 721.6980 - Dimer acids, polymer with polyalkylene glycol, bisphenol A-diglycidyl ether, and alky-lenepolyols...

Science.gov (United States)

2010-07-01

... reporting. (1) The chemical substance dimer acids, polymer with polyalkylene glycol, bisphenol A-diglycidyl... glycol, bisphenol A-diglycidyl ether, and alky-lenepolyols polyglycidyl ethers (generic name). 721.6980... Substances § 721.6980 Dimer acids, polymer with polyalkylene glycol, bisphenol A-diglycidyl ether, and alky...

C-reactive protein level in coronary artery disease and its correlation with serum d-dimer

International Nuclear Information System (INIS)

Gul, C.; Marwat, Z.I.; Israr, M.; Hanif, R.; Arshad, M.

2017-01-01

C-reactive protein concentration has continuous associations with risk of coronary artery disease, ischemic stroke and death from several cancers. In addition, several studies have shown that CRP could be used to predict first ever myocardial infarction and stroke in healthy subjects, as well as outcome in acute setting. High levels of another biomarker, D-dimer, have been found to be independently associated with occurrence of coronary events. Methods: This correlational study was carried out at the Department of Cardiology, Ayub Teaching Hospital Abbottabad, in collaboration with the department of Biochemistry Postgraduate Medical Institute Lahore from 15th July 2013 to 15th May 2014. Patients aged 30 years or more of either gender having coronary artery disease was included in the study. Their serum D-dimer levels and C-reactive protein levels were measured for correlation with coronary artery disease. Results: A total of 50 patients of CAD were included in this study. Out of these 30 (60 percent) were males and 20 (40 percent) were females. Elevated CRP levels and D-dimer levels were noted in all of these patients. Pearson correlation coefficient test was performed on both CRP and D-dimer levels. Pearson correlation coefficient was calculated to be r= -0.1522 and when a p value was calculated, it was found to be 0.292 which implied that the results were not significant. Conclusion: This study showed that there is no correlation between CRP levels and D-dimer levels in patients with Coronary Artery Disease. (author)

Density variations in a reactor during liquid full dimerization

NARCIS (Netherlands)

Golombok, M.; Bruijn, J.

2000-01-01

In a liquid full plug flow reactor during lower olefin dimerization, the assumption of constant density is not valid—the volume of a plug changes as it proceeds along the reactor. The observed kinetics depend on the density variation in the reactor as the conversion proceeds towards a distribution

Dimeric Complexes of Tryptophan with M2+ Metal Ions

NARCIS (Netherlands)

Dunbar, R. C.; Steill, J. D.; Polfer, N. C.; Oomens, J.

2009-01-01

IRMPD spectroscopy using the FELIX free electron laser and a Fourier transform ICR mass spectrometer was used to characterize the structures of electrosprayed dimer complexes M(2+)Trp(2) of tryptophan with a series of eight doubly charged metal ions, including alkaline earths Ca, Sr, and Ba, and

Phase behaviour of heteronuclear dimers in three-dimensional systems-a Monte Carlo study

International Nuclear Information System (INIS)

Rzysko, W; Binder, K

2008-01-01

Monte Carlo simulation in the grand canonical ensemble, the histogram reweighting technique and finite size scaling are used to study the phase behaviour of dimers in three-dimensional systems. A single molecule is composed of two segments A and B, and the bond between them cannot be broken. The phase diagrams have been estimated for a set of model systems. Different structures formed by heteronuclear dimers have been found. The results show a great variety of vapour-liquid coexistence behaviour depending on the strength of the interactions between segments

Self-Assembly of Dimeric Tetrathiafulvalene-Calix 4 pyrrole: Receptor for 1,375-Trinitrobenzene

DEFF Research Database (Denmark)

Nielsen, K. A.; Stein, P. C.

2011-01-01

The synthesis and binding properties of a tetrathiafulvalene (TTF)-calix[4]pyrrole receptor 2 appended with one 3,5-dinitrobenzoate guest moiety are reported. The preliminary studies revealed that the receptor is self-compiexing into a dimer receptor 2 center dot 2. The self-complexation of the r......The synthesis and binding properties of a tetrathiafulvalene (TTF)-calix[4]pyrrole receptor 2 appended with one 3,5-dinitrobenzoate guest moiety are reported. The preliminary studies revealed that the receptor is self-compiexing into a dimer receptor 2 center dot 2. The self...

Modified field enhancement and extinction by plasmonic nanowire dimers due to nonlocal response

DEFF Research Database (Denmark)

Toscano, Giuseppe; Raza, Søren; Jauho, Antti-Pekka

2012-01-01

We study the effect of nonlocal optical response on the optical properties of metallic nanowires, by numerically implementing the hydrodynamical Drude model for arbitrary nanowire geometries. We first demonstrate the accuracy of our frequency-domain finite-element implementation by benchmarking...... it in a wide frequency range against analytical results for the extinction cross section of a cylindrical plasmonic nanowire. Our main results concern more complex geometries, namely cylindrical and bow-tie nanowire dimers that can strongly enhance optical fields. For both types of dimers we find that nonlocal...

Solution structure of the dimeric cytoplasmic domain of syndecan-4

DEFF Research Database (Denmark)

Shin, J; Lee, W; Lee, D

2001-01-01

The syndecans, transmembrane proteoglycans which are involved in the organization of cytoskeleton and/or actin microfilaments, have important roles as cell surface receptors during cell-cell and/or cell-matrix interactions. Since previous studies indicate that the function of the syndecan-4...... between peptides at physiological pH. Commensurately, the NMR structures demonstrate that syndecan-4L is a compact intertwined dimer with a symmetric clamp shape in the central variable V region with a root-mean-square deviation between backbone atom coordinates of 0.95 A for residues Leu(186)-Ala(195...... in the center of the dimeric twist similar to our previously reported 4V structure. The overall topology of the central variable region within the 4L structure is very similar to that of 4V complexed with the phosphatidylinositol 4,5-bisphosphate; however, the intersubunit interaction mode is affected...

Electron-nuclear corellations for photoinduced dynamics in molecular dimers

Science.gov (United States)

Kilin, Dmitri S.; Pereversev, Yuryi V.; Prezhdo, Oleg V.

2003-03-01

Ultrafast photoinduced dynamics of electronic excitation in molecular dimers is drastically affected by dynamic reorganization of of inter- and intra- molecular nuclear configuration modelled by quantized nuclear degree of freedom [1]. The dynamics of the electronic population and nuclear coherence is analyzed with help of both numerical solution of the chain of coupled differential equations for mean coordinate, population inversion, electronic-vibrational correlation etc.[2] and by propagating the Gaussian wavepackets in relevant adiabatic potentials. Intriguing results were obtained in the approximation of small energy difference and small change of nuclear equilibrium configuration for excited electronic states. In the limiting case of resonance between electronic states energy difference and frequency of the nuclear mode these results have been justified by comparison to exactly solvable Jaynes-Cummings model. It has been found that the photoinduced processes in dimer are arranged according to their time scales:(i) fast scale of nuclear motion,(ii) intermediate scale of dynamical redistribution of electronic population between excited states as well as growth and dynamics of electronic -nuclear correlation,(iii) slow scale of electronic population approaching to the quasiequilibrium distribution, decay of electronic-nuclear correlation, and diminishing the amplitude of mean coordinate oscillations, accompanied by essential growth of the nuclear coordinate dispersion associated with the overall nuclear wavepacket width. Demonstrated quantum-relaxational features of photoinduced vibronic dinamical processess in molecular dimers are obtained by simple method, applicable to large biological systems with many degrees of freedom. [1] J. A. Cina, D. S. Kilin, T. S. Humble, J. Chem. Phys. (2003) in press. [2] O. V. Prezhdo, J. Chem. Phys. 117, 2995 (2002).

Non-Covalent Interactions and Impact of Charge Penetration Effects in Linear Oligoacene Dimers and Single Crystals

KAUST Repository

Ryno, Sean

2016-05-18

Non-covalent interactions determine in large part the thermodynamic aspects of molecular packing in organic crystals. Using a combination of symmetry-adapted perturbation theory (SAPT) and classical multipole electrostatics, we describe the interaction potential energy surfaces for dimers of the oligoacene family, from benzene to hexacene. An analysis of these surfaces and a thorough assessment of dimers extracted from the reported crystal structures underline that high-order interactions (i.e., three-body non-additive interactions) must be considered in order to rationalize the details of the crystal structures. A comparison of the SAPT electrostatic energy with the multipole interaction energy demonstrates the importance of the contribution of charge penetration, which is shown to account for up to 50% of the total interaction energy in dimers extracted from the experimental single crystals; in the case of the most stable co-facial model dimers, this contribution is even larger than the total interaction energy. Our results highlight the importance of taking account of charge penetration in studies of the larger oligoacenes.

Effects of gamma radiation and menadione (vit. K3) on dissolution and dimerization of δ-tocopherol

International Nuclear Information System (INIS)

Kupczyk, B.; Gogolewski, M.

1997-01-01

Effect of ionizing radiation and menadione (vit. K 3 ) on dissolution and dimerization of δ-tocopherol was studied. Mixture of δ-tocopherol and menadione (vit. K 3 ) dissolved in benzene, ethanol or used in substantia were irradiated at 2.5, 5, 10, 20 kGy dose using Co-60 as a radiation source. Dissolution of δ-tocopherol in substantia was lower then disintegration of δ-tocopherol dissolved in benzene or in ethanol. However, we did not observe any significant difference between dissolution of δ-tocopherol in both studied solvents. The number of formed dimers of δ-tocopherol were different for all three cases tested. The quantities of δ-tocopherol dimers were dependent on radiation dose. (author)

Structural and Thermodynamic Properties of the Argon Dimer: A Computational Chemistry Exercise in Quantum and Statistical Mechanics

Science.gov (United States)

Halpern, Arthur M.

2010-01-01

Using readily available computational applications and resources, students can construct a high-level ab initio potential energy surface (PES) for the argon dimer. From this information, they can obtain detailed molecular constants of the dimer, including its dissociation energy, which compare well with experimental determinations. Using both…

Super-pnicogen bonding in the radical anion of the fluorophosphine dimer

Science.gov (United States)

Setiawan, Dani; Cremer, Dieter

2016-10-01

The LUMO of the pnicogen-bonded fluoro-phosphine dimer has PP bonding character. Radical anion and dianion form relatively strong pnicogen bonds with some covalent character where however the dianion turns out to be a second order transition state. The binding energy of (FPH 2)2- is 30.4 kcal/mol (CCSD(T)/aug-cc-pVTZ; CASPT2(5,8): 30.7 kcal/mol) and the bond strength order measured with the local PP bond stretching force constant increases from 0.055 for the neutral dimer to 0.187 thus revealing that the stabilization of the radical anion is to a large extend a result of one-electron six-center delocalization. Pnicogen-bonded complexes have a stabilizing electron affinity.

Parametric sensitivity analysis for the helium dimers on a model potential

Directory of Open Access Journals (Sweden)

Nelson Henrique Teixeira Lemes

2012-01-01

Full Text Available Potential parameters sensitivity analysis for helium unlike molecules, HeNe, HeAr, HeKr and HeXe is the subject of this work. Number of bound states these rare gas dimers can support, for different angular momentum, will be presented and discussed. The variable phase method, together with the Levinson's theorem, is used to explore the quantum scattering process at very low collision energy using the Tang and Toennies potential. These diatomic dimers can support a bound state even for relative angular momentum equal to five, as in HeXe. Vibrational excited states, with zero angular momentum, are also possible for HeKr and HeXe. Results from sensitive analysis will give acceptable order of magnitude on potentials parameters.

Structural model and excitonic properties of the dimeric RC-LH1-PufX complex from Rhodobacter sphaeroides

International Nuclear Information System (INIS)

Sener, Melih; Hsin, Jen; Trabuco, Leonardo G.; Villa, Elizabeth; Qian, Pu; Hunter, C. Neil; Schulten, Klaus

2009-01-01

The light-harvesting apparatus of the purple bacterial photosynthetic unit consists of a pool of peripheral light-harvesting complexes that transfer excitation energy to a reaction center (RC) via the surrounding pigment-protein complex LH1. Recent electron microscopy and atomic force microscopy studies have revealed that RC-LH1 units of Rhodobacter (Rba.) sphaeroides form membrane-bending dimeric complexes together with the polypeptide PufX. We present a structural model for these RC-LH1-PufX dimeric complexes constructed using the molecular dynamics flexible fitting method based on an EM density map. The arrangement of the LH1 BChls displays a distortion near the proposed location of the PufX polypeptide. The resulting atomic model for BChl arrays is used to compute the excitonic properties of the dimeric RC-LH1 complex. A comparison is presented between the structural and excitonic features of the S-shaped dimeric BChl array of Rba. sphaeroides and the circular BChl arrangement found in other purple bacteria

Identification of Lynch syndrome mutations in the MLH1-PMS2 interface that disturb dimerization and mismatch repair.

Science.gov (United States)

Kosinski, Jan; Hinrichsen, Inga; Bujnicki, Janusz M; Friedhoff, Peter; Plotz, Guido

2010-08-01

Missense alterations of the mismatch repair gene MLH1 have been identified in a significant proportion of individuals suspected of having Lynch syndrome, a hereditary syndrome that predisposes for cancer of colon and endometrium. The pathogenicity of many of these alterations, however, is unclear. A number of MLH1 alterations are located in the C-terminal domain (CTD) of MLH1, which is responsible for constitutive dimerization with PMS2. We analyzed which alterations may result in pathogenic effects due to interference with dimerization. We used a structural model of CTD of MLH1-PMS2 heterodimer to select 19 MLH1 alterations located inside and outside two candidate dimerization interfaces in the MLH1-CTD. Three alterations (p.Gln542Leu, p.Leu749Pro, p.Tyr750X) caused decreased coexpression of PMS2, which is unstable in the absence of interaction with MLH1, suggesting that these alterations interfere with dimerization. All three alterations are located within the dimerization interface suggested by our model. They also compromised mismatch repair, suggesting that defects in dimerization abrogate repair and confirming that all three alterations are pathogenic. Additionally, we provided biochemical evidence that four alterations with uncertain pathogenicity (p.Ala586Pro, p.Leu636Pro, p.Thr662Pro, and p.Arg755Trp) are deleterious because of poor expression or poor repair efficiency, and confirm the deleterious effect of eight further alterations.

Repair of pyrimidine dimers in nuclear and mitochondrial DNA of yeast irradiated with low doses of ultraviolet light

Energy Technology Data Exchange (ETDEWEB)

Prakash, L [Rochester Univ., N.Y. (USA). Dept. of Radiation Biology and Biophysics

1975-01-01

The repair of damage induced by ultraviolet light has been examined in both the nuclear and mitochondrial DNA of the yeast Saccharomyces cerevisiae. The sensitive assay used in this study is based on the capacity of the bacteriophage T4 u.v. endonuclease to produce single-strand breaks in DNA that contains pyrimidine dimers, thus permitting the use of low fluences (doses) of u.v. The results demonstrate that virtually all of the dimers induced in the nuclear DNA of a repair-proficient strain (RAD+) are removed following dark incubation for four hours in growth medium. In contrast, the dimers induced in mitochondrial DNA by the same u.v. fluence are retained under the same conditions. In the excision-deficient mutant, rad1-2, no evidence was obtained for removal of pyrimidine dimers from nuclear DNA. Photoreactivation of both RAD + and rad1-2 cultures resulted in decreases of dimers from both nuclear and mitochondrial DNA. It is concluded that an excision-repair mechanism operates on nuclear but not mitochondrial DNA in repair-proficient yeast, and that the rad1-2 mutant is defective in this process.

Adsorption, mobility, and dimerization of benzaldehyde on Pt(111)

DEFF Research Database (Denmark)

Rasmussen, Anton Michael Havelund; Hammer, Bjørk

2012-01-01

to have low energy barriers. Aggregation of molecules in dimers bound by aryl C–H⋯O hydrogen bonds is investigated, and specific configurations are found to be up to 0.15 eV more favorable than optimally configured, separated adsorbates. The binding is significantly stronger than what is found for gas...

n-Dopants Based on Dimers of Benzimidazoline Radicals: Structures and Mechanism of Redox Reactions.

Science.gov (United States)

Zhang, Siyuan; Naab, Benjamin D; Jucov, Evgheni V; Parkin, Sean; Evans, Eric G B; Millhauser, Glenn L; Timofeeva, Tatiana V; Risko, Chad; Brédas, Jean-Luc; Bao, Zhenan; Barlow, Stephen; Marder, Seth R

2015-07-20

Dimers of 2-substituted N,N'-dimethylbenzimidazoline radicals, (2-Y-DMBI)2 (Y=cyclohexyl (Cyc), ferrocenyl (Fc), ruthenocenyl (Rc)), have recently been reported as n-dopants for organic semiconductors. Here their structural and energetic characteristics are reported, along with the mechanisms by which they react with acceptors, A (PCBM, TIPS-pentacene), in solution. X-ray data and DFT calculations both indicate a longer C-C bond for (2-Cyc-DMBI)2 than (2-Fc-DMBI)2 , yet DFT and ESR data show that the latter dissociates more readily due to stabilization of the radical by Fc. Depending on the energetics of dimer (D2 ) dissociation and of D2 -to-A electron transfer, D2 reacts with A to form D(+) and A(-) by either of two mechanisms, differing in whether the first step is endergonic dissociation or endergonic electron transfer. However, the D(+) /0.5 D2 redox potentials-the effective reducing strengths of the dimers-vary little within the series (ca. -1.9 V vs. FeCp2 (+/0) ) (Cp=cyclopentadienyl) due to cancelation of trends in the D(+/0) potential and D2 dissociation energy. The implications of these findings for use of these dimers as n-dopants, and for future dopant design, are discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

n-Dopants Based on Dimers of Benzimidazoline Radicals: Structures and Mechanism of Redox Reactions

KAUST Repository

Zhang, Siyuan

2015-06-18

Dimers of 2-substituted N,N\\'-dimethylbenzimidazoline radicals, (2-Y-DMBI)2 (Y=cyclohexyl (Cyc), ferrocenyl (Fc), ruthenocenyl (Rc)), have recently been reported as n-dopants for organic semiconductors. Here their structural and energetic characteristics are reported, along with the mechanisms by which they react with acceptors, A (PCBM, TIPS-pentacene), in solution. X-ray data and DFT calculations both indicate a longer C-C bond for (2-Cyc-DMBI)2 than (2-Fc-DMBI)2, yet DFT and ESR data show that the latter dissociates more readily due to stabilization of the radical by Fc. Depending on the energetics of dimer (D2) dissociation and of D2-to-A electron transfer, D2 reacts with A to form D+ and A- by either of two mechanisms, differing in whether the first step is endergonic dissociation or endergonic electron transfer. However, the D+/0.5D2 redox potentials-the effective reducing strengths of the dimers-vary little within the series (ca. -1.9V vs. FeCp2+/0) (Cp=cyclopentadienyl) due to cancelation of trends in the D+/0 potential and D2 dissociation energy. The implications of these findings for use of these dimers as n-dopants, and for future dopant design, are discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

n-Dopants Based on Dimers of Benzimidazoline Radicals: Structures and Mechanism of Redox Reactions

KAUST Repository

Zhang, Siyuan; Naab, Benjamin D.; Jucov, Evgheni V.; Parkin, Sean; Evans, Eric G B; Millhauser, Glenn L.; Timofeeva, Tatiana V.; Risko, Chad; Bredas, Jean-Luc; Bao, Zhenan; Barlow, Stephen; Marder, Seth R.

2015-01-01

Dimers of 2-substituted N,N'-dimethylbenzimidazoline radicals, (2-Y-DMBI)2 (Y=cyclohexyl (Cyc), ferrocenyl (Fc), ruthenocenyl (Rc)), have recently been reported as n-dopants for organic semiconductors. Here their structural and energetic characteristics are reported, along with the mechanisms by which they react with acceptors, A (PCBM, TIPS-pentacene), in solution. X-ray data and DFT calculations both indicate a longer C-C bond for (2-Cyc-DMBI)2 than (2-Fc-DMBI)2, yet DFT and ESR data show that the latter dissociates more readily due to stabilization of the radical by Fc. Depending on the energetics of dimer (D2) dissociation and of D2-to-A electron transfer, D2 reacts with A to form D+ and A- by either of two mechanisms, differing in whether the first step is endergonic dissociation or endergonic electron transfer. However, the D+/0.5D2 redox potentials-the effective reducing strengths of the dimers-vary little within the series (ca. -1.9V vs. FeCp2+/0) (Cp=cyclopentadienyl) due to cancelation of trends in the D+/0 potential and D2 dissociation energy. The implications of these findings for use of these dimers as n-dopants, and for future dopant design, are discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Slot-dimer babinet metamaterials as polarization shapers for terahertz waves

DEFF Research Database (Denmark)

Zhukovsky, Sergei; Chigrin, D. N.; Lavrinenko, Andrei

2013-01-01

We theoretically study optical properties of free-standing metallic membranes patterned with an array of two-slot elements (dimers) comprising two rectangular slots of different dimensions and orientation. It is shown that these structures feature extraordinary optical transmission with strong...

Synthesis and evaluation of a dimer of 2-(4-pyridylmethyl)-1-indanone as a novel nonsteroidal aromatase inhibitor.

Science.gov (United States)

Gupta, Ranju; Jindal, Dharam Paul; Jit, Birinder; Narang, Gaurav; Palusczak, Anja; Hartmann, Rolf W

2004-07-01

A novel dimer of 2-(4-pyridylmethyl)-1-indanone (2) was obtained while carrying out aldol condensation of 1-indanone with pyridine-4-carboxaldehyde in potassium hydroxide. The structure of dimer 3 has been established using various spectral techniques and was screened for its ability to inhibit the cytochrome P(450) enzyme aromatase. The dimer showed strong inhibition of human placental aromatase and was found 3 times more potent (RP = 3, IC(50) = 10.2 microM) as compared to aminoglutethimide (RP = 1, IC(50) = 18.5 microM.

Oxidation of NAD dimers by horseradish peroxidase.

OpenAIRE

Avigliano, L; Carelli, V; Casini, A; Finazzi-Agrò, A; Liberatore, F

1985-01-01

Horseradish peroxidase catalyses the oxidation of NAD dimers, (NAD)2, to NAD+ in accordance with a reaction that is pH-dependent and requires 1 mol of O2 per 2 mol of (NAD)2. Horseradish peroxidase also catalyses the peroxidation of (NAD)2 to NAD+. In contrast, bacterial NADH peroxidase does not catalyse the peroxidation or the oxidation of (NAD)2. A free-radical mechanism is proposed for both horseradish-peroxidase-catalysed oxidation and peroxidation of (NAD)2.

Laccase-mediated dimerization of the flavonolignan silybin

Czech Academy of Sciences Publication Activity Database

Gažák, Radek; Sedmera, Petr; Marzorati, M.; Riva, S.; Křen, Vladimír

2008-01-01

Roč. 50, 2-4 (2008), s. 87-92 ISSN 1381-1177 R&D Projects: GA AV ČR KJB400200701; GA MŠk OC D25.001; GA MŠk(CZ) LC06010; GA MŠk OC 170; GA MŠk ME 922 Grant - others:CZ(CZ) Bilateral Czech-Italian inter-academic projec Institutional research plan: CEZ:AV0Z50200510 Keywords : silybin * silymarin * dimer formation Subject RIV: EE - Microbiology, Virology Impact factor: 2.015, year: 2008

Pyrimidine dimers block simian virus 40 replication forks

International Nuclear Information System (INIS)

Berger, C.A.; Edenberg, H.J.

1986-01-01

UV light produces lesions, predominantly pyrimidine dimers, which inhibit DNA replication in mammalian cells. The mechanism of inhibition is controversial: is synthesis of a daughter strand halted at a lesion while the replication fork moves on and reinitiates downstream, or is fork progression itself blocked for some time at the site of a lesion? We directly addressed this question by using electron microscopy to examine the distances of replication forks from the origin in unirradiated and UV-irradiated simian virus 40 chromosomes. If UV lesions block replication fork progression, the forks should be asymmetrically located in a large fraction of the irradiated molecules; if replication forks move rapidly past lesions, the forks should be symmetrically located. A large fraction of the simian virus 40 replication forks in irradiated molecules were asymmetrically located, demonstrating that UV lesions present at the frequency of pyrimidine dimers block replication forks. As a mechanism for this fork blockage, we propose that polymerization of the leading strand makes a significant contribution to the energetics of fork movement, so any lesion in the template for the leading strand which blocks polymerization should also block fork movement

The Structure of the MAP2K MEK6 Reveals an Autoinhibitory Dimer

Energy Technology Data Exchange (ETDEWEB)

Min, Xiaoshan; Akella, Radha; He, Haixia; Humphreys, John M.; Tsutakawa, Susan E.; Lee, Seung-Jae; Tainer, John A.; Cobb, Melanie H.; Goldsmith, Elizabeth J.

2009-07-13

MAP2Ks are dual-specificity protein kinases functioning at the center of three-tiered MAP kinase modules. The structure of the kinase domain of the MAP2K MEK6 with phosphorylation site mimetic aspartic acid mutations (MEK6/{Delta}N/DD) has been solved at 2.3 {angstrom} resolution. The structure reveals an autoinhibited elongated ellipsoidal dimer. The enzyme adopts an inactive conformation, based upon structural queues, despite the phosphomimetic mutations. Gel filtration and small-angle X-ray scattering analysis confirm that the crystallographically observed ellipsoidal dimer is a feature of MEK6/{Delta}N/DD and full-length unphosphorylated wild-type MEK6 in solution. The interface includes the phosphate binding ribbon of each subunit, part of the activation loop, and a rare 'arginine stack' between symmetry-related arginine residues in the N-terminal lobe. The autoinhibited structure likely confers specificity on active MAP2Ks. The dimer may also serve the function in unphosphorylated MEK6 of preventing activation loop phosphorylation by inappropriate kinases.

Directed diffusion of reconstituting dimers

International Nuclear Information System (INIS)

Barma, Mustansir; Grynberg, Marcelo D; Stinchcombe, Robin B

2007-01-01

We discuss the dynamical aspects of an asymmetric version of assisted diffusion of hard core particles on a ring studied by Menon et al (1997 J. Stat. Phys. 86 1237). The asymmetry brings in phenomena like kinematic waves and effects of the Kardar-Parisi-Zhang non-linearity, which combine with the feature of strongly broken ergodicity, a characteristic of the model. A central role is played by a single non-local invariant, the irreducible string, whose interplay with the driven motion of reconstituting dimers, arising from the assisted hopping, determines the asymptotic dynamics and scaling regimes. These are investigated both analytically and numerically through sector-dependent mappings to the asymmetric simple exclusion process

Directed diffusion of reconstituting dimers

Energy Technology Data Exchange (ETDEWEB)

Barma, Mustansir [Department of Theoretical Physics, Tata Institute of Fundamental Research, Mumbai 400005 (India); Grynberg, Marcelo D [Departamento de Fisica, Universidad Nacional de La Plata (1900) La Plata (Argentina); Stinchcombe, Robin B [Isaac Newton Institute for Mathematical Sciences, 20 Clarkson Road, Cambridge CB3 0EH (United Kingdom)

2007-02-14

We discuss the dynamical aspects of an asymmetric version of assisted diffusion of hard core particles on a ring studied by Menon et al (1997 J. Stat. Phys. 86 1237). The asymmetry brings in phenomena like kinematic waves and effects of the Kardar-Parisi-Zhang non-linearity, which combine with the feature of strongly broken ergodicity, a characteristic of the model. A central role is played by a single non-local invariant, the irreducible string, whose interplay with the driven motion of reconstituting dimers, arising from the assisted hopping, determines the asymptotic dynamics and scaling regimes. These are investigated both analytically and numerically through sector-dependent mappings to the asymmetric simple exclusion process.

The specific monomer/dimer equilibrium of the corticotropin-releasing factor receptor type 1 is established in the endoplasmic reticulum.

Science.gov (United States)

Teichmann, Anke; Gibert, Arthur; Lampe, André; Grzesik, Paul; Rutz, Claudia; Furkert, Jens; Schmoranzer, Jan; Krause, Gerd; Wiesner, Burkhard; Schülein, Ralf

2014-08-29

G protein-coupled receptors (GPCRs) represent the most important drug targets. Although the smallest functional unit of a GPCR is a monomer, it became clear in the past decades that the vast majority of the receptors form dimers. Only very recently, however, data were presented that some receptors may in fact be expressed as a mixture of monomers and dimers and that the interaction of the receptor protomers is dynamic. To date, equilibrium measurements were restricted to the plasma membrane due to experimental limitations. We have addressed the question as to where this equilibrium is established for the corticotropin-releasing factor receptor type 1. By developing a novel approach to analyze single molecule fluorescence cross-correlation spectroscopy data for intracellular membrane compartments, we show that the corticotropin-releasing factor receptor type 1 has a specific monomer/dimer equilibrium that is already established in the endoplasmic reticulum (ER). It remains constant at the plasma membrane even following receptor activation. Moreover, we demonstrate for seven additional GPCRs that they are expressed in specific but substantially different monomer/dimer ratios. Although it is well known that proteins may dimerize in the ER in principle, our data show that the ER is also able to establish the specific monomer/dimer ratios of GPCRs, which sheds new light on the functions of this compartment. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Measurements of total collision cross section for dimers of simple atoms and molecules in the glory- and transition region, ch. 8

International Nuclear Information System (INIS)

Deursen, A.P.J. van

1976-01-01

A survey is presented of total collision cross sections for van der Waals dimers of the inert gases Ar and Ne, the molecules H 2 , N 2 , NO, O 2 , CO 2 , and C 2 H 4 , and for mixed dimers NeAr, HeNe and H 2 Ar. Most of the measurements of the dimer cross sections, sigma 2 , relative to the corresponding monomer cross section sigma 1 , have been described before. For a complete review, results for the He trimer and for the CO 2 and C 2 H 4 dimers have been added. (Auth.)

Dimer formation enhances structural differences between amyloid β-protein (1-40 and (1-42: an explicit-solvent molecular dynamics study.

Directory of Open Access Journals (Sweden)

Bogdan Barz

Full Text Available Amyloid β-protein (Aβ is central to the pathology of Alzheimer's disease. A 5% difference in the primary structure of the two predominant alloforms, Aβ(1-40 and Aβ(1-42, results in distinct assembly pathways and toxicity properties. Discrete molecular dynamics (DMD studies of Aβ(1-40 and Aβ(1-42 assembly resulted in alloform-specific oligomer size distributions consistent with experimental findings. Here, a large ensemble of DMD-derived Aβ(1-40 and Aβ(1-42 monomers and dimers was subjected to fully atomistic molecular dynamics (MD simulations using the OPLS-AA force field combined with two water models, SPCE and TIP3P. The resulting all-atom conformations were slightly larger, less compact, had similar turn and lower β-strand propensities than those predicted by DMD. Fully atomistic Aβ(1-40 and Aβ(1-42 monomers populated qualitatively similar free energy landscapes. In contrast, the free energy landscape of Aβ(1-42 dimers indicated a larger conformational variability in comparison to that of Aβ(1-40 dimers. Aβ(1-42 dimers were characterized by an increased flexibility in the N-terminal region D1-R5 and a larger solvent exposure of charged amino acids relative to Aβ(1-40 dimers. Of the three positively charged amino acids, R5 was the most and K16 the least involved in salt bridge formation. This result was independent of the water model, alloform, and assembly state. Overall, salt bridge propensities increased upon dimer formation. An exception was the salt bridge propensity of K28, which decreased upon formation of Aβ(1-42 dimers and was significantly lower than in Aβ(1-40 dimers. The potential relevance of the three positively charged amino acids in mediating the Aβ oligomer toxicity is discussed in the light of available experimental data.

The dimerization of thiophosgene and trichlorothioacetyl chloride S-imides - Head-to-head and/or head-to-tail?

DEFF Research Database (Denmark)

Voss, Jürgen; Buddensiek, Dirk; Senning, Alexander Erich Eugen

2016-01-01

It has been shown that certain N-aryltrichoromethanesulfenamides Cl3C-S-NHAr can be dehydrochlorinated to form red-colored thiocarbonyl S-imides CCl2=S=NAr which dimerize spontaneously. The dimers so far obtained were first assigned the 1,4,2,5-dithiadiazinane structure but later shown to be the ...

Viscosity and sedimentation behaviors of the magnetorheological suspensions with oleic acid/dimer acid as surfactants

Energy Technology Data Exchange (ETDEWEB)

Yang, Jianjian; Yan, Hua; Hu, Zhide; Ding, Ding

2016-11-01

This work deals with the role of polar interactions on the viscosity and sedimentation behaviors of magnetorheological suspensions with micro-sized magnetic particles dispersed in oil carriers. The oleic acid and dimer acid were employed to make an adjustment of the hydrophobicity of iron particles, in the interest of performing a comparative evaluation of the contributions of the surface polarity. The viscosity tests show that the adsorbed surfactant layer may impose a hindrance to the movement of iron particles in the oil medium. The polar attractions between dimer acid covered particles gave rise to a considerable increase in viscosity, indicating flocculation structure developed in the suspensions. The observed plateau-like region in the vicinity of 0.1 s{sup −1} for MRF containing dimer acid is possibly due to the flocculation provoked by the carboxylic polar attraction, in which the structure is stable against fragmentation. Moreover, a quick recovery of the viscosity and a higher viscosity-temperature index also suggest the existence of particle-particle polar interaction in the suspensions containing dimer acid. The sedimentation measurements reveal that the steric repulsion of oleic acid plays a limited role in the stability of suspensions only if a large quantity of surfactant was used. The sedimentation results observed in the dimer acid covered particles confirm that loose and open flocculation was formed and enhanced sedimentation stability. - Highlights: • Surfactants were employed to make adjustments of the hydrophobicity of particles. • Polar attractions between particles increased the viscosity considerably. • Loose and open flocculation was formed in CI/DA suspension. • The steric repulsion of oleic acid played a limited role in the stability.

Molecular recognition of epothilones by microtubules and tubulin dimers revealed by biochemical and NMR approaches.

Science.gov (United States)

Canales, Angeles; Nieto, Lidia; Rodríguez-Salarichs, Javier; Sánchez-Murcia, Pedro A; Coderch, Claire; Cortés-Cabrera, Alvaro; Paterson, Ian; Carlomagno, Teresa; Gago, Federico; Andreu, José M; Altmann, Karl-Heinz; Jiménez-Barbero, Jesús; Díaz, J Fernando

2014-04-18

The binding of epothilones to dimeric tubulin and to microtubules has been studied by means of biochemical and NMR techniques. We have determined the binding constants of epothilone A (EpoA) and B (EpoB) to dimeric tubulin, which are 4 orders of magnitude lower than those for microtubules, and we have elucidated the conformation and binding epitopes of EpoA and EpoB when bound to tubulin dimers and microtubules in solution. The determined conformation of epothilones when bound to dimeric tubulin is similar to that found by X-ray crystallographic techniques for the binding of EpoA to the Tubulin/RB3/TTL complex; it is markedly different from that reported for EpoA bound to zinc-induced sheets obtained by electron crystallography. Likewise, only the X-ray structure of EpoA bound to the Tubulin/RB3/TTL complex at the luminal site, but not the electron crystallography structure, is compatible with the results obtained by STD on the binding epitope of EpoA bound to dimeric tubulin, thus confirming that the allosteric change (structuring of the M-loop) is the biochemical mechanism of induction of tubulin assembly by epothilones. TR-NOESY signals of EpoA bound to microtubules have been obtained, supporting the interaction with a transient binding site with a fast exchange rate (pore site), consistent with the notion that epothilones access the luminal site through the pore site, as has also been observed for taxanes. Finally, the differences in the tubulin binding affinities of a series of epothilone analogues has been quantitatively explained using the newly determined binding pose and the COMBINE methodology.

Anisotropic anti-rod dimer metamaterial film for terahertz polarization manipulation

DEFF Research Database (Denmark)

Zalkovskij, Maksim; Malureanu, Radu; Novitsky, Andrey

2012-01-01

We demonstrate the concept of an anti-rod dimer planar metamaterial with strong birefringence and optical activity in the THz range. The retrieval of circular transmission components shows an asymmetric transmission effect for right-to-left and left-to-right polarization conversion....

In situ detection of estrogen receptor dimers in breast carcinoma cells in archival materials using proximity ligation assay (PLA).

Science.gov (United States)

Iwabuchi, Erina; Miki, Yasuhiro; Ono, Katsuhiko; Onodera, Yoshiaki; Suzuki, Takashi; Hirakawa, Hisashi; Ishida, Takanori; Ohuchi, Noriaki; Sasano, Hironobu

2017-01-01

Estrogen receptor (ER) is required for carcinoma cell proliferation in the great majority of breast cancer and also functions as a dimer. ER dimeric proteins have been largely identified by BRET/FRET analyses but their in situ visualization have not yet been reported. Recently, in situ Proximity Ligation Assay (PLA) has been developed as the methods detecting protein interactions in situ. Therefore, in this study we firstly demonstrated the dimerization of ERα in breast carcinoma cell lines and tissues using PLA. The human breast carcinoma cell lines MCF-7, T-47D and MDA-MB-231 were used in this study. Cells were treated with ER agonist or antagonist and fixed in 4% PFA, and ER dimers were subsequently detected using PLA. The evaluation of ER dimers in breast carcinoma cell lines were quantified by measuring the area of dots localized in the nuclei using image analysis. We also firstly demonstrated the visualization of ER dimer patterns in 10% formalin-fixed paraffin-embedded tissues of breast cancer using PLA technique. Estradiol (E2) administration induced ERα homodimers in the nuclei of MCF-7 and T-47D but not in ER-negative MDA-MB-231. 4-OH tamoxifen also induced ERα homodimers but the subcellular localization of these ERα homodimers was predominant in cytoplasm instead of the nuclei induced by E2 treatment. ICI182,780 treatment did decrease the number of formation of ERα homodimers in MCF-7. In breast cancer patients, ERα PLA score was significantly correlated positively with ERα- or PgR (progesterone receptor) immunohistochemical scores and inversely with Ki-67-labeling index, respectively. We also demonstrated the ERα/β heterodimer as well as ERα homodimers in both breast carcinoma cell lines and surgical pathology specimens. In summary, we did firstly succeed in the visualization of ER dimeric proteins using PLA method. The evaluation of ER dimer patterns could provide pivotal information as to the prediction of response to endocrine therapy of

Crystal Structure of Ripk4 Reveals Dimerization-Dependent Kinase Activity.

Science.gov (United States)

Huang, Christine S; Oberbeck, Nina; Hsiao, Yi-Chun; Liu, Peter; Johnson, Adam R; Dixit, Vishva M; Hymowitz, Sarah G

2018-05-01

Receptor-interacting protein kinase 4 (RIPK4) is a highly conserved regulator of epidermal differentiation. Members of the RIPK family possess a common kinase domain as well as unique accessory domains that likely dictate subcellular localization and substrate preferences. Mutations in human RIPK4 manifest as Bartsocas-Papas syndrome (BPS), a genetic disorder characterized by severe craniofacial and limb abnormalities. We describe the structure of the murine Ripk4 (MmRipk4) kinase domain, in ATP- and inhibitor-bound forms. The crystallographic dimer of MmRipk4 is similar to those of RIPK2 and BRAF, and we show that the intact dimeric entity is required for MmRipk4 catalytic activity through a series of engineered mutations and cell-based assays. We also assess the impact of BPS mutations on protein structure and activity to elucidate the molecular origins of the disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pulse radiolysis study of monomer and dimer cations of styrene, 1-methylstyrene and 1,1'-diphenylethylene

International Nuclear Information System (INIS)

Mehnert, R.; Helmstreit, W.; Boes, J.; Brede, O.

1977-01-01

In pulse-irradiated solutions of styrene, 1-methylstyrene and 1,1'-diphenylethylene, the decay kinetics of the olefin monomer cations and the formation kinetics of the corresponding dimer cations have been studied at room temperature. The solutions were irradiated with 15-nsec 15-ampere pulses of 1-MeV electrons from an Elit-type accelerator. The total dose per pulse was approximately 10 krad. The monomer cations were generated with rate constants of about 10 11 M -1 sec -1 . From the time decay of the monomer light absorption and the growth in time of the dimer absorption rate constants for the dimer formation between 0.8x10 10 and 1.2x10 10 M -1 sec -1 have been determined. (T.I.)

Development of empirical potential functions for the study of molecular geometry, and applications to chlorophyll a dimers

Energy Technology Data Exchange (ETDEWEB)

Oie, Tetsuro [Univ. of Rochester, NY (United States); Univ. of Kansas, Lawrence, KS (United States). Dept. of Chemistry

1980-07-28

A purpose of the present studies is twofold: (1) development of an empirical potential function (EPF) and (2) application of it to the studies of photoreaction center chlorophyll a dimer. The reliable estimate of geometric structures and energies of large molecules by quantum mechanical methods is not possible at the present time. An alternative method is, therefore, needed for the studies of large molecular systems, and Chapter I is dedicated to the development of this tool, i.e., an empirical potential function, which could suffice this purpose. Because of a large number of variable chemical compositions and functional groups characteristically present in a large molecule, it is important to include a large number of structurally diverse molecules in the development of the EPF. In Chapter II, the EPF is applied to study the geometrical structure of a chlorophyll a (Chl a) dimer, which is believed to exist at the photoreaction center of green plants and is known to play an essential role in photosynthetic energy conversion. Although various models have been proposed for this dimer structure, there is still a great need for information concerning the detailed geometric structure of this dimer. Therefore, in this chapter the structural stabilities of various dimer models are examined by the EPF, and detailed and quantitative information on the structure and stability of these models is provided.

Photoreactivation and excision repair of UV induced pyrimidine dimers in the unicellular cyanobacterium Gloeocapsa alpicola (Synechocystis PCC 6308)

International Nuclear Information System (INIS)

O'Brien, P.A.; Houghton, J.A.

1982-01-01

The survival curve obtained after UV irradiation of the unicellular cyanobacterium Synechocystis is typical of a DNA repair competent organism. Inhibition of DNA replication, by incubating cells in the dark, increased resistance to the lethal effects of UV at higher fluences. Exposure of irradiated cells to near ultraviolet light (350-500 nm) restored viability to pre-irradiation levels. In order to measure DNA repair activity, techniques have been developed for the chromatographic analysis of pyrimidine dimers in synechocystis. The specificity of this method was established using a haploid strain of Saccharomyces cerevisiae. In accordance with the physiological responses of irradiated cells to photoreactivating light, pyrimidine dimers were not detected after photoreactivation treatment. Incubation of irradiated cells under non-photoreactivating growth conditions for 15h resulted in complete removal of pyrimidine dimers. It is concluded that Synechocystis contains photoreactivation and excision repair systems for the removal of pyrimidine dimers. (author)

Therapeutic significance of a D-dimer cut-off level of >3 μg/ml in colorectal cancer patients treated with standard chemotherapy plus bevacizumab

International Nuclear Information System (INIS)

Mochizuki, Satoshi; Yoshino, Takayuki; Kojima, Takashi

2010-01-01

The risk of venous thromboembolism has been reported to increase when receiving bevacizumab. Many cancer patients are reported to have elevated D-dimer levels. It is not clear what D-dimer level might indicate an increased risk of venous thromboembolism in the colorectal cancer patients treated with bevacizumab-containing chemotherapy. The D-dimer levels and any event concurrent with an elevated D-dimer level were evaluated in patients receiving bevacizumab. The D-dimer cut-off level was determined using the receiver-operating characteristic analysis. The selection criteria were as follows: histologically proven metastatic and unresectable colorectal adenocarcinoma; no prior chemotherapy containing bevacizumab; D-dimer test performed repetitively on the baseline and during bevacizumab administration; no venous thromboembolism identified at the baseline; and enhanced computed tomographic scan performed every 2 months. Sixty-nine patients were included. The chemotherapy regimens with bevacizumab included the regimen of 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX), the regimen of 5-fluorouracil, leucovorin and irinotecan (FOLFIRI), and leucovorin-modulated 5-fluorouracil. The median baseline D-dimer level was 1.2 μg/ml. The appropriate D-dimer cut-off level was 3 μg/ml with the negative predictive value of 98% and relative risk of 6.9. Twenty-one of 69 patients showed elevated D-dimer levels of >3 μg/ml, with 11 patients for unknown reasons, 6 with tumor progression, 3 with venous thromboembolism and 1 with sepsis. In the remaining 48 patients whose D-dimer levels were ≤3 μg/ml, only one patient developed a venous thromboembolism. A D-dimer cut-off level of 3 μg/ml might be a useful indicator level to exclude venous thromboembolism or show an increased risk for venous thromboembolism in colorectal cancer patients treated with bevacizumab-containing chemotherapy. (author)

Neurodevelopmental Expression Profile of Dimeric and Monomeric Group 1 mGluRs: Relevance to Schizophrenia Pathogenesis and Treatment.

Science.gov (United States)

Lum, Jeremy S; Fernandez, Francesca; Matosin, Natalie; Andrews, Jessica L; Huang, Xu-Feng; Ooi, Lezanne; Newell, Kelly A

2016-10-10

Group 1 metabotropic glutamate receptors (mGluR1/mGluR5) play an integral role in neurodevelopment and are implicated in psychiatric disorders, such as schizophrenia. mGluR1 and mGluR5 are expressed as homodimers, which is important for their functionality and pharmacology. We examined the protein expression of dimeric and monomeric mGluR1α and mGluR5 in the prefrontal cortex (PFC) and hippocampus throughout development (juvenile/adolescence/adulthood) and in the perinatal phencyclidine (PCP) model of schizophrenia. Under control conditions, mGluR1α dimer expression increased between juvenile and adolescence (209-328%), while monomeric levels remained consistent. Dimeric mGluR5 was steadily expressed across all time points; monomeric mGluR5 was present in juveniles, dramatically declining at adolescence and adulthood (-97-99%). The mGluR regulators, Homer 1b/c and Norbin, significantly increased with age in the PFC and hippocampus. Perinatal PCP treatment significantly increased juvenile dimeric mGluR5 levels in the PFC and hippocampus (37-50%) but decreased hippocampal mGluR1α (-50-56%). Perinatal PCP treatment also reduced mGluR1α dimer levels in the PFC at adulthood (-31%). These results suggest that Group 1 mGluRs have distinct dimeric and monomeric neurodevelopmental patterns, which may impact their pharmacological profiles at specific ages. Perinatal PCP treatment disrupted the early expression of Group 1 mGluRs which may underlie neurodevelopmental alterations observed in this model.

Structures of DNA containing psoralen crosslink and thymine dimer

International Nuclear Information System (INIS)

Kim, S.H.; Pearlman, D.A.; Holbrook, S.R.; Pirkle, D.

1985-01-01

UV irradiation by itself or in conjunction with other chemicals can cause covalent damages to DNA in living cells. To overcome the detrimental effect of DNA damage, cells developed a repair mechanism by which damaged DNA is repaired. In the absence of such repair, cell malfunction or cell death can occur. Two most studied radiation-induced DNA damage are thymine dimer formation by UV irradiation and psoralen crosslink by combination of psoralens and UV: In the former, two adjacent thymine bases on a strand of DNA are fused by forming cyclobutane ring, and in the latter, one pyrimidine on one DNA strand is crosslinked to another pyrimidine on the other strand via a psoralen. The authors' objective is to deduce the structure of DNA segment which contains a psoralen crosslink or a thymine dimer using the combination of results of X-ray crystallographic studies, molecular model building, and energy minimization. These structural features may be important for understanding the biological effects of such damages and for the recognition by the repair enzymes

A redox-dependent dimerization switch regulates activity and tolerance for reactive oxygen species of barley seed glutathione peroxidase

DEFF Research Database (Denmark)

Navrot, Nicolas; Skjoldager, Nicklas; Bunkenborg, Jakob

2015-01-01

Monomeric and dimeric forms of recombinant barley (Hordeum vulgare subsp. vulgare) glutathione peroxidase 2 (HvGpx2) are demonstrated to display distinctly different functional properties in vitro. Monomeric HvGpx2 thus has five fold higher catalytic efficiency than the dimer towards tert-butyl h...

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

International Nuclear Information System (INIS)

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

2010-01-01

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

OPTICAL PULLING FORCES IN “NANOPARTICLES DIMER IN THE STRUCTURED FIELD” SYSTEM

Directory of Open Access Journals (Sweden)

S. V. Sukhov

2015-01-01

Full Text Available The subject area of this research is optical pulling forces as one of the manifestations of light mechanical action on material objects. In particular, we investigated optical forces acting on a dimer composed of nanoparticles with a small radius as compared to wavelength. The calculation of Lorentz optical forces was carried out by solving self-consistent system of equations, which made it possible to calculate electromagnetic fields in every point of the structure. We worked out analytic formula, representing the dependence of optical force on the parameters of dimer system and structured radiation made up of two crossing plane waves. For the first time we showed that dimer consisting of two equal dipolar particles can experience an optical pulling force (“negative radiation pressure” in the field of two crossing plane waves. It is shown that the increase of photons momentum (the projection of photons momentum on the direction of structured light propagation after scattering is responsible for this negative radiation pressure. The corresponding scattering diagram showed the increase of forward scattering, that is the conformation of the considered mechanism of pulling forces origination. Our findings would be very useful for increasing capabilities of optical manipulation of nano- and micro-particles.

Dimer self-organization of impurity ytterbium ions in synthetic forsterite single crystals

Science.gov (United States)

Tarasov, V. F.; Sukhanov, A. A.; Dudnikova, V. B.; Zharikov, E. V.; Lis, D. A.; Subbotin, K. A.

2017-07-01

Paramagnetic centers formed by impurity Yb3+ ions in synthetic forsterite (Mg2SiO4) grown by the Czochralski technique are studied by X-band CW and pulsed EPR spectroscopy. These centers are single ions substituting magnesium in two different crystallographic positions denoted M1 and M2, and dimer associates formed by two Yb3+ ions in nearby positions M1. It is established that there is a pronounced mechanism favoring self-organization of ytterbium ions in dimer associates during the crystal growth, and the mechanism of the spin-spin coupling between ytterbium ions in the associate has predominantly a dipole-dipole character, which makes it possible to control the energy of the spin-spin interaction by changing the orientation of the external magnetic field. The structural computer simulation of cluster ytterbium centers in forsterite crystals is carried out by the method of interatomic potentials using the GULP 4.0.1 code (General Utility Lattice Program). It is established that the formation of dimer associates in the form of a chain parallel to the crystallographic axis consisting of two ytterbium ions with a magnesium vacancy between them is the most energetically favorable for ytterbium ions substituting magnesium in the position M1.

Determining the nucleation rate from the dimer growth probability

NARCIS (Netherlands)

Ter Horst, J.H.; Kashchiev, D.

2005-01-01

A new method is proposed for the determination of the stationary one-component nucleation rate J with the help of data for the growth probability P2 of a dimer which is the smallest cluster of the nucleating phase. The method is based on an exact formula relating J and P2, and is readily applicable

Effects of excited state mixing on transient absorption spectra in dimers Application to photosynthetic light-harvesting complex II

CERN Document Server

Valkunas, L; Trinkunas, G; Müller, M G; Holzwarth, A R

1999-01-01

The excited state mixing effect is taken into account considering the difference spectra of dimers. Both the degenerate (homo) dimer as well as the nondegenerate (hetero) dimer are considered. Due to the higher excited state mixing with the two-exciton states in the homodimer, the excited state absorption (or the difference spectrum) can be strongly affected in comparison with the results obtained in the Heitler-London approximation. The difference spectrum of the heterodimer is influenced by two resonance effects (i) mixing of the ground state optical transitions of both monomers in the dimer and (ii) mixing of the excited state absorption of the excited monomer with the ground state optical transition in the nonexcited monomer. These effects have been tested by simulating the difference absorption spectra of the light-harvesting complex of photosystem II (LHC II) experimentally obtained with the 60 fs excitation pulses at zero delay times and various excitation wavelengths. The pairs of coupled chlorophylls...

Conformational stability of the epidermal growth factor (EGF) receptor as influenced by glycosylation, dimerization and EGF hormone binding.

Science.gov (United States)

Taylor, Eric S; Pol-Fachin, Laercio; Lins, Roberto D; Lower, Steven K

2017-04-01

The epidermal growth factor receptor (EGFR) is an important transmembrane glycoprotein kinase involved the initiation or perpetuation of signal transduction cascades within cells. These processes occur after EGFR binds to a ligand [epidermal growth factor (EGF)], thus inducing its dimerization and tyrosine autophosphorylation. Previous publications have highlighted the importance of glycosylation and dimerization for promoting proper function of the receptor and conformation in membranes; however, the effects of these associations on the protein conformational stability have not yet been described. Molecular dynamics simulations were performed to characterize the conformational preferences of the monomeric and dimeric forms of the EGFR extracellular domain upon binding to EGF in the presence and absence of N-glycan moieties. Structural stability analyses revealed that EGF provides the most conformational stability to EGFR, followed by glycosylation and dimerization, respectively. The findings also support that EGF-EGFR binding takes place through a large-scale induced-fitting mechanism. Proteins 2017; 85:561-570. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Age-adjusted D-dimer cut-off in the diagnostic strategy for deep vein thrombosis

DEFF Research Database (Denmark)

Nybo, Mads; Hvas, Anne-Mette

2017-01-01

BACKGROUND: Studies have indicated that use of an age-adjusted D-dimer cut-off value for patients above 50 years increases utility of the diagnostic strategy for pulmonary embolism. Evidence for the same approach regarding diagnosis of deep vein thrombosis (DVT) is, however, unclear. MATERIALS...... AND METHODS: A systematic literature review was conducted following the PRISMA Statement guideline to gather the existing knowledge on the use of an age-adjusted D-dimer cut-off in the diagnostic strategy for DVT. Studies were extracted from Medline and the Cochrane Library. The search period ended...

Electric-dipole-coupled H2O@C60 dimer: Translation-rotation eigenstates from twelve-dimensional quantum calculations.

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Felker, Peter M; Bačić, Zlatko

2017-02-28

We report on variational solutions to the twelve-dimensional (12D) Schrödinger equation appertaining to the translation-rotation (TR) eigenstates of H 2 O@C 60 dimer, associated with the quantized "rattling" motions of the two encapsulated H 2 O molecules. Both H 2 O and C 60 moieties are treated as rigid and the cage-cage geometry is taken to be fixed. We consider the TR eigenstates of H 2 O@C 60 monomers in the dimer to be coupled by the electric dipole-dipole interaction between water moieties and develop expressions for computing the matrix elements of that interaction in a dimer basis composed of products of monomer 6D TR eigenstates reported by us recently [P. M. Felker and Z. Bačić, J. Chem. Phys. 144, 201101 (2016)]. We use these expressions to compute TR Hamiltonian matrices of H 2 O@C 60 dimer for two values of the water dipole moment and for various dimer geometries. 12D TR eigenstates of the dimer are then obtained by filter diagonalization. The results reveal two classes of eigenstates, distinguished by the leading order (first or second) at which dipole-dipole coupling contributes to them. The two types of eigenstates differ in the general magnitude of their dipole-induced energy shifts and in the dependence of those shifts on the value of the water dipole moment and on the distance between the H 2 O@C 60 monomers. The dimer results are also found to be markedly insensitive to any change in the orientations of the C 60 cages. Finally, the results lend some support for the interpretation that electric dipole-dipole coupling is at least partially responsible for the apparent reduced-symmetry environment experienced by H 2 O in the powder samples of H 2 O@C 60 [K. S. K. Goh et al., Phys. Chem. Chem. Phys. 16, 21330 (2014)], but only if the water dipole is taken to have a magnitude close to that of free water. The methodology developed in the paper is transferable directly to the calculation of TR eigenstates of larger H 2 O@C 60 assemblies, that will

High-Throughput Simulations of Dimer and Trimer Assembly of Membrane Proteins. The DAFT Approach.

Science.gov (United States)

Wassenaar, Tsjerk A; Pluhackova, Kristyna; Moussatova, Anastassiia; Sengupta, Durba; Marrink, Siewert J; Tieleman, D Peter; Böckmann, Rainer A

2015-05-12

Interactions between membrane proteins are of great biological significance and are consequently an important target for pharmacological intervention. Unfortunately, it is still difficult to obtain detailed views on such interactions, both experimentally, where the environment hampers atomic resolution investigation, and computationally, where the time and length scales are problematic. Coarse grain simulations have alleviated the later issue, but the slow movement through the bilayer, coupled to the long life times of nonoptimal dimers, still stands in the way of characterizing binding distributions. In this work, we present DAFT, a Docking Assay For Transmembrane components, developed to identify preferred binding orientations. The method builds on a program developed recently for generating custom membranes, called insane (INSert membrANE). The key feature of DAFT is the setup of starting structures, for which optimal periodic boundary conditions are devised. The purpose of DAFT is to perform a large number of simulations with different components, starting from unbiased noninteracting initial states, such that the simulations evolve collectively, in a manner reflecting the underlying energy landscape of interaction. The implementation and characteristic features of DAFT are explained, and the efficacy and relaxation properties of the method are explored for oligomerization of glycophorin A dimers, polyleucine dimers and trimers, MS1 trimers, and rhodopsin dimers. The results suggest that, for simple helices, such as GpA and polyleucine, in POPC/DOPC membranes series of 500 simulations of 500 ns each allow characterization of the helix dimer orientations and allow comparing associating and nonassociating components. However, the results also demonstrate that short simulations may suffer significantly from nonconvergence of the ensemble and that using too few simulations may obscure or distort features of the interaction distribution. For trimers, simulation

Extracting dimer structures from simulations of organic-based materials using QM/MM methods

Energy Technology Data Exchange (ETDEWEB)

Pérez-Jiménez, A.J., E-mail: aj.perez@ua.es; Sancho-García, J.C., E-mail: jc.sancho@ua.es

2015-09-28

Highlights: • DFT geometries of isolated dimers in organic crystals differ from experimental ones. • This can be corrected using QM/MM geometry optimizations. • The QM = B3LYP–D3(ZD)/cc-pVDZ and MM = GAFF combination works reasonably well. - Abstract: The functionality of weakly bound organic materials, either in Nanoelectronics or in Materials Science, is known to be strongly affected by their morphology. Theoretical predictions of the underlying structure–property relationships are frequently based on calculations performed on isolated dimers, but the optimized structure of the latter may significantly differ from experimental data even when dispersion-corrected methods are used for it. Here, we address this problem on two organic crystals, namely coronene and 5,6,11,12-tetrachlorotetracene, concluding that it is caused by the absence of the surrounding monomers present in the crystal, and that it can be efficiently cured when the dimer is embedded into a general Quantum Mechanics/Molecular Mechanics (QM/MM) geometry optimization scheme. We also investigate how the size of the MM region affects the results. These findings may be helpful for the simulation of the morphology of active materials in crystalline or glassy samples.

Pentacene Dimers as a Critical Tool for the Investigation of Intramolecular Singlet Fission.

Science.gov (United States)

Hetzer, Constantin; Guldi, Dirk M; Tykwinski, Rik R

2018-01-11

Singlet fission (SF) involves the spontaneous splitting of a photoexcited singlet state into a pair of triplets, and it holds great promise toward the realization of more efficient solar cells. Although the process of SF has been known since the 1960s, debate regarding the underlying mechanism continues to this day, especially for molecular materials. A number of different chromophores have been synthesized and studied in order to better understand the process of SF. These previous reports have established that pentacene and its derivatives are especially well-suited for the study of SF, since the energetic requirement E(S 1 )≥2E(T 1 ) is fulfilled rendering the process exothermic and unidirectional. Dimeric pentacene derivatives, in which individual pentacene chromophores are tethered by a "spacer", have emerged as the system of choice toward exploring the mechanism of intramolecular singlet fission (iSF). The dimeric structure, and in particular the spacer, allows for controlling and tuning the distance, geometric relationship, and electronic coupling between the two pentacene moieties. This Minireview describes recent advances using pentacene dimers for the investigation of iSF. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

DENV gene of bacteriophage T4 codes for both pyrimidine dimer-DNA glycosylase and apyrimidinic endonuclease activities

International Nuclear Information System (INIS)

McMillan, S.; Edenberg, H.J.; Radany, E.H.; Friedberg, R.C.; Friedberg, E.C.

1981-01-01

Recent studies have shown that purified preparations of phage T4 UV DNA-incising activity (T4 UV endonuclease or endonuclease V of phase T4) contain a pyrimidine dimer-DNA glycosylase activity that catalyzes hydrolysis of the 5' glycosyl bond of dimerized pyrimidines in UV-irradiated DNA. Such enzyme preparations have also been shown to catalyze the hydrolysis of phosphodiester bonds in UV-irradiated DNA at a neutral pH, presumably reflecting the action of an apurinic/apyrimidinic endonuclease at the apyrimidinic sites created by the pyrimidine dimer-DNA glycosylase. In this study we found that preparations of T4 UV DNA-incising activity contained apurinic/apyrimidinic endonuclease activity that nicked depurinated form I simian virus 40 DNA. Apurinic/apyrimidinic endonuclease activity was also found in extracts of Escherichia coli infected with T4 denV + phage. Extracts of cells infected with T4 denV mutants contained significantly lower levels of apurinic/apyrimidinic endonuclease activity; these levels were no greater than the levels present in extracts of uninfected cells. Furthermore, the addition of DNA containing UV-irradiated DNA and T4 enzyme resulted in competition for pyrimidine dimer-DNA glycosylase activity against the UV-irradiated DNA. On the basis of these results, we concluded that apurinic/apyrimidinic endonuclease activity is encoded by the denV gene of phage T4, the same gene that codes for pyrimidine dimer-DNA glycosylase activity

Understanding the influence of low-frequency vibrations on the hydrogen bonds of acetic acid and acetamide dimers.

Science.gov (United States)

Copeland, Christopher; Menon, Omkaran; Majumdar, D; Roszak, Szczepan; Leszczynski, Jerzy

2017-09-20

Low-frequency vibrations coupled to high-frequency modes are known to influence the hydrogen bond strengths in a weakly interacting dimer. In this context, various acetic acid and acetamide dimers were analyzed using Møller-Plesset second-order perturbation (MP2) and density functional theory (DFT)-based approaches with explicit anharmonicity corrections. The computed low-frequency fundamentals as well as the high-frequency modes, which were found to be related to hydrogen bonding (OH/NH stretching modes), were analyzed and their computed intensities were correlated with their hydrogen-bond strengths/binding energies. There are similarities in the nature of eight low-frequency fundamentals of these two dimers, and the in-plane bending and stretch-bend fundamentals of the different dimers of these two species (in this low-frequency region) have specific roles in their relative stability order. The computed linear correlations were further verified against the results from coupled cluster calculations including triple excitation (CCSD(T)), Gaussian-G4 (G4), Gaussian-G2-MP2 (G2MP2) and complete basis set (CBS-QB3) methods of high accuracy energy calculations. As a consequence of such linear correlations, an additive property of local fragment energies (responsible for hydrogen bonding) was found to be a valid approximation to predict the binding energies of such dimers and the idea was found to be extendable to the other homologues of these acids/amides.

Thrombus Burden of Deep Vein Thrombosis and Its Association with Thromboprophylaxis and D-Dimer Measurement: Insights from the APEX Trial.

Science.gov (United States)

Chi, Gerald; Goldhaber, Samuel Z; Hull, Russell D; Hernandez, Adrian F; Kerneis, Mathieu; Al Khalfan, Fahad; Cohen, Alexander T; Harrington, Robert A; Gibson, C Michael

2017-12-01

Background The aim of this study was to evaluate the effect of betrixaban on the occurrence of deep vein thrombosis (DVT) and also the extent of thrombus and to assess the association of baseline D-dimer with subsequent thrombus burden. Methods In the APEX trial (ClinicalTrials.gov: NCT01583218), 7,513 acutely ill hospitalized medical patients were randomly assigned to extended-duration betrixaban (35–42 days) or enoxaparin (10 ± 4 days). D-dimer concentration was measured at baseline, and mandatory lower-extremity compression ultrasonography (CUS) was performed at 35 to 42 days. The thrombus burden of DVT was assessed by the number of non-compressible vascular segments in six target proximal veins and compared between treatment groups and D-dimer categories (≥2 × upper limit of normal [ULN] versus thrombus burden (p = 0.012 for any-dose and p = 0.001 for full-dose). Elevated D-dimer at baseline was independently associated with a 2.12-fold increased risk of developing DVT (p thrombus burden was also observed in those with D-dimer ≥ 2 × ULN compared with venous segments with thrombosis at 35 to 42 days compared with enoxaparin. A positive D-dimer was associated with a greater extent of thrombus burden among acutely ill medical patients who developed DVT despite receiving thromboprophylaxis.

How Does Thymine DNA Survive Ultrafast Dimerization Damage?

Directory of Open Access Journals (Sweden)

Hongjuan Wang

2016-12-01

Full Text Available The photodimerization reaction between the two adjacent thymine bases within a single strand has been the subject of numerous studies due to its potential to induce DNA mutagenesis and possible tumorigenesis in human skin cells. It is well established that the cycloaddition photoreaction takes place on a picosecond time scale along barrierless or low barrier singlet/triplet pathways. However, the observed dimerization quantum yield in different thymine multimer is considerable lower than might be expected. A reasonable explanation is required to understand why thymine in DNA is able to survive ultrafast dimerization damage. In this work, accurate quantum calculations based on the combined CASPT2//CASSCF/AMBER method were conducted to map the excited state relaxation pathways of the thymine monomer in aqueous solution and of the thymine oligomer in DNA. A monomer-like decay pathway, induced by the twisting of the methyl group, is found to provide a bypass channel to ensure the photostability of thymine in single-stranded oligomers. This fast relaxation path is regulated by the conical intersection between the bright SCT(1ππ* state with the intra-base charge transfer character and the ground state to remove the excess excitation energy, thereby achieving the ground-state recovery with high efficiency.

Van der Waals bond in dimers: H2Ne, H2Ar, H2Kr

International Nuclear Information System (INIS)

Waaijer, M.

1981-01-01

The H 2 -inert gas dimers H 2 X, and particularly H 2 Ne, H 2 Ar and H 2 Kr, form the subject of this thesis and are loosely bound van der Waals complexes, which is reflected in the low number of bound states and the small anisotropic interaction. The H 2 X dimers studied are formed in a supersonic nozzle expansion, in which the internal energy is converted into the macroscopic flow energy, establishing an internal temperature drop to 3 K, which favours dimer formation. Because of this cooling the H 2 X dimers relax to the lowest rotational states. The hyperfine transitions have been measured using magnetic beam resonance and yield information about the isotropic as well as the anisotropic intermolecular potential in the range between the classical turning points and in the adjacent part of the repulsive branch. The sensitivity of the method is very high and slight changes in the intermolecular potential cause significant effects. The analysis of the measured hyperfine transitions incorporates all interacting states of the molecule, bound as well as unbound (continuum) states. For H 2 Ne, which is the best studied H 2 -inert gas system from the experimental point of view, the author succeeded in establishing an intermolecular potential, that provides a solid ground for comparison with future ab initio calculations. (Auth.)

Pentapeptide-repeat proteins that act as topoisomerase poison resistance factors have a common dimer interface

International Nuclear Information System (INIS)

Vetting, Matthew W.; Hegde, Subray S.; Zhang, Yong; Blanchard, John S.

2011-01-01

The pentapeptide repeat protein AlbG, provides self-resistance to the nonribosomally encoded hybrid polyketide-peptide termed albicidin. Analysis of the AlbG three-dimensional structure and the sequences of other pentapeptide repeat proteins that confer resistance to topiosomerase poisons suggests they have a similar dimer interface which may be critical to their interaction with topoisomerases. The protein AlbG is a self-resistance factor against albicidin, a nonribosomally encoded hybrid polyketide-peptide with antibiotic and phytotoxic properties produced by Xanthomonas albilineans. Primary-sequence analysis indicates that AlbG is a member of the pentapeptide-repeat family of proteins (PRP). The structure of AlbG from X. albilineans was determined at 2.0 Å resolution by SAD phasing using data collected from a single trimethyllead acetate derivative on a home source. AlbG folds into a right-handed quadrilateral β-helix composed of approximately eight semi-regular coils. The regularity of the β-helix is blemished by a large loop/deviation in the β-helix between coils 4 and 5. The C-terminus of the β-helix is capped by a dimerization module, yielding a dimer with a 110 Å semi-collinear β-helical axis. This method of dimer formation appears to be common to all PRP proteins that confer resistance to topoisomerase poisons and contrasts with most PRP proteins, which are typically monomeric

Circulating fibrinogen but not D-dimer level is associated with vital exhaustion in school teachers.

Science.gov (United States)

Kudielka, Brigitte M; Bellingrath, Silja; von Känel, Roland

2008-07-01

Meta-analyses have established elevated fibrinogen and D-dimer levels in the circulation as biological risk factors for the development and progression of coronary artery disease (CAD). Here, we investigated whether vital exhaustion (VE), a known psychosocial risk factor for CAD, is associated with fibrinogen and D-dimer levels in a sample of apparently healthy school teachers. The teaching profession has been proposed as a potentially high stressful occupation due to enhanced psychosocial stress at the workplace. Plasma fibrinogen and D-dimer levels were measured in 150 middle-aged male and female teachers derived from the first year of the Trier-Teacher-Stress-Study. Log-transformed levels were analyzed using linear regression. Results yielded a significant association between VE and fibrinogen (p = 0.02) but not D-dimer controlling for relevant covariates. Further investigation of possible interaction effects resulted in a significant association between fibrinogen and the interaction term "VE x gender" (p = 0.05). In a secondary analysis, we reran linear regression models for males and females separately. Gender-specific results revealed that the association between fibrinogen and VE remained significant in males but not females. In sum, the present data support the notion that fibrinogen levels are positively related to VE. Elevated fibrinogen might be one biological pathway by which chronic work stress may impact on teachers' cardiovascular health in the long run.

Rhodium-catalyzed Chemo- and Regioselective Cross-dimerization of Two Terminal Alkynes

Science.gov (United States)

Xu, Hua-Dong; Zhang, Ren-Wei; Li, Xiaoxun; Huang, Suyu; Tang, Weiping; Hu, Wen-Hao

2013-01-01

Cross-dimerization of terminal arylacetylenes and terminal propargylic alcohols/amides has been achieved in the effect of a rhodium catalyst. This method features high chemo- and regioselectivities rendering convenient and atom economical access to functionalized enynes. PMID:23356993

Capacity for cooperative binding of thyroid hormone (T3) receptor dimers defines wild type T3 response elements.

Science.gov (United States)

Brent, G A; Williams, G R; Harney, J W; Forman, B M; Samuels, H H; Moore, D D; Larsen, P R

1992-04-01

Thyroid hormone response elements (T3REs) have been identified in a variety of promoters including those directing expression of rat GH (rGH), alpha-myosin heavy chain (rMHC), and malic enzyme (rME). A detailed biochemical and genetic analysis of the rGH element has shown that it consists of three hexamers related to the consensus [(A/G)GGT(C/A)A]. We have extended this analysis to the rMHC and rME elements. Binding of highly purified thyroid hormone receptor (T3R) to T3REs was determined using the gel shift assay, and thyroid hormone (T3) induction was measured in transient tranfections. We show that the wild type version of each of the three elements binds T3R dimers cooperatively. Mutational analysis of the rMHC and rME elements identified domains important for binding T3R dimers and allowed a direct determination of the relationship between T3R binding and function. In each element two hexamers are required for dimer binding, and mutations that interfere with dimer formation significantly reduce T3 induction. Similar to the rGH element, the rMHC T3RE contains three hexameric domains arranged as a direct repeat followed by an inverted copy, although the third domain is weaker than in rGH. All three are required for full function and T3R binding. The rME T3RE is a two-hexamer direct repeat T3RE, which also binds T3R monomer and dimer. Across a series of mutant elements, there was a strong correlation between dimer binding in vitro and function in vivo for rMHC (r = 0.99, P less than 0.01) and rME (r = 0.67, P less than 0.05) T3REs. Our results demonstrate a similar pattern of T3R dimer binding to a diverse array of hexameric sequences and arrangements in three wild type T3REs. Addition of nuclear protein enhanced T3R binding but did not alter the specificity of binding to wild type or mutant elements. Binding of purified T3R to T3REs was highly correlated with function, both with and without the addition of nuclear protein. T3R dimer formation is the common

Antibody-induced dimerization activates the epidermal growth factor receptor tyrosine kinase

NARCIS (Netherlands)

Spaargaren, M.; Defize, L. H.; Boonstra, J.; de Laat, S. W.

1991-01-01

The relationship between epidermal growth factor receptor (EGF-R) protein tyrosine kinase activation and ligand-induced receptor dimerization was investigated using several bivalent anti-EGF-R antibodies directed against various receptor epitopes. In A431 membrane preparations and permeabilized

Crystal Structure of PKG I:cGMP Complex Reveals a cGMP-Mediated Dimeric Interface that Facilitates cGMP-Induced Activation

KAUST Repository

Kim, Jeong Joo

2016-04-09

Cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is a key regulator of smooth muscle and vascular tone and represents an important drug target for treating hypertensive diseases and erectile dysfunction. Despite its importance, its activation mechanism is not fully understood. To understand the activation mechanism, we determined a 2.5 Å crystal structure of the PKG I regulatory (R) domain bound with cGMP, which represents the activated state. Although we used a monomeric domain for crystallization, the structure reveals that two R domains form a symmetric dimer where the cGMP bound at high-affinity pockets provide critical dimeric contacts. Small-angle X-ray scattering and mutagenesis support this dimer model, suggesting that the dimer interface modulates kinase activation. Finally, structural comparison with the homologous cyclic AMP-dependent protein kinase reveals that PKG is drastically different from protein kinase A in its active conformation, suggesting a novel activation mechanism for PKG. Kim et al. obtain the first crystal structure of the PKG I R domain bound with cGMP representing its activated state. It reveals a symmetric R dimer where cGMP molecules provide dimeric contacts. This R-R interaction prevents the high-affinity inhibitory interaction between R-C domain and sustains activation. © 2016 Elsevier Ltd.

Crystal Structure of PKG I:cGMP Complex Reveals a cGMP-Mediated Dimeric Interface that Facilitates cGMP-Induced Activation

KAUST Repository

Kim, Jeong  Joo; Lorenz, Robin; Arold, Stefan T.; Reger, Albert  S.; Sankaran, Banumathi; Casteel, Darren  E.; Herberg, Friedrich  W.; Kim, Choel

2016-01-01

Cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is a key regulator of smooth muscle and vascular tone and represents an important drug target for treating hypertensive diseases and erectile dysfunction. Despite its importance, its activation mechanism is not fully understood. To understand the activation mechanism, we determined a 2.5 Å crystal structure of the PKG I regulatory (R) domain bound with cGMP, which represents the activated state. Although we used a monomeric domain for crystallization, the structure reveals that two R domains form a symmetric dimer where the cGMP bound at high-affinity pockets provide critical dimeric contacts. Small-angle X-ray scattering and mutagenesis support this dimer model, suggesting that the dimer interface modulates kinase activation. Finally, structural comparison with the homologous cyclic AMP-dependent protein kinase reveals that PKG is drastically different from protein kinase A in its active conformation, suggesting a novel activation mechanism for PKG. Kim et al. obtain the first crystal structure of the PKG I R domain bound with cGMP representing its activated state. It reveals a symmetric R dimer where cGMP molecules provide dimeric contacts. This R-R interaction prevents the high-affinity inhibitory interaction between R-C domain and sustains activation. © 2016 Elsevier Ltd.

Efficient photosensitized splitting of the thymine dimer/oxetane unit on its modifying beta-cyclodextrin by a binding electron donor.

Science.gov (United States)

Tang, Wen-Jian; Song, Qin-Hua; Wang, Hong-Bo; Yu, Jing-Yu; Guo, Qing-Xiang

2006-07-07

Two modified beta-cyclodextrins (beta-CDs) with a thymine dimer and a thymine oxetane adduct respectively, TD-CD and Ox-CD, have been prepared, and utilized to bind an electron-rich chromophore, indole or N,N-dimethylaniline (DMA), to form a supramolecular complex. We have examined the photosensitized splitting of the dimer/oxetane unit in TD-CD/Ox-CD by indole or DMA via an electron-transfer pathway, and observed high splitting efficiencies of the dimer/oxetane unit. On the basis of measurements of fluorescence spectra and splitting quantum yields, it is suggested that the splitting reaction occurs in a supramolecular complex by an inclusion interaction between the modified beta-CDs and DMA or indole. The back electron transfer, which leads low splitting efficiencies for the covalently-linked chromophore-dimer/oxetane compounds, is suppressed in the non-covalently-bound complex, and the mechanism has been discussed.

Dimerization-Induced Allosteric Changes of the Oxyanion-Hole Loop Activate the Pseudorabies Virus Assemblin pUL26N, a Herpesvirus Serine Protease.

Directory of Open Access Journals (Sweden)

Martin Zühlsdorf

2015-07-01

Full Text Available Herpesviruses encode a characteristic serine protease with a unique fold and an active site that comprises the unusual triad Ser-His-His. The protease is essential for viral replication and as such constitutes a promising drug target. In solution, a dynamic equilibrium exists between an inactive monomeric and an active dimeric form of the enzyme, which is believed to play a key regulatory role in the orchestration of proteolysis and capsid assembly. Currently available crystal structures of herpesvirus proteases correspond either to the dimeric state or to complexes with peptide mimetics that alter the dimerization interface. In contrast, the structure of the native monomeric state has remained elusive. Here, we present the three-dimensional structures of native monomeric, active dimeric, and diisopropyl fluorophosphate-inhibited dimeric protease derived from pseudorabies virus, an alphaherpesvirus of swine. These structures, solved by X-ray crystallography to respective resolutions of 2.05, 2.10 and 2.03 Å, allow a direct comparison of the main conformational states of the protease. In the dimeric form, a functional oxyanion hole is formed by a loop of 10 amino-acid residues encompassing two consecutive arginine residues (Arg136 and Arg137; both are strictly conserved throughout the herpesviruses. In the monomeric form, the top of the loop is shifted by approximately 11 Å, resulting in a complete disruption of the oxyanion hole and loss of activity. The dimerization-induced allosteric changes described here form the physical basis for the concentration-dependent activation of the protease, which is essential for proper virus replication. Small-angle X-ray scattering experiments confirmed a concentration-dependent equilibrium of monomeric and dimeric protease in solution.

The insulin and IGF1 receptor kinase domains are functional dimers in the activated state

Science.gov (United States)

Cabail, M. Zulema; Li, Shiqing; Lemmon, Eric; Bowen, Mark E.; Hubbard, Stevan R.; Miller, W. Todd

2015-03-01

The insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R) are highly related receptor tyrosine kinases with a disulfide-linked homodimeric architecture. Ligand binding to the receptor ectodomain triggers tyrosine autophosphorylation of the cytoplasmic domains, which stimulates catalytic activity and creates recruitment sites for downstream signalling proteins. Whether the two phosphorylated tyrosine kinase domains within the receptor dimer function independently or cooperatively to phosphorylate protein substrates is not known. Here we provide crystallographic, biophysical and biochemical evidence demonstrating that the phosphorylated kinase domains of IR and IGF1R form a specific dimeric arrangement involving an exchange of the juxtamembrane region proximal to the kinase domain. In this dimer, the active position of α-helix C in the kinase N lobe is stabilized, which promotes downstream substrate phosphorylation. These studies afford a novel strategy for the design of small-molecule IR agonists as potential therapeutic agents for type 2 diabetes.

Dimers of fluorinated methanes with carbonyl sulfide: the rotational spectrum and structure of difluoromethane-OCS.

Science.gov (United States)

Serafin, Michal M; Peebles, Sean A

2008-12-11

The pure rotational spectra of four isotopologues of the difluoromethane-carbonyl sulfide dimer have been measured in the 5-15 GHz region with use of pulsed-nozzle Fourier-transform microwave spectroscopy. The complex was determined to possess an ab plane of symmetry with a center of mass separation of 3.41(2) A and dipole moment components mu(a) = 1.1386(18) D, mu(b) = 0.4840(63) D, mu(total) = 1.2372(41) D. Experimental planar moments indicate that the two fluorine atoms straddle the symmetry plane while one of the C-H bonds of the difluoromethane monomer is aligned to interact with the oxygen atom of the OCS molecule. The assignment of the rotational spectrum for this dimer completes the experimental studies of the series of dimers involving fluorinated methanes (HCF(3), H(2)CF(2), and H(3)CF) complexed with OCS and makes possible a comparison of properties within this series.

Dichroism, chirality, and polarization eigenstates in Babinet nanoslot-dimer membrane metamaterials

DEFF Research Database (Denmark)

Zhukovsky, Sergei; Chigrin, Dmitry N.; Kremers, Christian

2013-01-01

We present a detailed theoretical description of the optical properties of planar metamaterials comprising a metal membrane patterned with openings (microslots) arranged in closely located couples (dimers). Using the covariant coupled-dipole approach, the effective material tensors of such a meta...

Dimerization and oligomerization of the chaperone calreticulin

DEFF Research Database (Denmark)

Jørgensen, Charlotte S; Ryder, L Rebekka; Steinø, Anne

2003-01-01

protein. Using PAGE, urea gradient gel electrophoresis, capillary electrophoresis and MS, we show that dimerization through the SH group can be induced by lowering the pH to 5-6, heating, or under conditions that favour partial unfolding such as urea concentrations above 2.6 m or SDS concentrations above...... that favour partial unfolding or an intramolecular local conformational change that allows oligomerization, resulting in a heterogeneous mixture of oligomers consisting of up to 10 calreticulin monomers. The oligomeric calreticulin was very stable, but oligomerization was partially reversed by addition of 8 m...

Magnetic properties of a classical XY spin dimer in a “planar” magnetic field

Energy Technology Data Exchange (ETDEWEB)

Ciftja, Orion, E-mail: ogciftja@pvamu.edu [Department of Physics, Prairie View A& M University, Prairie View, TX 77446 (United States); Prenga, Dode [Department of Physics, Faculty of Natural Sciences, University of Tirana, Bul. Zog I, Tirana (Albania)

2016-10-15

Single-molecule magnetism originates from the strong intra-molecular magnetic coupling of a small number of interacting spins. Such spins generally interact very weakly with the neighboring spins in the other molecules of the compound, therefore, inter-molecular spin couplings are negligible. In certain cases the number of magnetically coupled spins is as small as a dimer, a system that can be considered the smallest nanomagnet capable of storing non-trivial magnetic information on the molecular level. Additional interesting patterns arise if the spin motion is confined to a two-dimensional space. In such a scenario, clusters consisting of spins with large-spin values are particularly attractive since their magnetic interactions can be described well in terms of classical Heisenberg XY spins. In this work we calculate exactly the magnetic properties of a nanomagnetic dimer of classical XY spins in a “planar” external magnetic field. The problem is solved by employing a mathematical approach whose idea is the introduction of auxiliary spin variables into the starting expression of the partition function. Results for the total internal energy, total magnetic moment, spin–spin correlation function and zero-field magnetic susceptibility can serve as a basis to understand the magnetic properties of large-spin dimer building blocks. - Highlights: • Exact magnetic properties of a dimer system of classical XY spins in magnetic field. • Partition function in nonzero magnetic field obtained in closed-form. • Novel exact analytic results are important for spin models in a magnetic field. • Result provides benchmarks to gauge the accuracy of computational techniques.

Communication: The highest frequency hydrogen bond vibration and an experimental value for the dissociation energy of formic acid dimer

DEFF Research Database (Denmark)

Kollipost, F.; Larsen, René Wugt; Domanskaya, A.V.

2012-01-01

The highest frequency hydrogen bond fundamental of formic acid dimer, ν24 (Bu), is experimentally located at 264 cm−1. FTIR spectra of this in-plane bending mode of (HCOOH)2 and band centers of its symmetric D isotopologues (isotopomers) recorded in a supersonic slit jet expansion are presented...... thermodynamics treatment of the dimerization process up to room temperature. We obtain D0 = 59.5(5) kJ/mol as the best experimental estimate for the dimer dissociation energy at 0 K. Further improvements have to wait for a more consistent determination of the room temperature equilibrium constant....

ANP, BNP and D-dimer predict right ventricular dysfunction in patients with acute pulmonary embolism

DEFF Research Database (Denmark)

Borgwardt, Henrik Gutte; Mortensen, Jann; Jensen, Claus V

2010-01-01

The aim of this study was to predict right ventricular dysfunction (RVD) using plasma concentration of D-dimer, pro-atrial natriuretic peptide (pro-ANP), brain natriuretic peptide (BNP), endothelin-1 (ET-1) and cardiac troponin I (TNI) in patients with pulmonary embolism (PE).......The aim of this study was to predict right ventricular dysfunction (RVD) using plasma concentration of D-dimer, pro-atrial natriuretic peptide (pro-ANP), brain natriuretic peptide (BNP), endothelin-1 (ET-1) and cardiac troponin I (TNI) in patients with pulmonary embolism (PE)....

Comparative studies on the correlation between pyrimidine dimer formation and tyrosinase activity in Cloudman S91 melanoma cells after ultraviolet-irradiation

International Nuclear Information System (INIS)

Niggli, H.J.

1990-01-01

The authors compared the induction of pyrimidine dimer densities after UV-irradiation in mouse melanoma cells before and after treatment with cholera toxin. Treatment with cholera toxin stimulated tyrosinase activity up to 50-fold, leading to a marked, visually apparent increase in cellular melanin concentrations. Results indicate that de novo melanin pigmentation induced via the c-AMP pathway is not involved in protection against UV-induced thymine-containing pyrimidine dimers. In separate experiments, irradiation of toxin-treated and untreated mouse melanoma cells with UVC or UVB light produced a 20-30% lower dimer density compared to irradiated human skin fibroblasts. This finding suggests that melanin has some protection properties against UV-induced pyrimidine dimers, although the exact defense mechanism seems highly complex. (author)

A Lys-Trp cation-π interaction mediates the dimerization and function of the chloride intracellular channel protein 1 transmembrane domain.

Science.gov (United States)

Peter, Bradley; Polyansky, Anton A; Fanucchi, Sylvia; Dirr, Heini W

2014-01-14

Chloride intracellular channel protein 1 (CLIC1) is a dual-state protein that can exist either as a soluble monomer or in an integral membrane form. The oligomerization of the transmembrane domain (TMD) remains speculative despite it being implicated in pore formation. The extent to which electrostatic and van der Waals interactions drive folding and association of the dimorphic TMD is unknown and is complicated by the requirement of interactions favorable in both aqueous and membrane environments. Here we report a putative Lys37-Trp35 cation-π interaction and show that it stabilizes the dimeric form of the CLIC1 TMD in membranes. A synthetic 30-mer peptide comprising a K37M TMD mutant was examined in 2,2,2-trifluoroethanol, sodium dodecyl sulfate micelles, and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine liposomes using far-ultraviolet (UV) circular dichroism, fluorescence, and UV absorbance spectroscopy. Our data suggest that Lys37 is not implicated in the folding, stability, or membrane insertion of the TMD peptide. However, removal of this residue impairs the formation of dimers and higher-order oligomers. This is accompanied by a 30-fold loss of chloride influx activity, suggesting that dimerization modulates the rate of chloride conductance. We propose that, within membranes, individual TMD helices associate via a Lys37-mediated cation-π interaction to form active dimers. The latter findings are also supported by results of modeling a putative TMD dimer conformation in which Lys37 and Trp35 form cation-π pairs at the dimer interface. Dimeric helix bundles may then associate to form fully active ion channels. Thus, within a membrane-like environment, aromatic interactions involving a polar lysine side chain provide a thermodynamic driving force for helix-helix association.

d-Dimer as a Screening Marker for Venous Thromboembolism After Surgery Among Patients Younger Than 50 With Lower Limb Fractures.

Science.gov (United States)