Lower Bound on the Mean Square Displacement of Particles in the Hard Disk Model

NASA Astrophysics Data System (ADS)

Richthammer, Thomas

2016-08-01

The hard disk model is a 2D Gibbsian process of particles interacting via pure hard core repulsion. At high particle density the model is believed to show orientational order, however, it is known not to exhibit positional order. Here we investigate to what extent particle positions may fluctuate. We consider a finite volume version of the model in a box of dimensions 2 n × 2 n with arbitrary boundary configuration, and we show that the mean square displacement of particles near the center of the box is bounded from below by c log n. The result generalizes to a large class of models with fairly arbitrary interaction.

A tight Cramér-Rao bound for joint parameter estimation with a pure two-mode squeezed probe

NASA Astrophysics Data System (ADS)

Bradshaw, Mark; Assad, Syed M.; Lam, Ping Koy

2017-08-01

We calculate the Holevo Cramér-Rao bound for estimation of the displacement experienced by one mode of an two-mode squeezed vacuum state with squeezing r and find that it is equal to 4 exp ⁡ (- 2 r). This equals the sum of the mean squared error obtained from a dual homodyne measurement, indicating that the bound is tight and that the dual homodyne measurement is optimal.

Hydrated Electrons React with High Specificity with Cisplatin Bound to Single-Stranded DNA

PubMed Central

Behmand, B.; Cloutier, P.; Girouard, S.; Wagner, J. R.; Sanche, L.; Hunting, D. J.

2015-01-01

Short oligonucleotides TTTTTGTGTTT and TTTTTTTGTTT in solution with and without cisplatin (cisPt) bound to the guanine bases were irradiated with γ-rays at doses varying from 0 to 2500 Gy. To determine the effect of hydrated electrons from water radiolysis on the oligonucleotides, we quenched •OH radicals with ethylenediaminetetraacetic acid (EDTA) and displaced oxygen, which reacts with hydrated electrons, by bubbling the solution with wet nitrogen. DNA strand breaks and platinum detachment were quantified by gel electrophoresis. Our results demonstrate that hydrated electrons react almost exclusively at the position of the cisPt adduct, where they induce cisPt detachment from one or both guanines in the oligonucleotide. Given the high yield of hydrated electrons in irradiated tissues, this reaction may be an important step in the mechanism of radiosensitization of DNA by cisPt. PMID:24205952

Strand displacement by DNA polymerase III occurs through a tau-psi-chi link to single-stranded DNA-binding protein coating the lagging strand template.

PubMed

Yuan, Quan; McHenry, Charles S

2009-11-13

In addition to the well characterized processive replication reaction catalyzed by the DNA polymerase III holoenzyme on single-stranded DNA templates, the enzyme possesses an intrinsic strand displacement activity on flapped templates. The strand displacement activity is distinguished from the single-stranded DNA-templated reaction by a high dependence upon single-stranded DNA binding protein and an inability of gamma-complex to support the reaction in the absence of tau. However, if gamma-complex is present to load beta(2), a truncated tau protein containing only domains III-V will suffice. This truncated protein is sufficient to bind both the alpha subunit of DNA polymerase (Pol) III and chipsi. This is reminiscent of the minimal requirements for Pol III to replicate short single-stranded DNA-binding protein (SSB)-coated templates where tau is only required to serve as a scaffold to hold Pol III and chi in the same complex (Glover, B., and McHenry, C. (1998) J. Biol. Chem. 273, 23476-23484). We propose a model in which strand displacement by DNA polymerase III holoenzyme depends upon a Pol III-tau-psi-chi-SSB binding network, where SSB is bound to the displaced strand, stabilizing the Pol III-template interaction. The same interaction network is probably important for stabilizing the leading strand polymerase interactions with authentic replication forks. The specificity constant (k(cat)/K(m)) for the strand displacement reaction is approximately 300-fold less favorable than reactions on single-stranded templates and proceeds with a slower rate (150 nucleotides/s) and only moderate processivity (approximately 300 nucleotides). PriA, the initiator of replication restart on collapsed or misassembled replication forks, blocks the strand displacement reaction, even if added to an ongoing reaction.

Fatty Acid Binding Proteins Expressed at the Human Blood-Brain Barrier Bind Drugs in an Isoform-Specific Manner.

PubMed

Lee, Gordon S; Kappler, Katharina; Porter, Christopher J H; Scanlon, Martin J; Nicolazzo, Joseph A

2015-10-01

To examine the expression of fatty acid binding proteins (FABPs) at the human blood-brain barrier (BBB) and to assess their ability to bind lipophilic drugs. mRNA and protein expression of FABP subtypes in immortalized human brain endothelial (hCMEC/D3) cells were examined by RT-qPCR and Western blot, respectively. FABPs that were found in hCMEC/D3 cells (hFABPs) were recombinantly expressed and purified from Escherichia coli C41(DE3) cells. Drug binding to these hFABPs was assessed using a fluorescence assay, which measured the ability of a panel of lipophilic drugs to displace the fluorescent probe compound 1-anilinonaphthalene-8-sulfonic acid (ANS). hFABP3, 4 and 5 were expressed in hCMEC/D3 cells at the mRNA and protein level. The competitive ANS displacement assay demonstrated that, in general, glitazones preferentially bound to hFABP5 (Ki: 1.0-28 μM) and fibrates and fenamates preferentially bound to hFABP4 (Ki: 0.100-17 μM). In general, lipophilic drugs appeared to show weaker affinities for hFABP3 relative to hFABP4 and hFABP5. No clear correlation was observed between the molecular structure or physicochemical properties of the drugs and their ability to displace ANS from hFABP3, 4 and 5. hFABP3, 4 and 5 are expressed at the human BBB and bind differentially to a diverse range of lipophilic drugs. The unique expression and binding patterns of hFABPs at the BBB may therefore influence drug disposition into the brain.

Revisiting the Cramér Rao Lower Bound for Elastography: Predicting the Performance of Axial, Lateral and Polar Strain Elastograms.

PubMed

Verma, Prashant; Doyley, Marvin M

2017-09-01

We derived the Cramér Rao lower bound for 2-D estimators employed in quasi-static elastography. To illustrate the theory, we modeled the 2-D point spread function as a sinc-modulated sine pulse in the axial direction and as a sinc function in the lateral direction. We compared theoretical predictions of the variance incurred in displacements and strains when quasi-static elastography was performed under varying conditions (different scanning methods, different configuration of conventional linear array imaging and different-size kernels) with those measured from simulated or experimentally acquired data. We performed studies to illustrate the application of the derived expressions when performing vascular elastography with plane wave and compounded plane wave imaging. Standard deviations in lateral displacements were an order higher than those in axial. Additionally, the derived expressions predicted that peak performance should occur when 2% strain is applied, the same order of magnitude as observed in simulations (1%) and experiments (1%-2%). We assessed how different configurations of conventional linear array imaging (number of active reception and transmission elements) influenced the quality of axial and lateral strain elastograms. The theoretical expressions predicted that 2-D echo tracking should be performed with wide kernels, but the length of the kernels should be selected using knowledge of the magnitude of the applied strain: specifically, longer kernels for small strains (<5%) and shorter kernels for larger strains. Although the general trends of theoretical predictions and experimental observations were similar, biases incurred during beamforming and subsample displacement estimation produced noticeable differences. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Oscillating potential well in the complex plane and the adiabatic theorem

NASA Astrophysics Data System (ADS)

Longhi, Stefano

2017-10-01

A quantum particle in a slowly changing potential well V (x ,t ) =V ( x -x0(ɛ t ) ) , periodically shaken in time at a slow frequency ɛ , provides an important quantum mechanical system where the adiabatic theorem fails to predict the asymptotic dynamics over time scales longer than ˜1 /ɛ . Specifically, we consider a double-well potential V (x ) sustaining two bound states spaced in frequency by ω0 and periodically shaken in a complex plane. Two different spatial displacements x0(t ) are assumed: the real spatial displacement x0(ɛ t ) =A sin(ɛ t ) , corresponding to ordinary Hermitian shaking, and the complex one x0(ɛ t ) =A -A exp(-i ɛ t ) , corresponding to non-Hermitian shaking. When the particle is initially prepared in the ground state of the potential well, breakdown of adiabatic evolution is found for both Hermitian and non-Hermitian shaking whenever the oscillation frequency ɛ is close to an odd resonance of ω0. However, a different physical mechanism underlying nonadiabatic transitions is found in the two cases. For the Hermitian shaking, an avoided crossing of quasienergies is observed at odd resonances and nonadiabatic transitions between the two bound states, resulting in Rabi flopping, can be explained as a multiphoton resonance process. For the complex oscillating potential well, breakdown of adiabaticity arises from the appearance of Floquet exceptional points at exact quasienergy crossing.

Transient response of multidegree-of-freedom linear systems to forcing functions with inequality constraints

NASA Technical Reports Server (NTRS)

Michalopoulos, C. D.

1974-01-01

Optimal control theory is applied to analyze the transient response of discrete linear systems to forcing functions with unknown time dependence but having known bounds. Particular attention is given to forcing functions which include: (1) maximum displacement of any given mass element, (2) maximum relative displacement of any two adjacent masses, and (3) maximum acceleration of a given mass. Linear mechanical systems with an arbitrary number of degrees of freedom and only one forcing function acting are considered. In the general case, the desired forcing function is found to be a function that switches from the upper-to-lower bound and vice-versa at certain moments of time. A general procedure for finding such switching times is set forth.

Modes of Diffusion of Cholera Toxin Bound to GM1 on Live Cell Membrane by Image Mean Square Displacement Analysis

PubMed Central

Moens, Pierre D.J.; Digman, Michelle A.; Gratton, Enrico

2015-01-01

The image-mean square displacement technique applies the calculation of the mean square displacement commonly used in single-molecule tracking to images without resolving single particles. The image-mean square displacement plot obtained is similar to the mean square displacement plot obtained using the single-particle tracking technique. This plot is then used to reconstruct the protein diffusion law and to identify whether the labeled molecules are undergoing pure isotropic, restricted, corralled, transiently confined, or directed diffusion. In our study total internal reflection fluorescence microscopy images were taken of Cholera toxin subunit B (CtxB) membrane-labeled NIH 3T3 mouse fibroblasts and MDA 231 MB cells. We found a population of CTxB undergoing purely isotropic diffusion and one displaying restricted diffusion with corral sizes ranging from 150 to ∼1800 nm. We show that the diffusion rate of CTxB bound to GM1 is independent of the size of the confinement, suggesting that the mechanism of confinement is different from the mechanism controlling the diffusion rate of CtxB. We highlight the potential effect of continuous illumination on the diffusion mode of CTxB. We also show that aggregation of CTxB/GM1 in large complexes occurs and that these aggregates tend to have slower diffusion rates. PMID:25809257

Modes of diffusion of cholera toxin bound to GM1 on live cell membrane by image mean square displacement analysis.

PubMed

Moens, Pierre D J; Digman, Michelle A; Gratton, Enrico

2015-03-24

The image-mean square displacement technique applies the calculation of the mean square displacement commonly used in single-molecule tracking to images without resolving single particles. The image-mean square displacement plot obtained is similar to the mean square displacement plot obtained using the single-particle tracking technique. This plot is then used to reconstruct the protein diffusion law and to identify whether the labeled molecules are undergoing pure isotropic, restricted, corralled, transiently confined, or directed diffusion. In our study total internal reflection fluorescence microscopy images were taken of Cholera toxin subunit B (CtxB) membrane-labeled NIH 3T3 mouse fibroblasts and MDA 231 MB cells. We found a population of CTxB undergoing purely isotropic diffusion and one displaying restricted diffusion with corral sizes ranging from 150 to ∼1800 nm. We show that the diffusion rate of CTxB bound to GM1 is independent of the size of the confinement, suggesting that the mechanism of confinement is different from the mechanism controlling the diffusion rate of CtxB. We highlight the potential effect of continuous illumination on the diffusion mode of CTxB. We also show that aggregation of CTxB/GM1 in large complexes occurs and that these aggregates tend to have slower diffusion rates. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

/sup 3/H-PAF-acether displacement and inhibition of binding in intact human platelets by BN 52021

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

Korth, R.; Le Couedic, J.P.; Benveniste, J.

1986-03-05

Intact washed human platelets incubated at 20/sup 0/C in Tyrode's buffer containing 0.25% (w/v) bovine serum albumin bound /sup 3/H paf-acether in a concentration (0-6.5 nM) and time (0-60 min) dependent manner (n=3). BN 52021 (60 ..mu..M) a chemically defined extract from Ginkgo biloba inhibited the binding of increasing concentrations of /sup 3/H paf-acether. Calculated differences between /sup 3/H paf-acether binding in the presence or absence of BN 52021 (60 ..mu..M) reached nearly a plateau in concentrations higher than 0.65 nM /sup 3/H paf-acether. Increasing concentrations of BN 52021 (0-60 ..mu..M) as well as of unlabelled paf-acether (0-50 nM) preventedmore » within 15 min /sup 3/H paf-acether binding (0.65 nM) to platelets in a concentration-dependent way. Increasing BN 52021 concentrations (0-60 ..mu..M) also displaced platelet-bound /sup 3/H paf-acether (0.65 nM) in a concentration-dependent way. Displacement increased with the time length of platelet incubation with BN 52021 and reached a plateau at 15 min. Platelet-bound /sup 3/H paf-acether displacement of 28.3 +/- 6.3%, 31.1 +/- 4.0% and 26.7 +/- 5.6% was observed using 50 nM unlabelled paf-acether, 60 ..mu..M BN 52021 or both substances together (vs 4.3 +/- 7.2% for vehicle alone). No degradation of /sup 3/H paf-acether occurred as assessed by high pressure liquid chromatography. These results demonstrate that BN 52021 competes directly with paf-acether binding sites on human platelets.« less

Characterization of insulin-like growth factor I receptor on human erythrocytes.

PubMed

Hizuka, N; Takano, K; Tanaka, I; Honda, N; Tsushima, T; Shizume, K

1985-12-01

[125I]Insulin-like growth factor I (IGF-I) specifically bound to erythrocytes; the binding was saturable, and time and temperature dependent. Steady state binding was reached at 16 h at 4 C, and specific binding averaged 14.3 +/- 0.7% (+/- SEM) at a concentration of 3.6 X 10(9) cells/ml in seven normal subjects. [125I]IGF-I binding to the cells was displaced by unlabeled IGF-I in a dose-dependent manner. Scatchard analysis indicated a linear plot, and Ka and number of binding sites/cell were 1.43 +/- 0.07 X 10(9) M-1 and 20.7 +/- 2.2, respectively. Compared to IGF-I, the relative potencies of multiplication-stimulating activity and insulin for displacing [125I]IGF-I binding were 20% and 1%, respectively. [125I]IGF-I binding to erythrocytes from patients with acromegaly was lower than binding to cells from pituitary dwarfs. An inverse correlation between plasma IGF-I level and the number of IGF-I-binding sites per cell was found (r = -0.75; P less than 0.005). These results demonstrate that [125I]IGF-I binding to erythrocytes can be used for clinical measurement of the IGF-I receptor.

[3H]aniracetam binds to specific recognition sites in brain membranes.

PubMed

Fallarino, F; Genazzani, A A; Silla, S; L'Episcopo, M R; Camici, O; Corazzi, L; Nicoletti, F; Fioretti, M C

1995-08-01

[3H]Aniracetam bound to specific and saturable recognition sites in membranes prepared from discrete regions of rat brain. In crude membrane preparation from rat cerebral cortex, specific binding was Na+ independent, was still largely detectable at low temperature (4 degrees C), and underwent rapid dissociation. Scatchard analysis of [3H]aniracetam binding revealed a single population of sites with an apparent KD value of approximately 70 nM and a maximal density of 3.5 pmol/mg of protein. Specifically bound [3H]aniracetam was not displaced by various metabolites of aniracetam, nor by other pyrrolidinone-containing nootropic drugs such as piracetam or oxiracetam. Subcellular distribution studies showed that a high percentage of specific [3H]aniracetam binding was present in purified synaptosomes or mitochondria, whereas specific binding was low in the myelin fraction. The possibility that at least some [3H]aniracetam binding sites are associated with glutamate receptors is supported by the evidence that specific binding was abolished when membranes were preincubated at 37 degrees C under fast shaking (a procedure that substantially reduced the amount of glutamate trapped in the membranes) and could be restored after addition of either glutamate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) but not kainate. The action of AMPA was antagonized by DNQX, which also reduced specific [3H]aniracetam binding in unwashed membranes. High levels of [3H]aniracetam binding were detected in hippocampal, cortical, or cerebellar membranes, which contain a high density of excitatory amino acid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantum sensing of the phase-space-displacement parameters using a single trapped ion

NASA Astrophysics Data System (ADS)

Ivanov, Peter A.; Vitanov, Nikolay V.

2018-03-01

We introduce a quantum sensing protocol for detecting the parameters characterizing the phase-space displacement by using a single trapped ion as a quantum probe. We show that, thanks to the laser-induced coupling between the ion's internal states and the motion mode, the estimation of the two conjugated parameters describing the displacement can be efficiently performed by a set of measurements of the atomic state populations. Furthermore, we introduce a three-parameter protocol capable of detecting the magnitude, the transverse direction, and the phase of the displacement. We characterize the uncertainty of the two- and three-parameter problems in terms of the Fisher information and show that state projective measurement saturates the fundamental quantum Cramér-Rao bound.

Both endothelin-A and endothelin-B receptors are present on adult rat cardiac ventricular myocytes.

PubMed

Allen, Bruce G; Phuong, Luu Lien; Farhat, Hala; Chevalier, Dominique

2003-02-01

Endothelin-A (ET(A)) and endothelin-B (ET(B)) receptors have been demonstrated in intact heart and cardiac membranes. ET(A) receptors have been demonstrated on adult ventricular myocytes. The aim of the present study was to determine the presence of ET(B) and the relative contribution of this receptor subtype to total endothelin-1 (ET-1) binding on adult ventricular myocytes. Saturation binding experiments indicated that ET-1 bound to a single population of receptors (Kd = 0.52 +/- 0.13 nM, n = 4) with an apparent maximum binding (Bmax) of 2.10 +/- 0.25 sites (x 10(5))/cell (n = 4). Competition experiments using 40 pM [125I]ET-1 and nonradioactive ET-1 revealed a Ki of 660 +/- 71 pM (n = 10) and a Hill coefficient (nH) of 0.99 +/- 0.10 (n = 10). A selective ET(A) antagonist, BQ610, displaced 80% of the bound [125I]ET-1. No displacement was observed by concentrations of an ET(B)-selective antagonist, BQ788, up to 1.0 microM. However, in the presence of 1.0 microM BQ610, BQ788 inhibited the remaining [125I]ET-1 binding. Similarly, in the presence of 1.0 microM BQ788, BQ610 inhibited the remaining specific [125I]ET-1 binding. Binding of an ET(B1)-selective agonist, [125I]IRL-1620, confirmed the presence of ET(B). ET(B) bound to ET-1 irreversibly, whereas binding to ET(A) demonstrated both reversible and irreversible components, and BQ610 and BQ788 bound reversibly. Reducing the incubation temperature to 0 degrees C did not alter the irreversible component of ET-1 binding. Hence, both ET(A) and ET(B) receptors are present on intact adult rat ventricular myocytes, and the ratio of ET(A):ET(B) binding sites is 4:1. Both receptor subtypes bind to ET-1 by a two-step association involving the formation of a tight receptor-ligand complex; however, the kinetics of ET-1 binding to ET(A) versus ET(B) differ.

Experimental and computational studies on the effects of valganciclovir as an antiviral drug on calf thymus DNA.

PubMed

Shahabadi, Nahid; Pourfoulad, Mehdi; Moghadam, Neda Hosseinpour

2017-01-02

DNA-binding properties of an antiviral drug, valganciclovir (valcyte) was studied by using emission, absorption, circular dichroism, viscosity, differential pulse voltammetry, fluorescence techniques, and computational studies. The drug bound to calf thymus DNA (ct-DNA) in a groove-binding mode. The calculated binding constant of UV-vis, K a , is comparable to groove-binding drugs. Competitive fluorimetric studies with Hoechst 33258 showed that valcyte could displace the DNA-bound Hoechst 33258. The drug could not displace intercalated methylene blue from DNA double helix. Furthermore, the induced detectable changes in the CD spectrum of ct-DNA as well as changes in its viscosity confirm the groove-binding mode. In addition, an integrated molecular docking was employed to further investigate the binding interactions between valcyte and calf thymus DNA.

Computational micromechanics of woven composites

NASA Technical Reports Server (NTRS)

Hopkins, Dale A.; Saigal, Sunil; Zeng, Xiaogang

1991-01-01

The bounds on the equivalent elastic material properties of a composite are presently addressed by a unified energy approach which is valid for both unidirectional and 2D and 3D woven composites. The unit cell considered is assumed to consist, first, of the actual composite arrangement of the fibers and matrix material, and then, of an equivalent pseudohomogeneous material. Equating the strain energies due to the two arrangements yields an estimate of the upper bound for the material equivalent properties; successive increases in the order of displacement field that is assumed in the composite arrangement will successively produce improved upper bound estimates.

Binding of the Biogenic Polyamines to Deoxyribonucleic Acids of Varying Base Composition: Base Specificity and the Associated Energetics of the Interaction

PubMed Central

Kabir, Ayesha; Suresh Kumar, Gopinatha

2013-01-01

Background The thermodynamics of the base pair specificity of the binding of the polyamines spermine, spermidine, putrescine, and cadaverine with three genomic DNAs Clostridium perfringens, 27% GC, Escherichia coli, 50% GC and Micrococcus lysodeikticus, 72% GC have been studied using titration calorimetry and the data supplemented with melting studies, ethidium displacement and circular dichroism spectroscopy results. Methodology/Principal Findings Isothermal titration calorimetry, differential scanning calorimetry, optical melting studies, ethidium displacement, circular dichroism spectroscopy are the various techniques employed to characterize the interaction of four polyamines, spermine, spermidine, putersine and cadaverine with the DNAs. Polyamines bound stronger with AT rich DNA compared to the GC rich DNA and the binding varied depending on the charge on the polyamine as spermine>spermidine >putrescine>cadaverine. Thermodynamics of the interaction revealed that the binding was entropy driven with small enthalpy contribution. The binding was influenced by salt concentration suggesting the contribution from electrostatic forces to the Gibbs energy of binding to be the dominant contributor. Each system studied exhibited enthalpy-entropy compensation. The negative heat capacity changes suggested a role for hydrophobic interactions which may arise due to the non polar interactions between DNA and polyamines. Conclusion/Significance From a thermodynamic analysis, the AT base specificity of polyamines to DNAs has been elucidated for the first time and supplemented by structural studies. PMID:23894663

Lepton flavor violation with displaced vertices

NASA Astrophysics Data System (ADS)

Heeck, Julian; Rodejohann, Werner

2018-01-01

If light new physics with lepton-flavor-violating couplings exists, the prime discovery channel might not be ℓ →ℓ‧ γ but rather ℓ →ℓ‧ X, where the new boson X could be an axion, majoron, familon or Z‧ gauge boson. The most conservative bound then comes from ℓ →ℓ‧ + inv , but if the on-shell X can decay back into leptons or photons, displaced-vertex searches could give much better limits. We show that only a narrow region in parameter space allows for displaced vertices in muon decays, μ → eX , X → γγ , ee, whereas tauon decays can have much more interesting signatures.

Fundamental uncertainty limit for speckle displacement measurements.

PubMed

Fischer, Andreas

2017-09-01

The basic metrological task in speckle photography is to quantify displacements of speckle patterns, allowing for instance the investigation of the mechanical load and modification of objects with rough surfaces. However, the fundamental limit of the measurement uncertainty due to photon shot noise is unknown. For this reason, the Cramér-Rao bound (CRB) is derived for speckle displacement measurements, representing the squared minimal achievable measurement uncertainty. As result, the CRB for speckle patterns is only two times the CRB for an ideal point light source. Hence, speckle photography is an optimal measurement approach for contactless displacement measurements on rough surfaces. In agreement with a derivation from Heisenberg's uncertainty principle, the CRB depends on the number of detected photons and the diffraction limit of the imaging system described by the speckle size. The theoretical results are verified and validated, demonstrating the capability for displacement measurements with nanometer resolution.

Formation flying for electric sails in displaced orbits. Part I: Geometrical analysis

NASA Astrophysics Data System (ADS)

Wang, Wei; Mengali, Giovanni; Quarta, Alessandro A.; Yuan, Jianping

2017-09-01

We present a geometrical methodology for analyzing the formation flying of electric solar wind sail based spacecraft that operate in heliocentric, elliptic, displaced orbits. The spacecraft orbit is maintained by adjusting its propulsive acceleration modulus, whose value is estimated using a thrust model that takes into account a variation of the propulsive performance with the sail attitude. The properties of the relative motion of the spacecraft are studied in detail and a geometrical solution is obtained in terms of relative displaced orbital elements, assumed to be small quantities. In particular, for the small eccentricity case (i.e. for a near-circular displaced orbit), the bounds characterized by the extreme values of relative distances are analytically calculated, thus providing an useful mathematical tool for preliminary design of the spacecraft formation structure.

Homogenous assay for protein detection based on proximity DNA hybridization and isothermal circular strand displacement amplification reaction.

PubMed

Zhang, Manjun; Li, Ruimin; Ling, Liansheng

2017-06-01

This work proposed a homogenous fluorescence assay for proteins, based on the target-triggered proximity DNA hybridization in combination with strand displacement amplification (SDA). It benefited from target-triggered proximity DNA hybridization to specifically recognize the target and SDA making recycling signal amplification. The system included a molecular beacon (MB), an extended probe (EP), and an assistant probe (AP), which were not self-assembly in the absence of target proteins, due to the short length of the designed complementary sequence among MB, EP, and AP. Upon addition of the target proteins, EP and AP are bound to the target proteins, which induced the occurrence of proximity hybridization between MB, EP, and AP and followed by strand displacement amplification. Through the primer extension, a tripartite complex of probes and target was displaced and recycled to hybridize with another MB, and the more opened MB enabled the detection signal to amplify. Under optimum conditions, it was used for the detection of streptavidin and thrombin. Fluorescence intensity was proportional to the concentration of streptavidin and thrombin in the range of 0.2-30 and 0.2-35 nmol/L, respectively. Furthermore, this fluorescent method has a good selectivity, in which the fluorescence intensity of thrombin was ~37-fold or even larger than that of the other proteins at the same concentration. It is a new and simple method for SDA-involved target protein detection and possesses a great potential for other protein detection in the future. Graphical abstract A homogenous assay for protein detection is based on proximity DNA hybridization and strand displacement amplification reaction.

Renal receptors for atrial and C-type natriuretic peptides in the rat.

PubMed

Brown, J; Zuo, Z

1992-07-01

Receptors for alpha-atrial natriuretic peptide (alpha-ANP) and C-type natriuretic peptide [CNP-(1-22)] were quantified in kidneys from adult Wistar rats by in vitro autoradiography. 125I-labeled alpha-ANP (100 pM) bound reversibly to glomeruli, outer medullary vasa recta, and inner medulla with an apparent dissociation constant (Kd) of 3-6 nM. The presence of 10 microM des-[Gln18,Ser19,Gly20,Leu21,Gly22]ANP-(4- 23) (C-ANP), a specific ligand of the ANPR-C subtype of alpha-ANP receptor, inhibited approximately 50% of the glomerular binding of 125I-alpha-ANP, and this moiety of glomerular binding was also inhibited by CNP-(1-22) with an apparent inhibitory constant (Ki) of 10.47 +/- 7.59 nM. C-ANP and CNP-(1-22) showed little affinity for the medullary binding sites of alpha-ANP. 125I-[Tyr0]CNP-(1-22) (110 pM) bound solely to glomeruli and was competitively displaced by increasing concentrations of [Tyr0]CNP-(1-22) with an apparent Kd of 1.42 +/- 0.48 nM. Binding of increasing concentrations (25 pM to 1 nM) of 125I-[Tyr0]CNP-(1-22) in the presence or absence of 1 microM [Tyr0]CNP-(1-22) also demonstrated a high affinity (Kd of 0.41 +/- 0.07 nM) for the glomerular binding of 125I-[Tyr0]CNP-(1-22). Bound 125I-[Tyr0]CNP-(1-22) could be displaced by excess alpha-ANP and excess CNP-(1-22), both with high affinities. The glomerular binding of 125I-[Tyr0]CNP-(1-22) was also prevented by 10 microM C-ANP. Guanosine 3',5'-cyclic monophosphate produced by isolated glomeruli was measured by radioimmunoassay.(ABSTRACT TRUNCATED AT 250 WORDS)

A study of the displacement of a Wankel rotary engine

NASA Astrophysics Data System (ADS)

Beard, J. E.; Pennock, G. R.

1993-03-01

The volumetric displacement of a Wankel rotary engine is a function of the trochoid ratio and the pin size ratio, assuming the engine has a unit depth and the number of lobes is specified. The mathematical expression which defines the displacement contains a function which can be evaluated directly and a normal elliptic integral of the second type which does not have an explicit solution. This paper focuses on the contribution of the elliptic integral to the total displacement of the engine. The influence of the elliptic integral is shown to account for as much as 20 percent of the total displacement, depending on the trochoid ratio and the pin size ratio. Two numerical integration techniques are compared in the paper, namely, the trapezoidal rule and Simpson's 1/3 rule. The bounds on the error, associated with each numerical method, are analyzed. The results indicate that the numerical method has a minimal effect on the accuracy of the calculated displacement for a practical number of integration steps. The paper also evaluates the influence of manufacturing tolerances on the calculated displacement and the actual displacement. Finally. a numerical example of the common three-lobed Wankel rotary engine is included for illustrative purposes.

Annual Progress Report, October 1, 1982 - September 15, 1983 on Contract N00014-79-C-0126,

DTIC Science & Technology

1983-09-15

bulk of bound Na+ (i.e., 77/) ar displaced by 300 rrM guar =dre. However, at 100 mrM concentration, the most effective displacement was not guanidine...polyvinylmethylether (PVME), and a counter and expressed as a ratio to thenumber of native gums , polysaccharides, etc.A labelled Na" concentration in...precipitation and deterioration of the organic components in the GIB medium. The GIB medium was obtained in sterile dry powder form from Grand Island

Instabilities and pattern formation on the pore scale

NASA Astrophysics Data System (ADS)

Juel, Anne

What links a baby's first breath to adhesive debonding, enhanced oil recovery, or even drop-on-demand devices? All these processes involve moving or expanding bubbles displacing fluid in a confined space, bounded by either rigid or elastic walls. In this talk, we show how spatial confinement may either induce or suppress interfacial instabilities and pattern formation in such flows. We demonstrate that a simple change in the bounding geometry can radically alter the behaviour of a fluid-displacing air finger both in rigid and elastic vessels. A rich array of propagation modes, including steady and oscillatory fingers, is uncovered when air displaces oil from axially uniform tubes that have local variations in flow resistance within their cross-sections. Moreover, we show that the experimentally observed states can all be captured by a two-dimensional depth-averaged model for bubble propagation through wide channels. Viscous fingering in Hele-Shaw cells is a classical and widely studied fluid-mechanical instability: when air is injected into the narrow, liquid-filled gap between parallel rigid plates, the axisymmetrically expanding air-liquid interface tends to be unstable to non-axisymmetric disturbances. We show how the introduction of wall elasticity (via the replacement of the upper bounding plate by an elastic membrane) can weaken or even suppress the fingering instability by allowing changes in cell confinement through the flow-induced deflection of the boundary. The presence of a deformable boundary also makes the system prone to additional solid-mechanical instabilities, and these wrinkling instabilities can in turn enhance viscous fingering. The financial support of EPSRC and the Leverhulme Trust is gratefully acknowledged.

Mechanism of synergistic activation of Arp2/3 complex by cortactin and N-WASP

PubMed Central

Helgeson, Luke A; Nolen, Brad J

2013-01-01

Nucleation promoting factors (NPFs) initiate branched actin network assembly by activating Arp2/3 complex, a branched actin filament nucleator. Cellular actin networks contain multiple NPFs, but how they coordinately regulate Arp2/3 complex is unclear. Cortactin is an NPF that activates Arp2/3 complex weakly on its own, but with WASP/N-WASP, another class of NPFs, potently activates. We dissect the mechanism of synergy and propose a model in which cortactin displaces N-WASP from nascent branches as a prerequisite for nucleation. Single-molecule imaging revealed that unlike WASP/N-WASP, cortactin remains bound to junctions during nucleation, and specifically targets junctions with a ∼160-fold increased on rate over filament sides. N-WASP must be dimerized for potent synergy, and targeted mutations indicate release of dimeric N-WASP from nascent branches limits nucleation. Mathematical modeling shows cortactin-mediated displacement but not N-WASP recycling or filament recruitment models can explain synergy. Our results provide a molecular basis for coordinate Arp2/3 complex regulation. DOI: http://dx.doi.org/10.7554/eLife.00884.001 PMID:24015358

A Feasibility Study to Control Airfoil Shape Using THUNDER

NASA Technical Reports Server (NTRS)

Pinkerton, Jennifer L.; Moses, Robert W.

1997-01-01

The objective of this study was to assess the capabilities of a new out-of-plane displacement piezoelectric actuator called thin-layer composite-unimorph ferroelectric driver and sensor (THUNDER) to alter the upper surface geometry of a subscale airfoil to enhance performance under aerodynamic loading. Sixty test conditions, consisting of combinations of five angles of attack, four dc applied voltages, and three tunnel velocities, were studied in a tabletop wind tunnel. Results indicated that larger magnitudes of applied voltage produced larger wafer displacements. Wind-off displacements were also consistently larger than wind-on. Higher velocities produced larger displacements than lower velocities because of increased upper surface suction. Increased suction also resulted in larger displacements at higher angles of attack. Creep and hysteresis of the wafer, which were identified at each test condition, contributed to larger negative displacements for all negative applied voltages and larger positive displacements for the smaller positive applied voltage (+102 V). An elastic membrane used to hold the wafer to the upper surface hindered displacements at the larger positive applied voltage (+170 V). Both creep and hysteresis appeared bounded based on the analysis of several displacement cycles. These results show that THUNDER can be used to alter the camber of a small airfoil under aerodynamic loads.

Estimation of uncertainty bounds for individual particle image velocimetry measurements from cross-correlation peak ratio

NASA Astrophysics Data System (ADS)

Charonko, John J.; Vlachos, Pavlos P.

2013-06-01

Numerous studies have established firmly that particle image velocimetry (PIV) is a robust method for non-invasive, quantitative measurements of fluid velocity, and that when carefully conducted, typical measurements can accurately detect displacements in digital images with a resolution well below a single pixel (in some cases well below a hundredth of a pixel). However, to date, these estimates have only been able to provide guidance on the expected error for an average measurement under specific image quality and flow conditions. This paper demonstrates a new method for estimating the uncertainty bounds to within a given confidence interval for a specific, individual measurement. Here, cross-correlation peak ratio, the ratio of primary to secondary peak height, is shown to correlate strongly with the range of observed error values for a given measurement, regardless of flow condition or image quality. This relationship is significantly stronger for phase-only generalized cross-correlation PIV processing, while the standard correlation approach showed weaker performance. Using an analytical model of the relationship derived from synthetic data sets, the uncertainty bounds at a 95% confidence interval are then computed for several artificial and experimental flow fields, and the resulting errors are shown to match closely to the predicted uncertainties. While this method stops short of being able to predict the true error for a given measurement, knowledge of the uncertainty level for a PIV experiment should provide great benefits when applying the results of PIV analysis to engineering design studies and computational fluid dynamics validation efforts. Moreover, this approach is exceptionally simple to implement and requires negligible additional computational cost.

Sulfolobus chromatin proteins modulate strand displacement by DNA polymerase B1

PubMed Central

Sun, Fei; Huang, Li

2013-01-01

Strand displacement by a DNA polymerase serves a key role in Okazaki fragment maturation, which involves displacement of the RNA primer of the preexisting Okazaki fragment into a flap structure, and subsequent flap removal and fragment ligation. We investigated the role of Sulfolobus chromatin proteins Sso7d and Cren7 in strand displacement by DNA polymerase B1 (PolB1) from the hyperthermophilic archaeon Sulfolobus solfataricus. PolB1 showed a robust strand displacement activity and was capable of synthesizing thousands of nucleotides on a DNA-primed 72-nt single-stranded circular DNA template. This activity was inhibited by both Sso7d and Cren7, which limited the flap length to 3–4 nt at saturating concentrations. However, neither protein inhibited RNA displacement on an RNA-primed single-stranded DNA minicircle by PolB1. Strand displacement remained sensitive to modulation by the chromatin proteins when PolB1 was in association with proliferating cell nuclear antigen. Inhibition of DNA instead of RNA strand displacement by the chromatin proteins is consistent with the finding that double-stranded DNA was more efficiently bound and stabilized than an RNA:DNA duplex by these proteins. Our results suggest that Sulfolobus chromatin proteins modulate strand displacement by PolB1, permitting efficient removal of the RNA primer while inhibiting excessive displacement of the newly synthesized DNA strand during Okazaki fragment maturation. PMID:23821667

Competitive displacement of sodium caseinate by low-molecular-weight emulsifiers and the effects on emulsion texture and rheology.

PubMed

Munk, M B; Larsen, F H; van den Berg, F W J; Knudsen, J C; Andersen, M L

2014-07-29

Low-molecular-weight (LMW) emulsifiers are used to promote controlled destabilization in many dairy-type emulsions in order to obtain stable foams in whippable products. The relation between fat globule aggregation induced by three LMW emulsifiers, lactic acid ester of monoglyceride (LACTEM), saturated monoglyceride (GMS), and unsaturated monoglyceride (GMU) and their effect on interfacial protein displacement was investigated. It was found that protein displacement by LMW emulsifiers was not necessary for fat globule aggregation in emulsions, and conversely fat globule aggregation was not necessarily accompanied by protein displacement. The three LMW emulsifiers had very different effects on emulsions. LACTEM induced shear instability of emulsions, which was accompanied by protein displacement. High stability was characteristic for emulsions with GMS where protein was displaced from the interface. Emulsions containing GMU were semisolid, but only low concentrations of protein were detected in the separated serum phase. The effects of LACTEM, GMS, and GMU may be explained by three different mechanisms involving formation of interfacial α-gel, pickering stabilization and increased exposure of bound casein to the water phase. The latter may facilitate partial coalescence. Stabilizing hydrocolloids did not have any effect on the LMW emulsifiers' ability to induce protein displacement.

Accessory replicative helicases and the replication of protein-bound DNA.

PubMed

Brüning, Jan-Gert; Howard, Jamieson L; McGlynn, Peter

2014-12-12

Complete, accurate duplication of the genetic material is a prerequisite for successful cell division. Achieving this accuracy is challenging since there are many barriers to replication forks that may cause failure to complete genome duplication or result in possibly catastrophic corruption of the genetic code. One of the most important types of replicative barriers are proteins bound to the template DNA, especially transcription complexes. Removal of these barriers demands energy input not only to separate the DNA strands but also to disrupt multiple bonds between the protein and DNA. Replicative helicases that unwind the template DNA for polymerases at the fork can displace proteins bound to the template. However, even occasional failures in protein displacement by the replicative helicase could spell disaster. In such circumstances, failure to restart replication could result in incomplete genome duplication. Avoiding incomplete genome duplication via the repair and restart of blocked replication forks also challenges viability since the involvement of recombination enzymes is associated with the risk of genome rearrangements. Organisms have therefore evolved accessory replicative helicases that aid replication fork movement along protein-bound DNA. These helicases reduce the dangers associated with replication blockage by protein-DNA complexes, aiding clearance of blocks and resumption of replication by the same replisome thus circumventing the need for replication repair and restart. This review summarises recent work in bacteria and eukaryotes that has begun to delineate features of accessory replicative helicases and their importance in genome stability. Copyright © 2014. Published by Elsevier Ltd.

Proceedings of the International Conference on Recent Advances in Structural Dynamics (2nd) held at the University of Southampton (England) on 9-13 April 1984. Volume 1,

DTIC Science & Technology

1984-01-01

and rings, together with consistent bound- ary, discontinuity and initial conditions in terms of the radial and tangential midsurface displacements... midsurface displacements, and the rotation. Using the classical form for the traveling wave solution, the frequency equation is derived in closed-form, in...a w/ 3xL and 32w/3y2) or twist (32w/axay) of the deformed midsurface . However, since these quantities depend, in turn, upon the amplitudes of the

The role of bed-parallel slip in the development of complex normal fault zones

NASA Astrophysics Data System (ADS)

Delogkos, Efstratios; Childs, Conrad; Manzocchi, Tom; Walsh, John J.; Pavlides, Spyros

2017-04-01

Normal faults exposed in Kardia lignite mine, Ptolemais Basin, NW Greece formed at the same time as bed-parallel slip-surfaces, so that while the normal faults grew they were intermittently offset by bed-parallel slip. Following offset by a bed-parallel slip-surface, further fault growth is accommodated by reactivation on one or both of the offset fault segments. Where one fault is reactivated the site of bed-parallel slip is a bypassed asperity. Where both faults are reactivated, they propagate past each other to form a volume between overlapping fault segments that displays many of the characteristics of relay zones, including elevated strains and transfer of displacement between segments. Unlike conventional relay zones, however, these structures contain either a repeated or a missing section of stratigraphy which has a thickness equal to the throw of the fault at the time of the bed-parallel slip event, and the displacement profiles along the relay-bounding fault segments have discrete steps at their intersections with bed-parallel slip-surfaces. With further increase in displacement, the overlapping fault segments connect to form a fault-bound lens. Conventional relay zones form during initial fault propagation, but with coeval bed-parallel slip, relay-like structures can form later in the growth of a fault. Geometrical restoration of cross-sections through selected faults shows that repeated bed-parallel slip events during fault growth can lead to complex internal fault zone structure that masks its origin. Bed-parallel slip, in this case, is attributed to flexural-slip arising from hanging-wall rollover associated with a basin-bounding fault outside the study area.

Plasma protein binding of an antisense oligonucleotide targeting human ICAM-1 (ISIS 2302).

PubMed

Watanabe, Tanya A; Geary, Richard S; Levin, Arthur A

2006-01-01

In vitro ultrafiltration was used to determine the plasma protein-binding characteristics of phosphorothioate oligonucleotides (PS ODNs). Although there are binding data on multiple PS ODNs presented here, the focus of this research is on the protein-binding characteristics of ISIS 2302, a PS ODN targeting human intercellular adhesion molecule-1 (ICAM-1) mRNA, which is currently in clinical trials for the treatment of ulcerative colitis. ISIS 2302 was shown to be highly bound (> 97%) across species (mouse, rat, monkey, human), with the mouse having the least degree of binding. ISIS 2302 was highly bound to albumin and, to a lesser, extent alpha2-macroglobulin and had negligible binding to alpha1-acid glycoprotein. Ten shortened ODN metabolites (8, 10, and 12-19 nucleotides [nt] in length, truncated from the 3' end) were evaluated in human plasma. The degree of binding was reduced as the ODN metabolite length decreased. Three additional 20-nt (20-mer) PS ODNs (ISIS 3521, ISIS 2503, and ISIS 5132) of varying sequence but similar chemistry were evaluated. Although the tested PS ODNs were highly bound to plasma proteins, suggesting a commonality within the chemical class, these results suggested that the protein-binding characteristics in human plasma may be sequence dependent. Lastly, drug displacement studies with ISIS 2302 and other concomitant drugs with known protein-binding properties were conducted to provide information on potential drug interactions. Coadministered ISIS 2302 and other high-binding drugs evaluated in this study did not displace one another at supraclinical plasma concentrations and, thus, are not anticipated to cause any pharmacokinetic interaction in the clinic as a result of the displacement of binding to plasma proteins.

Biochemical characterization of P-type copper ATPases

PubMed Central

Inesi, Giuseppe; Pilankatta, Rajendra; Tadini-Buoninsegni, Francesco

2014-01-01

Copper ATPases, in analogy with other members of the P-ATPase superfamily, contain a catalytic headpiece including an aspartate residue reacting with ATP to form a phosphoenzyme intermediate, and transmembrane helices containing cation-binding sites [TMBS (transmembrane metal-binding sites)] for catalytic activation and cation translocation. Following phosphoenzyme formation by utilization of ATP, bound copper undergoes displacement from the TMBS to the lumenal membrane surface, with no H+ exchange. Although PII-type ATPases sustain active transport of alkali/alkali-earth ions (i.e. Na+, Ca2+) against electrochemical gradients across defined membranes, PIB-type ATPases transfer transition metal ions (i.e. Cu+) from delivery to acceptor proteins and, prominently in mammalian cells, undergo trafficking from/to various membrane compartments. A specific component of copper ATPases is the NMBD (N-terminal metal-binding domain), containing up to six copper-binding sites in mammalian (ATP7A and ATP7B) enzymes. Copper occupancy of NMBD sites and interaction with the ATPase headpiece are required for catalytic activation. Furthermore, in the presence of copper, the NMBD allows interaction with protein kinase D, yielding phosphorylation of serine residues, ATP7B trafficking and protection from proteasome degradation. A specific feature of ATP7A is glycosylation and stabilization on plasma membranes. Cisplatin, a platinum-containing anti-cancer drug, binds to copper sites of ATP7A and ATP7B, and undergoes vectorial displacement in analogy with copper. PMID:25242165

XPD Helicase: Shifting the Inchworm into Reverse

ERIC Educational Resources Information Center

Pugh, Robert A.

2009-01-01

Directional translocation by helicases results in duplex separation and displacement of bound proteins which allows for the DNA processing events associated with DNA repair, replication, recombination, and transcription. Unresolved questions regarding DNA helicases include: (1) how is directional translocation determined in SF2 helicases; (2) do…

Symmetry breaking, Josephson oscillation and self-trapping in a self-bound three-dimensional quantum ball.

PubMed

Adhikari, S K

2017-11-22

We study spontaneous symmetry breaking (SSB), Josephson oscillation, and self-trapping in a stable, mobile, three-dimensional matter-wave spherical quantum ball self-bound by attractive two-body and repulsive three-body interactions. The SSB is realized by a parity-symmetric (a) one-dimensional (1D) double-well potential or (b) a 1D Gaussian potential, both along the z axis and no potential along the x and y axes. In the presence of each of these potentials, the symmetric ground state dynamically evolves into a doubly-degenerate SSB ground state. If the SSB ground state in the double well, predominantly located in the first well (z > 0), is given a small displacement, the quantum ball oscillates with a self-trapping in the first well. For a medium displacement one encounters an asymmetric Josephson oscillation. The asymmetric oscillation is a consequence of SSB. The study is performed by a variational and a numerical solution of a non-linear mean-field model with 1D parity-symmetric perturbations.

Knowledge-Based Elastic Potentials for Docking Drugs or Proteins with Nucleic Acids

PubMed Central

Ge, Wei; Schneider, Bohdan; Olson, Wilma K.

2005-01-01

Elastic ellipsoidal functions defined by the observed hydration patterns around the DNA bases provide a new basis for measuring the recognition of ligands in the grooves of double-helical structures. Here a set of knowledge-based potentials suitable for quantitative description of such behavior is extracted from the observed positions of water molecules and amino acid atoms that form hydrogen bonds with the nitrogenous bases in high resolution crystal structures. Energies based on the displacement of hydrogen-bonding sites on drugs in DNA-crystal complexes relative to the preferred locations of water binding around the heterocyclic bases are low, pointing to the reliability of the potentials and the apparent displacement of water molecules by drug atoms in these structures. The validity of the energy functions has been further examined in a series of sequence substitution studies based on the structures of DNA bound to polyamides that have been designed to recognize the minor-groove edges of Watson-Crick basepairs. The higher energies of binding to incorrect sequences superimposed (without conformational adjustment or displacement of polyamide ligands) on observed high resolution structures confirm the hypothesis that the drug subunits associate with specific DNA bases. The knowledge-based functions also account satisfactorily for the measured free energies of DNA-polyamide association in solution and the observed sites of polyamide binding on nucleosomal DNA. The computations are generally consistent with mechanisms by which minor-groove binding ligands are thought to recognize DNA basepairs. The calculations suggest that the asymmetric distributions of hydrogen-bond-forming atoms on the minor-groove edge of the basepairs may underlie ligand discrimination of G·C from C·G pairs, in addition to the commonly believed role of steric hindrance. The analysis of polyamide-bound nucleosomal structures reveals other discrepancies in the expected chemical design, including unexpected contacts to DNA and modified basepair targets of some ligands. The ellipsoidal potentials thus appear promising as a mathematical tool for the study of drug- and protein-DNA interactions and for gaining new insights into DNA-binding mechanisms. PMID:15501936

Pharmacological analysis of [3H]-senktide binding to NK3 tachykinin receptors in guinea-pig ileum longitudinal muscle-myenteric plexus and cerebral cortex membranes.

PubMed Central

Guard, S.; Watson, S. P.; Maggio, J. E.; Too, H. P.; Watling, K. J.

1990-01-01

1. The binding properties and pharmacological specificity of the selective NK3 tachykinin receptor agonist [3H))-senktide [( 3H]-succinyl[Asp6,MePhe8] substance P (6-11] have been examined in homogenates of guinea-pig ileum longitudinal muscle-myenteric plexus (LM/MP) and cerebral cortex. 2. Scatchard analysis of saturation binding studies in guinea-pig ileum LM/MP and cerebral cortex membranes indicated that [3H]-senktide bound to a single site with apparent high affinity, KD = 2.21 +/- 0.65 nM; Bmax = 13.49 +/- 0.04 fmol mg-1 protein in ileum and KD = 8.52 +/- 0.45 nM; Bmax = 76.3 +/- 1.6 fmol mg-1 protein in cortex (values are means +/- ranges; n = 2). 3. The pharmacological profile for tachykinins and analogues in displacing [3H]-senktide from ileum membranes was: [MePhe7] neurokinin B greater than neurokinin B (NKB) congruent to senktide greater than eledoisin greater than substance P (SP) greater than neurokinin A(NKA) greater than physalaemin greater than [Sar9,Met(O2)11]SP greater than [Nle10]NKA(4-10) = [Glp6,L-Pro9]-SP(6-11) greater than substance P methyl ester, consistent with [3H]-senktide binding to an NK3 subtype of tachykinin receptor. A similar rank order of affinity was obtained for these peptides in displacing [3H]-senktide from cortex membranes. 4. Several tachykinin receptor agonists were tested for their ability to displace [3H]-senktide from ileal and cortical NK3 binding sites and were found to be either weak displacers (pIC50 less than 5.00) or inactive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1694464

Reachability bounds for chemical reaction networks and strand displacement systems.

PubMed

Condon, Anne; Kirkpatrick, Bonnie; Maňuch, Ján

2014-01-01

Chemical reaction networks (CRNs) and DNA strand displacement systems (DSDs) are widely-studied and useful models of molecular programming. However, in order for some DSDs in the literature to behave in an expected manner, the initial number of copies of some reagents is required to be fixed. In this paper we show that, when multiple copies of all initial molecules are present, general types of CRNs and DSDs fail to work correctly if the length of the shortest sequence of reactions needed to produce any given molecule exceeds a threshold that grows polynomially with attributes of the system.

Evaluation of the transverse oscillation technique for cardiac phased-array imaging: A theoretical study

PubMed Central

Bottenus, Nick; D’hooge, Jan; Trahey, Gregg E.

2017-01-01

The transverse oscillation (TO) technique can improve the estimation of tissue motion perpendicular to the ultrasound beam direction. TOs can be introduced using plane wave (PW) insonification and bi-lobed Gaussian apodisation (BA) on receive (abbreviated as PWTO). Furthermore, the TO frequency can be doubled after a heterodyning demodulation process is performed (abbreviated as PWTO*). This study is concerned with identifying the limitations of the PWTO technique in the specific context of myocardial deformation imaging with phased arrays and investigating the conditions in which it remains advantageous over traditional focused (FOC) beamforming. For this purpose, several tissue phantoms were simulated using Field II, undergoing a wide range of displacement magnitudes and modes (lateral, axial and rotational motion). The Cramer-Rao lower bound (CRLB) was used to optimize TO beamforming parameters and theoretically predict the fundamental tracking performance limits associated with the FOC, PWTO and PWTO* beamforming scenarios. This framework was extended to also predict performance for BA functions which are windowed by the physical aperture of the transducer, leading to higher lateral oscillations. It was found that windowed BA functions resulted in lower jitter errors compared to tradional BA functions. PWTO* outperformed FOC at all investigated SNR levels but only up to a certain displacement, with the advantage rapidly decreasing when SNR increased. These results suggest that PWTO* improves lateral tracking performance, but only when inter-frame displacements remain relatively low. The study concludes by translating these findings to a clinical environment by suggesting optimal scanner settings. PMID:27810806

Magnetomotive Molecular Nanoprobes

PubMed Central

John, Renu; Boppart, Stephen A.

2012-01-01

Tremendous developments in the field of biomedical imaging in the past two decades have resulted in the transformation of anatomical imaging to molecular-specific imaging. The main approaches towards imaging at a molecular level are the development of high resolution imaging modalities with high penetration depths and increased sensitivity, and the development of molecular probes with high specificity. The development of novel molecular contrast agents and their success in molecular optical imaging modalities have lead to the emergence of molecular optical imaging as a more versatile and capable technique for providing morphological, spatial, and functional information at the molecular level with high sensitivity and precision, compared to other imaging modalities. In this review, we discuss a new class of dynamic contrast agents called magnetomotive molecular nanoprobes for molecular-specific imaging. Magnetomotive agents are superparamagnetic nanoparticles, typically iron-oxide, that are physically displaced by the application of a small modulating external magnetic field. Dynamic phase-sensitive position measurements are performed using any high resolution imaging modality, including optical coherence tomography (OCT), ultrasonography, or magnetic resonance imaging (MRI). The dynamics of the magnetomotive agents can be used to extract the biomechanical tissue properties in which the nanoparticles are bound, and the agents can be used to deliver therapy via magnetomotive displacements to modulate or disrupt cell function, or hyperthermia to kill cells. These agents can be targeted via conjugation to antibodies, and in vivo targeted imaging has been shown in a carcinogen-induced rat mammary tumor model. The iron-oxide nanoparticles also exhibit negative T2 contrast in MRI, and modulations can produce ultrasound imaging contrast for multimodal imaging applications. PMID:21517766

Unique self-assembly properties of a bridge-shaped protein dimer with quantum dots

NASA Astrophysics Data System (ADS)

Wang, Jianhao; Jiang, Pengju; Gao, Liqian; Yu, Yongsheng; Lu, Yao; Qiu, Lin; Wang, Cheli; Xia, Jiang

2013-09-01

How protein-protein interaction affects protein-nanoparticle self-assembly is the key to the understanding of biomolecular coating of nanoparticle in biological fluids. However, the relationship between protein shape and its interaction with nanoparticles is still under-exploited because of lack of a well-conceived binding system and a method to detect the subtle change in the protein-nanoparticle assemblies. Noticing this unresolved need, we cloned and expressed a His-tagged SpeA protein that adopts a bridge-shaped dimer structure, and utilized a high-resolution capillary electrophoresis method to monitor assembly formation between the protein and quantum dots (QDs, 5 nm in diameter). We observed that the bridge-shaped structure rendered a low SpeA:QD stoichiometry at saturation. Also, close monitoring of imidazole (Im) displacement of surface-bound protein revealed a unique two-step process. High-concentration Im could displace surface-bound SpeA protein and form a transient QD-protein intermediate, through a kinetically controlled displacement process. An affinity-driven equilibrium step then followed, resulting in re-assembling of the QD-protein complex in about 1 h. Through a temporarily formed intermediate, Im causes a rearrangement of His-tagged proteins on the surface. Thus, our work showcases that the synergistic interplay between QD-His-tag interaction and protein-protein interaction can result in unique properties of protein-nanoparticle assembly for the first time.

Late Neogene slip transfer and extension within the curved Whisky Flat fault system central Walker Lane, west-central Nevada

NASA Astrophysics Data System (ADS)

Biholar, Alexander Kenneth Casian

In Whisky Flat of west-central Nevada, northwest-striking faults in the Walker Lane curve to east-northeast orientations at the northern limits of the Mina deflection. This curve in strike results in the formation of ˜685 m deep depression bounded by north-south convex to the east range-front faults that at the apex of fault curvature are bisected at a high angle by a structural stepover. We use the vertical offset of a late Miocene erosional surface mapped in the highlands and inferred from gravity depth inversion in the basin to measure the magnitude of displacement on faults. A N65°W extensional axis determined through fault-slip inversion is used to constrain the direction in displacement models. Through the use of a forward rectilinear displacement model, we document that the complex array of faults is capable of developing with broadly contemporaneous displacements on all structures since the opening of the basin during the Pliocene.

Random walks on combs

NASA Astrophysics Data System (ADS)

Durhuus, Bergfinnur; Jonsson, Thordur; Wheater, John F.

2006-02-01

We develop techniques to obtain rigorous bounds on the behaviour of random walks on combs. Using these bounds, we calculate exactly the spectral dimension of random combs with infinite teeth at random positions or teeth with random but finite length. We also calculate exactly the spectral dimension of some fixed non-translationally invariant combs. We relate the spectral dimension to the critical exponent of the mass of the two-point function for random walks on random combs, and compute mean displacements as a function of walk duration. We prove that the mean first passage time is generally infinite for combs with anomalous spectral dimension.

Mechanism of the Exchange Reaction in HRAS from Multiscale Modeling

PubMed Central

Kapoor, Abhijeet; Travesset, Alex

2014-01-01

HRAS regulates cell growth promoting signaling processes by cycling between active (GTP-bound) and inactive (GDP-bound) states. Understanding the transition mechanism is central for the design of small molecules to inhibit the formation of RAS-driven tumors. Using a multiscale approach involving coarse-grained (CG) simulations, all-atom classical molecular dynamics (CMD; total of 3.02 µs), and steered molecular dynamics (SMD) in combination with Principal Component Analysis (PCA), we identified the structural features that determine the nucleotide (GDP) exchange reaction. We show that weakening the coupling between the SwitchI (residues 25–40) and SwitchII (residues 59–75) accelerates the opening of SwitchI; however, an open conformation of SwitchI is unstable in the absence of guanine nucleotide exchange factors (GEFs) and rises up towards the bound nucleotide to close the nucleotide pocket. Both I21 and Y32, play a crucial role in SwitchI transition. We show that an open SwitchI conformation is not necessary for GDP destabilization but is required for GDP/Mg escape from the HRAS. Further, we present the first simulation study showing displacement of GDP/Mg away from the nucleotide pocket. Both SwitchI and SwitchII, delays the escape of displaced GDP/Mg in the absence of GEF. Based on these results, a model for the mechanism of GEF in accelerating the exchange process is hypothesized. PMID:25272152

Structural basis for the ligand-binding specificity of fatty acid-binding proteins (pFABP4 and pFABP5) in gentoo penguin.

PubMed

Lee, Chang Woo; Kim, Jung Eun; Do, Hackwon; Kim, Ryeo-Ok; Lee, Sung Gu; Park, Hyun Ho; Chang, Jeong Ho; Yim, Joung Han; Park, Hyun; Kim, Il-Chan; Lee, Jun Hyuck

2015-09-11

Fatty acid-binding proteins (FABPs) are involved in transporting hydrophobic fatty acids between various aqueous compartments of the cell by directly binding ligands inside their β-barrel cavities. Here, we report the crystal structures of ligand-unbound pFABP4, linoleate-bound pFABP4, and palmitate-bound pFABP5, obtained from gentoo penguin (Pygoscelis papua), at a resolution of 2.1 Å, 2.2 Å, and 2.3 Å, respectively. The pFABP4 and pFABP5 proteins have a canonical β-barrel structure with two short α-helices that form a cap region and fatty acid ligand binding sites in the hydrophobic cavity within the β-barrel structure. Linoleate-bound pFABP4 and palmitate-bound pFABP5 possess different ligand-binding modes and a unique ligand-binding pocket due to several sequence dissimilarities (A76/L78, T30/M32, underlining indicates pFABP4 residues) between the two proteins. Structural comparison revealed significantly different conformational changes in the β3-β4 loop region (residues 57-62) as well as the flipped Phe60 residue of pFABP5 than that in pFABP4 (the corresponding residue is Phe58). A ligand-binding study using fluorophore displacement assays shows that pFABP4 has a relatively strong affinity for linoleate as compared to pFABP5. In contrast, pFABP5 exhibits higher affinity for palmitate than that for pFABP4. In conclusion, our high-resolution structures and ligand-binding studies provide useful insights into the ligand-binding preferences of pFABPs based on key protein-ligand interactions. Copyright © 2015 Elsevier Inc. All rights reserved.

Potential-specific structure at the hematite-electrolyte interface

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

McBriarty, Martin E.; Stubbs, Joanne; Eng, Peter

The atomic-scale structure of interfaces between metal oxides and aqueous electrolytes controls their catalytic, geochemical, and corrosion behavior. Measurements that probe these interfaces in situ provide important details of ion and solvent arrangements, but atomically precise structural models do not exist for common oxide-electrolyte interfaces far from equilibrium. Using a novel cell, we measured the structure of the hematite (a-Fe 2O 3) (110more » $$\\bar{2}$$)-electrolyte interface under controlled electrochemical bias using synchrotron crystal truncation rod X ray scattering. At increasingly cathodic potentials, charge-compensating protonation of surface oxygen groups increases the coverage of specifically bound water while adjacent water layers displace outwardly and became disordered. Returning to open circuit potential leaves the surface in a persistent metastable protonation state. The flux of current and ions at applied potential is thus regulated by a unique interfacial electrolyte environment, suggesting that electrical double layer models should be adapted to the dynamically changing interfacial structure far from equilibrium.« less

Development of seismic fragility curves for low-rise masonry infilled reinforced concrete buildings by a coefficient-based method

NASA Astrophysics Data System (ADS)

Su, Ray Kai Leung; Lee, Chien-Liang

2013-06-01

This study presents a seismic fragility analysis and ultimate spectral displacement assessment of regular low-rise masonry infilled (MI) reinforced concrete (RC) buildings using a coefficient-based method. The coefficient-based method does not require a complicated finite element analysis; instead, it is a simplified procedure for assessing the spectral acceleration and displacement of buildings subjected to earthquakes. A regression analysis was first performed to obtain the best-fitting equations for the inter-story drift ratio (IDR) and period shift factor of low-rise MI RC buildings in response to the peak ground acceleration of earthquakes using published results obtained from shaking table tests. Both spectral acceleration- and spectral displacement-based fragility curves under various damage states (in terms of IDR) were then constructed using the coefficient-based method. Finally, the spectral displacements of low-rise MI RC buildings at the ultimate (or nearcollapse) state obtained from this paper and the literature were compared. The simulation results indicate that the fragility curves obtained from this study and other previous work correspond well. Furthermore, most of the spectral displacements of low-rise MI RC buildings at the ultimate state from the literature fall within the bounded spectral displacements predicted by the coefficient-based method.

A Stack of Cards Rebuilt with Calculus

ERIC Educational Resources Information Center

Kazachkov, Alexander; Kireš, Marián

2017-01-01

Previous work covers building a tower from a stack of homogeneous rectangular plates, each with a maximum shift in displacement. We suggest using plates shaped as curvilinear triangles bounded by segments of power-law functions. The masses of the plates and the position of their center of mass are calculated and measured experimentally after…

Structures associated with strike-slip faults that bound landslide elements

USGS Publications Warehouse

Fleming, R.W.; Johnson, A.M.

1989-01-01

Large landslides are bounded on their flanks and on elements within the landslides by structures analogous to strike-slip faults. We observed the formation of thwse strike-slip faults and associated structures at two large landslides in central Utah during 1983-1985. The strike-slip faults in landslides are nearly vertical but locally may dip a few degrees toward or away from the moving ground. Fault surfaces are slickensided, and striations are subparallel to the ground surface. Displacement along strike-slip faults commonly produces scarps; scarps occur where local relief of the failure surface or ground surface is displaced and becomes adjacent to higher or lower ground, or where the landslide is thickening or thinning as a result of internal deformation. Several types of structures are formed at the ground surface as a strike-slip fault, which is fully developed at some depth below the ground surface, propagates upward in response to displacement. The simplest structure is a tension crack oriented at 45?? clockwise or counterclockwise from the trend of an underlying right- or left-lateral strike-slip fault, respectively. The tension cracks are typically arranged en echelon with the row of cracks parallel to the trace of the underlying strike-slip fault. Another common structure that forms above a developing strike-slip fault is a fault segment. Fault segments are discontinuous strike-slip faults that contain the same sense of slip but are turned clockwise or counterclockwise from a few to perhaps 20?? from the underlying strike-slip fault. The fault segments are slickensided and striated a few centimeters below the ground surface; continued displacement of the landslide causes the fault segments to open and a short tension crack propagates out of one or both ends of the fault segments. These structures, open fault segments containing a short tension crack, are termed compound cracks; and the short tension crack that propagates from the tip of the fault segment is typically oriented 45?? to the trend of the underlying fault. Fault segments are also typically arranged en echelon above the upward-propagating strike-slip fault. Continued displacement of the landslide causes the ground to buckle between the tension crack portions of the compound cracks. Still more displacement produces a thrust fault on one or both limbs of the buckle fold. These compressional structures form at right angles to the short tension cracks at the tips of the fault segments. Thus, the compressional structures are bounded on their ends by one face of a tension crack and detached from underlying material by thrusting or buckling. The tension cracks, fault segments, compound cracks, folds, and thrusts are ephemeral; they are created and destroyed with continuing displacement of the landslide. Ultimately, the structures are replaced by a throughgoing strike-slip fault. At one landslide, we observed the creation and destruction of the ephemeral structures as the landslide enlarged. Displacement of a few centimeters to about a decimeter was sufficient to produce scattered tension cracks and fault segments. Sets of compound cracks with associated folds and thrusts were produced by displacements of up to 1 m, and 1 to 2 m of displacement was required to produce a throughgoing strike-slip fault. The type of first-formed structure above an upward-propagating strike-slip fault is apparently controlled by the rheology of the material. Brittle material such as dry topsoil or the compact surface of a gravel road produces echelon tension cracks and sets of tension cracks and compressional structures, wherein the cracks and compressional structures are normal to each other and 45?? to the strike-slip fault at depth. First-formed structures in more ductile material such as moist cohesive soil are fault segments. In very ductile material such as soft clay and very wet soil in swampy areas, the first-formed structure is a throughgoing strike-slip fault. There are othe

Internal state variable approach for predicting stiffness reductions in fibrous laminated composites with matrix cracks

NASA Technical Reports Server (NTRS)

Lee, Jong-Won; Allen, D. H.; Harris, C. E.

1989-01-01

A mathematical model utilizing the internal state variable concept is proposed for predicting the upper bound of the reduced axial stiffnesses in cross-ply laminates with matrix cracks. The axial crack opening displacement is explicitly expressed in terms of the observable axial strain and the undamaged material properties. A crack parameter representing the effect of matrix cracks on the observable axial Young's modulus is calculated for glass/epoxy and graphite/epoxy material systems. The results show that the matrix crack opening displacement and the effective Young's modulus depend not on the crack length, but on its ratio to the crack spacing.

20007: Quantum particle displacement by a moving localized potential trap

NASA Astrophysics Data System (ADS)

Granot, E.; Marchewka, A.

2009-04-01

We describe the dynamics of a bound state of an attractive δ-well under displacement of the potential. Exact analytical results are presented for the suddenly moved potential. Since this is a quantum system, only a fraction of the initially confined wave function remains confined to the moving potential. However, it is shown that besides the probability to remain confined to the moving barrier and the probability to remain in the initial position, there is also a certain probability for the particle to move at double speed. A quasi-classical interpretation for this effect is suggested. The temporal and spectral dynamics of each one of the scenarios is investigated.

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

PubMed

Sullivan, Sarah M; Holyoak, Todd

2007-09-04

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

Fungal toxins bind to the URF13 protein in maize mitochondria and Escherichia coli.

PubMed Central

Braun, C J; Siedow, J N; Levings, C S

1990-01-01

Expression of the maize mitochondrial T-urf13 gene results in a sensitivity to a family of fungal pathotoxins and to methomyl, a structurally unrelated systemic insecticide. Similar effects of pathotoxins and methomyl are observed when T-urf13 is cloned and expressed in Escherichia coli. An interaction between these compounds and the membrane-bound URF13 protein permeabilizes the inner mitochondrial and bacterial plasma membranes. To understand the toxin-URF13 effects, we have investigated whether toxin specifically binds to the URF13 protein. Our studies indicate that toxin binds to the URF13 protein in maize mitochondria and in E. coli expressing URF13. Binding analysis in E. coli reveals cooperative toxin binding. A low level of specific toxin binding is also demonstrated in cms-T and cms-T-restored mitochondria; however, binding does not appear to be cooperative in maize mitochondria. Competition and displacement studies in E. coli demonstrate that toxin binding is reversible and that the toxins and methomyl compete for the same, or for overlapping, binding sites. Two toxin-insensitive URF13 mutants display a diminished capability to bind toxin in E. coli, which identifies residues of URF13 important in toxin binding. A third toxin-insensitive URF13 mutant shows considerable toxin binding in E. coli, demonstrating that toxin binding can occur without causing membrane permeabilization. Our results indicate that toxin-mediated membrane permeabilization only occurs when toxin or methomyl is bound to URF13. PMID:2136632

Tectonic geomorphology of large normal faults bounding the Cuzco rift basin within the southern Peruvian Andes

NASA Astrophysics Data System (ADS)

Byers, C.; Mann, P.

2015-12-01

The Cuzco basin forms a 80-wide, relatively flat valley within the High Andes of southern Peru. This larger basin includes the regional capital of Cuzco and the Urubamba Valley, or "Sacred Valley of the Incas" favored by the Incas for its mild climate and broader expanses of less rugged and arable land. The valley is bounded on its northern edge by a 100-km-long and 10-km-wide zone of down-to-the-south systems of normal faults that separate the lower area of the down-dropped plateau of central Peru and the more elevated area of the Eastern Cordillera foldbelt that overthrusts the Amazon lowlands to the east. Previous workers have shown that the normal faults are dipslip with up to 600 m of measured displacements, reflect north-south extension, and have Holocene displacments with some linked to destructive, historical earthquakes. We have constructed topographic and structural cross sections across the entire area to demonstrate the normal fault on a the plateau peneplain. The footwall of the Eastern Cordillera, capped by snowcapped peaks in excess of 6 km, tilts a peneplain surface northward while the hanging wall of the Cuzco basin is radially arched. Erosion is accelerated along the trend of the normal fault zone. As the normal fault zone changes its strike from east-west to more more northwest-southeast, normal displacement decreases and is replaced by a left-lateral strike-slip component.

Evaluation of the Transverse Oscillation Technique for Cardiac Phased Array Imaging: A Theoretical Study.

PubMed

Heyde, Brecht; Bottenus, Nick; D'hooge, Jan; Trahey, Gregg E

2017-02-01

The transverse oscillation (TO) technique can improve the estimation of tissue motion perpendicular to the ultrasound beam direction. TOs can be introduced using plane wave (PW) insonification and bilobed Gaussian apodization (BA) on receive (abbreviated as PWTO). Furthermore, the TO frequency of PWTO can be doubled after a heterodyning demodulation process is performed (abbreviated as PWTO*). This paper is concerned with identifying the limitations of the PWTO technique in the specific context of myocardial deformation imaging with phased arrays and investigating the conditions in which it remains advantageous over traditional focused (FOC) beamforming. For this purpose, several tissue phantoms were simulated using Field II, undergoing a wide range of displacement magnitudes and modes (lateral, axial, and rotational motions). The Cramer-Rao lower bound was used to optimize TO beamforming parameters and theoretically predict the fundamental tracking performance limits associated with the FOC, PWTO, and PWTO* beamforming scenarios. This framework was extended to also predict the performance for BA functions that are windowed by the physical aperture of the transducer, leading to higher lateral oscillations. It was found that windowed BA functions resulted in lower jitter errors compared with traditional BA functions. PWTO* outperformed FOC at all investigated signal-to-noise ratio (SNR) levels but only up to a certain displacement, with the advantage rapidly decreasing when the SNR increased. These results suggest that PWTO* improves lateral tracking performance, but only when interframe displacements remain relatively low. This paper concludes by translating these findings into a clinical environment by suggesting optimal scanner settings.

Hsp70 displaces small heat shock proteins from aggregates to initiate protein refolding.

PubMed

Żwirowski, Szymon; Kłosowska, Agnieszka; Obuchowski, Igor; Nillegoda, Nadinath B; Piróg, Artur; Ziętkiewicz, Szymon; Bukau, Bernd; Mogk, Axel; Liberek, Krzysztof

2017-03-15

Small heat shock proteins (sHsps) are an evolutionary conserved class of ATP-independent chaperones that protect cells against proteotoxic stress. sHsps form assemblies with aggregation-prone misfolded proteins, which facilitates subsequent substrate solubilization and refolding by ATP-dependent Hsp70 and Hsp100 chaperones. Substrate solubilization requires disruption of sHsp association with trapped misfolded proteins. Here, we unravel a specific interplay between Hsp70 and sHsps at the initial step of the solubilization process. We show that Hsp70 displaces surface-bound sHsps from sHsp-substrate assemblies. This Hsp70 activity is unique among chaperones and highly sensitive to alterations in Hsp70 concentrations. The Hsp70 activity is reflected in the organization of sHsp-substrate assemblies, including an outer dynamic sHsp shell that is removed by Hsp70 and a stable core comprised mainly of aggregated substrates. Binding of Hsp70 to the sHsp/substrate core protects the core from aggregation and directs sequestered substrates towards refolding pathway. The sHsp/Hsp70 interplay has major impact on protein homeostasis as it sensitizes substrate release towards cellular Hsp70 availability ensuring efficient refolding of damaged proteins under favourable folding conditions. © 2017 The Authors.

Normal-faulting slip maxima and stress-drop variability: a geological perspective

USGS Publications Warehouse

Hecker, S.; Dawson, T.E.; Schwartz, D.P.

2010-01-01

We present an empirical estimate of maximum slip in continental normal-faulting earthquakes and present evidence that stress drop in intraplate extensional environments is dependent on fault maturity. A survey of reported slip in historical earthquakes globally and in latest Quaternary paleoearthquakes in the Western Cordillera of the United States indicates maximum vertical displacements as large as 6–6.5 m. A difference in the ratio of maximum-to-mean displacements between data sets of prehistoric and historical earthquakes, together with constraints on bias in estimates of mean paleodisplacement, suggest that applying a correction factor of 1.4±0.3 to the largest observed displacement along a paleorupture may provide a reasonable estimate of the maximum displacement. Adjusting the largest paleodisplacements in our regional data set (~6 m) by a factor of 1.4 yields a possible upper-bound vertical displacement for the Western Cordillera of about 8.4 m, although a smaller correction factor may be more appropriate for the longest ruptures. Because maximum slip is highly localized along strike, if such large displacements occur, they are extremely rare. Static stress drop in surface-rupturing earthquakes in the Western Cordillera, as represented by maximum reported displacement as a fraction of modeled rupture length, appears to be larger on normal faults with low cumulative geologic displacement (<2 km) and larger in regions such as the Rocky Mountains, where immature, low-throw faults are concentrated. This conclusion is consistent with a growing recognition that structural development influences stress drop and indicates that this influence is significant enough to be evident among faults within a single intraplate environment.

Ovine cardiac Na,K-ATPase: isolation by means of selective solubilization in Lubrol and the effect of 1 alpha,2 alpha-epoxyscillirosidin on this enzyme.

PubMed

Venter, P A; Naudé, R J; Oelofsen, W; Swan, G E

1997-01-01

The inhibition of cardiac Na,K-ATPase by 1 alpha,2 alpha-epoxyscillirosidin is the principal cause of poisoning of cattle by the tulip, Homeria pallida. The ultimate goals of this study were to study the interaction between 1 alpha,2 alpha-epoxyscillirosidin and ovine Na,K-ATPase by means of inhibition and displacement binding studies. Ovine cardiac Na,K-ATPase was isolated in membrane-bound form by means of deoxycholate treatment, high-speed ultracentrifugation, NaI treatment and selective solubilization in Lubrol. The inhibition of ovine cardiac and commercial porcine cerebral cortex Na,K-ATPase by 1 alpha,2 alpha-epoxyscilirosidin and ouabain was studied using a discontinuous Na,K-ATPase assay. The binding of 1 alpha,2 alpha-epoxyscillirosidin, ouabain and digoxin to the above enzymes was compared using a displacement binding assay with [3H] oubain. The Lubrol-solubilized ovine cardiac Na,K-ATPase showed a specific activity of 0.3 U/mg with no ouabain insensitive activity. I50 values of 2.1 x 10(-8) and 2.7 x 10(-8) were obtained for the inhibition of this enzyme by 1 alpha,2 alpha-epoxyscillirosidin and ouabain, respectively. 1 alpha,2 alpha-Epoxyscillirosidin has a much higher KD value (1.5 x 10(-7) M), however, than ouabain (9.5 x 10(-9) M) and digoxin (1.7 x 10(-8) M) in displacement binding studies with [3H]ouabain. 1 alpha,2 alpha-Epoxyscillirosidin is a potent inhibitor of ovine cardiac Na,K-ATPase and is a slightly stronger inhibitor of the enzyme than ouabain. The anomalous result for the displacement of 1 alpha,2 alpha-epoxyscillirosidin from its receptor is either a result of different affinities that K+ has for the enzyme ouabain and enzyme-1 alpha,2 alpha-epoxyscillirosidin complexes or because of different complex stabilities of these complexes.

Direct modification and regulation of a nuclear receptor-PIP2 complex by the nuclear inositol-lipid kinase IPMK

PubMed Central

Blind, Raymond D.; Suzawa, Miyuki; Ingraham, Holly A.

2012-01-01

Phosphatidylinositol (4,5)-bisphosphate (PIP2) is best known as a plasma membrane-bound regulatory lipid. While PIP2 and phosphoinositide-modifying enzymes coexist in the nucleus, their roles in the nucleus remain unclear. Here we show that the nuclear inositol polyphosphate multikinase (IPMK), which functions both as an inositol- and a PI3-kinase, interacts with the nuclear receptor SF-1 (NR5A1) and phosphorylates its bound ligand, PIP2. IPMK failed to recognize SF-1/PIP2 after blocking or displacing PIP2 from SF-1’s large hydrophobic pocket. In contrast to IPMK, p110 catalytic subunits of type 1 PI3-kinases were inactive on SF-1/PIP2. These and other in vitro analyses demonstrated specificity of IPMK for the SF-1/PIP2 protein/lipid complex. Once generated, SF-1/PIP3 is readily dephosphorylated by the lipid phosphatase PTEN. Importantly, decreasing IPMK or increasing PTEN expression greatly reduced SF-1 transcriptional activity. This ability of lipid kinases and phosphatases to alter the activity and directly remodel a non-membrane protein/lipid complex such SF-1/PIP2, establishes a new pathway for promoting lipid-mediated signaling in the nucleus. PMID:22715467

Substrate complexes of human dipeptidyl peptidase III reveal the mechanism of enzyme inhibition

PubMed Central

Kumar, Prashant; Reithofer, Viktoria; Reisinger, Manuel; Wallner, Silvia; Pavkov-Keller, Tea; Macheroux, Peter; Gruber, Karl

2016-01-01

Human dipeptidyl-peptidase III (hDPP III) is a zinc-dependent hydrolase cleaving dipeptides off the N-termini of various bioactive peptides. Thus, the enzyme is likely involved in a number of physiological processes such as nociception and is also implicated in several forms of cancer. We present high-resolution crystal structures of hDPP III in complex with opioid peptides (Met-and Leu-enkephalin, endomorphin-2) as well as with angiotensin-II and the peptide inhibitor IVYPW. These structures confirm the previously reported large conformational change of the enzyme upon ligand binding and show that the structure of the closed conformation is independent of the nature of the bound peptide. The overall peptide-binding mode is also conserved ensuring the correct positioning of the scissile peptide bond with respect to the catalytic zinc ion. The structure of the angiotensin-II complex shows, how longer peptides are accommodated in the binding cleft of hDPP III. Differences in the binding modes allow a distinction between real substrates and inhibitory peptides or “slow” substrates. The latter displace a zinc bound water molecule necessitating the energetically much less favoured anhydride mechanism as opposed to the favoured promoted-water mechanism. The structural data also form the necessary framework for the design of specific hDPP III inhibitors. PMID:27025154

[Study on the interaction of doxycycline with human serum albumin].

PubMed

Hu, Tao-Ying; Chen, Lin; Liu, Ying

2014-05-01

The present study was designed to investigate the interaction of doxycycline (DC) with human serum albumin (HSA) by the inner filter effects, displacement experiments and molecular docking methods, based on classic multi-spectroscopy. With fluorescence quenching method at 298 and 310 K, the binding constants Ka, were determined to be 2. 73 X 10(5) and 0. 74X 10(5) L mol-1, respectively, and there was one binding site between DC and HSA, indicating that the binding of DC to HSA was strong, and the quenching mechanism was a static quenching. The thermodynamic parameters (enthalpy change, AH and enthropy change, delta S) were calculated to be -83. 55 kJ mol-1 and -176. 31 J mol-1 K-1 via the Vant' Hoff equation, which indicated that the interaction of DC with HSA was driven mainly by hydrogen bonding and van der Waals forces. Based on the Föster's theory of non-radiation energy transfer, the specific binding distance between Trp-214 (acceptor) and DC (donor) was 4. 98 nm, which was similar to the result confirmed by molecular docking. Through displacement experiments, sub-domain IIA of HSA was assigned to possess the high-affinity binding site of DC. Three-dimensional fluorescence spectra indicated that the binding of DC to HSA induced the conformation change of HSA and increased the disclosure of some part of hydrophobic regions that had been buried before. The results of FTIR spectroscopy showed that DC bound to HSA led to the slight unfolding of the polypeptide chain of HSA. Furthermore, the binding details between DC and HSA were further confirmed by molecular docking methods, which revealed that DC was bound at sub-domain IIA through multiple interactions, such as hydrophobic effect, polar forces and pi-pi interactions. The experimental results provide theoretical basis and reliable data for the study of the interaction between small drug molecule and human serum albumin

Precipitation in Ni-Si during electron and ion irradiation

NASA Astrophysics Data System (ADS)

Lucas, G. E.; Zama, T.; Ishino, S.

1986-11-01

This study was undertaken to further investigate how the nature of the irradiation condition affects precipitation in a dilute Ni-Si system. Transmission electron microscopy (TEM) discs of a solution annealed Ni alloy containing 5 at% Si were irradiated with 400 keV Ar + ions, 200 keV He + ions and 1 MeV electrons at average displacement rates in the range 2 × 10 -5dpa/s to 2 × 10 -3dpa/s at temperatures in the range 25°C to 450°C. Samples irradiated with electrons were observed in situ in an HVEM, while ion irradiated specimens were examined in a TEM after irradiation. Precipitation of Ni 3Si was detected by the appearance of superlattice spots in the electron diffraction patterns. It was found that as the mass of the irradiating species increased, the lower bound temperature at which Ni 3Si precipitation was first observed increased. For electron irradiation, the lower bound temperature at 2 × 10 -3dpa/s was ˜125°C, whereas for 400 keV Ar + irradiation at a similar average displacement rate the lower boundary was approximately 325°C. This suggests that cascade disordering competes with radiation induced solute segregation.

Functional Analyses of the Plant Photosystem I–Light-Harvesting Complex II Supercomplex Reveal That Light-Harvesting Complex II Loosely Bound to Photosystem II Is a Very Efficient Antenna for Photosystem I in State II[W

PubMed Central

Galka, Pierre; Santabarbara, Stefano; Khuong, Thi Thu Huong; Degand, Hervé; Morsomme, Pierre; Jennings, Robert C.; Boekema, Egbert J.; Caffarri, Stefano

2012-01-01

State transitions are an important photosynthetic short-term response that allows energy distribution balancing between photosystems I (PSI) and II (PSII). In plants when PSII is preferentially excited compared with PSI (State II), part of the major light-harvesting complex LHCII migrates to PSI to form a PSI-LHCII supercomplex. So far, little is known about this complex, mainly due to purification problems. Here, a stable PSI-LHCII supercomplex is purified from Arabidopsis thaliana and maize (Zea mays) plants. It is demonstrated that LHCIIs loosely bound to PSII in State I are the trimers mainly involved in state transitions and become strongly bound to PSI in State II. Specific Lhcb1-3 isoforms are differently represented in the mobile LHCII compared with S and M trimers. Fluorescence analyses indicate that excitation energy migration from mobile LHCII to PSI is rapid and efficient, and the quantum yield of photochemical conversion of PSI-LHCII is substantially unaffected with respect to PSI, despite a sizable increase of the antenna size. An updated PSI-LHCII structural model suggests that the low-energy chlorophylls 611 and 612 in LHCII interact with the chlorophyll 11145 at the interface of PSI. In contrast with the common opinion, we suggest that the mobile pool of LHCII may be considered an intimate part of the PSI antenna system that is displaced to PSII in State I. PMID:22822202

The reaction pathway of membrane-bound rat liver mitochondrial monoamine oxidase

PubMed Central

Houslay, Miles D.; Tipton, Keith F.

1973-01-01

1. A preparation of a partly purified mitochondrial outer-membrane fraction suitable for kinetic investigations of monoamine oxidase is described. 2. An apparatus suitable for varying the O2 concentration in a spectrophotometer cuvette is described. 3. The reaction catalysed by the membrane-bound enzyme is shown to proceed by a double-displacement (Ping Pong) mechanism, and a formal mechanism is proposed. 4. KCN, NaN3, benzyl cyanide and 4-cyanophenol are shown to be reversible inhibitors of the enzyme. 5. The non-linear reciprocal plot obtained with impure preparations of benzylamine, which is typical of high substrate inhibition, is shown to be due to aldehyde contamination of the substrate. PMID:4778271

The upper bounds of reduced axial and shear moduli in cross-ply laminates with matrix cracks

NASA Technical Reports Server (NTRS)

Lee, Jong-Won; Allen, D. H.; Harris, C. E.

1991-01-01

The present study proposes a mathematical model utilizing the internal state variable concept for predicting the upper bounds of the reduced axial and shear stiffnesses in cross-ply laminates with matrix cracks. The displacement components at the matrix crack surfaces are explicitly expressed in terms of the observable axial and shear strains and the undamaged material properties. The reduced axial and shear stiffnesses are predicted for glass/epoxy and graphite/epoxy laminates. Comparison of the model with other theoretical and experimental studies is also presented to confirm direct applicability of the model to angle-ply laminates with matrix cracks subjected to general in-plane loading.

1,2,6-Thiadiazinones as Novel Narrow Spectrum Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CaMKK2) Inhibitors.

PubMed

Asquith, Christopher R M; Godoi, Paulo H; Couñago, Rafael M; Laitinen, Tuomo; Scott, John W; Langendorf, Christopher G; Oakhill, Jonathan S; Drewry, David H; Zuercher, William J; Koutentis, Panayiotis A; Willson, Timothy M; Kalogirou, Andreas S

2018-05-19

We demonstrate for the first time that 4 H -1,2,6-thiadiazin-4-one (TDZ) can function as a chemotype for the design of ATP-competitive kinase inhibitors. Using insights from a co-crystal structure of a 3,5-bis(arylamino)-4 H -1,2,6-thiadiazin-4-one bound to calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2), several analogues were identified with micromolar activity through targeted displacement of bound water molecules in the active site. Since the TDZ analogues showed reduced promiscuity compared to their 2,4-dianilinopyrimidine counter parts, they represent starting points for development of highly selective kinase inhibitors.

A murine host cell factor required for nicking of the dimer bridge of MVM recognizes two CG nucleotides displaced by 10 basepairs.

PubMed

Liu, Q; Astell, C R

1996-10-01

During replication of the minute virus of mice (MVM) genome, a dimer replicative form (RF) intermediate is resolved into two monomer RF molecules in such a way as to retain a unique sequence within the left hand hairpin terminus of the viral genome. Although the proposed mechanism for resolution of the dimer RF remains uncertain, it likely involves site-specific nicking of the dimer bridge. The RF contains two double-stranded copies of the viral genome joined by the extended 3' hairpin. Minor sequence asymmetries within the 3' hairpin allow the two halves of the dimer bridge to be distinguished. The A half contains the sequence [sequence: see text], whereas the B half contains the sequence [sequence: see text]. Using an in vitro assay, we show that only the B half of the MVM dimer bridge is nicked site-specifically when incubated with crude NS-1 protein (expressed in insect cells) and mouse LA9 cellular extract. When highly purified NS-1, the major nonstructural protein of MVM, is used in this nicking reaction, there is an absolute requirement for the LA9 cellular extract, suggesting a cellular factor (or factors) is (are) required. A series of mutations were created in the putative host factor binding region (HFBR) on the B half of the MVM dimer bridge adjacent to the NS-1 binding site. Nicking assays of these B half mutants showed that two CG motifs displaced by 10 nucleotides are important for nicking. Gel mobility shift assays demonstrated that a host factor(s) can bind to the HFBR of the B half of the dimer bridge and efficient binding depends on the presence of both CG motifs. Competitor DNA containing the wild-type HFBR sequence is able to specifically inhibit nicking of the B half, indicating that the host factor(s) bound to the HFBR is(are) essential for site-specific nicking to occur.

Quantitative analysis of PEG-functionalized colloidal gold nanoparticles using charged aerosol detection.

PubMed

Smith, Mackensie C; Crist, Rachael M; Clogston, Jeffrey D; McNeil, Scott E

2015-05-01

Surface characteristics of a nanoparticle, such as functionalization with polyethylene glycol (PEG), are critical to understand and achieve optimal biocompatibility. Routine physicochemical characterization such as UV-vis spectroscopy (for gold nanoparticles), dynamic light scattering, and zeta potential are commonly used to assess the presence of PEG. However, these techniques are merely qualitative and are not sensitive enough to distinguish differences in PEG quantity, density, or presentation. As an alternative, two methods are described here which allow for quantitative measurement of PEG on PEGylated gold nanoparticles. The first, a displacement method, utilizes dithiothreitol to displace PEG from the gold surface. The dithiothreitol-coated gold nanoparticles are separated from the mixture via centrifugation, and the excess dithiothreitol and dissociated PEG are separated through reversed-phase high-performance liquid chromatography (RP-HPLC). The second, a dissolution method, utilizes potassium cyanide to dissolve the gold nanoparticles and liberate PEG. Excess CN(-), Au(CN)2 (-), and free PEG are separated using RP-HPLC. In both techniques, the free PEG can be quantified against a standard curve using charged aerosol detection. The displacement and dissolution methods are validated here using 2-, 5-, 10-, and 20-kDa PEGylated 30-nm colloidal gold nanoparticles. Further value in these techniques is demonstrated not only by quantitating the total PEG fraction but also by being able to be adapted to quantitate the free unbound PEG and the bound PEG fractions. This is an important distinction, as differences in the bound and unbound PEG fractions can affect biocompatibility, which would not be detected in techniques that only quantitate the total PEG fraction.

Sequential strand displacement beacon for detection of DNA coverage on functionalized gold nanoparticles.

PubMed

Paliwoda, Rebecca E; Li, Feng; Reid, Michael S; Lin, Yanwen; Le, X Chris

2014-06-17

Functionalizing nanomaterials for diverse analytical, biomedical, and therapeutic applications requires determination of surface coverage (or density) of DNA on nanomaterials. We describe a sequential strand displacement beacon assay that is able to quantify specific DNA sequences conjugated or coconjugated onto gold nanoparticles (AuNPs). Unlike the conventional fluorescence assay that requires the target DNA to be fluorescently labeled, the sequential strand displacement beacon method is able to quantify multiple unlabeled DNA oligonucleotides using a single (universal) strand displacement beacon. This unique feature is achieved by introducing two short unlabeled DNA probes for each specific DNA sequence and by performing sequential DNA strand displacement reactions. Varying the relative amounts of the specific DNA sequences and spacing DNA sequences during their coconjugation onto AuNPs results in different densities of the specific DNA on AuNP, ranging from 90 to 230 DNA molecules per AuNP. Results obtained from our sequential strand displacement beacon assay are consistent with those obtained from the conventional fluorescence assays. However, labeling of DNA with some fluorescent dyes, e.g., tetramethylrhodamine, alters DNA density on AuNP. The strand displacement strategy overcomes this problem by obviating direct labeling of the target DNA. This method has broad potential to facilitate more efficient design and characterization of novel multifunctional materials for diverse applications.

Identification of 6H1 as a P2Y purinoceptor: P2Y5.

PubMed

Webb, T E; Kaplan, M G; Barnard, E A

1996-02-06

We have determined the identity of the orphan G-protein coupled receptor cDNA, 6H1, present in activated chicken T cells, as a subtype of P2Y purinoceptor. This identification is based on first on the degree of sequence identity shared with recently cloned members of the P2Y receptor family and second on the pharmacological profile. Upon transient expression in COS-7 cells the 6H1 receptor bound the radiolabel [35S]dATP alpha S specifically and with high affinity (Kd, 10 nM). This specific binding could be competitively displaced by a range of ligands active at P2 purinoceptors, with ATP being the most active (K (i)), 116 nM). Such competition studies have established the following rank order of activity: ATP ADP 2-methylthioATP alpha, beta-methylene ATP, UTP, thus confirming 6H1 as a member of the growing family of P2Y purinoceptors. As the fifth receptor of this type to be identified we suggest that it be named P2Y5.

46 CFR 170.174 - Specific applicability.

Code of Federal Regulations, 2013 CFR

2013-10-01

... REQUIREMENTS FOR ALL INSPECTED VESSELS Determination of Lightweight Displacement and Centers of Gravity § 170.174 Specific applicability. This subpart applies to each vessel for which the lightweight displacement...

46 CFR 170.174 - Specific applicability.

Code of Federal Regulations, 2010 CFR

2010-10-01

... REQUIREMENTS FOR ALL INSPECTED VESSELS Determination of Lightweight Displacement and Centers of Gravity § 170.174 Specific applicability. This subpart applies to each vessel for which the lightweight displacement...

46 CFR 170.174 - Specific applicability.

Code of Federal Regulations, 2012 CFR

2012-10-01

... REQUIREMENTS FOR ALL INSPECTED VESSELS Determination of Lightweight Displacement and Centers of Gravity § 170.174 Specific applicability. This subpart applies to each vessel for which the lightweight displacement...

46 CFR 170.174 - Specific applicability.

Code of Federal Regulations, 2014 CFR

2014-10-01

... REQUIREMENTS FOR ALL INSPECTED VESSELS Determination of Lightweight Displacement and Centers of Gravity § 170.174 Specific applicability. This subpart applies to each vessel for which the lightweight displacement...

46 CFR 170.174 - Specific applicability.

Code of Federal Regulations, 2011 CFR

2011-10-01

... REQUIREMENTS FOR ALL INSPECTED VESSELS Determination of Lightweight Displacement and Centers of Gravity § 170.174 Specific applicability. This subpart applies to each vessel for which the lightweight displacement...

Mechanical characterization of municipal solid waste from two waste dumps at Delhi, India.

PubMed

Ramaiah, B J; Ramana, G V; Datta, Manoj

2017-10-01

The article presents the physical and mechanical properties of the emplaced municipal solid waste (MSW) recovered from different locations of the Ghazipur and Okhla dumps both located at Delhi, India. Mechanical compressibility and shear strength of the collected MSW were evaluated using a 300×300mm direct shear (DS) shear box. Compression ratio (C c ') of MSW at these two dumps varied between 0.11 and 0.17 and is falling on the lower bound of the range (0.1-0.5) of the data reported in the literature for MSW. Low C c ' of MSW is attributed to the relatively low percentages of compressible elements such as textiles, plastics and paper, coupled with relatively high percentages of inert materials such as soil-like and gravel sized fractions. Shear strength of MSW tested is observed to be displacement dependent. The mobilized shear strength parameters i.e., the apparent cohesion intercept (c') and friction angle (ϕ') of MSW at these two dumps are best characterized by c'=13kPa and ϕ'=23° at 25mm displacement and c'=17kPa and ϕ'=34° at 55mm displacement and are in the range reported for MSW in the literature. A large database on the shear strength of MSW from 18 countries that includes: the experimental data from 277 large-scale DS tests (in-situ and laboratory) and the data from back analysis of 11 failed landfill slopes is statistically analyzed. Based on the analysis, a simple linear shear strength envelope, characterized by c'=17kPa and ϕ'=32°, is proposed for MSW for preliminary use in the absence of site-specific data for stability evaluation of the solid waste landfill under drained conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Smoothing of Fault Slip Surfaces by Scale Invariant Wear

NASA Astrophysics Data System (ADS)

Dascher-Cousineau, K.; Kirkpatrick, J. D.

2017-12-01

Fault slip surface roughness plays a determining role in the overall strength, friction, and dynamic behavior of fault systems. Previous wear models and field observations suggest that roughness decreases with increasing displacement. However, measurements have yet to isolate the effect of displacement from other possible controls, such as lithology or tectonic setting. In an effort to understand the effect of displacement, we present comprehensive qualitative and quantitative description of the evolution of fault slip surfaces in and around the San-Rafael Desert, S.E. Utah, United States. In the study area, faults accommodated regional extension at shallow (1 to 3 km) depth and are hosted in the massive, well-sorted, high-porosity Navajo and Entrada sandstones. Existing displacement profiles along with tight displacement controls readily measureable in the field, combined with uniform lithology and tectonic history, allowed us to isolate for the effect of displacement during the embryonic stages of faulting (0 to 60 m in displacement). Our field observations indicate a clear compositional and morphological progression from isolated joints or deformation bands towards smooth, continuous, and mirror-like fault slip surfaces with increasing displacement. We scanned pristine slip surfaces with a white light interferometer, a laser scanner, and a ground-based LiDAR. We produce and analyses more than 120 individual scans of fault slip surfaces. Results for the surfaces with the best displacement constraints indicate that roughness as defined by the power spectral density at any given length scale decreases with displacement according to a power law with an exponent of -1. Roughness measurements associated with only maximum constraints on displacements corroborate this result. Moreover, maximum roughness for any given fault is bounded by a primordial roughness corresponding to that of joint surfaces and deformation band edges. Building upon these results, we propose a multi-scale wear model to explain the evolution of faults with displacement. We suggest that together, asperity failure as a scale invariant process, and the stochastic strength of host rocks are consistent with qualitative and quantitative observational constraints made in this study.

Searching for displaced Higgs boson decays

NASA Astrophysics Data System (ADS)

Csáki, Csaba; Kuflik, Eric; Lombardo, Salvator; Slone, Oren

2015-10-01

We study a simplified model of the Standard Model (SM) Higgs boson decaying to a degenerate pair of scalars which travel a macroscopic distance before decaying to SM particles. This is the leading signal for many well-motivated solutions to the hierarchy problem that do not propose additional light colored particles. Bounds for displaced Higgs boson decays below 10 cm are found by recasting existing tracker searches from Run I. New tracker search strategies, sensitive to the characteristics of these models and similar decays, are proposed with sensitivities projected for Run II at √{s }=13 TeV . With 20 fb-1 of data, we find that Higgs branching ratios down to 2 ×1 0-4 can be probed for centimeter decay lengths.

Coseismic and initial postseismic deformation from the 2004 Parkfield, California, earthquake, observed by global positioning system, electronic distance meter, creepmeters, and borehole strainmeters

USGS Publications Warehouse

Langbein, J.; Murray, J.R.; Snyder, H.A.

2006-01-01

Global Positioning System (GPS), electronic distance meter, creepmeter, and strainmeter measurements spanning the M 6.0 Parkfield, California, earthquake are examined. Using these data from 100 sec through 9 months following the main-shock, the Omori's law, with rate inversely related to time, l/t p and p ranging between 0.7 and 1.3, characterizes the time-dependent deformation during the post-seismic period; these results are consistent with creep models for elastic solids. With an accurate function of postseismic response, the coseismic displacements can be estimated from the high-rate, 1-min sampling GPS; and the coseismic displacements are approximately 75% of those estimated from the daily solutions. Consequently, fault-slip models using daily solutions overestimate coseismic slip. In addition, at 2 months and at 8 months following the mainshock, postseismic displacements are modeled as slip on the San Andreas fault with a lower bound on the moment exceeding that of the coseismic moment.

Analysis of cell mechanics in single vinculin-deficient cells using a magnetic tweezer

NASA Technical Reports Server (NTRS)

Alenghat, F. J.; Fabry, B.; Tsai, K. Y.; Goldmann, W. H.; Ingber, D. E.

2000-01-01

A magnetic tweezer was constructed to apply controlled tensional forces (10 pN to greater than 1 nN) to transmembrane receptors via bound ligand-coated microbeadswhile optically measuring lateral bead displacements within individual cells. Use of this system with wild-type F9 embryonic carcinoma cells and cells from a vinculin knockout mouse F9 Vin (-/-) revealed much larger differences in the stiffness of the transmembrane integrin linkages to the cytoskeleton than previously reported using related techniques that measured average mechanical properties of large cell populations. The mechanical properties measured varied widely among cells, exhibiting an approximately log-normal distribution. The median lateral bead displacement was 2-fold larger in F9 Vin (-/-) cells compared to wild-type cells whereas the arithmetic mean displacement only increased by 37%. We conclude that vinculin serves a greater mechanical role in cells than previously reported and that this magnetic tweezer device may be useful for probing the molecular basis of cell mechanics within single cells. Copyright 2000 Academic Press.

Huge landslide blocks in the growth of piton de la fournaise, La réunion, and Kilauea volcano, Hawaii

USGS Publications Warehouse

Duffield, Wendell A.; Stieltjes, Laurent; Varet, Jacques

1982-01-01

Piton de la Fournaise, on the island of La Réunion, and Kilauea volcano, on the island of Hawaii, are active, basaltic shield volcanoes growing on the flanks of much larger shield volcanoes in intraplate tectonic environments. Past studies have shown that the average rate of magma production and the chemistry of lavas are quite similar for both volcanoes. We propose a structural similarity — specifically, that periodic displacement of parts of the shields as huge landslide blocks is a common mode of growth. In each instance, the unstable blocks are within a rift-zone-bounded, unbuttressed flank of the shield. At Kilauea, well-documented landslide blocks form relatively surficial parts of a much larger rift-zone-bounded block; scarps of the Hilina fault system mark the headwalls of the active blocks. At Fournaise, Hilina-like slump blocks are also present along the unbuttressed east coast of the volcano. In addition, however, the existence of a set of faults nested around the present caldera and northeast and southeast rift zones suggests that past chapters in the history of Fournaise included the slumping of entire rift-zone-bounded blocks themselves. These nested faults become younger to the east southeast and apparently record one of the effects of a migration of the focus of volcanism in that direction. Repeated dilation along the present set of northeast and southeast rift zones, most recently exemplified by an eruption in 1977, suggests that the past history of rift-zone-bounded slumping will eventually be repeated. The record provided by the succession of slump blocks on Fournaise is apparently at a relatively detailed part of a migration of magmatic focus that has advanced at least 30 km to the east-southeast from neighboring Piton des Neiges, an extinct Pliocene to Pleistocene volcano.?? 1982.

Integrating a DNA Strand Displacement Reaction with a Whispering Gallery Mode Sensor for Label-Free Mercury (II) Ion Detection.

PubMed

Wu, Fengchi; Wu, Yuqiang; Niu, Zhongwei; Vollmer, Frank

2016-07-29

Mercury is an extremely toxic chemical pollutant of our environment. It has attracted the world's attention due to its high mobility and the ease with which it accumulates in organisms. Sensitive devices and methods specific for detecting mercury ions are, hence, in great need. Here, we have integrated a DNA strand displacement reaction with a whispering gallery mode (WGM) sensor for demonstrating the detection of Hg(2+) ions. Our approach relies on the displacement of a DNA hairpin structure, which forms after the binding of mercury ions to an aptamer DNA sequence. The strand displacement reaction of the DNA aptamer provides highly specific and quantitative means for determining the mercury ion concentration on a label-free WGM sensor platform. Our approach also shows the possibility for manipulating the kinetics of a strand displacement reaction with specific ionic species.

Integrating a DNA Strand Displacement Reaction with a Whispering Gallery Mode Sensor for Label-Free Mercury (II) Ion Detection

PubMed Central

Wu, Fengchi; Wu, Yuqiang; Niu, Zhongwei; Vollmer, Frank

2016-01-01

Mercury is an extremely toxic chemical pollutant of our environment. It has attracted the world’s attention due to its high mobility and the ease with which it accumulates in organisms. Sensitive devices and methods specific for detecting mercury ions are, hence, in great need. Here, we have integrated a DNA strand displacement reaction with a whispering gallery mode (WGM) sensor for demonstrating the detection of Hg2+ ions. Our approach relies on the displacement of a DNA hairpin structure, which forms after the binding of mercury ions to an aptamer DNA sequence. The strand displacement reaction of the DNA aptamer provides highly specific and quantitative means for determining the mercury ion concentration on a label-free WGM sensor platform. Our approach also shows the possibility for manipulating the kinetics of a strand displacement reaction with specific ionic species. PMID:27483277

Single-particle trajectories reveal two-state diffusion-kinetics of hOGG1 proteins on DNA.

PubMed

Vestergaard, Christian L; Blainey, Paul C; Flyvbjerg, Henrik

2018-03-16

We reanalyze trajectories of hOGG1 repair proteins diffusing on DNA. A previous analysis of these trajectories with the popular mean-squared-displacement approach revealed only simple diffusion. Here, a new optimal estimator of diffusion coefficients reveals two-state kinetics of the protein. A simple, solvable model, in which the protein randomly switches between a loosely bound, highly mobile state and a tightly bound, less mobile state is the simplest possible dynamic model consistent with the data. It yields accurate estimates of hOGG1's (i) diffusivity in each state, uncorrupted by experimental errors arising from shot noise, motion blur and thermal fluctuations of the DNA; (ii) rates of switching between states and (iii) rate of detachment from the DNA. The protein spends roughly equal time in each state. It detaches only from the loosely bound state, with a rate that depends on pH and the salt concentration in solution, while its rates for switching between states are insensitive to both. The diffusivity in the loosely bound state depends primarily on pH and is three to ten times higher than in the tightly bound state. We propose and discuss some new experiments that take full advantage of the new tools of analysis presented here.

Quaternary displacement rates on the Meeman‐Shelby fault and Joiner ridge horst, eastern Arkansas: Results from coring Mississippi River alluvium

USGS Publications Warehouse

Ward, Alex; Counts, Ronald C.; Van Arsdale, Roy; Larsen, Daniel; Mahan, Shannon

2017-01-01

This research used coring and optically stimulated luminescence (OSL) dating of displaced, deeply buried Quaternary alluvium to determine vertical displacement rates for the Meeman‐Shelby fault and the Joiner ridge horst, two structures in northeastern Arkansas that have no modern seismicity associated with them. We drilled continuous cores of the entire alluvial section in the hanging wall of each structure, performed detailed core descriptions and analyses, and obtained three OSL ages from each core. The Meeman‐Shelby fault core consists of 36 m of 4.3–5.2‐ka Holocene alluvium overlying 4 m of 14.3‐ka Kennett alluvium that in turn overlies the upper part of Eocene Claiborne Group sediments at a depth of 41 m. Seismic reflection indicates that the basal (Kennett) alluvium at the Meeman‐Shelby fault is displaced ∼28  m across the Meeman‐Shelby fault, which equates to a time‐averaged vertical displacement rate of 2  mm/yr within the last 14.3 ka. The Joiner ridge horst core consists, in descending order, of 11 m of 6.3‐ka Holocene alluvium, 14 m of 11.5‐ka Morehouse alluvium, a paleosol, 6 m of Kennett alluvium, and 4 m of 20.3‐ka Sikeston alluvium that in turn overlies the upper part of Eocene Claiborne Group sediments at a depth of 36 m. Lignite exploration drilling conducted in the 1970s indicates that basal (Sikeston) alluvium is displaced ∼20  m across the eastern bounding fault of the Joiner ridge horst, resulting in a time‐averaged vertical displacement rate of ∼1  mm/yr within the last 20.3 ka. These late Quaternary displacement rates are comparable to time‐averaged displacement rates of faults within the active New Madrid seismic zone.

Prompt signals and displaced vertices in sparticle searches for next-to-minimal gauge-mediated supersymmetric models

DOE PAGES

Allanach, B. C.; Badziak, Marcin; Cottin, Giovanna; ...

2016-09-01

Here, we study the LHC phenomenology of the next-to-minimal model of gauge-mediated supersymmetry breaking, both for Run I and Run II. The Higgs phenomenology of the model is consistent with observations: a 125 GeV standard model-like Higgs which mixes with singlet-like state of mass around 90 GeV that provides a 2 \\sigma excess at LEP II. The model possesses regions of parameter space where a longer-lived lightest neutralino decays in the detector into a gravitino and a b-jet pair or a tau pair resulting in potential displaced vertex signatures. We investigate current bounds on sparticle masses and the discovery potentialmore » of the model, both via conventional searches and via searches for displaced vertices. The searches based on promptly decaying sparticles currently give a lower limit on the gluino mass 1080 GeV and could be sensitive up to 1900 GeV with 100 fb -1, whereas the current displaced vertex searches cannot probe this model due to b-quarks in the final state. We also show how the displaced vertex cuts might be relaxed in order to improve signal efficiency, while simultaneously applied prompt cuts reduce background, resulting in a much better sensitivity than either strategy alone and motivating a fully fledged experimental study.« less

Response of discrete linear systems to forcing functions with inequality constraints.

NASA Technical Reports Server (NTRS)

Michalopoulos, C. D.; Riley, T. A.

1972-01-01

An analysis is made of the maximum response of discrete, linear mechanical systems to arbitrary forcing functions which lie within specified bounds. Primary attention is focused on the complete determination of the forcing function which will engender maximum displacement to any particular mass element of a multi-degree-of-freedom system. In general, the desired forcing function is found to be a bang-bang type function, i.e., a function which switches from the maximum to the minimum bound and vice-versa at certain instants of time. Examples of two-degree-of-freedom systems, with and without damping, are presented in detail. Conclusions are drawn concerning the effect of damping on the switching times and the general procedure for finding these times is discussed.

Optimized tomography of continuous variable systems using excitation counting

NASA Astrophysics Data System (ADS)

Shen, Chao; Heeres, Reinier W.; Reinhold, Philip; Jiang, Luyao; Liu, Yi-Kai; Schoelkopf, Robert J.; Jiang, Liang

2016-11-01

We propose a systematic procedure to optimize quantum state tomography protocols for continuous variable systems based on excitation counting preceded by a displacement operation. Compared with conventional tomography based on Husimi or Wigner function measurement, the excitation counting approach can significantly reduce the number of measurement settings. We investigate both informational completeness and robustness, and provide a bound of reconstruction error involving the condition number of the sensing map. We also identify the measurement settings that optimize this error bound, and demonstrate that the improved reconstruction robustness can lead to an order-of-magnitude reduction of estimation error with given resources. This optimization procedure is general and can incorporate prior information of the unknown state to further simplify the protocol.

Model for Providing Displaced Workers' Services. Research Report.

ERIC Educational Resources Information Center

Anderson, B. Harold; Naylor, Mary Lou

This handbook presents a model that helps vocational educators and other individuals, institutions, and agencies plan programs to maintain displaced workers' dignity and economic security. Section 1 discusses identification of displaced workers. Section 2 offers guidelines for developing a profile for a specific group of displaced workers. A list…

Counter-Radicalization: Best Practices in the United States and Lessons Learned from Abroad

DTIC Science & Technology

2011-09-01

LEADERSHIP FROM THE ISLAMIC PERSPECTIVE Historically, Sigmund Freud is well known for his theoretical conceptualization regarding the role of the leader...in directing negative influence onto out-group targets that appear to have unrelated or contradictory values and beliefs. Freud further argued that...bound together (Newman, 2006, pp. 749–772). Displacement of aggression and intergroup dynamics, as emphasized by Freud , explains how groups can

Effects of competitive red blood cell binding and reduced hematocrit on the blood and plasma levels of (/sup 14/C)Indapamide in the rat

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

Lettieri, J.T.; Portelli, S.T.

1983-02-01

The effects of chlorthalidone and acetazolamide on the red blood cell binding of indapamide were investigated. Both drugs caused a substantial decrease in the amount of indapamide bound to the erythrocytes in vitro. This effect was demonstrated by a change in the indapamide blood/plasma ratio from approximately 6 in control samples, to a value of 1 when either of the displacing agents was added. Coadministration of acetazolamide with /sup 14/C-labeled indapamide to rats, resulted in a 5-fold drop in the blood levels of total radioactivity, relative to rats dosed with (/sup 14/C)indapamide alone. Concomitantly, there was a 2-fold increase inmore » the plasma levels of total radioactivity after acetazolamide coadministration. In rats whose hematocrits had been reduced by extensive bleeding, there were only minor alterations in the blood/plasma partitioning of (/sup 14/C)indapamide. Thus, chlorthalidone and acetazolamide were able to displace indapamide from erythrocytes in vitro and in vivo, possibly by competition at a carbonic anhydrase binding site. The pharmacokinetics of drugs which are extensively bound to erythrocytes may be significantly altered by the presence of other agents capable of competitive binding.« less

Impact of Enhanced Health Interventions for United States-Bound Refugees: Evaluating Best Practices in Migration Health.

PubMed

Mitchell, Tarissa; Lee, Deborah; Weinberg, Michelle; Phares, Christina; James, Nicola; Amornpaisarnloet, Kittisak; Aumpipat, Lalita; Cooley, Gretchen; Davies, Anita; Tin Shwe, Valerie Daw; Gajdadziev, Vasil; Gorbacheva, Olga; Khwan-Niam, Chutharat; Klosovsky, Alexander; Madilokkowit, Waritorn; Martin, Diana; Htun Myint, Naing Zaw; Yen Nguyen, Thi Ngoc; Nutman, Thomas B; O'Connell, Elise M; Ortega, Luis; Prayadsab, Sugunya; Srimanee, Chetdanai; Supakunatom, Wasant; Vesessmith, Vattanachai; Stauffer, William M

2018-03-01

With an unprecedented number of displaced persons worldwide, strategies for improving the health of migrating populations are critical. United States-bound refugees undergo a required overseas medical examination to identify inadmissible conditions (e.g., tuberculosis) 2-6 months before resettlement, but it is limited in scope and may miss important, preventable infectious, chronic, or nutritional causes of morbidity. We sought to evaluate the feasibility and health impact of diagnosis and management of such conditions before travel. We offered voluntary testing for intestinal parasites, anemia, and hepatitis B virus infection, to U.S.-bound refugees from three Thailand-Burma border camps. Treatment and preventive measures (e.g., anemia and parasite treatment, vaccination) were initiated before resettlement. United States refugee health partners received overseas results and provided post-arrival medical examination findings. During July 9, 2012 to November 29, 2013, 2,004 refugees aged 0.5-89 years enrolled. Among 463 participants screened for seven intestinal parasites overseas and after arrival, helminthic infections decreased from 67% to 12%. Among 118 with positive Strongyloides -specific antibody responses, the median fluorescent intensity decreased by an average of 81% after treatment. The prevalence of moderate-to-severe anemia (hemoglobin < 10 g/dL) was halved from 14% at baseline to 7% at departure (McNemar P = 0.001). All 191 (10%) hepatitis B-infected participants received counseling and evaluation; uninfected participants were offered vaccination. This evaluation demonstrates that targeted screening, treatment, and prevention services can be conducted during the migration process to improve the health of refugees before resettlement. With more than 250 million migrants globally, this model may offer insights into healthier migration strategies.

Impact of Enhanced Health Interventions for United States–Bound Refugees: Evaluating Best Practices in Migration Health

PubMed Central

Mitchell, Tarissa; Lee, Deborah; Weinberg, Michelle; Phares, Christina; James, Nicola; Amornpaisarnloet, Kittisak; Aumpipat, Lalita; Cooley, Gretchen; Davies, Anita; Tin Shwe, Valerie Daw; Gajdadziev, Vasil; Gorbacheva, Olga; Khwan-Niam, Chutharat; Klosovsky, Alexander; Madilokkowit, Waritorn; Martin, Diana; Htun Myint, Naing Zaw; Yen Nguyen, Thi Ngoc; Nutman, Thomas B.; O’Connell, Elise M.; Ortega, Luis; Prayadsab, Sugunya; Srimanee, Chetdanai; Supakunatom, Wasant; Vesessmith, Vattanachai; Stauffer, William M.

2018-01-01

Abstract. With an unprecedented number of displaced persons worldwide, strategies for improving the health of migrating populations are critical. United States–bound refugees undergo a required overseas medical examination to identify inadmissible conditions (e.g., tuberculosis) 2–6 months before resettlement, but it is limited in scope and may miss important, preventable infectious, chronic, or nutritional causes of morbidity. We sought to evaluate the feasibility and health impact of diagnosis and management of such conditions before travel. We offered voluntary testing for intestinal parasites, anemia, and hepatitis B virus infection, to U.S.-bound refugees from three Thailand–Burma border camps. Treatment and preventive measures (e.g., anemia and parasite treatment, vaccination) were initiated before resettlement. United States refugee health partners received overseas results and provided post-arrival medical examination findings. During July 9, 2012 to November 29, 2013, 2,004 refugees aged 0.5–89 years enrolled. Among 463 participants screened for seven intestinal parasites overseas and after arrival, helminthic infections decreased from 67% to 12%. Among 118 with positive Strongyloides-specific antibody responses, the median fluorescent intensity decreased by an average of 81% after treatment. The prevalence of moderate-to-severe anemia (hemoglobin < 10 g/dL) was halved from 14% at baseline to 7% at departure (McNemar P = 0.001). All 191 (10%) hepatitis B–infected participants received counseling and evaluation; uninfected participants were offered vaccination. This evaluation demonstrates that targeted screening, treatment, and prevention services can be conducted during the migration process to improve the health of refugees before resettlement. With more than 250 million migrants globally, this model may offer insights into healthier migration strategies. PMID:29260657

Estimation of Viscoelastic Properties of Cells Using Acoustic Tweezing Cytometry.

PubMed

Yang, Chunmei; Chen, Di; Hong, Xiaowei

2016-12-01

Recently developed acoustic tweezing cytometry uses ultrasound-responsive targeted microbubbles for biomechanical stimulation of live cells at the subcellular level. The purpose of this research was to estimate the viscoelastic characteristics of cells from the displacements of cell-bound microbubbles in response to ultrasound pulses on acoustic tweezing cytometry. Microbubbles were bound to NIH/3T3 fibroblasts and ATDC5 cells through an integrin-cytoskeleton linkage. The evolution of microbubble behaviors under irradiation by ultrasound pulses was captured by a high-speed camera and tracked by a customized algorithm. The total damping constant, stiffness, and rigidity of the cells were estimated by fitting the measured temporal displacement profiles to a Kelvin-Voigt-based model. The mean maximum displacement of the microbubbles attached to NIH/3T3 fibroblasts was much greater than that for ATDC5 cells. The mean fitted damping constant and stiffness ± SD for ATDC5 cells were 28.16 ± 7.08 mg/s and 0.5041 ± 0.1381 mN/m, respectively, and the values for NIH/3T3 fibroblasts were 13.12 ± 4.23 mg/s and 0.2591 ± 0.0715 mN/m. The rigidity for ATDC5 cells was 331.46 ± 106.50 MPa, whereas that for NIH/3T3 fibroblasts was 117.92 ± 34.83 MPa. The Arg-Gly-Asp-integrin-cytoskeleton system of NIH/3T3 fibroblasts appears to be softer than that of ATDC5 cells. The rigidity of ATDC5 cells was significantly greater than that of NIH/3T3 fibroblasts at the 95% confidence level. This strategy provides a novel way to determine the viscoelastic properties of the live cells. © 2016 by the American Institute of Ultrasound in Medicine.

On the Role of Water Models in Quantifying the Binding Free Energy of Highly Conserved Water Molecules in Proteins: The Case of Concanavalin A.

PubMed

Fadda, Elisa; Woods, Robert J

2011-10-11

The ability of ligands to displace conserved water molecules in protein binding sites is of significant interest in drug design and is particularly pertinent in the case of glycomimetic drugs. This concept was explored in previous work [ Clarke et al. J. Am. Chem. Soc. 2001 , 123 , 12238 - 12247 and Kadirvelraj et al. J. Am. Chem. Soc. 2008 , 130 , 16933 - 16942 ] for a highly conserved water molecule located in the binding site of the prototypic carbohydrate-binding protein Concanavalin A (Con A). A synthetic ligand was designed with the aim of displacing such water. While the synthetic ligand bound to Con A in an analogous manner to that of the natural ligand, crystallographic analysis demonstrated that it did not displace the conserved water. In order to quantify the affinity of this particular water for the Con A surface, we report here the calculated standard binding free energy for this water in both ligand-bound and free Con A, employing three popular water models: TIP3P, TIP4P, and TIP5P. Although each model was developed to perform well in simulations of bulk-phase water, the computed binding energies for the isolated water molecule displayed a high sensitivity to the model. Both molecular dynamics simulation and free energy results indicate that the choice of water model may greatly influence the characterization of surface water molecules as conserved (TIP5P) or not (TIP3P) in protein binding sites, an observation of considerable significance to rational drug design. Structural and theoretical aspects at the basis of the different behaviors are identified and discussed.

Improving Free-Piston Stirling Engine Specific Power

NASA Technical Reports Server (NTRS)

Briggs, Maxwell Henry

2014-01-01

This work uses analytical methods to demonstrate the potential benefits of optimizing piston and/or displacer motion in a Stirling Engine. Isothermal analysis was used to show the potential benefits of ideal motion in ideal Stirling engines. Nodal analysis is used to show that ideal piston and displacer waveforms are not optimal in real Stirling engines. Constrained optimization was used to identify piston and displacer waveforms that increase Stirling engine specific power.

Improving Free-Piston Stirling Engine Specific Power

NASA Technical Reports Server (NTRS)

Briggs, Maxwell H.

2015-01-01

This work uses analytical methods to demonstrate the potential benefits of optimizing piston and/or displacer motion in a Stirling engine. Isothermal analysis was used to show the potential benefits of ideal motion in ideal Stirling engines. Nodal analysis is used to show that ideal piston and displacer waveforms are not optimal in real Stirling engines. Constrained optimization was used to identify piston and displacer waveforms that increase Stirling engine specific power.

Tetrazepam: a benzodiazepine which dissociates sedation from other benzodiazepine activities. II. In vitro and in vivo interactions with benzodiazepine binding sites

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

Keane, P.E.; Bachy, A.; Morre, M.

1988-05-01

Tetrazepam is a 1,4-benzodiazepine (BZD) derivative which, in rodents, appears to have very little sedative and ataxic effects. In an attempt to identify the molecular mechanisms underlying this particular pharmacological profile we examined the interaction of tetrazepam with BZD binding sites. Tetrazepam interacted competitively with central and peripheral BZD binding sites and exhibited comparable affinities for both sites. Tetrazepam was approximately one-seventh as potent as diazepam at the central receptor and as potent as diazepam at the peripheral binding site. Tetrazepam did not distinguish type I from type II central BZD receptors, as evidenced by comparable affinities for the cerebellarmore » and hippocampal receptors. In vitro autoradiographic studies showed that tetrazepam displaced (3H)flunitrazepam from rat brain membranes without any clear regional specificity. Like all BZD receptor agonists, tetrazepam exhibited a gamma-aminobutyric acid shift, a photoaffinity shift and potentiated the binding of 35S-t-butyl-bicyclophosphorothionate to rat brain membranes. However, the latter effect was observed at relatively high concentrations of tetrazepam. In vivo, tetrazepam displaced specifically bound (3H)flunitrazepam from mouse brain (ID50, 37 mg/kg p.o. vs 3.5 mg/kg p.o. for diazepam) and from mouse kidney (ID50, 38 mg/kg p.o. vs. 21 mg/kg p.o. for diazepam). It is concluded that tetrazepam is a BZD receptor agonist; the molecular mechanisms which underly the low sedative potential of the drug cannot at present be explained by a particular interaction with either central or peripheral BZD binding sites, but may be related to the drug's relatively weak effect on 35S-t-butyl-bicyclophosphorothionate binding.« less

Functional and structural analysis of AT-specific minor groove binders that disrupt DNA–protein interactions and cause disintegration of the Trypanosoma brucei kinetoplast

PubMed Central

Millan, Cinthia R.; Acosta-Reyes, Francisco J.; Lagartera, Laura; Ebiloma, Godwin U.; Lemgruber, Leandro; Nué Martínez, J. Jonathan; Saperas, Núria

2017-01-01

Abstract Trypanosoma brucei, the causative agent of sleeping sickness (Human African Trypanosomiasis, HAT), contains a kinetoplast with the mitochondrial DNA (kDNA), comprising of >70% AT base pairs. This has prompted studies of drugs interacting with AT-rich DNA, such as the N-phenylbenzamide bis(2-aminoimidazoline) derivatives 1 [4-((4,5-dihydro-1H-imidazol-2-yl)amino)-N-(4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)benzamide dihydrochloride] and 2 [N-(3-chloro-4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)-4-((4,5-dihydro-1H-imidazol-2-yl)amino)benzamide] as potential drugs for HAT. Both compounds show in vitro effects against T. brucei and in vivo curative activity in a mouse model of HAT. The main objective was to identify their cellular target inside the parasite. We were able to demonstrate that the compounds have a clear effect on the S-phase of T. brucei cell cycle by inflicting specific damage on the kinetoplast. Surface plasmon resonance (SPR)–biosensor experiments show that the drug can displace HMG box-containing proteins essential for kDNA function from their kDNA binding sites. The crystal structure of the complex of the oligonucleotide d[AAATTT]2 with compound 1 solved at 1.25 Å (PDB-ID: 5LIT) shows that the drug covers the minor groove of DNA, displaces bound water and interacts with neighbouring DNA molecules as a cross-linking agent. We conclude that 1 and 2 are powerful trypanocides that act directly on the kinetoplast, a structure unique to the order Kinetoplastida. PMID:28637278

An invariance property of generalized Pearson random walks in bounded geometries

NASA Astrophysics Data System (ADS)

Mazzolo, Alain

2009-03-01

Invariance properties of random walks in bounded domains are a topic of growing interest since they contribute to improving our understanding of diffusion in confined geometries. Recently, limited to Pearson random walks with exponentially distributed straight paths, it has been shown that under isotropic uniform incidence, the average length of the trajectories through the domain is independent of the random walk characteristic and depends only on the ratio of the volume's domain over its surface. In this paper, thanks to arguments of integral geometry, we generalize this property to any isotropic bounded stochastic process and we give the conditions of its validity for isotropic unbounded stochastic processes. The analytical form for the traveled distance from the boundary to the first scattering event that ensures the validity of the Cauchy formula is also derived. The generalization of the Cauchy formula is an analytical constraint that thus concerns a very wide range of stochastic processes, from the original Pearson random walk to a Rayleigh distribution of the displacements, covering many situations of physical importance.

Are MUPs a Toxic Waste Disposal System?

PubMed

Kwak, Jae; Strasser, Eva; Luzynski, Ken; Thoß, Michaela; Penn, Dustin J

2016-01-01

Male house mice produce large quantities of major urinary proteins (MUPs), which function to bind and transport volatile pheromones, though they may also function as scavengers that bind and excrete toxic compounds ('toxic waste hypothesis'). In this study, we demonstrate the presence of an industrial chemical, 2,4-di-tert-butylphenol (DTBP), in the urine of wild-derived house mice (Mus musculus musculus). Addition of guanidine hydrochloride to male and female urine resulted in an increased release of DTBP. This increase was only observed in the high molecular weight fractions (HMWF; > 3 kDa) separated from male or female urine, suggesting that the increased release of DTBP was likely due to the denaturation of MUPs and the subsequent release of MUP-bound DTBP. Furthermore, when DTBP was added to a HMWF isolated from male urine, an increase in 2-sec-butyl-4,5-dihydrothiazole (SBT), the major ligand of MUPs and a male-specific pheromone, was observed, indicating that DTBP was bound to MUPs and displaced SBT. These results suggest that DTBP is a MUP ligand. Moreover, we found evidence for competitive ligand binding between DTBP and SBT, suggesting that males potentially face a tradeoff between eliminating toxic wastes versus transporting pheromones. Our findings support the hypothesis that MUPs bind and eliminate toxic wastes, which may provide the most important fitness benefits of excreting large quantities of these proteins.

Mathematical model of rod oscillations with account of material relaxation behaviour

NASA Astrophysics Data System (ADS)

Kudinov, I. V.; Kudinov, V. A.; Eremin, A. V.; Zhukov, V. V.

2018-03-01

Taking into account the bounded velocity of strains and deformations propagation in the formula given in the Hooke’s law, the authors have obtained the differential equation of rod damped oscillations that includes the first and the third time derivatives of displacement as well as the mixed derivative (with respect to space and time variables). Study of its precise analytical solution found by means of separation of variables has shown that rod recovery after being disturbed is accompanied by low-amplitude damped oscillations that occur at the start time and only within the range of positive displacement values. The oscillations amplitude decreases with increase of relaxation factor. Rod is recovered virtually without an oscillating process both in the limit and with any high values of the relaxation factor.

Significant Shear Preceded Rupture in the Oblique Gulf of California Rift

NASA Astrophysics Data System (ADS)

Bennett, S. E.; Oskin, M. E.

2011-12-01

Significant shear deformation during the early history of a rift may profoundly affect the efficiency and success of lithospheric rupture and formation of a new ocean basin. The active Gulf of California (GOC) rift is well suited to study the role of rift obliquity in continental rupture. Transtensional strain in the GOC is accommodated along en-echelon pull-apart basins bounded by dip-slip and oblique-slip faults and linked by strike-slip faults and accommodation zones. Lithospheric rupture is well documented at ca. 6 Ma when >90% of Pacific-North American relative plate motion localized into the GOC. In the northern GOC, the eastern rift margin of the Upper Delfín-Upper Tiburón rift segment preserves an onshore record of the earliest phase of this localization process. Two NW-striking shear zones bound this rift segment, spaced ~37 km apart. Our geologic mapping, paleomagnetic measurements, and geochronology of pre-rift and syn-rift volcanic and sedimentary rocks provide timing and displacement constraints for these shear zones. The Coastal Sonora Fault Zone, exposed on northeast Isla Tiburón and in adjacent coastal Sonora, helped form and then truncate transtensional non-marine basins beginning ca. 7 Ma. On northeast Isla Tiburón, Tertiary units do not match across the ~10 km long Yawassag fault, providing a minimum estimate for total dextral displacement. In coastal Sonora, we document ~12 km of discrete dextral displacement, clockwise block rotations up to 53°, and up to 75% extension that together accommodated 15.7 km of transtensional strain towards azimuth 294° over a 1 Myr period. These estimates do not include tens of kilometers of dextral displacement on the Sacrificio fault that bounds the NE side of this shear zone. The southern of the two shear zones is the La Cruz fault, which transects southern Isla Tiburón. Associated dextral transpression and transtension formed the elongate Southwest Isla Tiburón-Sauzal basin. This basin transitions from non-marine in the SE to marine in the NW where fossil-rich marine sandstone and conglomerate is underlain by a 6.7 ± 0.8 Ma tuff. The base of the marine basin displays ~1 km of dextral displacement, while Early Miocene volcanic and sedimentary rocks are offset tens of kilometers. This displacement history supports significant proto-Gulf shear along the La Cruz fault. Overall, our results suggest that significant shearing along strike-slip faults initiated by ca. 7 Ma, at least 1 Myr prior and proximal to the locus of continental rupture in the GOC. Thus far, this documents the easternmost and earliest phase of rift-related shear at this latitude. We hypothesize that progressive localization of dextral shear into a broader region of extension may act as a catalyst for lithospheric rupture. Such a configuration would resemble how the dextral Walker Lane has become embedded within the extensional Basin and Range Province. We envision that normal faults kinematically linked to strike-slip faults are able to localize crustal thinning and overcome negative feedback processes that otherwise lead to formation of wide rifts. Thus, shearing on strike-slip faults may have been a critical mechanism for strain localization and efficient lithospheric thinning that preceded and eventually led to continental rupture in the Gulf of California.

Probing the human estrogen receptor-α binding requirements for phenolic mono- and di-hydroxyl compounds: A combined synthesis, binding and docking study

PubMed Central

McCullough, Christopher; Neumann, Terrence S.; Gone, Jayapal Reddy; He, Zhengjie; Herrild, Christian; Wondergem, Julie; Pandey, Rajesh K.; Donaldson, William A.; Sem, Daniel S.

2014-01-01

Various estrogen analogs were synthesized and tested for binding to human ERα using a fluorescence polarization displacement assay. Binding affinity and orientation were also predicted using docking calculations. Docking was able to accurately predict relative binding affinity and orientation for estradiol, but only if a tightly bound water molecule bridging Arg394/Glu353 is present. Di-hydroxyl compounds sometimes bind in two orientations, which are flipped in terms of relative positioning of their hydroxyl groups. Di-hydroxyl compounds were predicted to bind with their aliphatic hydroxyl group interacting with His524 in ERα. One nonsteroid-based dihdroxyl compound was 1000-fold specific for ERβ over ERα, and was also 25-fold specific for agonist ERβ versus antagonist activity. Docking predictions suggest this specificity may be due to interaction of the aliphatic hydroxyl with His475 in the agonist form of ERβ, versus with Thr299 in the antagonist form. But, the presence of this aliphatic hydroxyl is not required in all compounds, since mono-hydroxyl (phenolic) compounds bind ERα with high affinity, via hydroxyl hydrogen bonding interactions with the ERα Arg394/Glu353/water triad, and van der Waals interactions with the rest of the molecule. PMID:24315190

High-Resolution Mapping of Changes in Histone-DNA Contacts of Nucleosomes Remodeled by ISW2

PubMed Central

Kassabov, Stefan R.; Henry, Nathalia M.; Zofall, Martin; Tsukiyama, Toshio; Bartholomew, Blaine

2002-01-01

The imitation switch (ISWI) complex from yeast containing the Isw2 and Itc1 proteins was shown to preferentially slide mononucleosomes with as little as 23 bp of linker DNA from the end to the center of DNA. The contacts of unique residues in the histone fold regions of H4, H2B, and H2A with DNA were determined with base pair resolution before and after chromatin remodeling by a site-specific photochemical cross-linking approach. The path of DNA and the conformation of the histone octamer in the nucleosome remodeled or slid by ISW2 were not altered, because after adjustment for the new translational position, the DNA contacts at specific sites in the histone octamer had not been changed. Maintenance of the canonical nucleosome structure after sliding was also demonstrated by DNA photoaffinity labeling of histone proteins at specific sites within the DNA template. In addition, nucleosomal DNA does not become more accessible during ISW2 remodeling, as assayed by restriction endonuclease cutting. ISW2 was also shown to have the novel capability of counteracting transcriptional activators by sliding nucleosomes through Gal4-VP16 bound initially to linker DNA and displacing the activator from DNA. PMID:12370299

Fractional diffusion on bounded domains

DOE PAGES

Defterli, Ozlem; D'Elia, Marta; Du, Qiang; ...

2015-03-13

We found that the mathematically correct specification of a fractional differential equation on a bounded domain requires specification of appropriate boundary conditions, or their fractional analogue. In this paper we discuss the application of nonlocal diffusion theory to specify well-posed fractional diffusion equations on bounded domains.

Unusually Strong Binding to the DNA Minor Groove by a Highly Twisted Benzimidazole-Diphenylether: Induced Fit and Bound Water†

PubMed Central

Tanious, Farial A.; Laine, William; Peixoto, Paul; Bailly, Christian; Goodwin, Kristie D.; Lewis, Mark A.; Long, Eric C.; Georgiadis, Millie M.; Tidwell, Richard R.; Wilson, W. David

2008-01-01

RT29 is a dicationic diamidine derivative that does not obey the classical “rules” for shape and functional group placement that are expected to result in strong binding and specific recognition of the DNA minor groove. The compound contains a benzimidazole-diphenyl ether core that is flanked by the amidine cations. The diphenyl ether is highly twisted and gives the entire compound too much curvature to fit well to the shape of the minor groove. DNaseI footprinting, fluorescence intercalator displacement studies and circular dichroism spectra, however, indicate that the compound is an AT specific minor groove binding agent. Even more surprisingly, quantitative biosensor-surface plasmon resonance and isothermal titration calorimetric results indicate that the compound binds with exceptional strength to certain AT sequences in DNA with a large negative enthalpy of binding. Crystallographic results for the DNA complex of RT29 compared to calculated results for the free compound show that the compound undergoes significant conformational changes to enhance its minor groove interactions. In addition, a water molecule is incorporated directly into the complex to complete the compound-DNA interface and it forms an essential link between the compound and base pair edges at the floor of the minor groove. The calculated ΔCp value for complex formation is substantially less than the experimentally observed value in support of water being an intrinsic part of the complex with a major contribution to the ΔCp value. Both the induced fit conformational changes of the compound and the bound water are essential for strong binding to DNA by RT29. PMID:17506529

Experimental and Numerical Analysis of Axially Compressed Circular Cylindrical Fiber-Reinforced Panels with Various Boundary Conditions.

DTIC Science & Technology

1981-10-01

Numerical predictions used in the compari- sons were obtained from the energy -based, finite-difference computer proqram CLAPP. Test specimens were clamped...edges V LONGITUDINAL STIFFENERS 45 I. Introduction 45 2. Stiffener Strain Energy 46 3. Stiffener Energy in Matrix Form 47 4. Displacement Continuity 49...that theoretical bifurcation loads predicted by the energy method represent upper bounds to the classical bifurcation loads associated with the test

Assessment of articular disc displacement of temporomandibular joint with ultrasound.

PubMed

Razek, Ahmed Abdel Khalek Abdel; Al Mahdy Al Belasy, Fouad; Ahmed, Wael Mohamed Said; Haggag, Mai Ahmed

2015-06-01

To assess pattern of articular disc displacement in patients with internal derangement (ID) of temporomandibular joint (TMJ) with ultrasound. Prospective study was conducted upon 40 TMJ of 20 patients (3 male, 17 female with mean age of 26.1 years) with ID of TMJ. They underwent high-resolution ultrasound and MR imaging of TMJ. The MR images were used as the gold standard for calculating sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of ultrasound for diagnosis of anterior or sideway displacement of the disc. The anterior displaced disc was seen in 26 joints at MR and 22 joints at ultrasound. The diagnostic efficacy of ultrasound for anterior displacement has sensitivity of 79.3 %, specificity of 72.7 %, accuracy of 77.5 %, PPV of 88.5 %, NPV of 57.1 %, PLR of 2.9 and NLR of 0.34. The sideway displacement of disc was seen in four joints at MR and three joints at ultrasound. The diagnostic efficacy of ultrasound for sideway displacement has a sensitivity of 75 %, specificity of 63.6 %, accuracy of 66.7 %, PPV of 42.8, NPV of 87.5 %, PLR of 2.06, and NLR of 0.39. We concluded that ultrasound is a non-invasive imaging modality used for assessment of anterior and sideway displacement of the articular disc in patients with ID of TMJ.

The nature of the binding between LSD and a 5-HT receptor

PubMed Central

Berridge, M.J.; Prince, W.T.

1974-01-01

1 (+)-Lysergic acid diethylamide (LSD) mimicked 5-hydroxytryptamine (5-HT) in its ability to stimulate fluid secretion, to change transepithelial and intracellular potentials as well as to increase the cyclic 3′,5′-adenosine monophosphate (cyclic AMP) concentrations of isolated salivary glands of Calliphora. 2 Unlike 5-HT, LSD disengages slowly from the receptor and fluid secretion continues despite repeated washing. 3 Both 5-HT and tryptamine prevented LSD from acting on the glands. 4 LSD bound to the receptor was slowly displaced when glands were treated with agonists (tryptamine) or antagonists (gramine). 5 The property of LSD which permits it to function as an agonist despite remaining tightly bound to the receptor is discussed as a possible basis for its profound effects within the central nervous system. PMID:4375525

DNA probes for monitoring dynamic and transient molecular encounters on live cell membranes

NASA Astrophysics Data System (ADS)

You, Mingxu; Lyu, Yifan; Han, Da; Qiu, Liping; Liu, Qiaoling; Chen, Tao; Sam Wu, Cuichen; Peng, Lu; Zhang, Liqin; Bao, Gang; Tan, Weihong

2017-05-01

Cells interact with the extracellular environment through molecules expressed on the membrane. Disruption of these membrane-bound interactions (or encounters) can result in disease progression. Advances in super-resolution microscopy have allowed membrane encounters to be examined, however, these methods cannot image entire membranes and cannot provide information on the dynamic interactions between membrane-bound molecules. Here, we show a novel DNA probe that can transduce transient membrane encounter events into readable cumulative fluorescence signals. The probe, which translocates from one anchor site to another, mimicking motor proteins, is realized through a toehold-mediated DNA strand displacement reaction. Using this probe, we successfully monitored rapid encounter events of membrane lipid domains using flow cytometry and fluorescence microscopy. Our results show a preference for encounters within the same lipid domains.

The ecological impact of land restoration and cleanup. Technical report

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

Not Available

1978-08-01

The report is concerned with the ecological impacts of specific cleanup treatment on the land where they were carried out. The cleanup procedures given apply equally to chemical or radioactive materials. Guidance is provided for cleanup procedures likely to be suggested by government, industry, or environmental groups. The basic types of cleanup procedures for removing or deactiving spilled contamination involve moving people and animals from the affected area, scraping and grading the contaminated soil into windrows, plowing the contamination under, or digging up the contamination and hauling it away. The report describes and evaluates the various land-type cleanup effects inmore » terms of impact of the techniques on the environment. Part I defines several natural ecosystems and some of their natural derivations. Part II presents managed ecosystems which are imposed on natural ecosystems and are no longer bound by the initial native ecosystem balances. Part III deals with avion and mammilian wild life displaced by cleanup.« less

A recombinant dromedary antibody fragment (VHH or nanobody) directed against human Duffy antigen receptor for chemokines.

PubMed

Smolarek, Dorota; Hattab, Claude; Hassanzadeh-Ghassabeh, Gholamreza; Cochet, Sylvie; Gutiérrez, Carlos; de Brevern, Alexandre G; Udomsangpetch, Rachanee; Picot, Julien; Grodecka, Magdalena; Wasniowska, Kazimiera; Muyldermans, Serge; Colin, Yves; Le Van Kim, Caroline; Czerwinski, Marcin; Bertrand, Olivier

2010-10-01

Fy blood group antigens are carried by the Duffy antigen receptor for chemokines (DARC), a red cells receptor for Plasmodium vivax broadly implicated in human health and diseases. Recombinant VHHs, or nanobodies, the smallest intact antigen binding fragment derivative from the heavy chain-only antibodies present in camelids, were prepared from a dromedary immunized against DARC N-terminal extracellular domain and selected for DARC binding. A described VHH, CA52, does recognize native DARC on cells. It inhibits P. vivax invasion of erythrocytes and displaces interleukin-8 bound to DARC. The targeted epitope overlaps the well-defined DARC Fy6 epitope. K (D) of CA52-DARC equilibrium is sub-nanomolar, hence ideal to develop diagnostic or therapeutic compounds. Immunocapture by immobilized CA52 yielded highly purified DARC from engineered K562 cells. This first report on a VHH with specificity for a red blood cell protein exemplifies VHHs' potentialities to target, to purify, and to modulate the function of cellular markers.

N- and C-terminal substance P fragments: differential effects on striatal [3H]substance P binding and NK1 receptor internalization.

PubMed

Michael-Titus, A T; Blackburn, D; Connolly, Y; Priestley, J V; Whelpton, R

1999-07-13

N- and C-terminal substance P (SP) fragments increase striatal dopamine outflow at nanomolar concentrations. This contrasts with their low affinity for NK1 receptors. To explore this discrepancy, we investigated the interaction of SP and SP fragments with NK1 sites in fresh striatal slices, the same model used in the functional studies on dopamine outflow. [3H]SP bound specifically to one site (Kd = 6.6 +/- 0.9 nM; Bmax = 12.6 +/- 0.7 fmol/mg protein). [3H]SP binding was displaced by SP (IC50 = 11.8 nM), but not by SP(1-7) or SP(5-11), up to 10 microM. In contrast, 10 nM SP(1-7) or SP(5-11) induced significant internalization of the NK1 receptor, similar to that induced by SP. We suggest that SP fragments have high affinity for an NK1 receptor conformer which is different from that labelled by [3H]SP.

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

Feng,L.; Gell, D.; Zhou, S.

Hemoglobin A (HbA), the oxygen delivery system in humans, comprises two alpha and two beta subunits. Free alpha-hemoglobin (alphaHb) is unstable, and its precipitation contributes to the pathophysiology of beta thalassemia. In erythrocytes, the alpha-hemoglobin stabilizing protein (AHSP) binds alphaHb and inhibits its precipitation. The crystal structure of AHSP bound to Fe(II)-alphaHb reveals that AHSP specifically recognizes the G and H helices of alphaHb through a hydrophobic interface that largely recapitulates the alpha1-beta1 interface of hemoglobin. The AHSP-alphaHb interactions are extensive but suboptimal, explaining why beta-hemoglobin can competitively displace AHSP to form HbA. Remarkably, the Fe(II)-heme group in AHSP boundmore » alphaHb is coordinated by the distal but not the proximal histidine. Importantly, binding to AHSP facilitates the conversion of oxy-alphaHb to a deoxygenated, oxidized [Fe(III)], nonreactive form in which all six coordinate positions are occupied. These observations reveal the molecular mechanisms by which AHSP stabilizes free alphaHb.« less

A potent peptidomimetic inhibitor of botulinum neurotoxin serotype A has a very different conformation than SNAP-25 substrate.

PubMed

Zuniga, Jorge E; Schmidt, James J; Fenn, Timothy; Burnett, James C; Araç, Demet; Gussio, Rick; Stafford, Robert G; Badie, Shirin S; Bavari, Sina; Brunger, Axel T

2008-10-08

Botulinum neurotoxin serotype A is the most lethal of all known toxins. Here, we report the crystal structure, along with SAR data, of the zinc metalloprotease domain of BoNT/A bound to a potent peptidomimetic inhibitor (K(i)=41 nM) that resembles the local sequence of the SNAP-25 substrate. Surprisingly, the inhibitor adopts a helical conformation around the cleavage site, in contrast to the extended conformation of the native substrate. The backbone of the inhibitor's P1 residue displaces the putative catalytic water molecule and concomitantly interacts with the "proton shuttle" E224. This mechanism of inhibition is aided by residue contacts in the conserved S1' pocket of the substrate binding cleft and by the induction of new hydrophobic pockets, which are not present in the apo form, especially for the P2' residue of the inhibitor. Our inhibitor is specific for BoNT/A as it does not inhibit other BoNT serotypes or thermolysin.

Training improves interobserver reliability for the diagnosis of scaphoid fracture displacement.

PubMed

Buijze, Geert A; Guitton, Thierry G; van Dijk, C Niek; Ring, David

2012-07-01

The diagnosis of displacement in scaphoid fractures is notorious for poor interobserver reliability. We tested whether training can improve interobserver reliability and sensitivity, specificity, and accuracy for the diagnosis of scaphoid fracture displacement on radiographs and CT scans. Sixty-four orthopaedic surgeons rated a set of radiographs and CT scans of 10 displaced and 10 nondisplaced scaphoid fractures for the presence of displacement, using a web-based rating application. Before rating, observers were randomized to a training group (34 observers) and a nontraining group (30 observers). The training group received an online training module before the rating session, and the nontraining group did not. Interobserver reliability for training and nontraining was assessed by Siegel's multirater kappa and the Z-test was used to test for significance. There was a small, but significant difference in the interobserver reliability for displacement ratings in favor of the training group compared with the nontraining group. Ratings of radiographs and CT scans combined resulted in moderate agreement for both groups. The average sensitivity, specificity, and accuracy of diagnosing displacement of scaphoid fractures were, respectively, 83%, 85%, and 84% for the nontraining group and 87%, 86%, and 87% for the training group. Assuming a 5% prevalence of fracture displacement, the positive predictive value was 0.23 in the nontraining group and 0.25 in the training group. The negative predictive value was 0.99 in both groups. Our results suggest training can improve interobserver reliability and sensitivity, specificity and accuracy for the diagnosis of scaphoid fracture displacement, but the improvements are slight. These findings are encouraging for future research regarding interobserver variation and how to reduce it further.

Predicting Displaceable Water Sites Using Mixed-Solvent Molecular Dynamics.

PubMed

Graham, Sarah E; Smith, Richard D; Carlson, Heather A

2018-02-26

Water molecules are an important factor in protein-ligand binding. Upon binding of a ligand with a protein's surface, waters can either be displaced by the ligand or may be conserved and possibly bridge interactions between the protein and ligand. Depending on the specific interactions made by the ligand, displacing waters can yield a gain in binding affinity. The extent to which binding affinity may increase is difficult to predict, as the favorable displacement of a water molecule is dependent on the site-specific interactions made by the water and the potential ligand. Several methods have been developed to predict the location of water sites on a protein's surface, but the majority of methods are not able to take into account both protein dynamics and the interactions made by specific functional groups. Mixed-solvent molecular dynamics (MixMD) is a cosolvent simulation technique that explicitly accounts for the interaction of both water and small molecule probes with a protein's surface, allowing for their direct competition. This method has previously been shown to identify both active and allosteric sites on a protein's surface. Using a test set of eight systems, we have developed a method using MixMD to identify conserved and displaceable water sites. Conserved sites can be determined by an occupancy-based metric to identify sites which are consistently occupied by water even in the presence of probe molecules. Conversely, displaceable water sites can be found by considering the sites which preferentially bind probe molecules. Furthermore, the inclusion of six probe types allows the MixMD method to predict which functional groups are capable of displacing which water sites. The MixMD method consistently identifies sites which are likely to be nondisplaceable and predicts the favorable displacement of water sites that are known to be displaced upon ligand binding.

Strongly nonlinear composite dielectrics: A perturbation method for finding the potential field and bulk effective properties

NASA Astrophysics Data System (ADS)

Blumenfeld, Raphael; Bergman, David J.

1991-10-01

A class of strongly nonlinear composite dielectrics is studied. We develop a general method to reduce the scalar-potential-field problem to the solution of a set of linear Poisson-type equations in rescaled coordinates. The method is applicable for a large variety of nonlinear materials. For a power-law relation between the displacement and the electric fields, it is used to solve explicitly for the value of the bulk effective dielectric constant ɛe to second order in the fluctuations of its local value. A simlar procedure for the vector potential, whose curl is the displacement field, yields a quantity analogous to the inverse dielectric constant in linear dielectrics. The bulk effective dielectric constant is given by a set of linear integral expressions in the rescaled coordinates and exact bounds for it are derived.

Computational investigation of the selectivity of salen and tetrahydrosalen compounds towards the tumor-associated hCA XII isozyme.

PubMed

Akdemir, Atilla; De Monte, Celeste; Carradori, Simone; Supuran, Claudiu T

2015-02-01

In previous work, 14 salen and tetrahydrosalen compounds have been synthesized and tested in enzyme inhibition assays against cytosolic human carbonic anhydrase isozymes I and II (hCA I and II) and tumor-associated isozymes IX and XII (hCA IX and XII). These compounds show selectivity against hCA XII over hCA I, II and IX. In this study, molecular modeling and docking studies were applied to understand this preference of the compounds for hCA XII. Most likely, the compounds can displace the zinc-bound water molecule of hCA XII to form a direct interaction with the Zn(2+) ion. In the other isozymes, the compounds might not be able to displace the water molecule nor are they expected to interact with the Zn(2+) ion.

The specific interaction of the photosensitizer methylene blue with acetylcholinesterase provides a model system for studying the molecular consequences of photodynamic therapy.

PubMed

Silman, Israel; Roth, Esther; Paz, Aviv; Triquigneaux, Mathilde M; Ehrenshaft, Marilyn; Xu, Yechun; Shnyrov, Valery L; Sussman, Joel L; Deterding, Leesa J; Ashani, Yacov; Mason, Ronald P; Weiner, Lev

2013-03-25

The photosensitizer, methylene blue (MB), generates singlet oxygen ((1)O2) that irreversibly inhibits Torpedo californica acetylcholinesterase (TcAChE). In the dark MB inhibits reversibly, binding being accompanied by a bathochromic shift that can be used to show its displacement by other reversible inhibitors binding to the catalytic 'anionic' subsite (CAS), the peripheral 'anionic' subsite (PAS), or bridging them. Data concerning both reversible and irreversible inhibition are here reviewed. MB protects TcAChE from thermal denaturation, and differential scanning calorimetry reveals a ~8 °C increase in the denaturation temperature. The crystal structure of the MB/TcAChE complex reveals a single MB stacked against W279 in the PAS, pointing down the gorge towards the CAS. The intrinsic fluorescence of the irreversibly inhibited enzyme displays new emission bands that can be ascribed to N'-formylkynurenine (NFK); this was indeed confirmed using anti-NFK antibodies. Mass spectroscopy revealed that two Trp residues, Trp84 in the CAS, and Trp279 in the PAS, were the only Trp residues, out of a total of 14, significantly modified by photo-oxidation, both being converted to NFK. In the presence of competitive inhibitors that displace MB from the gorge, their modification is completely prevented. Thus, photo-oxidative damage caused by MB involves targeted release of (1)O2 by the bound photosensitizer within the aqueous milieu of the active-site gorge. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Circular dichroism study of the interaction between mutagens and bilirubin bound to different binding sites of serum albumins

NASA Astrophysics Data System (ADS)

Orlov, Sergey; Goncharova, Iryna; Urbanová, Marie

Although recent investigations have shown that bilirubin not only has a negative role in the organism but also exhibits significant antimutagenic properties, the mechanisms of interactions between bilirubin and mutagens are not clear. In this study, interaction between bilirubin bound to different binding sites of mammalian serum albumins with structural analogues of the mutagens 2-aminofluorene, 2,7-diaminofluorene and mutagen 2,4,7-trinitrofluorenone were investigated by circular dichroism and absorption spectroscopy. Homological human and bovine serum albumins were used as chiral matrices, which preferentially bind different conformers of bilirubin in the primary binding sites and make it observable by circular dichroism. These molecular systems approximated a real system for the study of mutagens in blood serum. Differences between the interaction of bilirubin bound to primary and to secondary binding sites of serum albumins with mutagens were shown. For bilirubin bound to secondary binding sites with low affinity, partial displacement and the formation of self-associates were observed in all studied mutagens. The associates of bilirubin bound to primary binding sites of serum albumins are formed with 2-aminofluorene and 2,4,7-trinitrofluorenone. It was proposed that 2,7-diaminofluorene does not interact with bilirubin bound to primary sites of human and bovine serum albumins due to the spatial hindrance of the albumins binding domains. The spatial arrangement of the bilirubin bound to serum albumin along with the studied mutagens was modelled using ligand docking, which revealed a possibility of an arrangement of the both bilirubin and 2-aminofluorene and 2,4,7-trinitrofluorenone in the primary binding site of human serum albumin.

Chemo-mechanical pushing of proteins along single-stranded DNA.

PubMed

Sokoloski, Joshua E; Kozlov, Alexander G; Galletto, Roberto; Lohman, Timothy M

2016-05-31

Single-stranded (ss)DNA binding (SSB) proteins bind with high affinity to ssDNA generated during DNA replication, recombination, and repair; however, these SSBs must eventually be displaced from or reorganized along the ssDNA. One potential mechanism for reorganization is for an ssDNA translocase (ATP-dependent motor) to push the SSB along ssDNA. Here we use single molecule total internal reflection fluorescence microscopy to detect such pushing events. When Cy5-labeled Escherichia coli (Ec) SSB is bound to surface-immobilized 3'-Cy3-labeled ssDNA, a fluctuating FRET signal is observed, consistent with random diffusion of SSB along the ssDNA. Addition of Saccharomyces cerevisiae Pif1, a 5' to 3' ssDNA translocase, results in the appearance of isolated, irregularly spaced saw-tooth FRET spikes only in the presence of ATP. These FRET spikes result from translocase-induced directional (5' to 3') pushing of the SSB toward the 3' ssDNA end, followed by displacement of the SSB from the DNA end. Similar ATP-dependent pushing events, but in the opposite (3' to 5') direction, are observed with EcRep and EcUvrD (both 3' to 5' ssDNA translocases). Simulations indicate that these events reflect active pushing by the translocase. The ability of translocases to chemo-mechanically push heterologous SSB proteins along ssDNA provides a potential mechanism for reorganization and clearance of tightly bound SSBs from ssDNA.

Role of the AP2 β-Appendage Hub in Recruiting Partners for Clathrin-Coated Vesicle Assembly

PubMed Central

Burtey, Anne; Praefcke, Gerrit J. K; Peak-Chew, Sew-Yeu; Mills, Ian G; Benmerah, Alexandre; McMahon, Harvey T

2006-01-01

Adaptor protein complex 2 α and β-appendage domains act as hubs for the assembly of accessory protein networks involved in clathrin-coated vesicle formation. We identify a large repertoire of β-appendage interactors by mass spectrometry. These interact with two distinct ligand interaction sites on the β-appendage (the “top” and “side” sites) that bind motifs distinct from those previously identified on the α-appendage. We solved the structure of the β-appendage with a peptide from the accessory protein Eps15 bound to the side site and with a peptide from the accessory cargo adaptor β-arrestin bound to the top site. We show that accessory proteins can bind simultaneously to multiple appendages, allowing these to cooperate in enhancing ligand avidities that appear to be irreversible in vitro. We now propose that clathrin, which interacts with the β-appendage, achieves ligand displacement in vivo by self-polymerisation as the coated pit matures. This changes the interaction environment from liquid-phase, affinity-driven interactions, to interactions driven by solid-phase stability (“matricity”). Accessory proteins that interact solely with the appendages are thereby displaced to areas of the coated pit where clathrin has not yet polymerised. However, proteins such as β-arrestin (non-visual arrestin) and autosomal recessive hypercholesterolemia protein, which have direct clathrin interactions, will remain in the coated pits with their interacting receptors. PMID:16903783

Supramolecular Structures with Blood Plasma Proteins, Sugars and Nanosilica

NASA Astrophysics Data System (ADS)

Turov, V. V.; Gun'ko, V. M.; Galagan, N. P.; Rugal, A. A.; Barvinchenko, V. M.; Gorbyk, P. P.

Supramolecular structures with blood plasma proteins (albumin, immunoglobulin and fibrinogen (HPF)), protein/water/silica and protein/water/ silica/sugar (glucose, fructose and saccharose) were studied by NMR, adsorption, IR and UV spectroscopy methods. Hydration parameters, amounts of weakly and strongly bound waters and interfacial energy (γ S) were determined over a wide range of component concentrations. The γ S(C protein,C silica) graphs were used to estimate the energy of protein-protein, protein-surface and particle-particle interactions. It was shown that interfacial energy of self-association (γ as) of protein molecules depends on a type of proteins. A large fraction of water bound to proteins can be displaced by sugars, and the effect of disaccharide (saccharose) was greater than that of monosugars. Changes in the structural parameters of cavities in HPF molecules and complexes with HPF/silica nanoparticles filled by bound water were analysed using NMR-cryoporometry showing that interaction of proteins with silica leads to a significant decrease in the amounts of water bound to both protein and silica surfaces. Bionanocomposites with BSA/nanosilica/sugar can be used to influence states of living cells and tissues after cryopreservation or other treatments. It was shown that interaction of proteins with silica leads to strong decrease in the volume of all types of internal cavities filled by water.

Binding of Dissolved Strontium by Micrococcus luteus

PubMed Central

Faison, Brendlyn D.; Cancel, Carmen A.; Lewis, Susan N.; Adler, Howard I.

1990-01-01

Resting cells of Micrococcus luteus have been shown to remove strontium (Sr) from dilute aqueous solutions of SrCl2 at pH 7. Loadings of 25 mg of Sr per g of cell dry weight were achieved by cells exposed to a solution containing 50 ppm (mg/liter) of Sr. Sr binding occurred in the absence of nutrients and did not require metabolic activity. Initial binding was quite rapid (<0.5 h), although a slow, spontaneous release of Sr was observed over time. Sr binding was inhibited in the presence of polyvalent cations but not monovalent cations. Ca and Sr were bound preferentially over all other cations tested. Sr-binding activity was localized on the cell envelope and was sensitive to various chemical and physical pretreatments. Bound Sr was displaced by divalent ions or by H+. Other monovalent ions were less effective. Bound Sr was also removed by various chelating agents. It was concluded that Sr binding by M. luteus is a reversible equilibrium process. Both ion exchange mediated by acidic cell surface components and intracellular uptake may be involved in this activity. PMID:16348370

Real-time biochemical assay telemetering system

NASA Technical Reports Server (NTRS)

Kern, Roger G. (Inventor); Mintz, Frederick W. (Inventor); Richards, Gil F. (Inventor); Kidwell, David A. (Inventor)

1999-01-01

The present invention is an apparatus and a method of detecting a chemical released by perspiration, typically through sweat and broadcasting the detection to a receiver. The chemical may be a drug of abuse. The device which is attached to the skin of a subject contains labeled antibodies or label containing microspheres attached to antibodies. The labeled antibodies are bound to solid phase drug via antigen-antibody interaction. These labeled antibodies are displaced from the solid phase support to which they are bound by free drug molecules in the perspiration. These labeled antibodies then migrate through a spacer layer and are trapped by a layer containing a suitable selective binding material. The label is illuminated or excited by a light source and detected by a photodetector. The signal can be recorded, or transmitted to a remote radio monitor.

DNA probe for monitoring dynamic and transient molecular encounters on live cell membranes

PubMed Central

You, Mingxu; Lyu, Yifan; Han, Da; Qiu, Liping; Liu, Qiaoling; Chen, Tao; Wu, Cuichen Sam; Peng, Lu; Zhang, Liqin; Bao, Gang; Tan, Weihong

2017-01-01

Cells interact with the extracellular environment through molecules expressed on the membrane. Disruption of these membrane-bound interactions (or encounters) can result in disease progression. Advances in super-resolution microscopy have allowed membrane encounters to be examined, however, these methods cannot image entire membranes and cannot provide information on the dynamic interactions between membrane-bound molecules. Here, we show a novel DNA probe that can transduce transient membrane encounter events into readable cumulative fluorescence signals. The probe, which translocates from one anchor site to another, such as motor proteins, is realized through a toehold-mediated DNA strand displacement reaction. Using this probe, we successfully monitored rapid encounter events of membrane lipid domains using flow cytometry and fluorescence microscopy. Our results show a preference for encounters within different lipid domains. PMID:28319616

Sequence-dependent effects in drug-DNA interaction: the crystal structure of Hoechst 33258 bound to the d(CGCAAATTTGCG)2 duplex.

PubMed Central

Spink, N; Brown, D G; Skelly, J V; Neidle, S

1994-01-01

The bis-benzimidazole drug Hoechst 33258 has been co-crystallized with the dodecanucleotide sequence d(CGCAAATTTGCG)2. The structure has been solved by molecular replacement and refined to an R factor of 18.5% for 2125 reflections collected on a Xentronics area detector. The drug is bound in the minor groove, at the five base-pair site 5'-ATTTG and is in a unique orientation. This is displaced by one base pair in the 5' direction compared to previously-determined structures of this drug with the sequence d(CGCGAATTCGCG)2. Reasons for this difference in behaviour are discussed in terms of several sequence-dependent structural features of the DNA, with particular reference to differences in propeller twist and minor-groove width. Images PMID:7515488

Prophylactic and therapeutic vaccination with carrier-bound Bet v 1 peptides lacking allergen-specific T cell epitopes reduces Bet v 1-specific T cell responses via blocking antibodies in a murine model for birch pollen allergy.

PubMed

Linhart, B; Narayanan, M; Focke-Tejkl, M; Wrba, F; Vrtala, S; Valenta, R

2014-02-01

Vaccines consisting of allergen-derived peptides lacking IgE reactivity and allergen-specific T cell epitopes bound to allergen-unrelated carrier molecules have been suggested as candidates for allergen-specific immunotherapy. To study whether prophylactic and therapeutic vaccination with carrier-bound peptides from the major birch pollen allergen Bet v 1 lacking allergen-specific T cell epitopes has influence on Bet v 1-specific T cell responses. Three Bet v 1-derived peptides, devoid of Bet v 1-specific T cell epitopes, were coupled to KLH and adsorbed to aluminium hydroxide to obtain a Bet v 1-specific allergy vaccine. Groups of BALB/c mice were immunized with the peptide vaccine before or after sensitization to Bet v 1. Bet v 1- and peptide-specific antibody responses were analysed by ELISA. T cell and cytokine responses to Bet v 1, KLH, and the peptides were studied in proliferation assays. The effects of peptide-specific and allergen-specific antibodies on T cell responses and allergic lung inflammation were studied using specific antibodies. Prophylactic and therapeutic vaccination with carrier-bound Bet v 1 peptides induced a Bet v 1-specific IgG antibody response without priming/boosting of Bet v 1-specific T cells. Prophylactic and therapeutic vaccination of mice with the peptide vaccine induced Bet v 1-specific antibodies which suppressed Bet v 1-specific T cell responses and allergic lung inflammation. Vaccination with carrier-bound allergen-derived peptides lacking allergen-specific T cell epitopes induces allergen-specific IgG antibodies which suppress allergen-specific T cell responses and allergic lung inflammation. © 2013 John Wiley & Sons Ltd.

Cs-137 immobilization in C-S-H gel nanopores.

PubMed

Duque-Redondo, Eduardo; Kazuo, Yamada; López-Arbeloa, Iñigo; Manzano, Hegoi

2018-04-04

Cementation is a widespread technique to immobilize nuclear waste due to the low leachability of cementitious materials. The capacity of calcium silicate hydrate (C-S-H), the main component of cement, to retain radionuclide Cs has been empirically studied at the macroscale, yet the specific molecular scale mechanisms that govern the retention have not been determined. In this work, we employed molecular dynamics simulations to investigate the adsorption and diffusivity of Cs into a C-S-H gel nanopore. From the simulations, it was possible to distinguish three types of Cs adsorption configurations on the C-S-H: an inner-sphere surface site where Cs is strongly bound, an outer-sphere surface site where Cs is loosely bound, and Cs free in the nanopore. For each configuration, we determined the sorption energy, and the diffusion coefficients, up to two orders of magnitude lower than in bulk water due to the effect of nanoconfinement in the worst case scenario. It has also proved that Cs cannot displace the intrinsic Ca from the C-S-H surface, and we calculated the binding strength and the residence time of the cations in the surface adsorption sites. Finally, we quantified the average number of adsorption sites per nm2 of the C-S-H surface. All these results are the first insights into Cs retention in cement at the molecular scale and will be useful to build macroscopic diffusion models and devise cement formulations to improve radionuclide Cs retention from spent nuclear fuel.

Site Competition During Coadsorption of Acetone with Methanol and Water on TiO2(110)

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

Shen, Mingmin; Henderson, Michael A.

2011-08-02

The competitive interaction between acetone and two solvent molecules (methanol and water) for surface sites on rutile TiO2(110) was studied using temperature programmed desorption (TPD). On a vacuum reduced TiO2(110) surface, which possessed ~5% oxygen vacancy sites, excess methanol displaced preadsorbed acetone molecules to weakly bound and physisorbed desorption states below 200 K, whereas acetone was stabilized to 250 K against displacement by methanol on an oxidized surface through formation of an acetone-diolate species. These behaviors of acetone differ from the competitive interactions between acetone and water in that acetone is less susceptible to displacement by water. Examination of acetone+methanolmore » and acetone+water multilayer combinations shows that acetone is more compatible in water-ice films than in methanol-ice films, presumably because water has greater potential as a hydrogen-bond donor than does methanol. Acetone molecules displaced from the TiO2(110) surface by water are more likely to be retained in the near-surface region, having a greater opportunity to revisit the surface, than when methanol is used as a coadsorbate. This work was supported by the US Department of Energy Basic Energy Sciences' Chemical Sciences, Geosciences & Biosciences Division. Pacific Northwest National Laboratory is operated by Battelle for the US Department of Energy.« less

Monitoring of photoluminescence decay by alkali and alkaline earth metal cations using a photoluminescent bolaamphiphile self-assembly as an optical probe.

PubMed

Kim, Sunhyung; Kwak, Jinyoung; Lee, Sang-Yup

2014-05-01

Photoluminescence (PL) decay induced by the displacement of an ionic fluorescence component, Tb(3+), with alkali and alkaline earth metal cations was investigated using photoluminescent spherical self-assemblies as optical probes. The photoluminescent spherical self-assembly was prepared by the self-organization of a tyrosine-containing bolaamphiphile molecule with a photosensitizer and Tb(3+) ion. The lanthanide ion, Tb(3+), electrically bound to the carboxyl group of the bolaamphiphile molecule, was displaced by alkali and alkaline earth metal cations that had stronger electrophilicity. The PL of the self-assembly decayed remarkably due to the substitution of lanthanide ions with alkali and alkaline earth metal cations. The PL decay showed a positive correlation with cation concentration and was sensitive to the cation valency. Generally, the PL decay was enhanced by the electrophilicity of the cations. However, Ca(2+) showed greater PL decay than Mg(2+) because Ca(2+) could create various complexes with the carboxyl groups of the bolaamphiphile molecule. Microscopic and spectroscopic investigations were conducted to study the photon energy transfer and displacement of Tb(3+) by the cation exchange. This study demonstrated that the PL decay by the displacement of the ionic fluorescent compound was applied to the detection of various cations in aqueous media and is applicable to the development of future optical sensors. Copyright © 2014 Elsevier B.V. All rights reserved.

Production of a Purified Marine Neurotoxin and Demonstration of its Binding Affinity to Ion Channel Receptors

DTIC Science & Technology

1989-06-10

the ciguatera Implicated toxins, maitotoxin, does not displace brevetoxin from its unique receptor and therefore must produce its toxic 49octs with a...James R. Balthrop, John A. Babinchak, Penny B. Travis, Teresa L. Herring and Pam Y. Brown-Eyo Ciguatera is a tropical fish-borne disease in which both a...synaptosome bound toxin from free toxin following in vitro bindina. we have demonstruted that one of the ciguatera implicated toxins, maitotoxin

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

PubMed

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

2015-07-10

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

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

DOE PAGES

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

2015-05-26

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

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

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

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

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

Thrust faults and related structures in the crater floor of Mount St. Helens volcano, Washington

USGS Publications Warehouse

Chadwick, W.W.; Swanson, D.A.

1989-01-01

A lava dome was built in the crater of Mount St. Helens by intermittent intrusion and extrusion of dacite lava between 1980 and 1986. Spectacular ground deformation was associated with the dome-building events and included the development of a system of radial cracks and tangential thrust faults in the surrounding crater floor. These cracks and thrusts, best developed and studied in 1981-1982, formed first and, as some evolved into strike-slip tear faults, influenced the subsequent geometry of thrusting. Once faulting began, deformation was localized near the thrust scarps and their bounding tear faults. The magnitude of displacements systematically increased before extrusions, whereas the azimuth and inclination of displacements remained relatively constant. The thrust-fault scarps were bulbous in profile, lobate in plan, and steepened during continued fault movement. The hanging walls of each thrust were increasingly disrupted as cumulative fault slip increased. -from Authors

Hepatic uptake and storage of warfarin. The relation with the target enzyme vitamin K 2,3-epoxide reductase

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

Thijssen, H.H.; Baars, L.G.

The mechanisms of the reported dose-dependent warfarin pharmacokinetics were investigated using (/sup 14/C)warfarin. When administered in microdoses (9 micrograms i.v.) to rats (male Wistars, 270-300 g), a steep distribution phase (T1/2 = 0.25 hr) was followed by a relatively slow beta-phase (T1/2 = 40 hr). The observed volume of distribution was 390 ml. This pharmacokinetic behavior contrasted highly with the one seen for higher (greater than 0.2 mg/kg) doses (unlabeled) warfarin; volume of distribution = 45 ml, T1/2 = 12.5 hr. If a macrodose (0.2 mg/kg) preceded (16 hr) the microdose, normal pharmacokinetics were observed for the latter, suggesting amore » saturable deep compartment. The administration of 4-hydroxycoumarins (i.e., acenocoumarol, phenprocoumon and warfarin) after the microdose of (/sup 14/C)warfarin was in its beta-phase caused a rapid rise of plasma (/sup 14/C)warfarin indicating (/sup 14/C)warfarin to be displaced from the deep compartment. The rate of appearance of (/sup 14/C)warfarin was 0.3 hr-1 irrespective the 4-hydroxycoumarin used. The hepatic distribution of (/sup 14/C)warfarin was investigated and the effect of a displacer thereupon. Fifty-three hours after the (/sup 14/C)warfarin administration, the liver contained about 40% of the dose; 45% of it was bound to microsomes. The administration of acenocoumarol (0.2 mg/kg) at 48 hr, halved the liver content. (/sup 14/C)warfarin was redistributed from microsomes (-65%) and from the 10,000 X g pellet (-65%) into the cytosol (+260%) and the plasma (+320%). Microsomal bound (/sup 14/C)warfarin in vitro could not be washed out or be displaced unless dithiothreitol (50 mM) was included in the washing buffers.« less

How East Asian westerly jet's meridional position affects the summer rainfall in Yangtze-Huaihe River Valley?

NASA Astrophysics Data System (ADS)

Wang, Shixin; Zuo, Hongchao; Zhao, Shuman; Zhang, Jiankai; Lu, Sha

2017-03-01

Existing studies show that the change in the meridional position of East Asian westerly jet (EAWJ) is associated with rainfall anomalies in Yangtze-Huaihe River Valley (YHRV) in summer. However, the dynamic mechanism has not been resolved yet. The present study reveals underlying mechanisms for this impact for early summer and midsummer, separately. Mechanism1: associated with EAWJ's anomalously southward displacement, the 500-hPa westerly wind over YHRV is strengthened through midtropospheric horizontal circulation anomalies; the westerly anomalies are related to the formation of warm advection anomalies over YHRV, which cause increased rainfall through adiabatic ascent motion and convective activities; the major difference in these processes between early summer and midsummer is the midtropospheric circulation anomaly pattern. Mechanism 2: associated with EAWJ's anomalously southward displacement, the large day-to-day variability of midtropospheric temperature advection in midlatitudes is displaced southward by the jet's trapping transient eddies; this change enhances the day-to-day variability of temperature advection over YHRV, which in turn causes the increased rainfall in most part of YHRV through "lower-bound effect" (rainfall amount can not become negative); there is not much difference in these processes between early summer and midsummer.

Research on joint parameter inversion for an integrated underground displacement 3D measuring sensor.

PubMed

Shentu, Nanying; Qiu, Guohua; Li, Qing; Tong, Renyuan; Shentu, Nankai; Wang, Yanjie

2015-04-13

Underground displacement monitoring is a key means to monitor and evaluate geological disasters and geotechnical projects. There exist few practical instruments able to monitor subsurface horizontal and vertical displacements simultaneously due to monitoring invisibility and complexity. A novel underground displacement 3D measuring sensor had been proposed in our previous studies, and great efforts have been taken in the basic theoretical research of underground displacement sensing and measuring characteristics by virtue of modeling, simulation and experiments. This paper presents an innovative underground displacement joint inversion method by mixing a specific forward modeling approach with an approximate optimization inversion procedure. It can realize a joint inversion of underground horizontal displacement and vertical displacement for the proposed 3D sensor. Comparative studies have been conducted between the measured and inversed parameters of underground horizontal and vertical displacements under a variety of experimental and inverse conditions. The results showed that when experimentally measured horizontal displacements and vertical displacements are both varied within 0~30 mm, horizontal displacement and vertical displacement inversion discrepancies are generally less than 3 mm and 1 mm, respectively, under three kinds of simulated underground displacement monitoring circumstances. This implies that our proposed underground displacement joint inversion method is robust and efficient to predict the measuring values of underground horizontal and vertical displacements for the proposed sensor.

Concentration-Dependent Exchange of Replication Protein A on Single-Stranded DNA Revealed by Single-Molecule Imaging

PubMed Central

Gibb, Bryan; Ye, Ling F.; Gergoudis, Stephanie C.; Kwon, YoungHo; Niu, Hengyao; Sung, Patrick; Greene, Eric C.

2014-01-01

Replication protein A (RPA) is a ubiquitous eukaryotic single-stranded DNA (ssDNA) binding protein necessary for all aspects of DNA metabolism involving an ssDNA intermediate, including DNA replication, repair, recombination, DNA damage response and checkpoint activation, and telomere maintenance [1], [2], [3]. The role of RPA in most of these reactions is to protect the ssDNA until it can be delivered to downstream enzymes. Therefore a crucial feature of RPA is that it must bind very tightly to ssDNA, but must also be easily displaced from ssDNA to allow other proteins to gain access to the substrate. Here we use total internal reflection fluorescence microscopy and nanofabricated DNA curtains to visualize the behavior of Saccharomyces cerevisiae RPA on individual strands of ssDNA in real-time. Our results show that RPA remains bound to ssDNA for long periods of time when free protein is absent from solution. In contrast, RPA rapidly dissociates from ssDNA when free RPA is present in solution allowing rapid exchange between the free and bound states. In addition, the S. cerevisiae DNA recombinase Rad51 and E. coli single-stranded binding protein (SSB) also promote removal of RPA from ssDNA. These results reveal an unanticipated exchange between bound and free RPA suggesting a binding mechanism that can confer exceptionally slow off rates, yet also enables rapid displacement through a direct exchange mechanism that is reliant upon the presence of free ssDNA-binding proteins in solution. Our results indicate that RPA undergoes constant microscopic dissociation under all conditions, but this is only manifested as macroscopic dissociation (i.e. exchange) when free proteins are present in solution, and this effect is due to mass action. We propose that the dissociation of RPA from ssDNA involves a partially dissociated intermediate, which exposes a small section of ssDNA allowing other proteins to access to the DNA. PMID:24498402

Missed Opportunities: Examining the Literacy Experiences of African American Students Displaced by Hurricane Katrina

ERIC Educational Resources Information Center

Pollard, Tamica McClarty

2011-01-01

The purpose of this study was to examine how five African American middle school students, who were displaced by Hurricane Katrina represent their literacy experiences before, during, and after their displacement. Specifically, the two research questions were: (a) What are the stories that these middle school students tell about their lives,…

Statewide Needs Assessment: Target Populations--Displaced Homemakers, Single Heads of Households, and Other Special Groups.

ERIC Educational Resources Information Center

Bromley, Ann

A statewide needs assessment in vocational education focused on the needs of displaced homemakers and other special groups in Florida. Specifically, the survey provided (1) a demographic profile of adults in Florida, particularly those described as displaced homemakers, single heads of households, part-time workers, and people desiring work in…

FPGA-Based Smart Sensor for Online Displacement Measurements Using a Heterodyne Interferometer

PubMed Central

Vera-Salas, Luis Alberto; Moreno-Tapia, Sandra Veronica; Garcia-Perez, Arturo; de Jesus Romero-Troncoso, Rene; Osornio-Rios, Roque Alfredo; Serroukh, Ibrahim; Cabal-Yepez, Eduardo

2011-01-01

The measurement of small displacements on the nanometric scale demands metrological systems of high accuracy and precision. In this context, interferometer-based displacement measurements have become the main tools used for traceable dimensional metrology. The different industrial applications in which small displacement measurements are employed requires the use of online measurements, high speed processes, open architecture control systems, as well as good adaptability to specific process conditions. The main contribution of this work is the development of a smart sensor for large displacement measurement based on phase measurement which achieves high accuracy and resolution, designed to be used with a commercial heterodyne interferometer. The system is based on a low-cost Field Programmable Gate Array (FPGA) allowing the integration of several functions in a single portable device. This system is optimal for high speed applications where online measurement is needed and the reconfigurability feature allows the addition of different modules for error compensation, as might be required by a specific application. PMID:22164040

Chemo-mechanical pushing of proteins along single-stranded DNA

PubMed Central

Sokoloski, Joshua E.; Kozlov, Alexander G.; Galletto, Roberto; Lohman, Timothy M.

2016-01-01

Single-stranded (ss)DNA binding (SSB) proteins bind with high affinity to ssDNA generated during DNA replication, recombination, and repair; however, these SSBs must eventually be displaced from or reorganized along the ssDNA. One potential mechanism for reorganization is for an ssDNA translocase (ATP-dependent motor) to push the SSB along ssDNA. Here we use single molecule total internal reflection fluorescence microscopy to detect such pushing events. When Cy5-labeled Escherichia coli (Ec) SSB is bound to surface-immobilized 3′-Cy3–labeled ssDNA, a fluctuating FRET signal is observed, consistent with random diffusion of SSB along the ssDNA. Addition of Saccharomyces cerevisiae Pif1, a 5′ to 3′ ssDNA translocase, results in the appearance of isolated, irregularly spaced saw-tooth FRET spikes only in the presence of ATP. These FRET spikes result from translocase-induced directional (5′ to 3′) pushing of the SSB toward the 3′ ssDNA end, followed by displacement of the SSB from the DNA end. Similar ATP-dependent pushing events, but in the opposite (3′ to 5′) direction, are observed with EcRep and EcUvrD (both 3′ to 5′ ssDNA translocases). Simulations indicate that these events reflect active pushing by the translocase. The ability of translocases to chemo-mechanically push heterologous SSB proteins along ssDNA provides a potential mechanism for reorganization and clearance of tightly bound SSBs from ssDNA. PMID:27185951

Structural characterization of synthetic and protein-bound porphyrins in terms of the lowest-frequency normal coordinates of the macrocycle

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

Jentzen, W.; Song, X.Z.; Shelnutt, J.A.

1997-02-27

The X-ray crystal structures of synthetic and protein-bound metalloporphyrins are analyzed using a new normal structural decomposition method for classifying and quantifying their out-of-plane and in-plane distortions. These distortions are characterized in terms of equivalent displacements along the normal coordinates of the D{sub 4h}-symmetric porphyrin macrocycle (normal deformations). It is shown that the macrocyclic structure is, even in highly distorted porphyrins, accurately represented by displacements along only the lowest-frequency normal coordinates. Accordingly, the macrocyclic structure obtained from just the out-of-plane normal deformations of the saddling (sad, B{sub 2u})-, ruffling (ruf, B{sub 1u})-, doming (dom, A{sub 2u})-, waving [wav(x), wav(y); E{submore » g}]-, and propellering (pro, A{sub 1u})-type essentially simulates the out-of-plane distortion of the X-ray crystal structure. Similarly, the observed in-plane distortions are decomposed into in-plane normal deformations corresponding to the lowest-frequency vibrational modes including macrocycle stretching in the direction of the meso-carbon atoms (meso-str, B{sub 2g}), stretching in the direction of the nitrogen atoms (N-str, B{sub 1g}), x and y pyrrole translations [trn(x), trn(y); E{sub u}], macrocycle breathing (bre, A{sub 1g}), and pyrrole rotation (rot, A{sub 2g}). 71 refs., 9 figs., 4 tabs.« less

The effect of interferon on the receptor sites to rabies virus on mouse neuroblastoma cells

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

Briggs, D.J.

1989-01-01

The binding of rabies virus to mouse neuroblastoma cells (MNA) primed with alpha interferon (IFN-{alpha}), beta interferon (IFN-{beta}), or alpha bungarotoxin (BTX) was examined. A saturable number of receptor sites to rabies virus was calculated by increasing the amount of {sup 3}H-CVS added to a constant number of untreated MNA cells. MNA cells were then exposed to 20 I.U. of IFN-{alpha}, IFN-{beta}, or 1 {mu}g of BTX and assayed to determine if these treatments had an effect on the number of receptor sites to rabies virus. Total amount of {sup 3}H-CVS bound to MNA cells was determined during a threemore » hour incubation period. Cold competition assays using 1,000 fold excess unlabeled CVS were used to determine non-specific binding for each treatment. Specific binding was then calculated by subtracting non-specific binding from the total amount of CVS bound to MNA cells. A similar amount of total viral protein bound to untreated and IFN-{beta}, and BTX treated cells after 180 minutes of incubation. The bound protein varied by only 0.07 {mu}g. However, the amount of specific and non-specific binding varied a great deal between treatments. BTX caused an increase in non-specific and a decrease in specific binding of rabies virus. IFN-{beta} produced variable results in non-specific and specific binding while IFN-{alpha} caused mainly specific binding to occur. The most significant change brought about by IFN-{alpha} was an increase in the rate of viral attachment. At 30 minutes post-infection, IFN-{alpha} treated cells had bound 90% of the total amount of virus bound to untreated cells after 180 minutes. The increased binding rate did not cause a productive infection of rabies virus. No viral production was evident after an incubation period of 48 hours in either IFN-{alpha} or IFN-{beta} treated cells.« less

Oral administration of clotrimazole and blockade of human erythrocyte Ca(++)-activated K+ channel: the imidazole ring is not required for inhibitory activity.

PubMed

Brugnara, C; Armsby, C C; Sakamoto, M; Rifai, N; Alper, S L; Platt, O

1995-04-01

The Ca(++)-activated K+ (Gardos) channel of erythrocytes plays a crucial role in K+ loss and dehydration of sickle erythrocytes; a potential therapeutic strategy would be to prevent dehydration by specifically blocking this channel. The authors report here on the activity of the clotrimazole (CLT) metabolite, 2-chlorophenyl-bis-phenyl-methanol, which accounts for a portion of the blockade of the erythrocyte Gardos channel when CLT is given orally to normal volunteers. Administration of a single oral dose of 1 g of CLT to four normal healthy volunteers (approximately 15 mg/kg of body weight) resulted in 51% to 92% peak inhibition of the Gardos channel measured in whole blood 2 to 4 hr later. Inhibition remained detectable for 24 to 34 hr. Inhibition of the Gardos channel correlated best with the summed levels of CLT plus its two major metabolites (P < .002; apparent IC50 = 0.65 +/- 0.19 microM). In vitro experiments with 2-chlorophenyl-bis-phenyl-methanol revealed dose-dependent inhibition of K transport and displacement of specifically bound 125I-charybdotoxin. Thus, the imidazole ring of CLT, which is required for antimycotic activity and associated with most of the historically observed toxicity, is not necessary for inhibition of the Gardos channel.

Hepatitis-C-virus-like internal ribosome entry sites displace eIF3 to gain access to the 40S subunit

NASA Astrophysics Data System (ADS)

Hashem, Yaser; Des Georges, Amedee; Dhote, Vidya; Langlois, Robert; Liao, Hstau Y.; Grassucci, Robert A.; Pestova, Tatyana V.; Hellen, Christopher U. T.; Frank, Joachim

2013-11-01

Hepatitis C virus (HCV) and classical swine fever virus (CSFV) messenger RNAs contain related (HCV-like) internal ribosome entry sites (IRESs) that promote 5'-end independent initiation of translation, requiring only a subset of the eukaryotic initiation factors (eIFs) needed for canonical initiation on cellular mRNAs. Initiation on HCV-like IRESs relies on their specific interaction with the 40S subunit, which places the initiation codon into the P site, where it directly base-pairs with eIF2-bound initiator methionyl transfer RNA to form a 48S initiation complex. However, all HCV-like IRESs also specifically interact with eIF3 (refs 2, 5, 6, 7, 9, 10, 11, 12), but the role of this interaction in IRES-mediated initiation has remained unknown. During canonical initiation, eIF3 binds to the 40S subunit as a component of the 43S pre-initiation complex, and comparison of the ribosomal positions of eIF3 and the HCV IRES revealed that they overlap, so that their rearrangement would be required for formation of ribosomal complexes containing both components. Here we present a cryo-electron microscopy reconstruction of a 40S ribosomal complex containing eIF3 and the CSFV IRES. Remarkably, although the position and interactions of the CSFV IRES with the 40S subunit in this complex are similar to those of the HCV IRES in the 40S-IRES binary complex, eIF3 is completely displaced from its ribosomal position in the 43S complex, and instead interacts through its ribosome-binding surface exclusively with the apical region of domain III of the IRES. Our results suggest a role for the specific interaction of HCV-like IRESs with eIF3 in preventing ribosomal association of eIF3, which could serve two purposes: relieving the competition between the IRES and eIF3 for a common binding site on the 40S subunit, and reducing formation of 43S complexes, thereby favouring translation of viral mRNAs.

HCV-like IRESs displace eIF3 to gain access to the 40S subunit

PubMed Central

Hashem, Yaser; des Georges, Amedee; Dhote, Vidya; Langlois, Robert; Liao, Hstau Y.; Grassucci, Robert A.; Pestova, Tatyana V.; Hellen, Christopher U.T.; Frank, Joachim

2014-01-01

Hepatitis C virus (HCV) and Classical swine fever virus (CSFV) mRNAs contain related (HCV-like) internal ribosome entry sites (IRESs) that promote 5’-end independent initiation of translation, requiring only a subset of the eukaryotic initiation factors (eIFs) needed for canonical initiation on cellular mRNAs1. Initiation on HCV-like IRESs relies on their specific interaction with the 40S subunit2–8, which places the initiation codon into the P site, where it directly base-pairs with eIF2-bound Met-tRNAiMet to form a 48S initiation complex. However, all HCV-like IRESs also specifically interact with eIF32,5–7,9–12, but the role of this interaction in IRES-mediated initiation has remained unknown. During canonical initiation, eIF3 binds to the 40S subunit as a component of the 43S pre-initiation complex, and comparison of the ribosomal positions of eIF313 and the HCV IRES8 revealed that they overlap, so that their rearrangement would be required for formation of ribosomal complexes containing both components13. Here, we present a cryo-electron microscopy reconstruction of a 40S ribosomal complex containing eIF3 and the CSFV IRES. Strikingly, although the position and interactions of the CSFV IRES with the 40S subunit in this complex are similar to those of the HCV IRES in the 40S/IRES binary complex8, eIF3 is completely displaced from its ribosomal position in the 43S complex, and instead interacts through its ribosome-binding surface exclusively with the apical region of domain III of the IRES. Our results suggest a role for the specific interaction of HCV-like IRESs with eIF3 in preventing ribosomal association of eIF3, which could serve two purposes: relieving the competition between the IRES and eIF3 for a common binding site on the 40S subunit, and reducing formation of 43S complexes, thereby favoring translation of viral mRNAs. PMID:24185006

Differential binding of /sup 3/H-imipramine and /sup 3/H-mianserin in rat cerebral cortex

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

Dumbrille-Ross, A.; Tang, S.W.; Coscina, D.V.

1981-11-16

Drug competition profiles, effect of raphe lesion, and sodium dependency of the binding of two antidepressant drugs /sup 3/H-imipramine and /sup 3/H-mianserin to rat cerebral cortex homogenate were compared to examine whether the drugs bound to a common ''antidepressant receptor.'' Of the neurotransmitters tested, only serotonin displaced binding of both /sup 3/H-imipramine and /sup 3/H-mianserin. /sup 3/H-Mianserin binding was potently displaced by serotonin S/sub 2/ antagonists and exhibited a profile similar to that of /sup 3/H-spiperone binding. In the presence of the serotonin S/sub 2/ antagonist spiperone, antihistamines (H/sub 1/) potently displaced /sup 3/H-mianserin binding. /sup 3/H-Imipramine binding was displacedmore » potently by serotonin uptake inhibitors. The order of potency of serotonergic drugs in displacing /sup 3/H-imipramine binding was not similar to their order in displacing /sup 3/H-spiperone or -3H-serotonin binding. Prior midbrain raphe lesions greatly decreased the binding of /sup 3/H-imipramine but did not alter binding of /sup 3/H-mianserin. Binding of /sup 3/H-imipramine but not /sup 3/H-mianserin was sodium dependent. These results show that /sup 3/H-imipramine and /sup 3/H-mianserin bind to different receptors. /sup 3/H-Imipramine binds to a presynaptic serotonin receptor which is probably related to a serotonin uptake recognition site, the binding of which is sodium dependent. /sup 3/H-Mianserin binds to postsynaptic receptors, possibly both serotonin S/sub 2/ and histamine H/sub 1/ receptors, the binding of which is sodium independent.« less

Research on Joint Parameter Inversion for an Integrated Underground Displacement 3D Measuring Sensor

PubMed Central

Shentu, Nanying; Qiu, Guohua; Li, Qing; Tong, Renyuan; Shentu, Nankai; Wang, Yanjie

2015-01-01

Underground displacement monitoring is a key means to monitor and evaluate geological disasters and geotechnical projects. There exist few practical instruments able to monitor subsurface horizontal and vertical displacements simultaneously due to monitoring invisibility and complexity. A novel underground displacement 3D measuring sensor had been proposed in our previous studies, and great efforts have been taken in the basic theoretical research of underground displacement sensing and measuring characteristics by virtue of modeling, simulation and experiments. This paper presents an innovative underground displacement joint inversion method by mixing a specific forward modeling approach with an approximate optimization inversion procedure. It can realize a joint inversion of underground horizontal displacement and vertical displacement for the proposed 3D sensor. Comparative studies have been conducted between the measured and inversed parameters of underground horizontal and vertical displacements under a variety of experimental and inverse conditions. The results showed that when experimentally measured horizontal displacements and vertical displacements are both varied within 0 ~ 30 mm, horizontal displacement and vertical displacement inversion discrepancies are generally less than 3 mm and 1 mm, respectively, under three kinds of simulated underground displacement monitoring circumstances. This implies that our proposed underground displacement joint inversion method is robust and efficient to predict the measuring values of underground horizontal and vertical displacements for the proposed sensor. PMID:25871714

Fluorescence detection of thrombin using autocatalytic strand displacement cycle reaction and a dual-aptamer DNA sandwich assay.

PubMed

Niu, Shuyan; Qu, Lijing; Zhang, Qing; Lin, Jiehua

2012-02-15

A sensitive and specific sandwich assay for the detection of thrombin is described. Two affiliative aptamers were used to increase the assay specificity through sandwich recognition. Recognition DNA loaded on gold nanoparticles (AuNPs) partially hybridized with the initiator DNA, which was displaced by surviving DNA. After the initiator DNA was released into the solution, one hairpin structure was opened, which in turn opened another hairpin structure. The initiator DNA was displaced and released into the solution again by another hairpin structure because of the hybridized reaction. Then the released initiator DNA initiated another autocatalytic strand displacement reaction. A sophisticated network of three such duplex formation cycles was designed to amplify the fluorescence signal. Other proteins, such as bovine serum albumin and lysozyme, did not interfere with the detection of thrombin. This approach enables rapid and specific thrombin detection with reduced costs and minimized material consumption compared with traditional assay processes. The detection limit of thrombin was as low as 4.3 × 10⁻¹³ M based on the AuNP amplification and the autocatalytic strand displacement cycle reaction. This method could be used in biological samples with excellent selectivity. Copyright © 2011 Elsevier Inc. All rights reserved.

How much articular displacement can be detected using fluoroscopy for tibial plateau fractures?

PubMed

Haller, Justin M; O'Toole, Robert; Graves, Matthew; Barei, David; Gardner, Michael; Kubiak, Erik; Nascone, Jason; Nork, Sean; Presson, Angela P; Higgins, Thomas F

2015-11-01

While there is conflicting evidence regarding the importance of anatomic reduction for tibial plateau fractures, there are currently no studies that analyse our ability to grade reduction based on fluoroscopic imaging. The purpose of this study was to determine the accuracy of fluoroscopy in judging tibial plateau articular reduction. Ten embalmed human cadavers were selected. The lateral plateau was sagitally sectioned, and the joint was reduced under direct visualization. Lateral, anterior-posterior (AP), and joint line fluoroscopic views were obtained. The same fluoroscopic views were obtained with 2mm displacement and 5mm displacement. The images were randomised, and eight orthopaedic traumatologists were asked whether the plateau was reduced. Within each pair of conditions (view and displacement from 0mm to 5mm) sensitivity, specificity, and intraclass correlations (ICC) were evaluated. The AP-lateral view with 5mm displacement yielded the highest accuracy for detecting reduction at 90% (95% CI: 83-94%). For the other conditions, accuracy ranged from (37-83%). Sensitivity was highest for the reduced lateral view (79%, 95% CI: 57-91%). Specificity was highest in the AP-lateral view 98% (95% CI: 93-99%) for 5mm step-off. ICC was perfect for the AP-lateral view with 5mm displacement, but otherwise agreement ranged from poor to moderate at ICC=0.09-0.46. Finally, there was no additional benefit to including the joint-line view with the AP and lateral views. Using both AP and lateral views for 5mm displacement had the highest accuracy, specificity, and ICC. Outside of this scenario, agreement was poor to moderate and accuracy was low. Applying this clinically, direct visualization of the articular surface may be necessary to ensure malreduction less than 5mm. Copyright © 2015 Elsevier Ltd. All rights reserved.

Constraints on geothermal reservoir volume change calculations from InSAR surface displacements and injection and production data

NASA Astrophysics Data System (ADS)

Kaven, J. Ole; Barbour, Andrew J.; Ali, Tabrez

2017-04-01

Continual production of geothermal energy at times leads to significant surface displacement that can be observed in high spatial resolution using InSAR imagery. The surface displacement can be analyzed to resolve volume change within the reservoir revealing the often-complicated patterns of reservoir deformation. Simple point source models of reservoir deformation in a homogeneous elastic or poro-elastic medium can be superimposed to provide spatially varying, kinematic representations of reservoir deformation. In many cases, injection and production data are known in insufficient detail; but, when these are available, the same Green functions can be used to constrain the reservoir deformation. Here we outline how the injection and production data can be used to constrain bounds on the solution by posing the inversion as a quadratic programming with inequality constraints and regularization rather than a conventional least squares solution with regularization. We apply this method to InSAR-derived surface displacements at the Coso and Salton Sea Geothermal Fields in California, using publically available injection and production data. At both geothermal fields the available surface deformation in conjunction with the injection and production data permit robust solutions for the spatially varying reservoir deformation. The reservoir deformation pattern resulting from the constrained quadratic programming solution is more heterogeneous when compared to a conventional least squares solution. The increased heterogeneity is consistent with the known structural controls on heat and fluid transport in each geothermal reservoir.

Transcription Factors Bind Thousands of Active and InactiveRegions in the Drosophila Blastoderm

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

Li, Xiao-Yong; MacArthur, Stewart; Bourgon, Richard

2008-01-10

Identifying the genomic regions bound by sequence-specific regulatory factors is central both to deciphering the complex DNA cis-regulatory code that controls transcription in metazoans and to determining the range of genes that shape animal morphogenesis. Here, we use whole-genome tiling arrays to map sequences bound in Drosophila melanogaster embryos by the six maternal and gap transcription factors that initiate anterior-posterior patterning. We find that these sequence-specific DNA binding proteins bind with quantitatively different specificities to highly overlapping sets of several thousand genomic regions in blastoderm embryos. Specific high- and moderate-affinity in vitro recognition sequences for each factor are enriched inmore » bound regions. This enrichment, however, is not sufficient to explain the pattern of binding in vivo and varies in a context-dependent manner, demonstrating that higher-order rules must govern targeting of transcription factors. The more highly bound regions include all of the over forty well-characterized enhancers known to respond to these factors as well as several hundred putative new cis-regulatory modules clustered near developmental regulators and other genes with patterned expression at this stage of embryogenesis. The new targets include most of the microRNAs (miRNAs) transcribed in the blastoderm, as well as all major zygotically transcribed dorsal-ventral patterning genes, whose expression we show to be quantitatively modulated by anterior-posterior factors. In addition to these highly bound regions, there are several thousand regions that are reproducibly bound at lower levels. However, these poorly bound regions are, collectively, far more distant from genes transcribed in the blastoderm than highly bound regions; are preferentially found in protein-coding sequences; and are less conserved than highly bound regions. Together these observations suggest that many of these poorly-bound regions are not involved in early-embryonic transcriptional regulation, and a significant proportion may be nonfunctional. Surprisingly, for five of the six factors, their recognition sites are not unambiguously more constrained evolutionarily than the immediate flanking DNA, even in more highly bound and presumably functional regions, indicating that comparative DNA sequence analysis is limited in its ability to identify functional transcription factor targets.« less

Mitochondrial Hsp90 is a ligand-activated molecular chaperone coupling ATP binding to dimer closure through a coiled-coil intermediate

PubMed Central

Sung, Nuri; Lee, Jungsoon; Kim, Ji-Hyun; Chang, Changsoo; Joachimiak, Andrzej; Lee, Sukyeong; Tsai, Francis T. F.

2016-01-01

Heat-shock protein of 90 kDa (Hsp90) is an essential molecular chaperone that adopts different 3D structures associated with distinct nucleotide states: a wide-open, V-shaped dimer in the apo state and a twisted, N-terminally closed dimer with ATP. Although the N domain is known to mediate ATP binding, how Hsp90 senses the bound nucleotide and facilitates dimer closure remains unclear. Here we present atomic structures of human mitochondrial Hsp90N (TRAP1N) and a composite model of intact TRAP1 revealing a previously unobserved coiled-coil dimer conformation that may precede dimer closure and is conserved in intact TRAP1 in solution. Our structure suggests that TRAP1 normally exists in an autoinhibited state with the ATP lid bound to the nucleotide-binding pocket. ATP binding displaces the ATP lid that signals the cis-bound ATP status to the neighboring subunit in a highly cooperative manner compatible with the coiled-coil intermediate state. We propose that TRAP1 is a ligand-activated molecular chaperone, which couples ATP binding to dramatic changes in local structure required for protein folding. PMID:26929380

Comparison of the ligand binding properties of two homologous rat apocellular retinol-binding proteins expressed in Escherichia coli.

PubMed

Levin, M S; Locke, B; Yang, N C; Li, E; Gordon, J I

1988-11-25

Cellular retinol-binding protein (CRBP) and cellular retinol-binding protein II (CRBP II) are 132-residue cytosolic proteins which have 56% amino acid sequence identity and bind all-trans-retinol as their endogenous ligand. They belong to a family of cytoplasmic proteins which have evolved to bind distinct hydrophobic ligands. Their patterns of tissue-specific and developmental regulation are distinct. We have compared the ligand binding properties of rat apo-CRBP and apo-CRBP II that have been expressed in Escherichia coli. Several observations indicate that the E. coli-derived apoproteins are structurally similar to the native rat proteins: they co-migrate on isoelectric focusing gels; and when complexed with all-trans-retinol, their absorption and excitation/emission spectra are nearly identical to those of the authentic rat holoproteins. Comparative lifetime and acrylamide quenching studies suggest that there are differences in the conformations of apo-CRBP and apo-CRBP II. The interaction of E. coli-derived apo-CRBP and apo-CRBP II with a variety of retinoids was analyzed using spectroscopic techniques. Both apoproteins formed high affinity complexes with all-trans-retinol (K'd approximately 10 nM). In direct binding assays, all-trans-retinal bound to both apoproteins (K'd approximately 50 nM for CRBP; K'd approximately 90 nM for CRBP II). However, all-trans-retinal could displace all-trans-retinol bound to CRBP II but not to CRBP. These observations suggests that there is a specific yet distinct interaction between these two proteins and all-trans-retinal. Apo-CRBP and apo-CRBP II did not demonstrate significant binding to either retinoic acid or methyl retinoate, an uncharged derivative of all-trans-retinoic acid. This indicates that the carboxymethyl group of methyl retinoate cannot be sterically accommodated in their binding pockets and that failure to bind retinoic acid probably is not simply due to the negative charge of its C-15 carboxylate group. Finally, neither all-trans-retinol nor retinoic acid bound to E. coli-derived rat intestinal fatty acid-binding protein, a homologous protein whose tertiary structure is known. Together, the data suggest that these three family members have acquired unique functional capabilities.

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes.

PubMed

Kürten, Charlotte; Syrén, Per-Olof

2016-01-16

Enzyme catalysis evolved in an aqueous environment. The influence of solvent dynamics on catalysis is, however, currently poorly understood and usually neglected. The study of water dynamics in enzymes and the associated thermodynamical consequences is highly complex and has involved computer simulations, nuclear magnetic resonance (NMR) experiments, and calorimetry. Water tunnels that connect the active site with the surrounding solvent are key to solvent displacement and dynamics. The protocol herein allows for the engineering of these motifs for water transport, which affects specificity, activity and thermodynamics. By providing a biophysical framework founded on theory and experiments, the method presented herein can be used by researchers without previous expertise in computer modeling or biophysical chemistry. The method will advance our understanding of enzyme catalysis on the molecular level by measuring the enthalpic and entropic changes associated with catalysis by enzyme variants with obstructed water tunnels. The protocol can be used for the study of membrane-bound enzymes and other complex systems. This will enhance our understanding of the importance of solvent reorganization in catalysis as well as provide new catalytic strategies in protein design and engineering.

Binding of the cyclic AMP receptor protein of Escherichia coli and DNA bending at the P4 promoter of pBR322.

PubMed

Brierley, I; Hoggett, J G

1992-07-01

The binding of the Escherichia coli cyclic AMP receptor protein (CRP) to its specific site on the P4 promoter of pBR322 has been studied by gel electrophoresis. Binding to the P4 site was about 40-50-fold weaker than to the principal CRP site on the lactose promoter at both low (0.01 M) and high (0.1 M) ionic strengths. CRP-induced bending at the P4 site was investigated from the mobilities of CRP bound to circularly permuted P4 fragments. The estimated bending angle, based on comparison with Zinkel & Crothers [(1990) Biopolymers 29, 29-38] A-tract bending standards, was found to be approximately 96 degrees, similar to that found for binding to the lac site. These observations suggest that there is not a simple relationship between strength of CRP binding and the extent of induced bending for different CRP sites. The apparent centre of bending in P4 is displaced about 6-8 bp away from the conserved TGTGA sequence and the P4 transcription start site.

Crystal structure of substrate free form of glycerol dehydratase

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

Liao, Der-Ing; Dotson, Garry; Turner, Jr., Ivan

2010-03-08

Glycerol dehydratase (GDH) and diol dehydratase (DDH) are highly homologous isofunctional enzymes that catalyze the elimination of water from glycerol and 1,2-propanediol (1,2-PD) to the corresponding aldehyde via a coenzyme B{sub 12}-dependent radical mechanism. The crystal structure of substrate free form of GDH in complex with cobalamin and K{sup +} has been determined at 2.5 {angstrom} resolution. Its overall fold and the subunit assembly closely resemble those of DDH. Comparison of this structure and the DDH structure, available only in substrate bound form, shows the expected change of the coordination of the essential K{sup +} from hexacoordinate to heptacoordinate withmore » the displacement of a single coordinated water by the substrate diol. In addition, there appears to be an increase in the rigidity of the K{sup +} coordination (as measured by lower B values) upon the binding of the substrate. Structural analysis of the locations of conserved residues among various GDH and DDH sequences has aided in identification of residues potentially important for substrate preference or specificity of protein-protein interactions.« less

Surface imprinted beads for the recognition of human serum albumin.

PubMed

Bonini, Francesca; Piletsky, Sergey; Turner, Anthony P F; Speghini, Adolfo; Bossi, Alessandra

2007-04-15

The synthesis of poly-aminophenylboronic acid (ABPA) imprinted beads for the recognition of the protein human serum albumin (HSA) is reported. In order to create homogeneous recognition sites, covalent immobilisation of the template HSA was exploited. The resulting imprinted beads were selective for HSA. The indirect imprinting factor (IF) calculated from supernatant was 1.6 and the direct IF, evaluated from the protein recovered from the beads, was 1.9. The binding capacity was 1.4 mg/g, which is comparable to commercially available affinity materials. The specificity of the HSA recognition was evaluated with competitive experiments, indicating a molar ratio 4.5/1 of competitor was necessary to displace half of the bound HSA. The recognition and binding of the imprinted beads was also tested with a complex sample, human serum and targeted removal of HSA without a loss of the other protein components was demonstrated. The easy preparation protocol of derivatised beads and a good protein recognition properties make the approach an attractive solution to analytical and bio-analytical problems in the field of biotechnology.

Shock spectra applications to a class of multiple degree-of-freedom structures system

NASA Technical Reports Server (NTRS)

Hwang, Shoi Y.

1988-01-01

The demand on safety performance of launching structure and equipment system from impulsive excitations necessitates a study which predicts the maximum response of the system as well as the maximum stresses in the system. A method to extract higher modes and frequencies for a class of multiple degree-of-freedom (MDOF) Structure system is proposed. And, along with the shock spectra derived from a linear oscillator model, a procedure to obtain upper bound solutions for maximum displacement and maximum stresses in the MDOF system is presented.

Long-lived stop at the LHC with or without R-parity

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

Covi, L.; Dradi, F., E-mail: laura.covi@theorie.physik.uni-goettingen.de, E-mail: federico.dradi@theorie.physik.uni-goettingen.de

2014-10-01

We consider scenarios of gravitino LSP and DM with stop NLSP both within R-parity conserving and R-parity violating supersymmetry (RPC and RPV SUSY, respectively). We discuss cosmological bounds from Big Bang Nucleosynthesis (BBN) and the gravitino abundance and then concentrate on the signals of long-lived stops at the LHC as displaced vertices or metastable particles. Finally we discuss how to distinguish R-parity conserving and R-parity breaking stop decays if they happen within the detector and how to suppress SM backgrounds.

Subsurface Constraints on Late Cenozoic Basin Geometry in Northern Fish Lake Valley and Displacement Transfer Along the Northern Fish Lake Valley Fault Zone, Western Nevada

NASA Astrophysics Data System (ADS)

Mueller, N.; Kerstetter, S. R.; Katopody, D. T.; Oldow, J. S.

2016-12-01

The NW-striking, right-oblique Fish Lake Valley fault zone (FLVFZ) forms the northern segment of the longest active structure in the western Great Basin; the Death Valley - Furnace Creek - Fish Lake Valley fault system. Since the mid-Miocene, 50 km of right-lateral displacement is documented on the southern FLVFZ and much of that displacement was and is transferred east and north on active WNW left-lateral faults. Prior to the Pliocene, displacement was transferred east and north on a low-angle detachment. Displacement on the northern part of the FLVFZ continues and is transferred to a fanned array of splays striking (west to east) WNW, NNW, ENE and NNE. To determine the displacement budget on these structures, we conducted a gravity survey to determine subsurface basin morphology and its relation to active faults. Over 2450 stations were collected and combined with existing PACES and proprietary data for a total of 3388 stations. The data were terrain corrected and reduced to a 2.67 g/cm3 density to produce a residual complete Bouguer anomaly. The eastern part of northern Fish Lake Valley is underlain by several prominent gravity lows forming several sub-basins with maximum RCBA values ranging from -24 to -28 mGals. The RCBA was inverted for depth using Geosoft Oasis Montaj GM-SYS 3D modeling software. Density values for the inversion were constrained by lithologic and density logs from wells that penetrate the entire Cenozoic section into the Paleozoic basement. Best fitting gravity measurements taken at the wellheads yielded an effective density of 2.4 g/cm3 for the basin fill. Modeled basement depths range between 2.1 to 3 km. The sub-basins form an arc opening to the NW and are bounded by ENE and NNE faults in the south and NS to NNW in the north. At the northern end of the valley, the faults merge with ENE left-lateral strike slip faults of the Mina deflection, which carries displacement to NW dextral strike-slip faults of the central Walker Lane.

Trapping of quantum particles and light beams by switchable potential wells

NASA Astrophysics Data System (ADS)

Sonkin, Eduard; Malomed, Boris A.; Granot, Er'El; Marchewka, Avi

2010-09-01

We consider basic dynamical effects in settings based on a pair of local potential traps that may be effectively switched on and off, or suddenly displaced, by means of appropriate control mechanisms, such as scanning tunneling microscopy or photo-switchable quantum dots. The same models, based on the linear Schrödinger equation with time-dependent trapping potentials, apply to the description of optical planar systems designed for the switching of trapped light beams. The analysis is carried out in the analytical form, using exact solutions of the Schrödinger equation. The first dynamical problem considered in this work is the retention of a particle released from a trap which was suddenly turned off, while another local trap was switched on at a distance—immediately or with a delay. In this case, we demonstrate that the maximum of the retention rate is achieved at a specific finite value of the strength of the new trap, and at a finite value of the temporal delay, depending on the distance between the two traps. Another problem is retrapping of the bound particle when the addition of the second trap transforms the single-well setting into a double-well potential (DWP). In that case, we find probabilities for the retrapping into the ground or first excited state of the DWP. We also analyze effects entailed by the application of a kick to a bound particle, the most interesting one being a kick-induced transition between the DWP’s ground and excited states. In the latter case, the largest transition probability is achieved at a particular strength of the kick.

Structural and Biochemical Characterization of a Copper-Binding Mutant of the Organomercurial Lyase MerB: Insight into the Key Role of the Active Site Aspartic Acid in Hg-Carbon Bond Cleavage and Metal Binding Specificity.

PubMed

Wahba, Haytham M; Lecoq, Lauriane; Stevenson, Michael; Mansour, Ahmed; Cappadocia, Laurent; Lafrance-Vanasse, Julien; Wilkinson, Kevin J; Sygusch, Jurgen; Wilcox, Dean E; Omichinski, James G

2016-02-23

In bacterial resistance to mercury, the organomercurial lyase (MerB) plays a key role in the detoxification pathway through its ability to cleave Hg-carbon bonds. Two cysteines (C96 and C159; Escherichia coli MerB numbering) and an aspartic acid (D99) have been identified as the key catalytic residues, and these three residues are conserved in all but four known MerB variants, where the aspartic acid is replaced with a serine. To understand the role of the active site serine, we characterized the structure and metal binding properties of an E. coli MerB mutant with a serine substituted for D99 (MerB D99S) as well as one of the native MerB variants containing a serine residue in the active site (Bacillus megaterium MerB2). Surprisingly, the MerB D99S protein copurified with a bound metal that was determined to be Cu(II) from UV-vis absorption, inductively coupled plasma mass spectrometry, nuclear magnetic resonance, and electron paramagnetic resonance studies. X-ray structural studies revealed that the Cu(II) is bound to the active site cysteine residues of MerB D99S, but that it is displaced following the addition of either an organomercurial substrate or an ionic mercury product. In contrast, the B. megaterium MerB2 protein does not copurify with copper, but the structure of the B. megaterium MerB2-Hg complex is highly similar to the structure of the MerB D99S-Hg complexes. These results demonstrate that the active site aspartic acid is crucial for both the enzymatic activity and metal binding specificity of MerB proteins and suggest a possible functional relationship between MerB and its only known structural homologue, the copper-binding protein NosL.

Evaluation of a Computer-Assisted Dental Diagnostic System by Navy Hospital Corpsmen

DTIC Science & Technology

1989-06-23

hypersensitivity 1 Defective restoration Displace/mobility of tooth, favorable prognosis Displace/mobility of tooth, guarded prognosis 2 Endo / perio ... injury Osseous sequestrum 2 Occlusal trauma _1 Periodontal abscess 3 Periocoronitis/erupting tooth 2 Reversible pulpitis Root fracture Total...Trauma Related Injury 1 1 0 *Tooth, Specific 18 26 17 *Teeth, Generalized 1 1 0 *Gingiva, Specific Area 6 1 1 *Gingiva, Generalized Area 2 2 2 *Oral

Single-molecule dilution and multiple displacement amplification for molecular haplotyping.

PubMed

Paul, Philip; Apgar, Josh

2005-04-01

Separate haploid analysis is frequently required for heterozygous genotyping to resolve phase ambiguity or confirm allelic sequence. We demonstrate a technique of single-molecule dilution followed by multiple strand displacement amplification to haplotype polymorphic alleles. Dilution of DNA to haploid equivalency, or a single molecule, is a simple method for separating di-allelic DNA. Strand displacement amplification is a robust method for non-specific DNA expansion that employs random hexamers and phage polymerase Phi29 for double-stranded DNA displacement and primer extension, resulting in high processivity and exceptional product length. Single-molecule dilution was followed by strand displacement amplification to expand separated alleles to microgram quantities of DNA for more efficient haplotype analysis of heterozygous genes.

Lattice Boltzmann simulation of immiscible fluid displacement in porous media: Homogeneous versus heterogeneous pore network

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

Liu, Haihu, E-mail: haihu.liu@mail.xjtu.edu.cn; James Weir Fluids Laboratory, Department of Mechanical and Aerospace Engineering, University of Strathclyde, Glasgow G1 1XJ; Department of Civil and Environmental Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801

Injection of anthropogenic carbon dioxide (CO{sub 2}) into geological formations is a promising approach to reduce greenhouse gas emissions into the atmosphere. Predicting the amount of CO{sub 2} that can be captured and its long-term storage stability in subsurface requires a fundamental understanding of multiphase displacement phenomena at the pore scale. In this paper, the lattice Boltzmann method is employed to simulate the immiscible displacement of a wetting fluid by a non-wetting one in two microfluidic flow cells, one with a homogeneous pore network and the other with a randomly heterogeneous pore network. We have identified three different displacement patterns,more » namely, stable displacement, capillary fingering, and viscous fingering, all of which are strongly dependent upon the capillary number (Ca), viscosity ratio (M), and the media heterogeneity. The non-wetting fluid saturation (S{sub nw}) is found to increase nearly linearly with logCa for each constant M. Increasing M (viscosity ratio of non-wetting fluid to wetting fluid) or decreasing the media heterogeneity can enhance the stability of the displacement process, resulting in an increase in S{sub nw}. In either pore networks, the specific interfacial length is linearly proportional to S{sub nw} during drainage with equal proportionality constant for all cases excluding those revealing considerable viscous fingering. Our numerical results confirm the previous experimental finding that the steady state specific interfacial length exhibits a linear dependence on S{sub nw} for either favorable (M ≥ 1) or unfavorable (M < 1) displacement, and the slope is slightly higher for the unfavorable displacement.« less

Identification of Prostate Cancer-Specific microDNAs

DTIC Science & Technology

2014-12-01

displacement amplification (MDA). 2 adopted multiple displacement amplification (MDA) with random primers for enriched circular DNA by rolling circle ... amplification (RCA) (Fig. 1) and then amplified DNA fragments were subject to deep sequencing. Sequence NO of Reads seq 1 184 seq 2 133 seq 3 2407 seq...prostate cancer cells through multiple displacement amplification .  Clone #7 is the top candidate which has been cloned in an expression vector and it

Time-optimal thermalization of single-mode Gaussian states

NASA Astrophysics Data System (ADS)

Carlini, Alberto; Mari, Andrea; Giovannetti, Vittorio

2014-11-01

We consider the problem of time-optimal control of a continuous bosonic quantum system subject to the action of a Markovian dissipation. In particular, we consider the case of a one-mode Gaussian quantum system prepared in an arbitrary initial state and which relaxes to the steady state due to the action of the dissipative channel. We assume that the unitary part of the dynamics is represented by Gaussian operations which preserve the Gaussian nature of the quantum state, i.e., arbitrary phase rotations, bounded squeezing, and unlimited displacements. In the ideal ansatz of unconstrained quantum control (i.e., when the unitary phase rotations, squeezing, and displacement of the mode can be performed instantaneously), we study how control can be optimized for speeding up the relaxation towards the fixed point of the dynamics and we analytically derive the optimal relaxation time. Our model has potential and interesting applications to the control of modes of electromagnetic radiation and of trapped levitated nanospheres.

Dna2 nuclease-helicase structure, mechanism and regulation by Rpa.

PubMed

Zhou, Chun; Pourmal, Sergei; Pavletich, Nikola P

2015-11-02

The Dna2 nuclease-helicase maintains genomic integrity by processing DNA double-strand breaks, Okazaki fragments and stalled replication forks. Dna2 requires ssDNA ends, and is dependent on the ssDNA-binding protein Rpa, which controls cleavage polarity. Here we present the 2.3 Å structure of intact mouse Dna2 bound to a 15-nucleotide ssDNA. The nuclease active site is embedded in a long, narrow tunnel through which the DNA has to thread. The helicase domain is required for DNA binding but not threading. We also present the structure of a flexibly-tethered Dna2-Rpa interaction that recruits Dna2 to Rpa-coated DNA. We establish that a second Dna2-Rpa interaction is mutually exclusive with Rpa-DNA interactions and mediates the displacement of Rpa from ssDNA. This interaction occurs at the nuclease tunnel entrance and the 5' end of the Rpa-DNA complex. Hence, it only displaces Rpa from the 5' but not 3' end, explaining how Rpa regulates cleavage polarity.

Fault kinematics and localised inversion within the Troms-Finnmark Fault Complex, SW Barents Sea

NASA Astrophysics Data System (ADS)

Zervas, I.; Omosanya, K. O.; Lippard, S. J.; Johansen, S. E.

2018-04-01

The areas bounding the Troms-Finnmark Fault Complex are affected by complex tectonic evolution. In this work, the history of fault growth, reactivation, and inversion of major faults in the Troms-Finnmark Fault Complex and the Ringvassøy Loppa Fault Complex is interpreted from three-dimensional seismic data, structural maps and fault displacement plots. Our results reveal eight normal faults bounding rotated fault blocks in the Troms-Finnmark Fault Complex. Both the throw-depth and displacement-distance plots show that the faults exhibit complex configurations of lateral and vertical segmentation with varied profiles. Some of the faults were reactivated by dip-linkages during the Late Jurassic and exhibit polycyclic fault growth, including radial, syn-sedimentary, and hybrid propagation. Localised positive inversion is the main mechanism of fault reactivation occurring at the Troms-Finnmark Fault Complex. The observed structural styles include folds associated with extensional faults, folded growth wedges and inverted depocentres. Localised inversion was intermittent with rifting during the Middle Jurassic-Early Cretaceous at the boundaries of the Troms-Finnmark Fault Complex to the Finnmark Platform. Additionally, tectonic inversion was more intense at the boundaries of the two fault complexes, affecting Middle Triassic to Early Cretaceous strata. Our study shows that localised folding is either a product of compressional forces or of lateral movements in the Troms-Finnmark Fault Complex. Regional stresses due to the uplift in the Loppa High and halokinesis in the Tromsø Basin are likely additional causes of inversion in the Troms-Finnmark Fault Complex.

Binding modes of phosphotriesterase-like lactonase complexed with δ-nonanoic lactone and paraoxon using molecular dynamics simulations.

PubMed

Guan, Shanshan; Zhao, Li; Jin, Hanyong; Shan, Ning; Han, Weiwei; Wang, Song; Shan, Yaming

2017-02-01

Phosphotriesterase-like lactonases (PLLs) have received much attention because of their physical and chemical properties. They may have widespread applications in various fields. For example, they show potential for quorum-sensing signaling pathways and organophosphorus (OP) detoxification in agricultural science. However, the mechanism by which PLLs hydrolyze, which involves OP compounds and lactones and a variety of distinct catalytic efficiencies, has only rarely been explored. In the present study, molecular dynamics (MD) simulations were performed to characterize and contrast the structural dynamics of DrPLL, a member of the PLL superfamily in Deinococcus radiodurans, bound to two substrates, δ-nonanoic lactone and paraoxon. It has been observed that there is a 16-fold increase in the catalytic efficiency of the two mutant strains of DrPLL (F26G/C72I) vs. the wild-type enzyme toward the hydrolysis of paraoxon, but an explanation for this behavior is currently lacking. The analysis of the molecular trajectories of DrPLL bound to δ-nonanoic lactone indicated that lactone-induced conformational changes take place in loop 8, which is near the active site. Binding to paraoxon may lead to conformational displacement of loop 1 residues, which could lead to the deformation of the active site and so trigger the entry of the paraoxon into the active site. The efficiency of the F26G/C72I mutant was increased by decreasing the displacement of loop 1 residues and increasing the flexibility of loop 8 residues. These results provide a molecular-level explanation for the experimental behavior.

Dependence of the quantum speed limit on system size and control complexity

NASA Astrophysics Data System (ADS)

Lee, Juneseo; Arenz, Christian; Rabitz, Herschel; Russell, Benjamin

2018-06-01

We extend the work in 2017 New J. Phys. 19 103015 by deriving a lower bound for the minimum time necessary to implement a unitary transformation on a generic, closed quantum system with an arbitrary number of classical control fields. This bound is explicitly analyzed for a specific N-level system similar to those used to represent simple models of an atom, or the first excitation sector of a Heisenberg spin chain, both of which are of interest in quantum control for quantum computation. Specifically, it is shown that the resultant bound depends on the dimension of the system, and on the number of controls used to implement a specific target unitary operation. The value of the bound determined numerically, and an estimate of the true minimum gate time are systematically compared for a range of system dimension and number of controls; special attention is drawn to the relationship between these two variables. It is seen that the bound captures the scaling of the minimum time well for the systems studied, and quantitatively is correct in the order of magnitude.

Global surface displacement data for assessing variability of displacement at a point on a fault

USGS Publications Warehouse

Hecker, Suzanne; Sickler, Robert; Feigelson, Leah; Abrahamson, Norman; Hassett, Will; Rosa, Carla; Sanquini, Ann

2014-01-01

This report presents a global dataset of site-specific surface-displacement data on faults. We have compiled estimates of successive displacements attributed to individual earthquakes, mainly paleoearthquakes, at sites where two or more events have been documented, as a basis for analyzing inter-event variability in surface displacement on continental faults. An earlier version of this composite dataset was used in a recent study relating the variability of surface displacement at a point to the magnitude-frequency distribution of earthquakes on faults, and to hazard from fault rupture (Hecker and others, 2013). The purpose of this follow-on report is to provide potential data users with an updated comprehensive dataset, largely complete through 2010 for studies in English-language publications, as well as in some unpublished reports and abstract volumes.

Linear and angular retroreflecting interferometric alignment target

DOEpatents

Maxey, L. Curtis

2001-01-01

The present invention provides a method and apparatus for measuring both the linear displacement and angular displacement of an object using a linear interferometer system and an optical target comprising a lens, a reflective surface and a retroreflector. The lens, reflecting surface and retroreflector are specifically aligned and fixed in optical connection with one another, creating a single optical target which moves as a unit that provides multi-axis displacement information for the object with which it is associated. This displacement information is useful in many applications including machine tool control systems and laser tracker systems, among others.

Outward Bound...Into the Mainstream of Education.

ERIC Educational Resources Information Center

Outward Bound, Inc., Andover, MA.

Outward Bound schools have instituted advanced courses designed specifically for adults engaged in education and youth work. Benefits for teachers include greater development of capacitites and potentialities, greater confidence in their abilities, and the ability to relate more effectively to others. Some of the specific training elements in an…

Binding of D-phenylalanine and D-tyrosine to carboxypeptidase A.

PubMed

Christianson, D W; Mangani, S; Shoham, G; Lipscomb, W N

1989-08-05

The structures of the complexes of carboxypeptidase A with the amino acids D-phenylalanine and D-tyrosine are reported as determined by x-ray crystallographic methods to a resolution of 2.0 A. In each individual study one molecule of amino acids binds to the enzyme in the COOH-terminal hydrophobic pocket: the carboxylate of the bound ligand salt links with Arg-145, and the alpha-amino group salt links with Glu-270. The carboxylate of Glu-270 must break its hydrogen bond with the native zinc-bound water molecule in order to exploit the latter interaction. This result is in accord with spectroscopic studies which indicate that the binding of D or L amino acids (or analogues thereof) allows for more facile displacement of the metal-bound water by anions (Bicknell, R., Schaffer, A., Bertini, I., Luchinat, C., Vallee, B. L., and Auld, D. S. (1988) Biochemistry 27, 1050-1057). Additionally, we observe a significant movement of the zinc-bound water molecule (approximately 1 A) upon the binding of D-ligands. We propose that this unanticipated movement also contributes to anion sensitivity. The structural results of the current x-ray study correct predictions made in an early model building study regarding the binding of D-phenylalanine (Lipscomb, W. N., Hartsuck, J. A., Reeke, G. N., Jr., Quiocho, F. A., Bethge, P. H., Ludwig, M. L., Steitz, T. A., Muirhead, H., and Coppola, J. C. (1968) Brookhaven Symp. Biol. 21, 24-90).

Membrane position control

NASA Technical Reports Server (NTRS)

Su, Ji (Inventor); Harrison, Joycelyn S. (Inventor)

2004-01-01

A membrane structure includes at least one electroactive bending actuator fixed to a supporting base. Each electroactive bending actuator is operatively connected to the membrane for controlling membrane position. Any displacement of each electroactive bending actuator effects displacement of the membrane. More specifically, the operative connection is provided by a guiding wheel assembly and a track, wherein displacement of the bending actuator effects translation of the wheel assembly along the track, thereby imparting movement to the membrane.

Class-specific Error Bounds for Ensemble Classifiers

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

Prenger, R; Lemmond, T; Varshney, K

2009-10-06

The generalization error, or probability of misclassification, of ensemble classifiers has been shown to be bounded above by a function of the mean correlation between the constituent (i.e., base) classifiers and their average strength. This bound suggests that increasing the strength and/or decreasing the correlation of an ensemble's base classifiers may yield improved performance under the assumption of equal error costs. However, this and other existing bounds do not directly address application spaces in which error costs are inherently unequal. For applications involving binary classification, Receiver Operating Characteristic (ROC) curves, performance curves that explicitly trade off false alarms and missedmore » detections, are often utilized to support decision making. To address performance optimization in this context, we have developed a lower bound for the entire ROC curve that can be expressed in terms of the class-specific strength and correlation of the base classifiers. We present empirical analyses demonstrating the efficacy of these bounds in predicting relative classifier performance. In addition, we specify performance regions of the ROC curve that are naturally delineated by the class-specific strengths of the base classifiers and show that each of these regions can be associated with a unique set of guidelines for performance optimization of binary classifiers within unequal error cost regimes.« less

Comparing (semi-) analytic solutions used to model the impact of deep carbon injection on the displacement and pressurization of the resident brine

NASA Astrophysics Data System (ADS)

Bandilla, K.; Kraemer, S. R.

2009-12-01

Injection of carbon dioxide into deep saline formations is seen as one possible technology for mitigating carbon emissions from utilities. The safety of the sequestered carbon dioxide is the focus of many studies with leakage through faults or abandoned wells as some of the main failure mechanisms. The focus of this study is on the displacement of resident brine and the resulting changes in pressure due to the injection of large volumes of super-critical phase carbon dioxide into the subsurface. The movement of brine becomes important if it travels vertically and reaches an existing or potential underground source of drinking water where an increase in salt content may threaten the viability of the drinking water source. Vertical displacement of brine may occur slowly through confining layers, or more rapidly through faults and abandoned wells. This presentation compares several (semi-) analytic solutions to determine their applicability to the problem of brine pressurization and displacement. The goal is to find ranges of formation parameters (e.g., formation seal conductivity, distance to lateral boundary, … ) for which simplifying assumption are justifiable Each simplification in the conceptual model (e.g., neglecting the lateral boundary turns a bounded domain into an infinite one) leads to a simpler (semi-) analytic solution. The process involves a solution hierarchy from the most complex solution down to the basic Theis solution. A software tool-kit implementing several (semi-) analytic solutions was developed for this study to facilitate the comparison of the solutions.

Interaction of LY171883 and other peroxisome proliferators with fatty-acid-binding protein isolated from rat liver.

PubMed Central

Cannon, J R; Eacho, P I

1991-01-01

Fatty-acid-binding protein (FABP) is a 14 kDa protein found in hepatic cytosol which binds and transports fatty acids and other hydrophobic ligands throughout the cell. The purpose of this investigation was to determine whether LY171883, a leukotriene D4 antagonist, and other peroxisome proliferators bind to FABP and displace an endogenous fatty acid. [3H]Oleic acid was used to monitor the elution of FABP during chromatographic purification. [14C]LY171883 had a similar elution profile when substituted in the purification, indicating a common interaction with FABP. LY171883 and its structural analogue, LY189585, as well as the hypolipidaemic peroxisome proliferators clofibric acid, ciprofibrate, bezafibrate and WY14,643, displaced [3H]oleic acid binding to FABP. Analogues of LY171883 that do not induce peroxisome proliferation only weakly displaced oleate binding. [3H]Ly171883 bound directly to FABP with a Kd of 10.8 microM, compared with a Kd of 0.96 microM for [3H]oleate. LY171883 binding was inhibited by LY189585, clofibric acid, ciprofibrate and bezafibrate. These findings demonstrate that peroxisome proliferators, presumably due to their structural similarity to fatty acids, are able to bind to FABP and displace an endogenous ligand from its binding site. Interaction of peroxisome proliferators with FABP may be involved in perturbations of fatty acid metabolism caused by these agents as well as in the development of the pleiotropic response of peroxisome proliferation. Images Fig. 2. PMID:1747111

Characterizing and estimating noise in InSAR and InSAR time series with MODIS

USGS Publications Warehouse

Barnhart, William D.; Lohman, Rowena B.

2013-01-01

InSAR time series analysis is increasingly used to image subcentimeter displacement rates of the ground surface. The precision of InSAR observations is often affected by several noise sources, including spatially correlated noise from the turbulent atmosphere. Under ideal scenarios, InSAR time series techniques can substantially mitigate these effects; however, in practice the temporal distribution of InSAR acquisitions over much of the world exhibit seasonal biases, long temporal gaps, and insufficient acquisitions to confidently obtain the precisions desired for tectonic research. Here, we introduce a technique for constraining the magnitude of errors expected from atmospheric phase delays on the ground displacement rates inferred from an InSAR time series using independent observations of precipitable water vapor from MODIS. We implement a Monte Carlo error estimation technique based on multiple (100+) MODIS-based time series that sample date ranges close to the acquisitions times of the available SAR imagery. This stochastic approach allows evaluation of the significance of signals present in the final time series product, in particular their correlation with topography and seasonality. We find that topographically correlated noise in individual interferograms is not spatially stationary, even over short-spatial scales (<10 km). Overall, MODIS-inferred displacements and velocities exhibit errors of similar magnitude to the variability within an InSAR time series. We examine the MODIS-based confidence bounds in regions with a range of inferred displacement rates, and find we are capable of resolving velocities as low as 1.5 mm/yr with uncertainties increasing to ∼6 mm/yr in regions with higher topographic relief.

Conformational preferences of DNA following damage by aristolochic acids: Structural and energetic insights into the different mutagenic potential of the ALI and ALII-N(6)-dA adducts.

PubMed

Kathuria, Preetleen; Sharma, Purshotam; Abendong, Minette N; Wetmore, Stacey D

2015-04-21

Aristolochic acids (AAI and AAII), produced by the Aristolochiaceae family of plants, are classified as group I (human) carcinogens by the International Agency for Research on Cancer. These acids are metabolized in cells to yield aristolactams (ALI and ALII, respectively), which further form bulky adducts with the purine nucleobases. Specifically, the adenine lesions are more persistent in cells and have been associated with chronic renal diseases and related carcinogenesis. To understand the structural basis of the nephrotoxicity induced by AAs, the ALI-N(6)-dA and ALII-N(6)-dA lesions are systematically studied using computational methods. Density functional theory calculations indicate that the aristolactam moiety intrinsically prefers a planar conformation with respect to adenine. Nucleoside and nucleotide models suggest that the anti and syn orientations about the glycosidic bond are isoenergetic for both adducts. Molecular dynamics simulations and free energy calculations reveal that the anti base-displaced intercalated conformation is the most stable conformer for both types of AL-N(6)-dA adducted DNA, which agrees with previous experimental work on the ALII-N(6)-dA adduct and thereby validates our approach. Interestingly, this conformer differs from the dominant conformations adopted by other N6-linked adenine lesions, including those derived from polycyclic aromatic hydrocarbons. Furthermore, the second most stable syn base-displaced intercalated conformation lies closer in energy to the anti base-displaced intercalated conformation for ALI-N(6)-dA compared to ALII-N(6)-dA. This indicates that a mixture of conformations may be detectable for ALI-N(6)-dA in DNA. If this enhanced conformational flexibility of double-stranded DNA persists when bound to a lesion-bypass polymerase, this provides a possible structural explanation for the previously observed greater nephrotoxic potential for the ALI versus ALII-N(6)-dA adduct. In addition, the structural characteristics of the preferred conformations of adducted DNA explain the resistance of these adducts to repair and thereby add to our current understanding of the toxicity of AAs within living cells.

Nature's polyoxometalate chemistry: X-ray structure of the Mo storage protein loaded with discrete polynuclear Mo-O clusters.

PubMed

Kowalewski, Björn; Poppe, Juliane; Demmer, Ulrike; Warkentin, Eberhard; Dierks, Thomas; Ermler, Ulrich; Schneider, Klaus

2012-06-13

Some N(2)-fixing bacteria prolong the functionality of nitrogenase in molybdenum starvation by a special Mo storage protein (MoSto) that can store more than 100 Mo atoms. The presented 1.6 Å X-ray structure of MoSto from Azotobacter vinelandii reveals various discrete polyoxomolybdate clusters, three covalently and three noncovalently bound Mo(8), three Mo(5-7), and one Mo(3) clusters, and several low occupied, so far undefinable clusters, which are embedded in specific pockets inside a locked cage-shaped (αβ)(3) protein complex. The structurally identical Mo(8) clusters (three layers of two, four, and two MoO(n) octahedra) are distinguishable from the [Mo(8)O(26)](4-) cluster formed in acidic solutions by two displaced MoO(n) octahedra implicating three kinetically labile terminal ligands. Stabilization in the covalent Mo(8) cluster is achieved by Mo bonding to Hisα156-N(ε2) and Gluα129-O(ε1). The absence of covalent protein interactions in the noncovalent Mo(8) cluster is compensated by a more extended hydrogen-bond network involving three pronounced histidines. One displaced MoO(n) octahedron might serve as nucleation site for an inhomogeneous Mo(5-7) cluster largely surrounded by bulk solvent. In the Mo(3) cluster located on the 3-fold axis, the three accurately positioned His140-N(ε2) atoms of the α subunits coordinate to the Mo atoms. The formed polyoxomolybdate clusters of MoSto, not detectable in bulk solvent, are the result of an interplay between self- and protein-driven assembly processes that unite inorganic supramolecular and protein chemistry in a host-guest system. Template, nucleation/protection, and catalyst functions of the polypeptide as well as perspectives for designing new clusters are discussed.

A homogeneous nucleic acid hybridization assay based on strand displacement.

PubMed Central

Vary, C P

1987-01-01

A homogeneous nucleic acid hybridization assay which is conducted in solution and requires no separation steps is described. The assay is based on the concept of strand displacement. In the strand displacement assay, an RNA "signal strand" is hybridized within a larger DNA strand termed the "probe strand", which is, in turn, complementary to the target nucleic acid of interest. Hybridization of the target nucleic acid with the probe strand ultimately results in displacement of the RNA signal strand. Strand displacement, therefore, causes conversion of the RNA from double to single-stranded form. The single-strand specificity of polynucleotide phosphorylase (EC 2.7.7.8) allows discrimination between double-helical and single-stranded forms of the RNA signal strand. As displacement proceeds, free RNA signal strands are preferentially phosphorolyzed to component nucleoside diphosphates, including adenosine diphosphate. The latter nucleotide is converted to ATP by pyruvate kinase(EC 2.7.1.40). Luciferase catalyzed bioluminescence is employed to measure the ATP generated as a result of strand displacement. Images PMID:3309890

A Novel Computational Method to Reduce Leaky Reaction in DNA Strand Displacement.

PubMed

Li, Xin; Wang, Xun; Song, Tao; Lu, Wei; Chen, Zhihua; Shi, Xiaolong

2015-01-01

DNA strand displacement technique is widely used in DNA programming, DNA biosensors, and gene analysis. In DNA strand displacement, leaky reactions can cause DNA signals decay and detecting DNA signals fails. The mostly used method to avoid leakage is cleaning up after upstream leaky reactions, and it remains a challenge to develop reliable DNA strand displacement technique with low leakage. In this work, we address the challenge by experimentally evaluating the basic factors, including reaction time, ratio of reactants, and ion concentration to the leakage in DNA strand displacement. Specifically, fluorescent probes and a hairpin structure reporting DNA strand are designed to detect the output of DNA strand displacement, and thus can evaluate the leakage of DNA strand displacement reactions with different reaction time, ratios of reactants, and ion concentrations. From the obtained data, mathematical models for evaluating leakage are achieved by curve derivation. As a result, it is obtained that long time incubation, high concentration of fuel strand, and inappropriate amount of ion concentration can weaken leaky reactions. This contributes to a method to set proper reaction conditions to reduce leakage in DNA strand displacement.

Tc-99m galactosyl-neoglycoalbumin: in vitro characterization of receptor-mediated binding

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

Vera, D.R.; Krohn, K.A.; Stadalnik, R.C.

1984-07-01

Hepatic binding protein (HBP) is a membrane receptor that binds and transports plasma glycoproteins from hepatic blood to hepatocellular lysosomes. A characterization is made of the in vitro binding of Tc-99m galactosyl-neoglycoalbumin (Tc-NGA), a synthetic HBP ligand, to liver membrane. Structural modifications of NGA resulted in the alteration of the equilibrium constant, KA, and the forward-binding rate constant, kb. Binding was second-order; the relative amount of membrane-bound NGA depended on the initial concentrations of ligand and membrane. Membrane displacement studies, using carrier ligands in contrast to previously bound Tc-NGA or I-NGA, correlated with the binding characteristics of a native HBPmore » ligand, asialo-orosomucoid. Computer simulation was used to study the detectability of the changes in HBP concentration at different values of kb. The simulations indicated that radiopharmacokinetic sensitivity to alterations in (HBP) should be possible using a neoglycoalbumin preparation with a carbohydrate density within the range of 15 to 25 galactose units per albumin molecule.« less

Properties of branching exponential flights in bounded domains

NASA Astrophysics Data System (ADS)

Zoia, A.; Dumonteil, E.; Mazzolo, A.

2012-11-01

In a series of recent works, important results have been reported concerning the statistical properties of exponential flights evolving in bounded domains, a widely adopted model for finite-speed transport phenomena (Blanco S. and Fournier R., Europhys. Lett., 61 (2003) 168; Mazzolo A., Europhys. Lett., 68 (2004) 350; Bénichou O. et al., Europhys. Lett., 70 (2005) 42). Motivated by physical and biological systems where random spatial displacements are coupled with Galton-Watson birth-death mechanisms, such as neutron multiplication, diffusion of reproducing bacteria or spread of epidemics, in this letter we extend those results in two directions, via a Feynman-Kac formalism. First, we characterize the occupation statistics of exponential flights in the presence of absorption and branching, and give explicit moment formulas for the total length travelled by the walker and the number of performed collisions in a given domain. Then, we show that the survival and escape probability can be derived as well by resorting to a similar approach.

Image-guided radiotherapy quality control: Statistical process control using image similarity metrics.

PubMed

Shiraishi, Satomi; Grams, Michael P; Fong de Los Santos, Luis E

2018-05-01

The purpose of this study was to demonstrate an objective quality control framework for the image review process. A total of 927 cone-beam computed tomography (CBCT) registrations were retrospectively analyzed for 33 bilateral head and neck cancer patients who received definitive radiotherapy. Two registration tracking volumes (RTVs) - cervical spine (C-spine) and mandible - were defined, within which a similarity metric was calculated and used as a registration quality tracking metric over the course of treatment. First, sensitivity to large misregistrations was analyzed for normalized cross-correlation (NCC) and mutual information (MI) in the context of statistical analysis. The distribution of metrics was obtained for displacements that varied according to a normal distribution with standard deviation of σ = 2 mm, and the detectability of displacements greater than 5 mm was investigated. Then, similarity metric control charts were created using a statistical process control (SPC) framework to objectively monitor the image registration and review process. Patient-specific control charts were created using NCC values from the first five fractions to set a patient-specific process capability limit. Population control charts were created using the average of the first five NCC values for all patients in the study. For each patient, the similarity metrics were calculated as a function of unidirectional translation, referred to as the effective displacement. Patient-specific action limits corresponding to 5 mm effective displacements were defined. Furthermore, effective displacements of the ten registrations with the lowest similarity metrics were compared with a three dimensional (3DoF) couch displacement required to align the anatomical landmarks. Normalized cross-correlation identified suboptimal registrations more effectively than MI within the framework of SPC. Deviations greater than 5 mm were detected at 2.8σ and 2.1σ from the mean for NCC and MI, respectively. Patient-specific control charts using NCC evaluated daily variation and identified statistically significant deviations. This study also showed that subjective evaluations of the images were not always consistent. Population control charts identified a patient whose tracking metrics were significantly lower than those of other patients. The patient-specific action limits identified registrations that warranted immediate evaluation by an expert. When effective displacements in the anterior-posterior direction were compared to 3DoF couch displacements, the agreement was ±1 mm for seven of 10 patients for both C-spine and mandible RTVs. Qualitative review alone of IGRT images can result in inconsistent feedback to the IGRT process. Registration tracking using NCC objectively identifies statistically significant deviations. When used in conjunction with the current image review process, this tool can assist in improving the safety and consistency of the IGRT process. © 2018 American Association of Physicists in Medicine.

76 FR 36961 - Standards and Specifications for Timber Products Acceptable for Use by Rural Utilities Service...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

... limited to the equivalent displacement of a knot \\3/8\\ of an inch deep on one face and the maximum round.../2\\ the equivalent displacement of a round knot permitted at that location, provided that the depth...

21 CFR 173.350 - Combustion product gas.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) SECONDARY DIRECT FOOD ADDITIVES PERMITTED IN FOOD FOR HUMAN CONSUMPTION Specific Usage Additives § 173.350... displacing oxygen in accordance with the following prescribed conditions: (a) The food additive is... displace or remove oxygen in the processing, storage, or packaging of beverage products and other food...

Optimization-based controller design for rotorcraft

NASA Technical Reports Server (NTRS)

Tsing, N.-K.; Fan, M. K. H.; Barlow, J.; Tits, A. L.; Tischler, M. B.

1993-01-01

An optimization-based methodology for linear control system design is outlined by considering the design of a controller for a UH-60 rotorcraft in hover. A wide range of design specifications is taken into account: internal stability, decoupling between longitudinal and lateral motions, handling qualities, and rejection of windgusts. These specifications are investigated while taking into account physical limitations in the swashplate displacements and rates of displacement. The methodology crucially relies on user-machine interaction for tradeoff exploration.

Split-Stirling-cycle displacer linear-electric drive

NASA Technical Reports Server (NTRS)

Ackermann, R. A.; Bhate, S. K.; Byrne, D. V.

1983-01-01

The retrofit of a 1/4-W split-Stirling cooler with a linear driven on the displacer was achieved and its performance characterized. The objective of this work was to demonstrate that a small linear motor could be designed to meet the existing envelope specifications of the cooler and that an electric linear drive on the displacer could improve the cooler's reliability and performance. The paper describes the characteristics of this motor and presents cooler test results.

Static aeroelastic analysis and tailoring of missile control fins

NASA Technical Reports Server (NTRS)

Mcintosh, S. C., Jr.; Dillenius, M. F. E.

1989-01-01

A concept for enhancing the design of control fins for supersonic tactical missiles is described. The concept makes use of aeroelastic tailoring to create fin designs (for given planforms) that limit the variations in hinge moments that can occur during maneuvers involving high load factors and high angles of attack. It combines supersonic nonlinear aerodynamic load calculations with finite-element structural modeling, static and dynamic structural analysis, and optimization. The problem definition is illustrated. The fin is at least partly made up of a composite material. The layup is fixed, and the orientations of the material principal axes are allowed to vary; these are the design variables. The objective is the magnitude of the difference between the chordwise location of the center of pressure and its desired location, calculated for a given flight condition. Three types of constraints can be imposed: upper bounds on static displacements for a given set of load conditions, lower bounds on specified natural frequencies, and upper bounds on the critical flutter damping parameter at a given set of flight speeds and altitudes. The idea is to seek designs that reduce variations in hinge moments that would otherwise occur. The block diagram describes the operation of the computer program that accomplishes these tasks. There is an option for a single analysis in addition to the optimization.

Interaction of the Retinoblastoma Protein with Orc1 and Its Recruitment to Human Origins of DNA Replication

PubMed Central

Mendoza-Maldonado, Ramiro; Paolinelli, Roberta; Galbiati, Laura; Giadrossi, Sara; Giacca, Mauro

2010-01-01

Background The retinoblastoma protein (Rb) is a crucial regulator of cell cycle progression by binding with E2F transcription factor and repressing the expression of a variety of genes required for the G1-S phase transition. Methodology/Principal Findings Here we show that Rb and E2F1 directly participate in the control of initiation of DNA replication in human HeLa, U2OS and T98G cells by specifically binding to origins of DNA replication in a cell cycle regulated manner. We show that, both in vitro and inside the cells, the largest subunit of the origin recognition complex (Orc1) specifically binds hypo-phosphorylated Rb and that this interaction is competitive with the binding of Rb to E2F1. The displacement of Rb-bound Orc1 by E2F1 at origins of DNA replication marks the progression of the G1 phase of the cell cycle toward the G1-S border. Conclusions/Significance The participation of Rb and E2F1 in the formation of the multiprotein complex that binds origins of DNA replication in mammalian cells appears to represent an effective mechanism to couple the expression of genes required for cell cycle progression to the activation of DNA replication. PMID:21085491

Identification and Cloning of Centaurin-α

PubMed Central

Hammonds-Odie, Latanya P.; Jackson, Trevor R.; Profit, Adam A.; Blader, Ira J.; Turck, Christoph W.; Prestwich, Glenn D.; Theibert, Anne B.

2015-01-01

Using an affinity resin and photoaffinity label based on phospholipid analogs of inositol 1,3,4,5-tetrakisphosphate (InsP4), we have isolated, characterized, and cloned a 46-kDa protein from rat brain, which we have named centaurin-α. Binding specificity was determined using displacement of 1-O-[3H](3-[4-benzoyldihydrocinnamidyl]propyl)-InsP4 photoaffinity labeling. Centaurin-α displayed highest affinity for phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) (IC50 = 120 nm), whereas InsP4, PtdInsP2, and InsP3 bound with 5-, 12-, and >50-fold lower affinity, respectively. Screening a rat brain cDNA library with a polymerase chain reaction product, generated using partial amino acid sequence from tryptic peptides, yielded a full-length clone. The 2,450-base pair cDNA contained an open reading frame (ORF) encoding a novel protein of 419 amino acids. Northern analysis revealed a 2.5-kilobase transcript that is highly expressed in brain. The deduced sequence contains a novel putative zinc finger motif, 10 ankyrin-like repeats, and shows homology to recently identified yeast and mammalian Arf GTPase-activating proteins. Given the specificity of binding and enrichment in brain, centaurin-α is a candidate PtdInsP3 receptor that may link the activation of phosphoinositide 3-kinase to downstream responses in the brain. PMID:8702546

On the Use of the Beta Distribution in Probabilistic Resource Assessments

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

Olea, Ricardo A., E-mail: olea@usgs.gov

2011-12-15

The triangular distribution is a popular choice when it comes to modeling bounded continuous random variables. Its wide acceptance derives mostly from its simple analytic properties and the ease with which modelers can specify its three parameters through the extremes and the mode. On the negative side, hardly any real process follows a triangular distribution, which from the outset puts at a disadvantage any model employing triangular distributions. At a time when numerical techniques such as the Monte Carlo method are displacing analytic approaches in stochastic resource assessments, easy specification remains the most attractive characteristic of the triangular distribution. Themore » beta distribution is another continuous distribution defined within a finite interval offering wider flexibility in style of variation, thus allowing consideration of models in which the random variables closely follow the observed or expected styles of variation. Despite its more complex definition, generation of values following a beta distribution is as straightforward as generating values following a triangular distribution, leaving the selection of parameters as the main impediment to practically considering beta distributions. This contribution intends to promote the acceptance of the beta distribution by explaining its properties and offering several suggestions to facilitate the specification of its two shape parameters. In general, given the same distributional parameters, use of the beta distributions in stochastic modeling may yield significantly different results, yet better estimates, than the triangular distribution.« less

High-stringency screening of target-binding partners using a microfluidic device

DOEpatents

Soh, Hyongsok; Lou, Xinhui; Lagally, Eric

2015-12-01

The invention provides a method of screening a library of candidate agents by contacting the library with a target in a reaction mixture under a condition of high stringency, wherein the target includes a tag that responds to a controllable force applied to the tag, and passing the members of the library through a microfluidic device in a manner that exposes the library members to the controllable force, thereby displacing members of the library that are bound to the target relative to their unbound counterparts. Kits and systems for use with the methods of the invention are also provided.

Asymptotic Bounds for Solutions to a System of Damped Integrodifferential Equations of Electromagnetic Theory.

DTIC Science & Technology

1979-05-28

of integrodiffereiTaT~- equations governs the evolution of the components of the electric displacement field in a simple class of rigid holohedral...vacuum so that j — C and J~ — c E , H = B. In0 [3] and [4] this author has treated the evolution equations associated with the Maxwell—Hopkinsofl...F .~~~~~~‘ r - — ~~~~~ ’~~~ “~ I I be viewed as a linearized version of a more general theory introduced by Volterra in 1912 [5] to treat the case

Helium vs. Proton Induced Displacement Damage in Electronic Materials

NASA Technical Reports Server (NTRS)

Ringo, Sawnese; Barghouty, A. F.

2010-01-01

In this project, the specific effects of displacement damage due to the passage of protons and helium nuclei on some typical electronic materials will be evaluated and contrasted. As the electronic material absorbs the energetic proton and helium momentum, degradation of performance occurs, eventually leading to overall failure. Helium nuclei traveling at the same speed as protons are expected to impart more to the material displacement damage; due to the larger mass, and thus momentum, of helium nuclei compared to protons. Damage due to displacement of atoms in their crystalline structure can change the physical properties and hence performance of the electronic materials.

RETRAINING BY PRIVATE INDUSTRY.

ERIC Educational Resources Information Center

HOOS, IDA R.

SEVERAL SAN FRANCISCO BAY AREA COMPANIES WERE EXAMINED FOR SPECIFIC PROGRAMS FOR DISPLACED EMPLOYEES. ARMOUR AND COMPANY SOUGHT TO GUIDE DISPLACED EMPLOYEES TO CLASSES OR COURSES OF ACTION OUTSIDE ITS OWN SPHERE OF OPERATION. LOCKHEED HAS PROVIDED UNUSUALLY WELL FOR UPGRADING AND RETRAINING, MAINLY BECAUSE OF INDUSTRY FLUCTUATIONS AND RAPID…

A mechanistic study of the interaction of water-soluble borate glass with apatite-bound heterocyclic nitrogen-containing bisphosphonates.

PubMed

Pramanik, Chandrani; Sood, Parveen; Niu, Li-Na; Yuan, He; Ghoshal, Sushanta; Henderson, Walter; Liu, Yaodong; Jang, Seung Soon; Kumar, Satish; Pashley, David H; Tay, Franklin R

2016-02-01

Long-term oral and intravenous use of nitrogen-containing bisphosphonates (N-BPs) is associated with osteonecrosis of the jaw. Although N-BPs bind strongly to bone surfaces via non-covalent bonds, it is possible for extrinsic ions to dissociate bound N-BPs from mineralized bone by competitive desorption. Here, we investigate the effects and mechanism of using an ionic cocktail derived from borate bioactive glass for sequestration of heterocyclic N-BPs bound to apatite. By employing solid-state and solution-state analytical techniques, we confirmed that sequestration of N-BPs from bisphosphonate-bound apatite occurs in the presence of the borate-containing ionic cocktail. Simulations by density functional theory computations indicate that magnesium cation and borate anion are well within the extent of the risedronate or zoledronate anion to form precipitate complexes. The sequestration mechanism is due to the borate anion competing with bisphosphonates for similar electron-deficient sites on the apatite surface for binding. Thus, application of the borate-containing ionic cocktail represents a new topical lavage approach for removing apatite-bound heterocyclic N-BPs from exposed necrotic bone in bisphosphonate-related osteonecrosis of the jaw. Long-term oral consumption and injections of nitrogen-containing bisphosphonates (N-BPs) may result in death of the jaw bone when there is traumatic injury to the bone tissues. To date, there is no effective treatment for such a condition. This work reported the use of an ionic cocktail derived from water-soluble borate glass microfibers to displace the most potent type of N-BPs that are bound strongly to the mineral component on bone surfaces. The mechanism responsible for such an effect has been identified to be cation-mediated complexation of borate anions with negatively-charged N-BPs, allowing them to be released from the mineral surface. This borate-containing cocktail may be developed into a novel topical rinse for removing mineral-bound N-BPs from exposed dead bone. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Japanese Culture-Bound Disorders: The Relationship between "Taijin Kyofusho, Hikikomori," and Shame

ERIC Educational Resources Information Center

Cole, Levi Edward

2013-01-01

First conceptualized in the 1960s, the term culture-bound disorders refers to a classification of mental disorders or syndromes that are considered specific or closely related to cultural factors and or particular ethnocultural groups. In Japan, two culture-bound disorders, "taijin kyofusho" and "hikikomori," have seized the…

Outward Bound Giwaykiwin: Connecting to Land and Culture through Indigenous Outdoor Education

ERIC Educational Resources Information Center

Lowan, Greg

2007-01-01

Outward Bound Canada's (OBC) Giwaykiwin Program was founded in 1985 in response to a recognized need for programming specific to students from Indigenous backgrounds. The Giwaykiwin program aims to integrate Outward Bound (OB) and Indigenous philosophies and traditions. Giwaykiwin means "coming home" in Ojibwa and signifies the program's…

Predicted bounds on peak global mean sea level during marine isotope stages 5a and 5c

NASA Astrophysics Data System (ADS)

Creveling, Jessica R.; Mitrovica, Jerry X.; Clark, Peter U.; Waelbroeck, Claire; Pico, Tamara

2017-05-01

Estimates of marine isotope stage (MIS) 5c and 5a global mean sea level (GMSL) based on marine terraces and coastal indicators range from 15-37 m and 9-30 m below present, respectively. Tectonic displacement and glacial isostatic adjustment (GIA) complicate efforts to refine this range. We revisit this issue using numerical predictions of post-glacial sea-level change and updated estimates of site-specific tectonic signals based upon these predictions. Laurentide and Cordilleran peripheral bulge dynamics and variations in the gravitational effect of these ice masses dominate the GIA signal along the east and west coasts of North America. Published compilations suggest that MIS 5 sea-level indicators extending from Virginia to the Caribbean lie on the outer flank of the peripheral bulge, while those along a transect from Oregon to Baja California sit on the inner flank of the bulge. Our GIA modeling reconciles these data by adopting a significantly weaker (i.e., lower viscosity) upper mantle in analyzing data on the Pacific coast relative to the Atlantic, an inference supported by seismic tomography. We present a sensitivity analysis that compares the observed elevation of globally distributed high stand markers to a suite of GIA simulations that vary the Earth model and GMSL from the Last Interglaciation (MIS 5e, ∼130-115 ka) to 70 ka. We conclude that GMSL peaked at -8.5 ± 4.6 m (1σ) during MIS 5a and -9.4 ± 5.3 m during MIS 5c. A more restrictive analysis yields slightly wider bounds corresponding to -10.5 ± 5.5 m and -11.1 ± 6.6 m, respectively.

Reducing Conservatism of Analytic Transient Response Bounds via Shaping Filters

NASA Technical Reports Server (NTRS)

Kwan, Aiyueh; Bedrossian, Nazareth; Jan, Jiann-Woei; Grigoriadis, Karolos; Hua, Tuyen (Technical Monitor)

1999-01-01

Recent results show that the peak transient response of a linear system to bounded energy inputs can be computed using the energy-to-peak gain of the system. However, analytically computed peak response bound can be conservative for a class of class bounded energy signals, specifically pulse trains generated from jet firings encountered in space vehicles. In this paper, shaping filters are proposed as a Methodology to reduce the conservatism of peak response analytic bounds. This Methodology was applied to a realistic Space Station assembly operation subject to jet firings. The results indicate that shaping filters indeed reduce the predicted peak response bounds.

Constraining Basin Depth and Fault Displacement in the Malombe Basin Using Potential Field Methods

NASA Astrophysics Data System (ADS)

Beresh, S. C. M.; Elifritz, E. A.; Méndez, K.; Johnson, S.; Mynatt, W. G.; Mayle, M.; Atekwana, E. A.; Laó-Dávila, D. A.; Chindandali, P. R. N.; Chisenga, C.; Gondwe, S.; Mkumbwa, M.; Kalaguluka, D.; Kalindekafe, L.; Salima, J.

2017-12-01

The Malombe Basin is part of the Malawi Rift which forms the southern part of the Western Branch of the East African Rift System. At its southern end, the Malawi Rift bifurcates into the Bilila-Mtakataka and Chirobwe-Ntcheu fault systems and the Lake Malombe Rift Basin around the Shire Horst, a competent block under the Nankumba Peninsula. The Malombe Basin is approximately 70km from north to south and 35km at its widest point from east to west, bounded by reversing-polarity border faults. We aim to constrain the depth of the basin to better understand displacement of each border fault. Our work utilizes two east-west gravity profiles across the basin coupled with Source Parameter Imaging (SPI) derived from a high-resolution aeromagnetic survey. The first gravity profile was done across the northern portion of the basin and the second across the southern portion. Gravity and magnetic data will be used to constrain basement depths and the thickness of the sedimentary cover. Additionally, Shuttle Radar Topography Mission (SRTM) data is used to understand the topographic expression of the fault scarps. Estimates for minimum displacement of the border faults on either side of the basin were made by adding the elevation of the scarps to the deepest SPI basement estimates at the basin borders. Our preliminary results using SPI and SRTM data show a minimum displacement of approximately 1.3km for the western border fault; the minimum displacement for the eastern border fault is 740m. However, SPI merely shows the depth to the first significantly magnetic layer in the subsurface, which may or may not be the actual basement layer. Gravimetric readings are based on subsurface density and thus circumvent issues arising from magnetic layers located above the basement; therefore expected results for our work will be to constrain more accurate basin depth by integrating the gravity profiles. Through more accurate basement depth estimates we also gain more accurate displacement estimates for the Basin's faults. Not only do the improved depth estimates serve as a proxy to the viability of hydrocarbon exploration efforts in the region, but the improved displacement estimates also provide a better understanding of extension accommodation within the Malawi Rift.

Kinematics of polygonal fault systems: observations from the northern North Sea

NASA Astrophysics Data System (ADS)

Wrona, Thilo; Magee, Craig; Jackson, Christopher A.-L.; Huuse, Mads; Taylor, Kevin G.

2017-12-01

Layer-bound, low-displacement normal faults, arranged into a broadly polygonal pattern, are common in many sedimentary basins. Despite having constrained their gross geometry, we have a relatively poor understanding of the processes controlling the nucleation and growth (i.e. the kinematics) of polygonal fault systems. In this study we use high-resolution 3-D seismic reflection and borehole data from the northern North Sea to undertake a detailed kinematic analysis of faults forming part of a seismically well-imaged polygonal fault system hosted within the up to 1000 m thick, Early Palaeocene-to-Middle Miocene mudstones of the Hordaland Group. Growth strata and displacement-depth profiles indicate faulting commenced during the Eocene to early Oligocene, with reactivation possibly occurring in the late Oligocene to middle Miocene. Mapping the position of displacement maxima on 137 polygonal faults suggests that the majority (64%) nucleated in the lower 500 m of the Hordaland Group. The uniform distribution of polygonal fault strikes in the area indicates that nucleation and growth were not driven by gravity or far-field tectonic extension as has previously been suggested. Instead, fault growth was likely facilitated by low coefficients of residual friction on existing slip surfaces, and probably involved significant layer-parallel contraction (strains of 0.01-0.19) of the host strata. To summarize, our kinematic analysis provides new insights into the spatial and temporal evolution of polygonal fault systems.

The influence of geologic structures on deformation due to ground water withdrawal.

PubMed

Burbey, Thomas J

2008-01-01

A 62 day controlled aquifer test was conducted in thick alluvial deposits at Mesquite, Nevada, for the purpose of monitoring horizontal and vertical surface deformations using a high-precision global positioning system (GPS) network. Initial analysis of the data indicated an anisotropic aquifer system on the basis of the observed radial and tangential deformations. However, new InSAR data seem to indicate that the site may be bounded by an oblique normal fault as the subsidence bowl is both truncated to the northwest and offset from the pumping well to the south. A finite-element numerical model was developed using ABAQUS to evaluate the potential location and hydromechanical properties of the fault based on the observed horizontal deformations. Simulation results indicate that for the magnitude and direction of motion at the pumping well and at other GPS stations, which is toward the southeast (away from the inferred fault), the fault zone (5 m wide) must possess a very high permeability and storage coefficient and cross the study area in a northeast-southwest direction. Simulated horizontal and vertical displacements that include the fault zone closely match observed displacements and indicate the likelihood of the presence of the inferred fault. This analysis shows how monitoring horizontal displacements can provide valuable information about faults, and boundary conditions in general, in evaluating aquifer systems during an aquifer test.

Use of statistical analysis of long term displacement rate time series for the definition of Early Warning thresholds. The case studies of the Ruinon and Mont de La Saxe landslides (N Italy)

NASA Astrophysics Data System (ADS)

Alberti, Stefano; Battista Crosta, Giovanni; Rivolta, Carlo

2016-04-01

Rockslides are characterized by complex spatial and temporal evolution. Forecasting their behaviour is a hard task, due to non-linear displacement trends and the significant effects of seasonal or occasional events. The displacement rate and the landslide evolution are influenced by various factors like lithology, structural and hydrological settings, as well as meteo-climatic factors (e.g. snowmelt and rainfall). The nature of the relationships among these factors is clearly non linear, site specific and even specific to each sector that can be individuated within the main landslide mass. In this contribution, total displacement and displacement rate time series are extracted from Ground-based Interferometric synthetic aperture radar (GB-InSAR) surveys, monitoring of optical targets by total stations, a GPS network and multi-parametric borehole probes. Different Early Warning domains, characterized by different velocity regimes (slow to fast domains) and with different sensitivity to external perturbations (e.g. snowmelt and rainfall), have been identified in previous studies at the two sites. The Mont de La Saxe rockslide (ca. 8 x 106 m3) is located in the Upper Aosta Valley, and it has been intensively monitored since 2009 by the Valle D'Aosta Geological Survey. The Ruinon landslide (ca. 15 x 106 to 20 x 106 m3) is located in the Upper Valtellina (Lombardy region) and monitoring data are available starting since 2006 and have been provided by ARPA Lombardia. Both phenomena are alpine deep-seated rockslides characterized by different displacement velocity, from few centimetres to over 1 meter per year, and which have undergone exceptional accelerations during some specific events. We experiment the use of normal probability plots for the analysis of displacement rates of specific points belonging to different landslide sectors and recorded during almost ten years of monitoring. This analyses allow us to define: (i) values with a specific probability value expressed in terms of percentiles; (ii) values for which a specific change in behaviour is observed which could be associated to a specific type of triggering event (e.g. rainfall intensity, duration or amount; snowmelt amount) . These values could be used to support the choice of threshold values for the management of Early Warning System, by considering also the minimization of false alarms. The analyses have been performed by using data averaged over different time intervals so to study the effects of noise on the threshold values. Analyses of false alarm triggered by the choice of different threshold values (i.e. different percentiles) have been performed and analysed. This could be an innovative approach to define velocity thresholds of Early Warning system and to analyse the quantitative data derived from remote sensing monitoring and filed surveys, by linking them to both spatial and temporal changes.

Sensitivity and specificity of a new MRI method evaluating temporo-mandibular joint disc-condyle relationships: an in vivo study.

PubMed

Benbelaïd, R; Fleiter, B

2006-03-01

The aim of this study was to evaluate sensitivity and specificity of a new method to locate temporo-mandibular joint (TMJ) disc using magnetic resonance imaging (MRI) and analyze disc-condyle relationships, in asymptomatic subjects and patients with disc displacement. Twenty-nine sagittal MRI of 16 subjects, 8 asymptomatic volunteers and 8 subjects with anterior disc displacement, were carried out during controlled opening from intercuspal position up to a 25 mm opening. Selected sections were analyzed with a graphic computerized system of coordinates. The total surface area (TS) of disc section was separated into anterior surface area (AS) and posterior surface area. Areas were determined by computer. Two trained examiners drew images at random. The reliability of AS/TS ratio index was evaluated in a previous study. AS/TS ratio sensitivity (Se) and specificity (Sp) were calculated closed mouth, 5 mm open and 25 mm open mouth. Best sensitivity (Se=0.63) and specificity (Sp=0.81) were obtained when MRI was realized with closed mouth and 25 mm open mouth. Lower sensitivity was observed when MRI was performed either with closed mouth (Se=0.54) or 25 mm open mouth (Se=0.18). Lower specificity was observed with 5 mm open mouth (Sp=0.68). In conclusion, it was confirmed as well that MRI of anterior disc displacement should be performed with closed mouth and opened mouth. Thus, further studies are required to assess disc displacement and mechanical alterations and to evaluate the risk of direct damage on TMJ tissues.

Reactive Balance Control in Response to Perturbation in Unilateral Stance: Interaction Effects of Direction, Displacement and Velocity on Compensatory Neuromuscular and Kinematic Responses

PubMed Central

Freyler, Kathrin; Gollhofer, Albert; Colin, Ralf; Brüderlin, Uli; Ritzmann, Ramona

2015-01-01

Unexpected sudden perturbations challenge postural equilibrium and require reactive compensation. This study aimed to assess interaction effects of the direction, displacement and velocity of perturbations on electromyographic (EMG) activity, centre of pressure (COP) displacement and joint kinematics to detect neuromuscular characteristics (phasic and segmental) and kinematic strategies of compensatory reactions in an unilateral balance paradigm. In 20 subjects, COP displacement and velocity, ankle, knee and hip joint excursions and EMG during short (SLR), medium (MLR) and long latency response (LLR) of four shank and five thigh muscles were analysed during random surface translations varying in direction (anterior-posterior (sagittal plane), medial-lateral (frontal plane)), displacement (2 vs. 3cm) and velocity (0.11 vs. 0.18m/s) of perturbation when balancing on one leg on a movable platform. Phases: SLR and MLR were scaled to increased velocity (P<0.05); LLR was scaled to increased displacement (P<0.05). Segments: phasic interrelationships were accompanied by segmental distinctions: distal muscles were used for fast compensation in SLR (P<0.05) and proximal muscles to stabilise in LLR (P<0.05). Kinematics: ankle joints compensated for both increasing displacement and velocity in all directions (P<0.05), whereas knee joint deflections were particularly sensitive to increasing displacement in the sagittal (P<0.05) and hip joint deflections to increasing velocity in the frontal plane (P<0.05). COP measures increased with increasing perturbation velocity and displacement (P<0.05). Interaction effects indicate that compensatory responses are based on complex processes, including different postural strategies characterised by phasic and segmental specifications, precisely adjusted to the type of balance disturbance. To regain balance after surface translation, muscles of the distal segment govern the quick regain of equilibrium; the muscles of the proximal limb serve as delayed stabilisers after a balance disturbance. Further, a kinematic distinction regarding the compensation for balance disturbance indicated different plane- and segment-specific sensitivities with respect to the determinants displacement and velocity. PMID:26678061

Physical Uncertainty Bounds (PUB)

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

Vaughan, Diane Elizabeth; Preston, Dean L.

2015-03-19

This paper introduces and motivates the need for a new methodology for determining upper bounds on the uncertainties in simulations of engineered systems due to limited fidelity in the composite continuum-level physics models needed to simulate the systems. We show that traditional uncertainty quantification methods provide, at best, a lower bound on this uncertainty. We propose to obtain bounds on the simulation uncertainties by first determining bounds on the physical quantities or processes relevant to system performance. By bounding these physics processes, as opposed to carrying out statistical analyses of the parameter sets of specific physics models or simply switchingmore » out the available physics models, one can obtain upper bounds on the uncertainties in simulated quantities of interest.« less

Identification of a GTP-bound Rho specific scFv molecular sensor by phage display selection

PubMed Central

Goffinet, Marine; Chinestra, Patrick; Lajoie-Mazenc, Isabelle; Medale-Giamarchi, Claire; Favre, Gilles; Faye, Jean-Charles

2008-01-01

Background The Rho GTPases A, B and C proteins, members of the Rho family whose activity is regulated by GDP/GTP cycling, function in many cellular pathways controlling proliferation and have recently been implicated in tumorigenesis. Although overexpression of Rho GTPases has been correlated with tumorigenesis, only their GTP-bound forms are able to activate the signalling pathways implicated in tumorigenesis. Thus, the focus of much recent research has been to identify biological tools capable of quantifying the level of cellular GTP-bound Rho, or determining the subcellular location of activation. However useful, these tools used to study the mechanism of Rho activation still have limitations. The aim of the present work was to employ phage display to identify a conformationally-specific single chain fragment variable (scFv) that recognizes the active, GTP-bound, form of Rho GTPases and is able to discriminate it from the inactive, GDP-bound, Rho in endogenous settings. Results After five rounds of phage selection using a constitutively activated mutant of RhoB (RhoBQ63L), three scFvs (A8, C1 and D11) were selected for subsequent analysis. Further biochemical characterization was pursued for the single clone, C1, exhibiting an scFv structure. C1 was selective for the GTP-bound form of RhoA, RhoB, as well as RhoC, and failed to recognize GTP-loaded Rac1 or Cdc42, two other members of the Rho family. To enhance its production, soluble C1 was expressed in fusion with the N-terminal domain of phage protein pIII (scFv C1-N1N2), it appeared specifically associated with GTP-loaded recombinant RhoA and RhoB via immunoprecipitation, and endogenous activated Rho in HeLa cells as determined by immunofluorescence. Conclusion We identified an antibody, C1-N1N2, specific for the GTP-bound form of RhoB from a phage library, and confirmed its specificity towards GTP-bound RhoA and RhoC, as well as RhoB. The success of C1-N1N2 in discriminating activated Rho in immunofluorescence studies implies that this new tool, in collaboration with currently used RhoA and B antibodies, has the potential to analyze Rho activation in cell function and tumor development. PMID:18377644

Tissue specific resonance frequencies of water and metabolites within the human brain

NASA Astrophysics Data System (ADS)

Chadzynski, Grzegorz L.; Bender, Benjamin; Groeger, Adriane; Erb, Michael; Klose, Uwe

2011-09-01

Chemical shift imaging (CSI) without water suppression was used to examine tissue-specific resonance frequencies of water and metabolites within the human brain. The aim was to verify if there are any regional differences in those frequencies and to determine the influence of chemical shift displacement in slice-selection direction. Unsuppressed spectra were acquired at 3 T from nine subjects. Resonance frequencies of water and after water signal removal of total choline, total creatine and NAA were estimated. Furthermore, frequency distances between the water and those resonances were calculated. Results were corrected for chemical shift displacement. Frequency distances between water and metabolites were consistent and greater for GM than for WM. The highest value of WM to GM difference (14 ppb) was observed for water to NAA frequency distance. This study demonstrates that there are tissue-specific differences between frequency distances of water and metabolites. Moreover, the influence of chemical shift displacement in slice-selection direction is showed to be negligible.

Tissue specific resonance frequencies of water and metabolites within the human brain.

PubMed

Chadzynski, Grzegorz L; Bender, Benjamin; Groeger, Adriane; Erb, Michael; Klose, Uwe

2011-09-01

Chemical shift imaging (CSI) without water suppression was used to examine tissue-specific resonance frequencies of water and metabolites within the human brain. The aim was to verify if there are any regional differences in those frequencies and to determine the influence of chemical shift displacement in slice-selection direction. Unsuppressed spectra were acquired at 3T from nine subjects. Resonance frequencies of water and after water signal removal of total choline, total creatine and NAA were estimated. Furthermore, frequency distances between the water and those resonances were calculated. Results were corrected for chemical shift displacement. Frequency distances between water and metabolites were consistent and greater for GM than for WM. The highest value of WM to GM difference (14ppb) was observed for water to NAA frequency distance. This study demonstrates that there are tissue-specific differences between frequency distances of water and metabolites. Moreover, the influence of chemical shift displacement in slice-selection direction is showed to be negligible. Copyright © 2011 Elsevier Inc. All rights reserved.

The Hydrogenase Activity of the Molybdenum/Copper-containing Carbon Monoxide Dehydrogenase of Oligotropha carboxidovorans*

PubMed Central

Wilcoxen, Jarett; Hille, Russ

2013-01-01

The reaction of the air-tolerant CO dehydrogenase from Oligotropha carboxidovorans with H2 has been examined. Like the Ni-Fe CO dehydrogenase, the enzyme can be reduced by H2 with a limiting rate constant of 5.3 s−1 and a dissociation constant Kd of 525 μm; both kred and kred/Kd, reflecting the breakdown of the Michaelis complex and the reaction of free enzyme with free substrate in the low [S] regime, respectively, are largely pH-independent. During the reaction with H2, a new EPR signal arising from the Mo/Cu-containing active site of the enzyme is observed which is distinct from the signal seen when the enzyme is reduced by CO, with greater g anisotropy and larger hyperfine coupling to the active site 63,65Cu. The signal also exhibits hyperfine coupling to at least two solvent-exchangeable protons of bound substrate that are rapidly exchanged with solvent. Proton coupling is also evident in the EPR signal seen with the dithionite-reduced native enzyme, and this coupling is lost in the presence of bicarbonate. We attribute the coupled protons in the dithionite-reduced enzyme to coordinated water at the copper site in the native enzyme and conclude that bicarbonate is able to displace this water from the copper coordination sphere. On the basis of our results, a mechanism for H2 oxidation is proposed which involves initial binding of H2 to the copper of the binuclear center, displacing the bound water, followed by sequential deprotonation through a copper-hydride intermediate to reduce the binuclear center. PMID:24165123

Northward expansion of Tibet beyond the Altyn Tagh Fault

NASA Astrophysics Data System (ADS)

Cunningham, D.; Zhang, J.; Yanfeng, L.; Vernon, R.

2017-12-01

For many tectonicists, the evolution of northern Tibet stops at the Altyn Tagh Fault (ATF). This study challenges that assumption. Structural field observations and remote sensing analysis indicate that the Sanweishan and Nanjieshan basement-cored ridges of the Archean Dunhuang Block, which interrupt the north Tibetan foreland directly north of the ATF, are bound and cut by an array of strike-slip, thrust and oblique-slip faults that have been active in the Quaternary and remain potentially active. The Sanweishan is essentially a SE-tilted block that is bound on its NW margin by a steep south-dipping thrust fault that has also accommodated sinistral strike-slip displacements. The Nanjieshan consists of parallel, but offset basement ridges that record NNW and SSE thrust displacements and sinistral strike-slip. Regional folds characterize the extreme eastern Nanjieshan perhaps above blind thrust faults which are emergent further west. At the surface, local fault reactivation of basement fabrics is an important control on the kinematics of deformation. Previously published magnetotelluric data for the region suggest that the major faults of the Sanweishan and Nanjieshan ultimately root to the south within conductive zones that merge into the ATF. Therefore, although the southern margin of the Dunhuang Block focuses significant deformation along the ATF, the adjacent cratonic basement to the north is also affected. Collectively, the ATF and structurally linked Sanweishan and Nanjieshan fault array represent a regional asymmetric half-flower structure that is dominated by non-strain partitioned sinistral transpression. The NW-trending Dengdengshan thrust fault array near Yumen City appears to define the northeastern limit of the Sanweishan-Nanjieshan block, which may be viewed regionally as the most northern, but early-stage expression of Tibetan Plateau growth into a reluctantly deforming, mechanically stiff Archean craton.

Horse Liver Alcohol Dehydrogenase: Zinc Coordination and Catalysis

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

Plapp, Bryce V.; Savarimuthu, Baskar Raj; Ferraro, Daniel J.

During catalysis by liver alcohol dehydrogenase (ADH), a water bound to the catalytic zinc is replaced by the oxygen of the substrates. The mechanism might involve a pentacoordinated zinc or a double-displacement reaction with participation by a nearby glutamate residue, as suggested by studies of human ADH3, yeast ADH1, and some other tetrameric ADHs. Zinc coordination and participation of water in the enzyme mechanism were investigated by X-ray crystallography. The apoenzyme and its complex with adenosine 5'-diphosphoribose have an open protein conformation with the catalytic zinc in one position, tetracoordinated by Cys-46, His-67, Cys-174, and a water molecule. The bidentatemore » chelators 2,2'-bipyridine and 1,10-phenanthroline displace the water and form a pentacoordinated zinc. The enzyme–NADH complex has a closed conformation similar to that of ternary complexes with coenzyme and substrate analogues; the coordination of the catalytic zinc is similar to that found in the apoenzyme, except that a minor, alternative position for the catalytic zinc is ~1.3 Å from the major position and closer to Glu-68, which could form the alternative coordination to the catalytic zinc. Complexes with NADH and N-1-methylhexylformamide or N-benzylformamide (or with NAD+ and fluoro alcohols) have the classical tetracoordinated zinc, and no water is bound to the zinc or the nicotinamide rings. The major forms of the enzyme in the mechanism have a tetracoordinated zinc, where the carboxylate group of Glu-68 could participate in the exchange of water and substrates on the zinc. Hydride transfer in the Michaelis complexes does not involve a nearby water.« less

Horse Liver Alcohol Dehydrogenase: Zinc Coordination and Catalysis

PubMed Central

2017-01-01

During catalysis by liver alcohol dehydrogenase (ADH), a water bound to the catalytic zinc is replaced by the oxygen of the substrates. The mechanism might involve a pentacoordinated zinc or a double-displacement reaction with participation by a nearby glutamate residue, as suggested by studies of human ADH3, yeast ADH1, and some other tetrameric ADHs. Zinc coordination and participation of water in the enzyme mechanism were investigated by X-ray crystallography. The apoenzyme and its complex with adenosine 5′-diphosphoribose have an open protein conformation with the catalytic zinc in one position, tetracoordinated by Cys-46, His-67, Cys-174, and a water molecule. The bidentate chelators 2,2′-bipyridine and 1,10-phenanthroline displace the water and form a pentacoordinated zinc. The enzyme–NADH complex has a closed conformation similar to that of ternary complexes with coenzyme and substrate analogues; the coordination of the catalytic zinc is similar to that found in the apoenzyme, except that a minor, alternative position for the catalytic zinc is ∼1.3 Å from the major position and closer to Glu-68, which could form the alternative coordination to the catalytic zinc. Complexes with NADH and N-1-methylhexylformamide or N-benzylformamide (or with NAD+ and fluoro alcohols) have the classical tetracoordinated zinc, and no water is bound to the zinc or the nicotinamide rings. The major forms of the enzyme in the mechanism have a tetracoordinated zinc, where the carboxylate group of Glu-68 could participate in the exchange of water and substrates on the zinc. Hydride transfer in the Michaelis complexes does not involve a nearby water. PMID:28640600

Three-dimensional modeling of pull-apart basins: implications for the tectonics of the Dead Sea Basin

USGS Publications Warehouse

Katzman, Rafael; ten Brink, Uri S.; Lin, Jian

1995-01-01

We model the three-dimensional (3-D) crustal deformation in a deep pull-apart basin as a result of relative plate motion along a transform system and compare the results to the tectonics of the Dead Sea Basin. The brittle upper crust is modeled by a boundary element technique as an elastic block, broken by two en echelon semi-infinite vertical faults. The deformation is caused by a horizontal displacement that is imposed everywhere at the bottom of the block except in a stress-free “shear zone” in the vicinity of the fault zone. The bottom displacement represents the regional relative plate motion. Results show that the basin deformation depends critically on the width of the shear zone and on the amount of overlap between basin-bounding faults. As the width of the shear zone increases, the depth of the basin decreases, the rotation around a vertical axis near the fault tips decreases, and the basin shape (the distribution of subsidence normalized by the maximum subsidence) becomes broader. In contrast, two-dimensional plane stress modeling predicts a basin shape that is independent of the width of the shear zone. Our models also predict full-graben profiles within the overlapped region between bounding faults and half-graben shapes elsewhere. Increasing overlap also decreases uplift near the fault tips and rotation of blocks within the basin. We suggest that the observed structure of the Dead Sea Basin can be described by a 3-D model having a large overlap (more than 30 km) that probably increased as the basin evolved as a result of a stable shear motion that was distributed laterally over 20 to 40 km.

Tectonic history of the Illinois basin

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

Kolata, D.R.; Nelson, J.W.

1990-05-01

The Illinois basin began as a failed rift that developed during breakup of a supercontinent approximately 550 Ma. A rift basin in the southernmost part of the present Illinois basin subsided rapidly and filled with about 3,000 m of probable Early and Middle Cambrian sediments. By the Late Cambrian, the rift-bounding faults became inactive and a broad relatively slowly subsiding embayment, extending well beyond the rift and open to the Iapetus Ocean, persisted through most of the Paleozoic Era. Widespread deformation swept through the proto-Illinois basin beginning in the latest Mississippian, continuing to the end of the Paleozoic Era. Upliftmore » of basement fault blocks resulted in the formation of many major folds and faults. The timing of deformation and location of these structures in the forelands of the Ouachita and Alleghanian orogenic belts suggest that much of the deformation resulted from continental collision between North America and Gondwana. The associated compressional stress reactivated the ancient rift-bounding faults, upthrusting the northern edge of a crustal block approximately 1,000 m within the rift. Concurrently, dikes (radiometrically dated as Early Permian), sills, and explosion breccias formed in or adjacent to the reactivated rift. Subsequent extensional stress, probably associated with breakup of Pangea, caused the crustal block within the rift to sink back to near its original position. High-angle, northeast- to east-west-trending normal faults, with as much as 1,000 m of displacement, formed in the southern part of the basin. These faults displace some of the northwest trending Early Permian dikes. Structural closure of the southern end of the Illinois basin was caused by uplift of the Pascola arch sometime between the Late Pennsylvanian and Late Cretaceous.« less

Late Cenozoic transpressional mountain building directly north of the Altyn Tagh Fault in the Sanweishan and Nanjieshan, North Tibetan Foreland, China

NASA Astrophysics Data System (ADS)

Cunningham, Dickson; Zhang, Jin; Li, Yanfeng

2016-09-01

For many tectonicists, the structural development of the northern Tibetan Plateau stops at the Altyn Tagh Fault (ATF). This study challenges that assumption. Structural field observations and remote sensing analysis indicate that the Sanweishan and Nanjieshan basement cored ridges of the Archean Dunhuang Block, which interrupt the north Tibetan foreland directly north of the ATF, are bound and cut by an array of strike-slip, thrust and oblique-slip faults that have been active in the Quaternary and remain potentially active. The Sanweishan is a SE-tilted block that is bound on its NW margin by a steep south-dipping thrust fault that has also accommodated sinistral strike-slip displacements. The Nanjieshan consists of parallel, but offset basement ridges that record NNW and SSE thrust displacements and sinistral strike-slip. Regional folds characterize the extreme eastern Nanjieshan and appear to have formed above blind thrust faults which break the surface further west. Previously published magnetotelluric data suggest that the major faults of the Sanweishan and Nanjieshan ultimately root to the south within conductive zones that are inferred to merge into the ATF. Therefore, although the southern margin of the Dunhuang Block focuses significant deformation along the ATF, the adjacent cratonic basement to the north is also affected. Collectively, the ATF and structurally linked Sanweishan and Nanjieshan fault array represent a regional asymmetric half-flower structure that is dominated by non-strain partitioned sinistral transpression. The NW-trending Dengdengshan thrust fault system near Yumen City appears to define the northeastern limit of the Sanweishan-Nanjieshan block, which may be regionally viewed as the most northern, but early-stage expression of Tibetan Plateau growth into a slowly deforming, mechanically stiff Archean craton.

San Antonio relay ramp: Area of stratal continuity between large-displacement barrier faults of the Edwards aquifer and Balcones fault zone, central Texas

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

Collins, E.W.

1996-09-01

The San Antonio relay ramp, a gentle southwest-dipping monocline, formed between the tips of two en echelon master faults having maximum throws of >240 in. Structural analysis of this relay ramp is important to studies of Edwards aquifer recharge and ground-water flow because the ramp is an area of relatively good stratal continuity linking the outcrop belt recharge zone and unconfined aquifer with the downdip confined aquifer. Part of the relay ramp lies within the aquifer recharge zone and is crossed by several southeast-draining creeks, including Salado, Cibolo, and Comal Creeks, that supply water to the ramp recharge area. Thismore » feature is an analog for similar structures within the aquifer and for potential targets for hydrocarbons in other Gulf Coast areas. Defining the ramp is an {approximately}13-km-wide right step of the Edwards Group outcrop belt and the en echelon master faults that bound the ramp. The master faults strike N55-75{degrees}E, and maximum displacement exceeds the {approximately}165-m thickness of the Edwards Group strata. The faults therefore probably serve as barriers to Edwards ground-water flow. Within the ramp, tilted strata gently dip southwestward at {approximately}5 m/km, and the total structural relief along the ramp`s southwest-trending axis is <240 in. The ramp`s internal framework is defined by three fault blocks that are {approximately}4 to {approximately}6 km wide and are bound by northeast-striking faults having maximum throws between 30 and 150 m. Within the fault blocks, local areas of high fracture permeability may exist where smaller faults and joints are well connected.« less

Search for new long-lived particles at √{ s } = 13 TeV

NASA Astrophysics Data System (ADS)

Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Ambrogi, F.; Asilar, E.; Bergauer, T.; Brandstetter, J.; Brondolin, E.; Dragicevic, M.; Erö, J.; Flechl, M.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Grossmann, J.; Hrubec, J.; Jeitler, M.; König, A.; Krammer, N.; Krätschmer, I.; Liko, D.; Madlener, T.; Mikulec, I.; Pree, E.; Rabady, D.; Rad, N.; Rohringer, H.; Schieck, J.; Schöfbeck, R.; Spanring, M.; Spitzbart, D.; Strauss, J.; Waltenberger, W.; Wittmann, J.; Wulz, C.-E.; Zarucki, M.; Chekhovsky, V.; Mossolov, V.; Suarez Gonzalez, J.; De Wolf, E. A.; Di Croce, D.; Janssen, X.; Lauwers, J.; Van De Klundert, M.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Abu Zeid, S.; Blekman, F.; D'Hondt, J.; De Bruyn, I.; De Clercq, J.; Deroover, K.; Flouris, G.; Lontkovskyi, D.; Lowette, S.; Moortgat, S.; Moreels, L.; Olbrechts, A.; Python, Q.; Skovpen, K.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Parijs, I.; Brun, H.; Clerbaux, B.; De Lentdecker, G.; Delannoy, H.; Fasanella, G.; Favart, L.; Goldouzian, R.; Grebenyuk, A.; Karapostoli, G.; Lenzi, T.; Luetic, J.; Maerschalk, T.; Marinov, A.; Randle-conde, A.; Seva, T.; Vander Velde, C.; Vanlaer, P.; Vannerom, D.; Yonamine, R.; Zenoni, F.; Zhang, F.; Cimmino, A.; Cornelis, T.; Dobur, D.; Fagot, A.; Gul, M.; Khvastunov, I.; Poyraz, D.; Roskas, C.; Salva, S.; Tytgat, M.; Verbeke, W.; Zaganidis, N.; Bakhshiansohi, H.; Bondu, O.; Brochet, S.; Bruno, G.; Caudron, A.; De Visscher, S.; Delaere, C.; Delcourt, M.; Francois, B.; Giammanco, A.; Jafari, A.; Komm, M.; Krintiras, G.; Lemaitre, V.; Magitteri, A.; Mertens, A.; Musich, M.; Piotrzkowski, K.; Quertenmont, L.; Vidal Marono, M.; Wertz, S.; Beliy, N.; Aldá Júnior, W. L.; Alves, F. L.; Alves, G. A.; Brito, L.; Correa Martins Junior, M.; Hensel, C.; Moraes, A.; Pol, M. E.; Rebello Teles, P.; Belchior Batista Das Chagas, E.; Carvalho, W.; Chinellato, J.; Custódio, A.; Da Costa, E. M.; Da Silveira, G. G.; De Jesus Damiao, D.; Fonseca De Souza, S.; Huertas Guativa, L. M.; Malbouisson, H.; Melo De Almeida, M.; Mora Herrera, C.; Mundim, L.; Nogima, H.; Santoro, A.; Sznajder, A.; Tonelli Manganote, E. J.; Torres Da Silva De Araujo, F.; Vilela Pereira, A.; Ahuja, S.; Bernardes, C. A.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Mercadante, P. G.; Novaes, S. F.; Padula, Sandra S.; Romero Abad, D.; Ruiz Vargas, J. C.; Aleksandrov, A.; Hadjiiska, R.; Iaydjiev, P.; Misheva, M.; Rodozov, M.; Shopova, M.; Stoykova, S.; Sultanov, G.; Dimitrov, A.; Glushkov, I.; Litov, L.; Pavlov, B.; Petkov, P.; Fang, W.; Gao, X.; Ahmad, M.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Chen, Y.; Jiang, C. H.; Leggat, D.; Liao, H.; Liu, Z.; Romeo, F.; Shaheen, S. M.; Spiezia, A.; Tao, J.; Wang, C.; Wang, Z.; Yazgan, E.; Zhang, H.; Zhao, J.; Ban, Y.; Chen, G.; Li, Q.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Xu, Z.; Avila, C.; Cabrera, A.; Chaparro Sierra, L. F.; Florez, C.; González Hernández, C. F.; Ruiz Alvarez, J. D.; Courbon, B.; Godinovic, N.; Lelas, D.; Puljak, I.; Ribeiro Cipriano, P. M.; Sculac, T.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Ferencek, D.; Kadija, K.; Mesic, B.; Starodumov, A.; Susa, T.; Ather, M. W.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Rykaczewski, H.; Finger, M.; Finger, M.; Carrera Jarrin, E.; El-khateeb, E.; Elgammal, S.; Mohamed, A.; Dewanjee, R. K.; Kadastik, M.; Perrini, L.; Raidal, M.; Tiko, A.; Veelken, C.; Eerola, P.; Pekkanen, J.; Voutilainen, M.; Härkönen, J.; Järvinen, T.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Tuominen, E.; Tuominiemi, J.; Tuovinen, E.; Talvitie, J.; Tuuva, T.; Besancon, M.; Couderc, F.; Dejardin, M.; Denegri, D.; Faure, J. L.; Ferri, F.; Ganjour, S.; Ghosh, S.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Kucher, I.; Locci, E.; Machet, M.; Malcles, J.; Negro, G.; Rander, J.; Rosowsky, A.; Sahin, M. Ö.; Titov, M.; Abdulsalam, A.; Antropov, I.; Baffioni, S.; Beaudette, F.; Busson, P.; Cadamuro, L.; Charlot, C.; Granier de Cassagnac, R.; Jo, M.; Lisniak, S.; Lobanov, A.; Martin Blanco, J.; Nguyen, M.; Ochando, C.; Ortona, G.; Paganini, P.; Pigard, P.; Regnard, S.; Salerno, R.; Sauvan, J. B.; Sirois, Y.; Stahl Leiton, A. G.; Strebler, T.; Yilmaz, Y.; Zabi, A.; Zghiche, A.; Agram, J.-L.; Andrea, J.; Bloch, D.; Brom, J.-M.; Buttignol, M.; Chabert, E. C.; Chanon, N.; Collard, C.; Conte, E.; Coubez, X.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Jansová, M.; Le Bihan, A.-C.; Tonon, N.; Van Hove, P.; Gadrat, S.; Beauceron, S.; Bernet, C.; Boudoul, G.; Chierici, R.; Contardo, D.; Depasse, P.; El Mamouni, H.; Fay, J.; Finco, L.; Gascon, S.; Gouzevitch, M.; Grenier, G.; Ille, B.; Lagarde, F.; Laktineh, I. B.; Lethuillier, M.; Mirabito, L.; Pequegnot, A. L.; Perries, S.; Popov, A.; Sordini, V.; Vander Donckt, M.; Viret, S.; Toriashvili, T.; Bagaturia, I.; Autermann, C.; Beranek, S.; Feld, L.; Kiesel, M. K.; Klein, K.; Lipinski, M.; Preuten, M.; Schomakers, C.; Schulz, J.; Verlage, T.; Albert, A.; Dietz-Laursonn, E.; Duchardt, D.; Endres, M.; Erdmann, M.; Erdweg, S.; Esch, T.; Fischer, R.; Güth, A.; Hamer, M.; Hebbeker, T.; Heidemann, C.; Hoepfner, K.; Knutzen, S.; Merschmeyer, M.; Meyer, A.; Millet, P.; Mukherjee, S.; Olschewski, M.; Padeken, K.; Pook, T.; Radziej, M.; Reithler, H.; Rieger, M.; Scheuch, F.; Teyssier, D.; Thüer, S.; Flügge, G.; Kargoll, B.; Kress, T.; Künsken, A.; Lingemann, J.; Müller, T.; Nehrkorn, A.; Nowack, A.; Pistone, C.; Pooth, O.; Stahl, A.; Aldaya Martin, M.; Arndt, T.; Asawatangtrakuldee, C.; Beernaert, K.; Behnke, O.; Behrens, U.; Bermúdez Martínez, A.; Bin Anuar, A. A.; Borras, K.; Botta, V.; Campbell, A.; Connor, P.; Contreras-Campana, C.; Costanza, F.; Diez Pardos, C.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Eren, E.; Gallo, E.; Garay Garcia, J.; Geiser, A.; Gizhko, A.; Grados Luyando, J. M.; Grohsjean, A.; Gunnellini, P.; Harb, A.; Hauk, J.; Hempel, M.; Jung, H.; Kalogeropoulos, A.; Kasemann, M.; Keaveney, J.; Kleinwort, C.; Korol, I.; Krücker, D.; Lange, W.; Lelek, A.; Lenz, T.; Leonard, J.; Lipka, K.; Lohmann, W.; Mankel, R.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Mittag, G.; Mnich, J.; Mussgiller, A.; Ntomari, E.; Pitzl, D.; Placakyte, R.; Raspereza, A.; Roland, B.; Savitskyi, M.; Saxena, P.; Shevchenko, R.; Spannagel, S.; Stefaniuk, N.; Van Onsem, G. P.; Walsh, R.; Wen, Y.; Wichmann, K.; Wissing, C.; Zenaiev, O.; Bein, S.; Blobel, V.; Centis Vignali, M.; Draeger, A. R.; Dreyer, T.; Garutti, E.; Gonzalez, D.; Haller, J.; Hinzmann, A.; Hoffmann, M.; Karavdina, A.; Klanner, R.; Kogler, R.; Kovalchuk, N.; Kurz, S.; Lapsien, T.; Marchesini, I.; Marconi, D.; Meyer, M.; Niedziela, M.; Nowatschin, D.; Pantaleo, F.; Peiffer, T.; Perieanu, A.; Scharf, C.; Schleper, P.; Schmidt, A.; Schumann, S.; Schwandt, J.; Sonneveld, J.; Stadie, H.; Steinbrück, G.; Stober, F. M.; Stöver, M.; Tholen, H.; Troendle, D.; Usai, E.; Vanelderen, L.; Vanhoefer, A.; Vormwald, B.; Akbiyik, M.; Barth, C.; Baur, S.; Butz, E.; Caspart, R.; Chwalek, T.; Colombo, F.; De Boer, W.; Dierlamm, A.; Freund, B.; Friese, R.; Giffels, M.; Gilbert, A.; Haitz, D.; Hartmann, F.; Heindl, S. M.; Husemann, U.; Kassel, F.; Kudella, S.; Mildner, H.; Mozer, M. U.; Müller, Th.; Plagge, M.; Quast, G.; Rabbertz, K.; Schröder, M.; Shvetsov, I.; Sieber, G.; Simonis, H. J.; Ulrich, R.; Wayand, S.; Weber, M.; Weiler, T.; Williamson, S.; Wöhrmann, C.; Wolf, R.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Giakoumopoulou, V. A.; Kyriakis, A.; Loukas, D.; Topsis-Giotis, I.; Kesisoglou, S.; Panagiotou, A.; Saoulidou, N.; Evangelou, I.; Foudas, C.; Kokkas, P.; Mallios, S.; Manthos, N.; Papadopoulos, I.; Paradas, E.; Strologas, J.; Triantis, F. A.; Csanad, M.; Filipovic, N.; Pasztor, G.; Bencze, G.; Hajdu, C.; Horvath, D.; Hunyadi, Á.; Sikler, F.; Veszpremi, V.; Vesztergombi, G.; Zsigmond, A. 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R.; Olmedo Negrete, M.; Paneva, M. I.; Shrinivas, A.; Si, W.; Wang, L.; Wei, H.; Wimpenny, S.; Yates, B. R.; Branson, J. G.; Cittolin, S.; Derdzinski, M.; Gerosa, R.; Hashemi, B.; Holzner, A.; Klein, D.; Kole, G.; Krutelyov, V.; Letts, J.; Macneill, I.; Masciovecchio, M.; Olivito, D.; Padhi, S.; Pieri, M.; Sani, M.; Sharma, V.; Simon, S.; Tadel, M.; Vartak, A.; Wasserbaech, S.; Wood, J.; Würthwein, F.; Yagil, A.; Zevi Della Porta, G.; Amin, N.; Bhandari, R.; Bradmiller-Feld, J.; Campagnari, C.; Dishaw, A.; Dutta, V.; Franco Sevilla, M.; George, C.; Golf, F.; Gouskos, L.; Gran, J.; Heller, R.; Incandela, J.; Mullin, S. D.; Ovcharova, A.; Qu, H.; Richman, J.; Stuart, D.; Suarez, I.; Yoo, J.; Anderson, D.; Bendavid, J.; Bornheim, A.; Lawhorn, J. M.; Newman, H. B.; Nguyen, T.; Pena, C.; Spiropulu, M.; Vlimant, J. R.; Xie, S.; Zhang, Z.; Zhu, R. Y.; Andrews, M. B.; Ferguson, T.; Mudholkar, T.; Paulini, M.; Russ, J.; Sun, M.; Vogel, H.; Vorobiev, I.; Weinberg, M.; Cumalat, J. P.; Ford, W. T.; Jensen, F.; Johnson, A.; Krohn, M.; Leontsinis, S.; Mulholland, T.; Stenson, K.; Wagner, S. R.; Alexander, J.; Chaves, J.; Chu, J.; Dittmer, S.; Mcdermott, K.; Mirman, N.; Patterson, J. R.; Rinkevicius, A.; Ryd, A.; Skinnari, L.; Soffi, L.; Tan, S. M.; Tao, Z.; Thom, J.; Tucker, J.; Wittich, P.; Zientek, M.; Abdullin, S.; Albrow, M.; Apollinari, G.; Apresyan, A.; Apyan, A.; Banerjee, S.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Bolla, G.; Burkett, K.; Butler, J. N.; Canepa, A.; Cerati, G. B.; Cheung, H. W. K.; Chlebana, F.; Cremonesi, M.; Duarte, J.; Elvira, V. D.; Freeman, J.; Gecse, Z.; Gottschalk, E.; Gray, L.; Green, D.; Grünendahl, S.; Gutsche, O.; Harris, R. M.; Hasegawa, S.; Hirschauer, J.; Hu, Z.; Jayatilaka, B.; Jindariani, S.; Johnson, M.; Joshi, U.; Klima, B.; Kreis, B.; Lammel, S.; Lincoln, D.; Lipton, R.; Liu, M.; Liu, T.; Lopes De Sá, R.; Lykken, J.; Maeshima, K.; Magini, N.; Marraffino, J. M.; Maruyama, S.; Mason, D.; McBride, P.; Merkel, P.; Mrenna, S.; Nahn, S.; O'Dell, V.; Pedro, K.; Prokofyev, O.; Rakness, G.; Ristori, L.; Schneider, B.; Sexton-Kennedy, E.; Soha, A.; Spalding, W. J.; Spiegel, L.; Stoynev, S.; Strait, J.; Strobbe, N.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vernieri, C.; Verzocchi, M.; Vidal, R.; Wang, M.; Weber, H. A.; Whitbeck, A.; Acosta, D.; Avery, P.; Bortignon, P.; Bourilkov, D.; Brinkerhoff, A.; Carnes, A.; Carver, M.; Curry, D.; Das, S.; Field, R. D.; Furic, I. K.; Konigsberg, J.; Korytov, A.; Kotov, K.; Ma, P.; Matchev, K.; Mei, H.; Mitselmakher, G.; Rank, D.; Sperka, D.; Terentyev, N.; Thomas, L.; Wang, J.; Wang, S.; Yelton, J.; Joshi, Y. R.; Linn, S.; Markowitz, P.; Rodriguez, J. L.; Ackert, A.; Adams, T.; Askew, A.; Hagopian, S.; Hagopian, V.; Johnson, K. F.; Kolberg, T.; Martinez, G.; Perry, T.; Prosper, H.; Saha, A.; Santra, A.; Yohay, R.; Baarmand, M. M.; Bhopatkar, V.; Colafranceschi, S.; Hohlmann, M.; Noonan, D.; Roy, T.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Berry, D.; Betts, R. R.; Cavanaugh, R.; Chen, X.; Evdokimov, O.; Gerber, C. E.; Hangal, D. A.; Hofman, D. J.; Jung, K.; Kamin, J.; Sandoval Gonzalez, I. D.; Tonjes, M. B.; Trauger, H.; Varelas, N.; Wang, H.; Wu, Z.; Zhang, J.; Bilki, B.; Clarida, W.; Dilsiz, K.; Durgut, S.; Gandrajula, R. P.; Haytmyradov, M.; Khristenko, V.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Ogul, H.; Onel, Y.; Ozok, F.; Penzo, A.; Snyder, C.; Tiras, E.; Wetzel, J.; Yi, K.; Blumenfeld, B.; Cocoros, A.; Eminizer, N.; Fehling, D.; Feng, L.; Gritsan, A. V.; Maksimovic, P.; Roskes, J.; Sarica, U.; Swartz, M.; Xiao, M.; You, C.; Al-bataineh, A.; Baringer, P.; Bean, A.; Boren, S.; Bowen, J.; Castle, J.; Khalil, S.; Kropivnitskaya, A.; Majumder, D.; Mcbrayer, W.; Murray, M.; Royon, C.; Sanders, S.; Schmitz, E.; Stringer, R.; Tapia Takaki, J. D.; Wang, Q.; Ivanov, A.; Kaadze, K.; Maravin, Y.; Mohammadi, A.; Saini, L. K.; Skhirtladze, N.; Toda, S.; Rebassoo, F.; Wright, D.; Anelli, C.; Baden, A.; Baron, O.; Belloni, A.; Calvert, B.; Eno, S. C.; Ferraioli, C.; Hadley, N. J.; Jabeen, S.; Jeng, G. Y.; Kellogg, R. G.; Kunkle, J.; Mignerey, A. C.; Ricci-Tam, F.; Shin, Y. H.; Skuja, A.; Tonwar, S. C.; Abercrombie, D.; Allen, B.; Azzolini, V.; Barbieri, R.; Baty, A.; Bi, R.; Brandt, S.; Busza, W.; Cali, I. A.; D'Alfonso, M.; Demiragli, Z.; Gomez Ceballos, G.; Goncharov, M.; Hsu, D.; Iiyama, Y.; Innocenti, G. M.; Klute, M.; Kovalskyi, D.; Lai, Y. S.; Lee, Y.-J.; Levin, A.; Luckey, P. D.; Maier, B.; Marini, A. C.; Mcginn, C.; Mironov, C.; Narayanan, S.; Niu, X.; Paus, C.; Roland, C.; Roland, G.; Salfeld-Nebgen, J.; Stephans, G. S. F.; Tatar, K.; Velicanu, D.; Wang, J.; Wang, T. W.; Wyslouch, B.; Benvenuti, A. C.; Chatterjee, R. M.; Evans, A.; Hansen, P.; Kalafut, S.; Kubota, Y.; Lesko, Z.; Mans, J.; Nourbakhsh, S.; Ruckstuhl, N.; Rusack, R.; Turkewitz, J.; Acosta, J. G.; Oliveros, S.; Avdeeva, E.; Bloom, K.; Claes, D. R.; Fangmeier, C.; Gonzalez Suarez, R.; Kamalieddin, R.; Kravchenko, I.; Monroy, J.; Siado, J. E.; Snow, G. R.; Stieger, B.; Alyari, M.; Dolen, J.; Godshalk, A.; Harrington, C.; Iashvili, I.; Nguyen, D.; Parker, A.; Rappoccio, S.; Roozbahani, B.; Alverson, G.; Barberis, E.; Hortiangtham, A.; Massironi, A.; Morse, D. M.; Nash, D.; Orimoto, T.; Teixeira De Lima, R.; Trocino, D.; Wood, D.; Bhattacharya, S.; Charaf, O.; Hahn, K. A.; Mucia, N.; Odell, N.; Pollack, B.; Schmitt, M. H.; Sung, K.; Trovato, M.; Velasco, M.; Dev, N.; Hildreth, M.; Hurtado Anampa, K.; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Loukas, N.; Marinelli, N.; Meng, F.; Mueller, C.; Musienko, Y.; Planer, M.; Reinsvold, A.; Ruchti, R.; Smith, G.; Taroni, S.; Wayne, M.; Wolf, M.; Woodard, A.; Alimena, J.; Antonelli, L.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Francis, B.; Hart, A.; Hill, C.; Ji, W.; Liu, B.; Luo, W.; Puigh, D.; Winer, B. L.; Wulsin, H. W.; Benaglia, A.; Cooperstein, S.; Driga, O.; Elmer, P.; Hardenbrook, J.; Hebda, P.; Higginbotham, S.; Lange, D.; Luo, J.; Marlow, D.; Mei, K.; Ojalvo, I.; Olsen, J.; Palmer, C.; Piroué, P.; Stickland, D.; Tully, C.; Malik, S.; Norberg, S.; Barker, A.; Barnes, V. E.; Folgueras, S.; Gutay, L.; Jha, M. K.; Jones, M.; Jung, A. W.; Khatiwada, A.; Miller, D. H.; Neumeister, N.; Peng, C. C.; Schulte, J. F.; Sun, J.; Wang, F.; Xie, W.; Cheng, T.; Parashar, N.; Stupak, J.; Adair, A.; Akgun, B.; Chen, Z.; Ecklund, K. M.; Geurts, F. J. M.; Guilbaud, M.; Li, W.; Michlin, B.; Northup, M.; Padley, B. P.; Roberts, J.; Rorie, J.; Tu, Z.; Zabel, J.; Bodek, A.; de Barbaro, P.; Demina, R.; Duh, Y. t.; Ferbel, T.; Galanti, M.; Garcia-Bellido, A.; Han, J.; Hindrichs, O.; Khukhunaishvili, A.; Lo, K. H.; Tan, P.; Verzetti, M.; Ciesielski, R.; Goulianos, K.; Mesropian, C.; Agapitos, A.; Chou, J. P.; Gershtein, Y.; Gómez Espinosa, T. A.; Halkiadakis, E.; Heindl, M.; Hughes, E.; Kaplan, S.; Kunnawalkam Elayavalli, R.; Kyriacou, S.; Lath, A.; Montalvo, R.; Nash, K.; Osherson, M.; Saka, H.; Salur, S.; Schnetzer, S.; Sheffield, D.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Delannoy, A. G.; Foerster, M.; Heideman, J.; Riley, G.; Rose, K.; Spanier, S.; Thapa, K.; Bouhali, O.; Castaneda Hernandez, A.; Celik, A.; Dalchenko, M.; De Mattia, M.; Delgado, A.; Dildick, S.; Eusebi, R.; Gilmore, J.; Huang, T.; Kamon, T.; Mueller, R.; Pakhotin, Y.; Patel, R.; Perloff, A.; Perniè, L.; Rathjens, D.; Safonov, A.; Tatarinov, A.; Ulmer, K. A.; Akchurin, N.; Damgov, J.; De Guio, F.; Dudero, P. R.; Faulkner, J.; Gurpinar, E.; Kunori, S.; Lamichhane, K.; Lee, S. W.; Libeiro, T.; Peltola, T.; Undleeb, S.; Volobouev, I.; Wang, Z.; Greene, S.; Gurrola, A.; Janjam, R.; Johns, W.; Maguire, C.; Melo, A.; Ni, H.; Sheldon, P.; Tuo, S.; Velkovska, J.; Xu, Q.; Arenton, M. W.; Barria, P.; Cox, B.; Hirosky, R.; Ledovskoy, A.; Li, H.; Neu, C.; Sinthuprasith, T.; Sun, X.; Wang, Y.; Wolfe, E.; Xia, F.; Harr, R.; Karchin, P. E.; Sturdy, J.; Zaleski, S.; Brodski, M.; Buchanan, J.; Caillol, C.; Dasu, S.; Dodd, L.; Duric, S.; Gomber, B.; Grothe, M.; Herndon, M.; Hervé, A.; Hussain, U.; Klabbers, P.; Lanaro, A.; Levine, A.; Long, K.; Loveless, R.; Pierro, G. A.; Polese, G.; Ruggles, T.; Savin, A.; Smith, N.; Smith, W. H.; Taylor, D.; Woods, N.; CMS Collaboration

2018-05-01

A search for long-lived particles was performed with data corresponding to an integrated luminosity of 2.6 fb-1 collected at a center-of-mass energy of 13 TeV by the CMS experiment in 2015. The analysis exploits two customized topological trigger algorithms, and uses the multiplicity of displaced jets to search for the presence of a signal decay occurring at distances between 1 and 1000 mm. The results can be interpreted in a variety of different models. For pair-produced long-lived particles decaying to two b quarks and two leptons with equal decay rates between lepton flavors, cross sections larger than 2.5 fb are excluded for proper decay lengths between 70-100 mm for a long-lived particle mass of 1130 GeV at 95% confidence. For a specific model of pair-produced, long-lived top squarks with R-parity violating decays to a b quark and a lepton, masses below 550-1130 GeV are excluded at 95% confidence for equal branching fractions between lepton flavors, depending on the squark decay length. This mass bound is the most stringent to date for top squark proper decay lengths greater than 3 mm.

Optimal design of structures with multiple design variables per group and multiple loading conditions on the personal computer

NASA Technical Reports Server (NTRS)

Nguyen, D. T.; Rogers, J. L., Jr.

1986-01-01

A finite element based programming system for minimum weight design of a truss-type structure subjected to displacement, stress, and lower and upper bounds on design variables is presented. The programming system consists of a number of independent processors, each performing a specific task. These processors, however, are interfaced through a well-organized data base, thus making the tasks of modifying, updating, or expanding the programming system much easier in a friendly environment provided by many inexpensive personal computers. The proposed software can be viewed as an important step in achieving a 'dummy' finite element for optimization. The programming system has been implemented on both large and small computers (such as VAX, CYBER, IBM-PC, and APPLE) although the focus is on the latter. Examples are presented to demonstrate the capabilities of the code. The present programming system can be used stand-alone or as part of the multilevel decomposition procedure to obtain optimum design for very large scale structural systems. Furthermore, other related research areas such as developing optimization algorithms (or in the larger level: a structural synthesis program) for future trends in using parallel computers may also benefit from this study.

A High Affinity Red Fluorescence and Colorimetric Probe for Amyloid β Aggregates

NASA Astrophysics Data System (ADS)

Rajasekhar, K.; Narayanaswamy, Nagarjun; Murugan, N. Arul; Kuang, Guanglin; Ågren, Hans; Govindaraju, T.

2016-04-01

A major challenge in the Alzheimer’s disease (AD) is its timely diagnosis. Amyloid β (Aβ) aggregates have been proposed as the most viable biomarker for the diagnosis of AD. Here, we demonstrate hemicyanine-based benzothiazole-coumarin (TC) as a potential probe for the detection of highly toxic Aβ42 aggregates through switch-on, enhanced (~30 fold) red fluorescence (Emax = 654 nm) and characteristic colorimetric (light red to purple) optical outputs. Interestingly, TC exhibits selectivity towards Aβ42 fibrils compared to other abnormal protein aggregates. TC probe show nanomolar binding affinity (Ka = 1.72 × 107 M-1) towards Aβ42 aggregates and also displace ThT bound to Aβ42 fibrils due to its high binding affinity. The Aβ42 fibril-specific red-shift in the absorption spectra of TC responsible for the observed colorimetric optical output has been attributed to micro-environment change around the probe from hydrophilic-like to hydrophobic-like nature. The binding site, binding energy and changes in optical properties observed for TC upon interaction with Aβ42 fibrils have been further validated by molecular docking and time dependent density functional theory studies.

Binding of the cyclic AMP receptor protein of Escherichia coli and DNA bending at the P4 promoter of pBR322.

PubMed Central

Brierley, I; Hoggett, J G

1992-01-01

The binding of the Escherichia coli cyclic AMP receptor protein (CRP) to its specific site on the P4 promoter of pBR322 has been studied by gel electrophoresis. Binding to the P4 site was about 40-50-fold weaker than to the principal CRP site on the lactose promoter at both low (0.01 M) and high (0.1 M) ionic strengths. CRP-induced bending at the P4 site was investigated from the mobilities of CRP bound to circularly permuted P4 fragments. The estimated bending angle, based on comparison with Zinkel & Crothers [(1990) Biopolymers 29, 29-38] A-tract bending standards, was found to be approximately 96 degrees, similar to that found for binding to the lac site. These observations suggest that there is not a simple relationship between strength of CRP binding and the extent of induced bending for different CRP sites. The apparent centre of bending in P4 is displaced about 6-8 bp away from the conserved TGTGA sequence and the P4 transcription start site. Images Fig. 1. Fig. 3. Fig. 4. PMID:1322129

Structure of the thermophilic l-Arabinose isomerase from Geobacillus kaustophilus reveals metal-mediated intersubunit interactions for activity and thermostability.

PubMed

Choi, Jin Myung; Lee, Yong-Jik; Cao, Thinh-Phat; Shin, Sun-Mi; Park, Min-Kyu; Lee, Han-Seung; di Luccio, Eric; Kim, Seong-Bo; Lee, Sang-Jae; Lee, Sang Jun; Lee, Sung Haeng; Lee, Dong-Woo

2016-04-15

Thermophilic l-arabinose isomerase (AI), which catalyzes the interconversion of l-arabinose and l-ribulose, can be used to produce d-tagatose, a sugar substitute, from d-galactose. Unlike mesophilic AIs, thermophilic AIs are highly dependent on divalent metal ions for their catalytic activity and thermostability at elevated temperatures. However, the molecular basis underlying the substrate preferences and metal requirements of multimeric AIs remains unclear. Here we report the first crystal structure of the apo and holo forms of thermophilic Geobacillus kaustophilus AI (GKAI) in hexamer form. The structures, including those of GKAI in complex with l-arabitol, and biochemical analyses revealed not only how the substrate-binding site of GKAI is formed through displacement of residues at the intersubunit interface when it is bound to Mn(2+), but also revealed the water-mediated H-bonding networks that contribute to the structural integrity of GKAI during catalysis. These observations suggest metal-mediated isomerization reactions brought about by intersubunit interactions at elevated temperatures are responsible for the distinct active site features that promote the substrate specificity and thermostability of thermophilic AIs. Copyright © 2016 Elsevier Inc. All rights reserved.

Intracellular NADPH Levels Affect the Oligomeric State of the Glucose 6-Phosphate Dehydrogenase

PubMed Central

Tramonti, Angela; Lanini, Claudio; Cialfi, Samantha; De Biase, Daniela; Falcone, Claudio

2012-01-01

In the yeast Kluyveromyces lactis, glucose 6-phosphate dehydrogenase (G6PDH) is detected as two differently migrating forms on native polyacrylamide gels. The pivotal metabolic role of G6PDH in K. lactis led us to investigate the mechanism controlling the two activities in respiratory and fermentative mutant strains. An extensive analysis of these mutants showed that the NAD+(H)/NADP+(H)-dependent cytosolic alcohol (ADH) and aldehyde (ALD) dehydrogenase balance affects the expression of the G6PDH activity pattern. Under fermentative/ethanol growth conditions, the concomitant activation of ADH and ALD activities led to cytosolic accumulation of NADPH, triggering an alteration in the oligomeric state of the G6PDH caused by displacement/release of the structural NADP+ bound to each subunit of the enzyme. The new oligomeric G6PDH form with faster-migrating properties increases as a consequence of intracellular redox unbalance/NADPH accumulation, which inhibits G6PDH activity in vivo. The appearance of a new G6PDH-specific activity band, following incubation of Saccharomyces cerevisiae and human cellular extracts with NADP+, also suggests that a regulatory mechanism of this activity through NADPH accumulation is highly conserved among eukaryotes. PMID:23064253

Monitoring transient elastic energy storage within the rotary motors of single FoF1-ATP synthase by DCO-ALEX FRET

NASA Astrophysics Data System (ADS)

Ernst, Stefan; Düser, Monika G.; Zarrabi, Nawid; Börsch, Michael

2012-03-01

The enzyme FoF1-ATP synthase provides the 'chemical energy currency' adenosine triphosphate (ATP) for living cells. Catalysis is driven by mechanochemical coupling of subunit rotation within the enzyme with conformational changes in the three ATP binding sites. Proton translocation through the membrane-bound Fo part of ATP synthase powers a 10-step rotary motion of the ring of c subunits. This rotation is transmitted to the γ and ɛ subunits of the F1 part. Because γ and ɛ subunits rotate in 120° steps, we aim to unravel this symmetry mismatch by real time monitoring subunit rotation using single-molecule Förster resonance energy transfer (FRET). One fluorophore is attached specifically to the F1 motor, another one to the Fo motor of the liposome-reconstituted enzyme. Photophysical artifacts due to spectral fluctuations of the single fluorophores are minimized by a previously developed duty cycle-optimized alternating laser excitation scheme (DCO-ALEX). We report the detection of reversible elastic deformations between the rotor parts of Fo and F1 and estimate the maximum angular displacement during the load-free rotation using Monte Carlo simulations.

A Novel Computational Method to Reduce Leaky Reaction in DNA Strand Displacement

PubMed Central

Li, Xin; Wang, Xun; Song, Tao; Lu, Wei; Chen, Zhihua; Shi, Xiaolong

2015-01-01

DNA strand displacement technique is widely used in DNA programming, DNA biosensors, and gene analysis. In DNA strand displacement, leaky reactions can cause DNA signals decay and detecting DNA signals fails. The mostly used method to avoid leakage is cleaning up after upstream leaky reactions, and it remains a challenge to develop reliable DNA strand displacement technique with low leakage. In this work, we address the challenge by experimentally evaluating the basic factors, including reaction time, ratio of reactants, and ion concentration to the leakage in DNA strand displacement. Specifically, fluorescent probes and a hairpin structure reporting DNA strand are designed to detect the output of DNA strand displacement, and thus can evaluate the leakage of DNA strand displacement reactions with different reaction time, ratios of reactants, and ion concentrations. From the obtained data, mathematical models for evaluating leakage are achieved by curve derivation. As a result, it is obtained that long time incubation, high concentration of fuel strand, and inappropriate amount of ion concentration can weaken leaky reactions. This contributes to a method to set proper reaction conditions to reduce leakage in DNA strand displacement. PMID:26491602

Approaching population thresholds in presence of uncertainty: Assessing displacement of seabirds from offshore wind farms

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

Busch, Malte, E-mail: der.malte.busch@gmail.com; Garthe, Stefan

Assessment of the displacement impacts of offshore wind farms on seabirds is impeded by a lack of evidence regarding species-specific reactions to developed sites and the potential ecological consequences faced by displaced individuals. In this study, we present a method that makes best use of the currently limited understanding of displacement impacts. The combination of a matrix table displaying the full range of potential displacement and mortality levels together with seasonal potential biological removal (PBR) assessments provides a tool that increases confidence in the conclusions of impact assessments. If unrealistic displacement levels and/or mortality rates are required to equal ormore » approach seasonal PBRs, this gives an indication of the likeliness of adverse impacts on the assessed population. This approach is demonstrated by assessing the displacement impacts of an offshore wind farm cluster in the German North Sea on the local common guillemot (Uria aalge) population. - Highlights: • A novel approach for assessing displacement impacts of offshore wind farms on seabirds is presented making best use of limited data • A displacement matrix approach is linked with PBR analysis to increased confidence in assessment conclusions drawn • A case example demonstrates the applicability of the methods described in practice.« less

Identification of New Serum Biomarkers for Early Breast Cancer Diagnosis and Prognosis Using Lipid Microarrays

DTIC Science & Technology

2008-09-01

specific for asialo-GM1 bound specifically to GM1, but not to the closely related gangliosides GM1 or GM2 (Fig. 2). Monoclonal antibodies raised...against GD3 specifically bound GD3, but not to asialo-GM1, GM1 and GM2 (Fig. 2). The secondary antibodies did not show reactivity against lipids (data not...fluorescent intensity on different membranes. Asialo GM1 GM1 GM2 GD3 Fig 2. Lipids on the PVDF membrane can be detected by specific

Identification of New Serum Biomarkers for Early Breast Cancer Diagnosis and Prognosis Using Lipid Microarrays

DTIC Science & Technology

2007-09-01

specific for asialo-GM1 bound specifically to GM1, but not to the closely related gangliosides GM1 or GM2 (Fig. 2). Monoclonal antibodies raised against...GD3 specifically bound GD3, but not to asialo-GM1, GM1 and GM2 (Fig. 2). The secondary antibodies did not show reactivity against lipids (data not...fluorescent intensity on different membranes. Asialo GM1 GM1 GM2 GD3 Fig 2. Lipids on the PVDF membrane can be detected by specific antibodies

Etravirine in CSF is highly protein bound

PubMed Central

Nguyen, Anh; Rossi, Steven; Croteau, David; Best, Brookie M.; Clifford, David; Collier, Ann C.; Gelman, Benjamin; Marra, Christina; McArthur, Justin; McCutchan, J. Allen; Morgello, Susan; Simpson, David; Ellis, Ronald J.; Grant, Igor; Capparelli, Edmund; Letendre, Scott; Ellis, Ronald J.; Letendre, Scott; Abramson, Ian; Al-Lozi, Muhammad; Atkinson, J. Hampton; Capparelli, Edmund; Clifford, David; Collier, Ann C.; Fennema-Notestine, Christine; Gamst, Anthony C.; Gelman, Benjamin; Heaton, Robert K.; Marcotte, Thomas D.; Marra, Christina; McCutchan, J. Allen; McArthur, Justin; Morgello, Susan; Simpson, David; Smith, Davey M.; Taylor, Michael J.; Theilmann, Rebecca; Vaida, Florin; Paul Woods, Steven; Cushman, Clint; Dawson, Matthew; Franklin, Donald; Jones, Trudy; Lewis, Kristen; Mintz, Letty; Teshome, Mengesha; Toperoff, Will

2013-01-01

Objectives Etravirine has high affinity for plasma drug-binding proteins, such as albumin and α1-acid glycoprotein, which limits the amount of unbound etravirine available to enter the CNS. The objective of this study was to compare total and unbound etravirine concentrations in CSF with plasma concentrations and the in vitro median inhibitory concentration (IC50) for wild-type HIV (0.9 ng/mL). Methods Total and bound etravirine concentrations were measured in 17 CSF and plasma pairs by isotope-dilution liquid chromatography tandem mass spectroscopy, radioligand displacement and ultracentrifugation. Unbound etravirine concentrations were calculated from the bound fraction. The dynamic range of the assay was 7.8–2000 (plasma) and 0.78–200 (CSF) ng/mL. Results Subjects were mostly middle-aged (median 43 years) white (78%) men (89%). All CSF etravirine concentrations were above the limit of quantification. Total and unbound median etravirine concentrations in CSF were 9.5 (IQR 6.4, 26.4) and 0.13 (IQR 0.08, 0.27) ng/mL, respectively. Etravirine was 96% (IQR 94.5, 97.2) protein bound in plasma and 98.4% (IQR 97.8, 98.8) in CSF. Total etravirine in CSF was 4.3% (IQR 3, 5.9) of total and 101% (IQR 76, 160) of unbound etravirine in plasma. There were no significant correlations between unbound etravirine concentrations and concentrations of albumin in plasma or CSF. Unbound etravirine concentrations in CSF did not reach the wild-type IC50 in any of the specimens. Conclusions Unbound etravirine may not achieve optimal concentrations to inhibit HIV replication in the CNS. PMID:23335197

Characterization of digitalis-like factors in human plasma. Interactions with NaK-ATPase and cross-reactivity with cardiac glycoside-specific antibodies.

PubMed

Kelly, R A; O'Hara, D S; Canessa, M L; Mitch, W E; Smith, T W

1985-09-25

Much of the evidence for a physiologically important endogenous inhibitor of the sodium pump has been either contradictory or indirect. We have identified three discrete fractions in desalted deproteinized plasma from normal humans that resemble the digitalis glycosides in that they: are of low molecular weight; are resistant to acid and enzymatic proteolysis; inhibit NaK-ATPase activity; inhibit Na+ pump activity in human erythrocytes; displace [3H]ouabain bound to the enzyme; and cross-react with high-affinity polyclonal and monoclonal digoxin-specific antibodies but not with anti-ouabain or anti-digitoxin antibodies. An additional fraction cross-reacted with digoxin-specific antibodies but had no detectable activity against NaK-ATPase. The three inhibitory fractions differed from cardiac glycosides in that their concentration-effect curves in a NaK-ATPase inhibition and [3H]ouabain radioreceptor assays were steeper than unlabeled ouabain. This suggests that these inhibitors are not simple competitive ligands for binding to NaK-ATPase. In the presence of sodium, no fraction required ATP for binding to NaK-ATPase, and in the presence of potassium, only one fraction had the reduced affinity for the enzyme that is characteristic of cardiac glycosides. Unlike digitalis, all three NaK-ATPase inhibitory fractions stimulated the activity of skeletal muscle sarcoplasmic reticulum Ca-ATPase. The presence of at least three fractions in human plasma that inhibit NaK-ATPase and cross-react to a variable degree with different digoxin-specific antibody populations could explain much of the conflicting evidence for the existence of endogenous digitalis-like compounds in plasma.

Cloning and Characterization of a Hybridoma Secreting a 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-Specific Monoclonal Antibody and Recombinant F(ab)

PubMed Central

Wanczyk, Heather; Barker, Tolga; Rood, Debra; Zapata, Daniel I.; Howell, Amy R.; Richardson, Stewart K.; Zinckgraf, John; Marusov, Gregory P.; Lynes, Michael A.; Silbart, Lawrence K.

2013-01-01

Smokeless tobacco products have been associated with increased risks of oro-pharyngeal cancers, due in part to the presence of tobacco-specific nitrosamines (TSNAs) such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These potent carcinogens are formed during tobacco curing and as a result of direct nitrosation reactions that occur in the oral cavity. In the current work we describe the isolation and characterization of a hybridoma secreting a high-affinity, NNK-specific monoclonal antibody. A structurally-related benzoyl derivative was synthesized to facilitate coupling to NNK-carrier proteins, which were characterized for the presence of the N-nitroso group using the Griess reaction, and used to immunize BALB/c mice. Splenocytes from mice bearing NNK-specific antibodies were used to create hybridomas. Out of four, one was selected for subcloning and characterization. Approximately 99% of the monoclonal antibodies from this clone were competitively displaced from plate-bound NNKB conjugates in the presence of free NNK. The affinity of the monoclonal antibody to the NNKB conjugates was Kd = 2.93 nM as determined by surface plasmon resonance. Free nicotine was a poor competitor for the NNKB binding site. The heavy and light chain antibody F(ab) fragments were cloned, sequenced and inserted in tandem into an expression vector, with an FMDV Furin 2A cleavage site between them. Expression in HEK 293 cells revealed a functional F(ab) with similar binding features to that of the parent hybridoma. This study lays the groundwork for synthesizing transgenic tobacco that expresses carcinogen-sequestration properties, thereby rendering it less harmful to consumers. PMID:23518474

Sequence-Specific DNA Photosplitting of Crosslinked DNAs Containing the 3-Cyanovinylcarbazole Nucleoside by Using DNA Strand Displacement.

PubMed

Nakamura, Shigetaka; Kawabata, Hayato; Fujimoto, Kenzo

2016-08-17

An oligodeoxynucleotide (ODN) containing the ultrafast reversible 3-cyanovinylcarbazole ((CNV) K) photo-crosslinker was photo-crosslinked to a complementary strand upon exposure to 366 nm irradiation and photosplit by use of 312 nm irradiation. In this paper we report that the photoreaction of (CNV) K on irradiation at 366 nm involves a photostationary state and that its reaction can be controlled by temperature. Guided by this new insight, we proposed and have now demonstrated previously unknown photosplitting of (CNV) K aided by DNA strand displacement as an alternative to heating. The photo-crosslinked double-stranded DNA (dsDNA) underwent >80 % photosplitting aided by DNA strand displacement on irradiation at 366 nm without heating. In this photosplitting based on DNA strand displacement, the relative thermal stability of the invader strand with respect to the template strands plays an important role, and an invader strand/template strand system that is more stable than the passenger strand/template strand system induces photosplitting without heating. This new strand-displacement-aided photosplitting occurred in a sequence-specific manner through irradiation at 366 nm in the presence of an invader strand. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nothing From Everything- A Unified Theory

NASA Astrophysics Data System (ADS)

Mehra, Vijay Kumar

2016-07-01

Nothing From Everything-A Unified Theory is a philosophical insight into principles of nature through principle of complementary spontaneity and principle of vertical continuity. This work is intended to explain various cosmological phenomena in light of behaviour of particles in range of their respective and relative speed of light. This theory explains creation of Universe from nothing or zero spacetime through scalar energy field collapsing into Higgs field resulting into giving mass to various particles. The energy particles taking origin from nothing while moving away from zero space-time would create space-time of their own order because energy/matter needs space to exist. The particles while moving away from zero space-time would end up in breaking symmetry of matter/energy at their mass infinity (highest possible mass of any particle, which is function of speed of spin). This break in symmetry would lead to curving of particles upon themselves and hence would lead to creation of antiparticles going back in time towards zero spacetime. Therefore the Universe could have been created by alternate layers of particles and antiparticles and also alternate layers of matter and antimatter with decelerating speed of light, which would lead to creation a closed and flat Universe. With increase in mass of Universe (creation of more and more Universe's matter from nothing), the gravitational force of Universe is bound to increase and hence with quantum by quantum increase in gravity, it would apply brakes on relative speed of photon/light out of its reference frame or designated space and hence speed of photon would decrease. If closed and flat Universe was created with decelerating speed of light, then such Universe is bound to contract back with accelerating speed of light which would have inverse impact on gravitational constant across various spacetime zones of Universe. And hence mass bodies would drift away spontaneously purely on basis and proportional to distance square between mass bodies with accelerating speed of light, but in actual such Universe would be contracting rather than expanding. Furthermore, this theory explains how particles (when moving away from zero space-time) acquire spin, whose force vector acts centrifugally and neutralizes the quantum gravitational force of particle which acts centripetally. While in case of antiparticles both spin force and gravitational force acts towards centre of particles and they are bound to create singularity of zero spacetime. This theory further explains motion of photon/anti-photon in light of space displacement. The time is nothing but is a measure of rate of space displacement. Where there is no space displacement, there is no time. Any force, like gravity, which acts against space displacement must act against time and hence such forces would lead to slowing of time. This theory further explains about curvature of space-time, relative existence of time orders across Universe, black holes including atomic black holes, other Universes, virtual Universe, time travel, existence of life on other planets, numbers of Universe which govern dynamics of Universe, quantum of Universe i.e. existence of particle-antiparticle in space-time and relation of particles with Higgs field, origin of spin and charge of particles, reason for uncertainty principle and Pauli's exclusion principle, space-time dimensions, and other relevant topics of Astrophysics and quantum Physics.

The metamorphosis of 'culture-bound' syndromes.

PubMed

Jilek, W G; Jilek-Aall, L

1985-01-01

Starting from a critical review of the concept of 'culture-bound' disorders and its development in comparative psychiatry, the authors present the changing aspects of two so-called culture-bound syndromes as paradigms of transcultural metamorphosis (koro) and intra-cultural metamorphosis (Salish Indian spirit sickness), respectively. The authors present recent data on epidemics of koro, which is supposedly bound to Chinese culture, in Thailand and India among non-Chinese populations. Neither the model of Oedipal castration anxiety nor the model of culture-specific pathogenicity, commonly adduced in psychiatric and ethnological literature, explain these phenomena. The authors' data on Salish Indian spirit sickness describes the contemporary condition as anomic depression, which is significantly different from its traditional namesake. The traditional concept was redefined by Salish ritual specialists in response to current needs imposed by social changes. The stresses involved in creating the contemporary phenomena of koro and spirit sickness are neither culture-specific nor culture-inherent, as postulated for 'culture-bound' syndromes, rather they are generated by a feeling of powerlessness caused by perceived threats to ethnic survival.

Investigation of the fiber/matrix interphase under high loading rates

NASA Astrophysics Data System (ADS)

Tanoglu, Metin

2000-10-01

This research focuses on characterization of the interphases of various sized E-glass-fiber/epoxy-amine systems under high loading rates. The systems include unsized, epoxy-amine compatible, and epoxy-amine incompatible glass fibers. A new experimental technique (dynamic micro-debonding technique) was developed to directly characterize the fiber/matrix interphase properties under various loading rates. Displacement rates of up to 3000 mum/sec that induce high-strain-rate interphase loading were obtained using the rapid expansion capability of the piezoelectric actuators (PZT). A straightforward data reduction scheme, which does not require complex numerical solutions, was also developed by employing thin specimens. This method enables quantification of the strength and specific absorbed energies due to debonding and frictional sliding. Moreover, the technique offers the potential to obtain the shear stress/strain response of the interphases at various rates. A new methodology was also developed to independently investigate the properties of the fiber/matrix interphase. This methodology is based on the assumption that the portion of sizing bound to the glass fiber strongly affects the interphase formation. Conventional burnout and acetone extraction experiments in conjunction with nuclear magnetic spectroscopy were used to determine the composition of the bound sizing. Using the determined composition, model interphase compounds were made to replicate the actual interphase and tested utilizing dynamic mechanical analyzer (DMA) and differential scanning calorimeter (DSC) techniques. The rate-dependent behavior of the model interphase materials and the bulk epoxy matrix were characterized by constructing storage modulus master curves as a function of strain rate using the time-temperature superposition principle. The results of dynamic micro-debonding experiments showed that the values of interphase strength and specific absorbed energies vary dependent on the sizing and exhibited significant sensitivity to loading rates. The unsized fibers exhibit greater energy-absorbing capability that could provide better ballistic resistance while the compatible sized fibers show higher strength values that improve the structural integrity of the polymeric composites. The calculated interphase shear modulus values from micro-debonding experiments increase with the loading rate consistent with DMA results. In addition, significantly higher amounts of energy are absorbed within the frictional sliding regime compared to debonding. Characterization of model interphase compounds revealed that the interphase formed due to the presence of bound sizing has a Tg below room temperature, a modulus more compliant than that of the bulk matrix, and a thickness of about 10 nm. The results showed that the properties of the interphases are significantly affected by the interphase network structure.

Temporal and spatial constraints on the evolution of a Rio Grande rift sub-basin, Guadalupe Mountain area, northern New Mexico

NASA Astrophysics Data System (ADS)

Thompson, R. A.; Turner, K. J.; Cosca, M. A.; Drenth, B.; Hudson, M. R.; Lee, J.

2013-12-01

The Taos Plateau volcanic field (TPVF) in the southern San Luis Valley of northern New Mexico is the most voluminous of the predominantly basaltic Neogene (6-1 Ma) volcanic fields of the Rio Grande rift. Volcanic deposits of the TPVF are intercalated with alluvial deposits of the Santa Fe Group and compose the N-S-trending San Luis Basin, the largest basin of the northern rift (13,500 km2 in area). Pliocene volcanic rocks of the Guadalupe Mountain area of northern New Mexico are underlain by the southern end of one of the larger sub-basins of the San Luis Valley, the Sunshine sub-basin (~ 450 km2 in area) juxtaposed against the down-to-west frontal fault of the Precambrian-cored Sangre de Cristo Range. The sub-basin plunges northward and extends to near the Colorado-New Mexico border. The western margin (~15 km west of the Sangre de Cristo fault) is constrained by outcrops of Oligocene to Miocene volcanic rocks of the Latir volcanic field, interpreted here as a broad pre-Pliocene intra-rift platform underlying much of the northern TPVF. The southern sub-basin border is derived, in part, from modeling of gravity and aeromagnetic data and is interpreted as a subsurface extension of this intra-rift platform that extends southeastward to nearly the Sangre de Cristo range front. Broadly coincident with this subsurface basement high is the northwest-trending, curvilinear terminus of the down-to-northeast Red River fault zone. South of the gravity high, basin-fill alluvium and ~3.84 Ma Servilleta basalt lava flows thicken along a poorly exposed, down-to-south, basin-bounding fault of the northern Taos graben, the largest of the San Luis Valley sub-basins. The uppermost, western sub-basin fill is exposed along steep canyon walls near the confluence of the Rio Grande and the Red River. Unconformity-bound, lava flow packages are intercalated with paleo Red River fan alluvium and define six eruptive sequences in the Guadalupe Mountain area: (1) Guadalupe Mtn. lavas (dacite ~5.27-4.8 Ma), (2) lower Servilleta basalt lavas (olivine tholeiite ~5.26-4.92 Ma), (3) Hatchery volcano lavas (basaltic andesite to andesite ~4.93 Ma), (4) Red River lavas (high silica andesite ~4.93 Ma), (5) UCEM lavas (dacite ~4.85 Ma), and (6) upper Servilleta basalt lavas (olivine tholeiite ~3.84-3.45 Ma). Mapped eruptive centers are interpreted to reflect discrete pulses of volcanic activity characterized by limited compositional range and short eruption cycles. Four major, northwest-trending, dip-slip faults cut the volcanic fill. From west to east these are: (1) down-to-east Red River fault zone (post 3.84 Ma displacement), (2) down-to-east Fish Hatchery fault zone including fault splays of opposite displacement (pre- upper Servilleta displacement < 3.84 Ma and contemporaneous with eruption of Hatchery volcano lavas, ~4.93 Ma), (3) Guadalupe Mtn. fault zone, both down-to-west and down-to-east components (post ~5 Ma displacement), and (4) Tailings Pond fault zone, down-to-east (post ~5 Ma displacement). The Red River and Tailings Pond fault zones appear to have the largest cumulative displacements and may reflect eastward migration of the western sub-basin margin. This may reflect coupled partitioning of extensional strain reflected as local expressions of sub-basin development and contemporaneous volcanism.

[Displaced women's opinion of the impact of forced displacement on their health].

PubMed

Mogollón Pérez, Amparo Susana; Vázquez Navarrete, María Luisa

2006-01-01

To analyze the adaptation process of women internally displaced to the city and the relationship between displacement and their self-perceived main health problems. A qualitative, exploratory, descriptive study was carried out by means of semi-structured individual interviews with a maximum variation sample of 25 internally displaced women. A narrative content analysis was conducted with mixed generation of categories and data segmentation by age and themes. The area under study consisted of five localities in the city of Bogotá (Colombia). According to the interviewed women's discourses, their adaptation to city life depended on the new socioeconomic and environmental conditions and the psychosocial impact of displacement on the family. Precarious economic conditions forced them to live in an unhealthy environment and, occasionally, to adopt the role of head of household. In this role, many of these women, particularly young women, faced great difficulties in ensuring that the family's needs were met. Young women and teenagers reported behavioral changes due to displacement, including reproduction of violence in the home. The main self-perceived health problems among displaced women were mental health, access to food, infections and gynecological alterations. Displaced women identified the main factors hindering their access to health services as their economic situation and home responsibilities. Displaced women face new environmental and family challenges that negatively affect their health and access to healthcare. Specific interventions aimed at displaced women are required to foster better health through access to work and long -term socioeconomic stability.

Program Specificity for Ptf1a in Pancreas versus Neural Tube Development Correlates with Distinct Collaborating Cofactors and Chromatin Accessibility

PubMed Central

Meredith, David M.; Borromeo, Mark D.; Deering, Tye G.; Casey, Bradford H.; Savage, Trisha K.; Mayer, Paul R.; Hoang, Chinh; Tung, Kuang-Chi; Kumar, Manonmani; Shen, Chengcheng; Swift, Galvin H.

2013-01-01

The lineage-specific basic helix-loop-helix transcription factor Ptf1a is a critical driver for development of both the pancreas and nervous system. How one transcription factor controls diverse programs of gene expression is a fundamental question in developmental biology. To uncover molecular strategies for the program-specific functions of Ptf1a, we identified bound genomic regions in vivo during development of both tissues. Most regions bound by Ptf1a are specific to each tissue, lie near genes needed for proper formation of each tissue, and coincide with regions of open chromatin. The specificity of Ptf1a binding is encoded in the DNA surrounding the Ptf1a-bound sites, because these regions are sufficient to direct tissue-restricted reporter expression in transgenic mice. Fox and Sox factors were identified as potential lineage-specific modifiers of Ptf1a binding, since binding motifs for these factors are enriched in Ptf1a-bound regions in pancreas and neural tube, respectively. Of the Fox factors expressed during pancreatic development, Foxa2 plays a major role. Indeed, Ptf1a and Foxa2 colocalize in embryonic pancreatic chromatin and can act synergistically in cell transfection assays. Together, these findings indicate that lineage-specific chromatin landscapes likely constrain the DNA binding of Ptf1a, and they identify Fox and Sox gene families as part of this process. PMID:23754747

Bacterial dehalogenases: biochemistry, genetics, and biotechnological applications.

PubMed Central

Fetzner, S; Lingens, F

1994-01-01

This review is a survey of bacterial dehalogenases that catalyze the cleavage of halogen substituents from haloaromatics, haloalkanes, haloalcohols, and haloalkanoic acids. Concerning the enzymatic cleavage of the carbon-halogen bond, seven mechanisms of dehalogenation are known, namely, reductive, oxygenolytic, hydrolytic, and thiolytic dehalogenation; intramolecular nucleophilic displacement; dehydrohalogenation; and hydration. Spontaneous dehalogenation reactions may occur as a result of chemical decomposition of unstable primary products of an unassociated enzyme reaction, and fortuitous dehalogenation can result from the action of broad-specificity enzymes converting halogenated analogs of their natural substrate. Reductive dehalogenation either is catalyzed by a specific dehalogenase or may be mediated by free or enzyme-bound transition metal cofactors (porphyrins, corrins). Desulfomonile tiedjei DCB-1 couples energy conservation to a reductive dechlorination reaction. The biochemistry and genetics of oxygenolytic and hydrolytic haloaromatic dehalogenases are discussed. Concerning the haloalkanes, oxygenases, glutathione S-transferases, halidohydrolases, and dehydrohalogenases are involved in the dehalogenation of different haloalkane compounds. The epoxide-forming halohydrin hydrogen halide lyases form a distinct class of dehalogenases. The dehalogenation of alpha-halosubstituted alkanoic acids is catalyzed by halidohydrolases, which, according to their substrate and inhibitor specificity and mode of product formation, are placed into distinct mechanistic groups. beta-Halosubstituted alkanoic acids are dehalogenated by halidohydrolases acting on the coenzyme A ester of the beta-haloalkanoic acid. Microbial systems offer a versatile potential for biotechnological applications. Because of their enantiomer selectivity, some dehalogenases are used as industrial biocatalysts for the synthesis of chiral compounds. The application of dehalogenases or bacterial strains in environmental protection technologies is discussed in detail. PMID:7854251

Deletion and anergy of polyclonal B cells specific for ubiquitous membrane-bound self-antigen

PubMed Central

Taylor, Justin J.; Martinez, Ryan J.; Titcombe, Philip J.; Barsness, Laura O.; Thomas, Stephanie R.; Zhang, Na; Katzman, Shoshana D.; Jenkins, Marc K.

2012-01-01

B cell tolerance to self-antigen is critical to preventing antibody-mediated autoimmunity. Previous work using B cell antigen receptor transgenic animals suggested that self-antigen–specific B cells are either deleted from the repertoire, enter a state of diminished function termed anergy, or are ignorant to the presence of self-antigen. These mechanisms have not been assessed in a normal polyclonal repertoire because of an inability to detect rare antigen-specific B cells. Using a novel detection and enrichment strategy to assess polyclonal self-antigen–specific B cells, we find no evidence of deletion or anergy of cells specific for antigen not bound to membrane, and tolerance to these types of antigens appears to be largely maintained by the absence of T cell help. In contrast, a combination of deleting cells expressing receptors with high affinity for antigen with anergy of the undeleted lower affinity cells maintains tolerance to ubiquitous membrane-bound self-antigens. PMID:23071255

High-resolution ultrasonography in assessing temporomandibular joint disc position.

PubMed

Talmaceanu, Daniel; Lenghel, Lavinia Manuela; Bolog, Nicolae; Popa Stanila, Roxana; Buduru, Smaranda; Leucuta, Daniel Corneliu; Rotar, Horatiu; Baciut, Mihaela; Baciut, Grigore

2018-02-04

The purpose of this study was to determine the diagnostic value of high-resolution ultrasonography (US) in temporomandibular joint (TMJ) disc displacements. A number of 74 patients (148 TMJs) with signs and symptoms of TMJ disorders, according to the Research Diagnostic Criteria for Temporomandibular Disorders, were included in this study. All patients received US and magnetic resonance imaging (MRI) of both TMJs 1 to 5 days after the clinical examination. MRI examinations were performed using 1.5 T MRI equipment (Siemens Avanto, Siemens, Erlangen). Ultrasonographic examination was performed on a Hitachi EUB 8500 (Hitachi Medical Corp., Tokyo, Japan) scanner with L 54 M6.5-13 MHz linear transducer. MRI depicted 68 (45.95%) normal joints, 47 (31.76%) with disc displacement with reduction, 33 (22.3%) with disc displacement without reduction and 34 (22.97%) with degenerative changes. US detected 78 (52.7%) normal joints, 37 (25%) with disc displacement with reduction, 33 (22.3%) with disc displacement without reduction and 21 (14.19%) with degenerative changes. Compared to MRI, US showed a sensitivity of 93.1%, specificity of 87.88%, accuracy of 90.32%, a positive predictive value of 87.1% and a negative predictive value of 93.55% for overall diagnosis of disc displacement. The Youden index was 0.81. Based on our results, high-resolution ultrasonography showed high sensitivity, specificity and accuracy in the diagnosis of TMJ disc displacement. It could be a valuable imaging technique in assessing TMJ disc position. The diagnostic value of high-resolution ultrasonography depends strictly on the examiner's skills and on the equipment used.

Air Pollution and Deaths among Elderly Residents of São Paulo, Brazil: An Analysis of Mortality Displacement.

PubMed

Costa, Amine Farias; Hoek, Gerard; Brunekreef, Bert; Ponce de Leon, Antônio C M

2017-03-01

Evaluation of short-term mortality displacement is essential to accurately estimate the impact of short-term air pollution exposure on public health. We quantified mortality displacement by estimating single-day lag effects and cumulative effects of air pollutants on mortality using distributed lag models. We performed a daily time series of nonaccidental and cause-specific mortality among elderly residents of São Paulo, Brazil, between 2000 and 2011. Effects of particulate matter smaller than 10 μm (PM 10 ), nitrogen dioxide (NO 2 ) and carbon monoxide (CO) were estimated in Poisson generalized additive models. Single-day lag effects of air pollutant exposure were estimated for 0-, 1- and 2-day lags. Distributed lag models with lags of 0-10, 0-20 and 0-30 days were used to assess mortality displacement and potential cumulative exposure effects. PM 10 , NO 2 and CO were significantly associated with nonaccidental and cause-specific deaths in both single-day lag and cumulative lag models. Cumulative effect estimates for 0-10 days were larger than estimates for single-day lags. Cumulative effect estimates for 0-30 days were essentially zero for nonaccidental and circulatory deaths but remained elevated for respiratory and cancer deaths. We found evidence of mortality displacement within 30 days for nonaccidental and circulatory deaths in elderly residents of São Paulo. We did not find evidence of mortality displacement within 30 days for respiratory or cancer deaths. Citation: Costa AF, Hoek G, Brunekreef B, Ponce de Leon AC. 2017. Air pollution and deaths among elderly residents of São Paulo, Brazil: an analysis of mortality displacement. Environ Health Perspect 125:349-354; http://dx.doi.org/10.1289/EHP98.

Development and Evolution of Character Displacement

PubMed Central

Pfennig, David W.; Pfennig, Karin S.

2012-01-01

Character displacement occurs when competition for either resources or successful reproduction imposes divergent selection on interacting species, causing divergence in traits associated with resource use or reproduction. Here, we describe how character displacement can be mediated either by genetically canalized changes (i.e., changes that reflect allelic or genotype frequency changes) or by phenotypic plasticity. We also discuss how these two mechanisms influence the tempo of character displacement. Specifically, we suggest that, under some conditions, character displacement mediated by phenotypic plasticity might occur more rapidly than that mediated by genetically canalized changes. Finally, we describe how these two mechanisms may act together and determine character displacement’s mode, such that it proceeds through an initial phase in which trait divergence is environmentally induced to a later phase in which divergence becomes genetically canalized. This plasticity-first hypothesis predicts that character displacement should be generally mediated by ancestral plasticity and that it will arise similarly in multiple, independently evolving populations. We conclude by highlighting future directions for research that would test these predictions. PMID:22257002

33 CFR 157.03 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... port of final cargo discharge. Breadth or B means the maximum molded breadth of a vessel in meters... lightweight displacement and the total displacement of a vessel measured in water of specific gravity 1.025 at... of each is more than 1/15 of the total depth of the tank. Length or L means the distance in meters...

33 CFR 157.03 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... port of final cargo discharge. Breadth or B means the maximum molded breadth of a vessel in meters... lightweight displacement and the total displacement of a vessel measured in water of specific gravity 1.025 at... of each is more than 1/15 of the total depth of the tank. Length or L means the distance in meters...

33 CFR 157.03 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... port of final cargo discharge. Breadth or B means the maximum molded breadth of a vessel in meters... lightweight displacement and the total displacement of a vessel measured in water of specific gravity 1.025 at... of each is more than 1/15 of the total depth of the tank. Length or L means the distance in meters...

New Beginnings. A Manual for Facilitating Growth for Displaced Homemakers.

ERIC Educational Resources Information Center

Burnside, Nancy; And Others

This resource manual shares ideas and exercises with those persons interested in and working with the specific concerns of displaced homemakers. Sections correspond to steps in an adjustment process leading to job search. An introduction overviews the manual and provides helpful hints for use by peer counselors, professional therapists, and group…

Search for long-lived, weakly interacting particles that decay to displaced hadronic jets in proton-proton collisions at s = 8 TeV with the ATLAS detector

DOE PAGES

Aad, G.; Abbott, B.; Abdallah, J.; ...

2015-07-17

A search for the decay of neutral, weakly interacting, long-lived particles using data collected by the ATLAS detector at the LHC is presented. This analysis uses the full data set recorded in 2012: 20.3 fb –1 of proton-proton collision data at √s = 8 TeV. The search employs techniques for reconstructing decay vertices of long-lived particles decaying to jets in the inner tracking detector and muon spectrometer. Signal events require at least two reconstructed vertices. No significant excess of events over the expected background is found, and limits as a function of proper lifetime are reported for the decay ofmore » the Higgs boson and other scalar bosons to long-lived particles and for Hidden Valley Z' and Stealth SUSY benchmark models. The first search results for displaced decays in Z' and Stealth SUSY models are presented. The upper bounds of the excluded proper lifetimes are the most stringent to date.« less

Dna2 nuclease-helicase structure, mechanism and regulation by Rpa

PubMed Central

Zhou, Chun; Pourmal, Sergei; Pavletich, Nikola P

2015-01-01

The Dna2 nuclease-helicase maintains genomic integrity by processing DNA double-strand breaks, Okazaki fragments and stalled replication forks. Dna2 requires ssDNA ends, and is dependent on the ssDNA-binding protein Rpa, which controls cleavage polarity. Here we present the 2.3 Å structure of intact mouse Dna2 bound to a 15-nucleotide ssDNA. The nuclease active site is embedded in a long, narrow tunnel through which the DNA has to thread. The helicase domain is required for DNA binding but not threading. We also present the structure of a flexibly-tethered Dna2-Rpa interaction that recruits Dna2 to Rpa-coated DNA. We establish that a second Dna2-Rpa interaction is mutually exclusive with Rpa-DNA interactions and mediates the displacement of Rpa from ssDNA. This interaction occurs at the nuclease tunnel entrance and the 5’ end of the Rpa-DNA complex. Hence, it only displaces Rpa from the 5’ but not 3’ end, explaining how Rpa regulates cleavage polarity. DOI: http://dx.doi.org/10.7554/eLife.09832.001 PMID:26491943

Geologic map of the Sunshine 7.5' quadrangle, Taos County, New Mexico

USGS Publications Warehouse

Thompson, Ren A.; Turner, Kenzie J.; Shroba, Ralph R.; Cosca, Michael A.; Ruleman, Chester A.; Lee, John P.; Brandt, Theodore R.

2014-01-01

Pliocene and younger basin deposition was accommodated along predominantly north-trending fault-bounded grabens and is preserved as poorly exposed fault scarps that cut lava flows of Ute Mountain volcano, north of the map area. The Servilleta Basalt and younger surficial deposits record largely down-to-east basinward displacement. Faults are identified with varying confidence levels in the map area. Recognizing and mapping faults developed near the surface in relatively young, brittle volcanic rocks is difficult because: (1) they tend to form fractured zones tens of meters wide rather than discrete fault planes, (2) the relative youth of the deposits has resulted in only modest displacements on most faults, and (3) some of the faults may have significant strike-slip components that do not result in large vertical offsets that are readily apparent in offset of sub-horizontal contacts. Those faults characterized as “certain” either have distinct offset of map units or had slip planes that were directly observed in the field. Lineaments defined from magnetic anomalies form an additional constraint on potential fault locations.

Characterization of NK1 and NK2 tachykinin receptors in guinea-pig and rat bronchopulmonary and vascular systems.

PubMed Central

Floch, A.; Fardin, V.; Cavero, I.

1994-01-01

1. NK1 and NK2 tachykinin receptors were characterized in guinea-pig and rat bronchopulmonary systems and in the vasculature of the rat by use of radioligand binding and/or functional studies. 2. The radioligands for NK1 and NK2 receptors ([3H]-SP and [3H]-pNKA, respectively) did not label tachykinin receptors in homogenates of rat lungs or bronchi. In contrast, in the guinea-pig, [3H]-SP bound with high affinity to these tissues (KD = 0.23 +/- 0.08 nM and 0.34 +/- 0.05 nM, for lungs and bronchi, respectively). The total number of binding sites was 4.6 fold greater in bronchus (Bmax = 135 +/- 27 fmol mg-1 protein) than in lung homogenates (Bmax = 29.3 +/- 0.1 fmol mg-1 protein). Furthermore, this binding was markedly displaced by CP-96,345 (pKi = 9.5 +/- 0.1) and RP 67580 (pKi = 7.6 +/- 0.1), antagonists of NK1 receptors, slightly displaced by SR 48968 (pKi = 6.6 +/- 0.1), but not affected by actinomycin D or L-659,877, antagonists of NK2 receptors. Specific binding of [3H]-pNKA, detected in guinea-pig bronchi (KD = 5.2 +/- 0.1 nM, and Bmax = 203 +/- 19 fmol mg-1 protein) but not in lungs, was similarly (40 to 53%) displaced by RP 67580 (1 microM), CP-96,345 (10 and 100 nM) or SR 48968 (10 and 100 nM). The displacement approximately doubled (87 to 91%) when SR 48968 (10 nM) was combined with either RP 67580 (1 microM) or CP-96,345 (10 nM), but not when RP 67580 was combined with CP-96,345. 3. In urethane-anaesthetized guinea-pigs, i.v. injections of the NK1 receptor agonists SP, [Pro9]-SP, [Sar9,Met(O2)11]-SP and septide, as well as the NK2 receptor agonists NKA and [Lys5,MeLeu9,NLeu10]-NKA(4-10) (0.1-10 micrograms kg-1, i.v.), dose-dependently increased lung inflation pressure. The most potent of these peptides were septide and [Lys5, MeLeu9,NLeu10]-NKA(4-10) (EC50 = 0.38 +/- 0.07 and 0.07 +/- 0.02 microgram kg-1, respectively). Interestingly, septide was 130 fold less potent than SP in displacing [3H]-SP from its binding sites in the guinea-pig lung, whereas it was 14 fold more potent than SP as a bronchoconstrictor. RP 67580 (0.3-5 mg kg-1, i.v.) and CP-96,345 (0.01-3 mg kg-1, i.v.) dose-dependently reduced the bronchoconstriction produced by the NK1 receptor agonists.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7517328

Improved tool grinding machine

DOEpatents

Dial, C.E. Sr.

The present invention relates to an improved tool grinding mechanism for grinding single point diamond cutting tools to precise roundness and radius specifications. The present invention utilizes a tool holder which is longitudinally displaced with respect to the remainder of the grinding system due to contact of the tool with the grinding surface with this displacement being monitored so that any variation in the grinding of the cutting surface such as caused by crystal orientation or tool thicknesses may be compensated for during the grinding operation to assure the attainment of the desired cutting tool face specifications.

Tool grinding machine

DOEpatents

Dial, Sr., Charles E.

1980-01-01

The present invention relates to an improved tool grinding mechanism for grinding single point diamond cutting tools to precise roundness and radius specifications. The present invention utilizes a tool holder which is longitudinally displaced with respect to the remainder of the grinding system due to contact of the tool with the grinding surface with this displacement being monitored so that any variation in the grinding of the cutting surface such as caused by crystal orientation or tool thickness may be compensated for during the grinding operation to assure the attainment of the desired cutting tool face specifications.

Assessing and Evaluating Department of Defense Efforts to Inform, Influence, and Persuade: Work Example

DTIC Science & Technology

2017-01-01

reviewing and refining their initial objectives to ensure that these objectives are SMART: specific, measurable, achievable, relevant, and time -bound...should not conflate exposure and effectiveness where messaging is concerned, and they should aim to capture trends over time . Assessors should use...specific, measurable, achievable, relevant, and time -bound TAA target audience analysis TCO transnational criminal organization UN United Nations VEO

The Lag Model, a Turbulence Model for Wall Bounded Flows Including Separation

NASA Technical Reports Server (NTRS)

Olsen, Michael E.; Coakley, Thomas J.; Kwak, Dochan (Technical Monitor)

2001-01-01

A new class of turbulence model is described for wall bounded, high Reynolds number flows. A specific turbulence model is demonstrated, with results for favorable and adverse pressure gradient flowfields. Separation predictions are as good or better than either Spalart Almaras or SST models, do not require specification of wall distance, and have similar or reduced computational effort compared with these models.

Photoaffinity labelling and solubilization on the central 5-HT1A receptor binding site.

PubMed

Gozlan, H; Emerit, M B; el Mestikawy, S; Cossery, J M; Marquet, A; Besselievre, R; Hamon, M

1987-01-01

Two complementary approaches, covalent labelling and solubilization, have been used to study the biochemical properties of the central 5-HT1A receptor binding site. We have first designed a photoaffinity ligand containing the structure of 8-OH-DPAT, a potent and specific agonist of 5-HT1A sites. Thus, 8-methoxy-2[N-n-propyl,N-3-(2-nitro-4-azido-phenyl)- aminopropyl]aminotetralin or 8-methoxy-3'-NAP-amino-PAT, was found to displace, in the dark, [3H]8-OH-DPAT from 5-HT1A sites in rat hippocampal membranes with an IC50 of 6.6 nM. Under two cumulative UV irradiations (366 nm, for 20 min at 4 degrees C), 8-methoxy-3-'-NAP-amino-PAT (30 nM) blocked irreversibly 55-60% of 5-HT1A binding sites. This blockade was specific of 5-HT1A sites since the other serotoninergic sites, 5-HT1B, 5-HT2 and also the presynaptic 5-HT3 sites were not affected by the treatment. In addition, the binding of [3H]Spiperone and [3H]7-OH-DPAT to striatal dopamine sites remained unchanged under similar photolysis conditions. The tritiated derivative of the photoaffinity ligand (92 Ci/mmol) was then synthesized for the identification of the covalently bound protein(s). SDS-PAGE of solubilized membranes irradiated in the presence of 20 nM 3H-8-methoxy-3'-NAP-amino-PAT allowed the detection of a 63 kD protein whose labelling appeared specific. Thus, 3H-incorporation into the 63 kD band could be prevented by microM concentrations of 5-HT, 8-OH-DPAT and other selective 5-HT1A ligands such as isapirone. In contrast, the 5-HT2 antagonist ketanserin, norepinephrine and dopamine-related ligands (including 7-OH-DPAT) were ineffective. Direct solubilization of 5-HT1A receptor binding sites was also attempted from rat hippocampal membranes. The best results were obtained using CHAPS (10 mM) plus NaCl (0.2 M), which led to 50% recovery of 5-HT1A sites in the 100,000 g supernatant. The pharmacological properties and sensitivity to N-ethyl-maleimide and GppNHp of soluble sites appeared near identical to those of membrane-bound 5-HT1A sites.

Estimates of Internal Tide Energy Fluxes from Topex/Poseidon Altimetry: Central North Pacific

NASA Technical Reports Server (NTRS)

Ray, Richard D.; Cartwright, David E.; Smith, David E. (Technical Monitor)

2000-01-01

Energy fluxes for first-mode M(sub 2) internal tides are deduced throughout the central North Pacific Ocean from Topex/Poseidon satellite altimeter data. Temporally coherent internal tide signals in the altimetry, combined with climatological hydrographic data, determine the tidal displacements, pressures, and currents at depth, which yield power transmission rates. For a variety of reasons the deduced rates should be considered lower bounds. Internal tides were found to emanate from several large bathymetric structures, especially the Hawaiian Ridge, where the integrated flux amounts to about six gigawatts. Internal tides are generated at the Aleutian Trench near 172 deg west and propagate southwards nearly 2000 km.

Permanent uplift in magmatic systems with application to the Tharsis region of Mars

NASA Astrophysics Data System (ADS)

Phillips, R. J.; Sleep, N. H.; Banerdt, W. B.

1990-04-01

A model is derived for predicting both crustal displacement (leading to permanent uplift) and topographic elevation in regional large-scale magmatic systems associated with partial melting of mantle rocks. The model is then applied to the Tharsis region of Mars to test the uplift versus construction. It was found that a lower bound estimate of the fraction of intrusives necessary for any uplift at all is about 85 percent of the total magmatic products at Tharsis. Thus, it is proposed that most of the magmas associated with Tharsis evolution ended up as intrusive bodies in the crust and upper mantle.

InSAR observations of low slip rates on the major faults of western Tibet.

PubMed

Wright, Tim J; Parsons, Barry; England, Philip C; Fielding, Eric J

2004-07-09

Two contrasting views of the active deformation of Asia dominate the debate about how continents deform: (i) The deformation is primarily localized on major faults separating crustal blocks or (ii) deformation is distributed throughout the continental lithosphere. In the first model, western Tibet is being extruded eastward between the major faults bounding the region. Surface displacement measurements across the western Tibetan plateau using satellite radar interferometry (InSAR) indicate that slip rates on the Karakoram and Altyn Tagh faults are lower than would be expected for the extrusion model and suggest a significant amount of internal deformation in Tibet.

Permanent uplift in magmatic systems with application to the Tharsis region of Mars

NASA Technical Reports Server (NTRS)

Phillips, Roger J.; Sleep, Norman H.; Banerdt, W. Bruce

1990-01-01

A model is derived for predicting both crustal displacement (leading to permanent uplift) and topographic elevation in regional large-scale magmatic systems associated with partial melting of mantle rocks. The model is then applied to the Tharsis region of Mars to test the uplift versus construction. It was found that a lower bound estimate of the fraction of intrusives necessary for any uplift at all is about 85 percent of the total magmatic products at Tharsis. Thus, it is proposed that most of the magmas associated with Tharsis evolution ended up as intrusive bodies in the crust and upper mantle.

Application of Classical Land Surveying Measurement Methods for Determining the Vertical Displacement of Railway Bridges

NASA Astrophysics Data System (ADS)

Gawronek, Pelagia; Makuch, Maria

2017-12-01

The classical measurements of stability of railway bridge, in the context of determining the vertical displacements of the object, consisted on precise leveling of girders and trigonometric leveling of controlled points (fixed into girders' surface). The construction elements, which were measured in two ways, in real terms belonged to the same vertical planes. Altitude measurements of construction were carried out during periodic structural stability tests and during static load tests of bridge by train. The specificity of displacement measurements, the type of measured object and the rail land surveying measurement conditions were determinants to define methodology of altitude measurement. The article presents compatibility of vertical displacements of steel railway bridge, which were developed in two measurement methods. In conclusion, the authors proposed the optimum concept of determining the vertical displacements of girders by using precise and trigonometric leveling (in terms of accuracy, safety and economy of measurement).

Platelet binding sites for factor VIII in relation to fibrin and phosphatidylserine

PubMed Central

Novakovic, Valerie A.; Shi, Jialan; Rasmussen, Jan; Pipe, Steven W.

2015-01-01

Thrombin-stimulated platelets expose very little phosphatidylserine (PS) but express binding sites for factor VIII (fVIII), casting doubt on the role of exposed PS as the determinant of binding sites. We previously reported that fVIII binding sites are increased three- to sixfold when soluble fibrin (SF) binds the αIIbβ3 integrin. This study focuses on the hypothesis that platelet-bound SF is the major source of fVIII binding sites. Less than 10% of fVIII was displaced from thrombin-stimulated platelets by lactadherin, a PS-binding protein, and an fVIII mutant defective in PS-dependent binding retained platelet affinity. Therefore, PS is not the determinant of most binding sites. FVIII bound immobilized SF and paralleled platelet binding in affinity, dependence on separation from von Willebrand factor, and mediation by the C2 domain. SF also enhanced activity of fVIII in the factor Xase complex by two- to fourfold. Monoclonal antibody (mAb) ESH8, against the fVIII C2 domain, inhibited binding of fVIII to SF and platelets but not to PS-containing vesicles. Similarly, mAb ESH4 against the C2 domain, inhibited >90% of platelet-dependent fVIII activity vs 35% of vesicle-supported activity. These results imply that platelet-bound SF is a component of functional fVIII binding sites. PMID:26162408

A calorimetric investigation of the interaction of the lac repressor with inducer.

PubMed

Donnér, J; Caruthers, M H; Gill, S J

1982-12-25

A calorimetric study has been made of the interaction between the lac repressor and isopropyl-1-thio-beta-D-galactopyranoside (IPTG). The buffer-corrected enthalpy of reaction at 25 degrees C was found to be -15.6, -24.7, -4.6 kJ/mol of bound IPTG at pH 7.0, pH 8.1, and pH 9.0, respectively. This large range of enthalpy values is in contrast to a maximum difference in the free energy of the reaction of only 1.5 kJ/mol of bound IPTG between these pH values. The reaction was found by calorimetric measurements in different buffers to be accompanied by an uptake of 0.29 mol of protons/mol of bound IPTG at pH 8.1. The pH dependency of the reaction enthalpy suggests differences in the extent of protonation of the binding site and the involvement of H bonding with IPTG. The lack of strong hydrophobic contributions in the IPTG binding process is revealed by the absence of any determinable heat capacity change for the reaction at pH 7.0. The presence of phosphate buffer significantly alters the enthalpy of IPTG binding at higher pH values, but has little effect upon the binding constant. This implies that highly negative phosphate species change the nature of the IPTG binding site without any displacement of phosphate upon IPTG binding.

Antibodies Targeting Closely Adjacent or Minimally Overlapping Epitopes Can Displace One Another

PubMed Central

Abdiche, Yasmina Noubia; Yeung, Andy Yik; Ni, Irene; Stone, Donna; Miles, Adam; Morishige, Winse; Rossi, Andrea; Strop, Pavel

2017-01-01

Here we describe how real-time label-free biosensors can be used to identify antibodies that compete for closely adjacent or minimally overlapping epitopes on their specific antigen via a mechanism of antibody displacement. By kinetically perturbing one another’s binding towards their antigen via the formation of a transient trimolecular complex, antibodies can displace one another in a fully reversible and dose-dependent manner. Displacements can be readily identified when epitope binning assays are performed in a classical sandwich assay format whereby a solution antibody (analyte) is tested for binding to its antigen that is first captured via an immobilized antibody (ligand) because an inverted sandwiching response is observed when an analyte displaces a ligand, signifying the antigen’s unusually rapid dissociation from its ligand. In addition to classifying antibodies within a panel in terms of their ability to block or sandwich pair with one another, displacement provides a hybrid mechanism of competition. Using high-throughput epitope binning studies we demonstrate that displacements can be observed on any target, if the antibody panel contains appropriate epitope diversity. Unidirectional displacements occurring between disparate-affinity antibodies can generate apparent asymmetries in a cross-blocking experiment, confounding their interpretation. However, examining competition across a wide enough concentration range will often reveal that these displacements are reversible. Displacement provides a gentle and efficient way of eluting antigen from an otherwise high affinity binding partner which can be leveraged in designing reagents or therapeutic antibodies with unique properties. PMID:28060885

Antibodies Targeting Closely Adjacent or Minimally Overlapping Epitopes Can Displace One Another.

PubMed

Abdiche, Yasmina Noubia; Yeung, Andy Yik; Ni, Irene; Stone, Donna; Miles, Adam; Morishige, Winse; Rossi, Andrea; Strop, Pavel

2017-01-01

Here we describe how real-time label-free biosensors can be used to identify antibodies that compete for closely adjacent or minimally overlapping epitopes on their specific antigen via a mechanism of antibody displacement. By kinetically perturbing one another's binding towards their antigen via the formation of a transient trimolecular complex, antibodies can displace one another in a fully reversible and dose-dependent manner. Displacements can be readily identified when epitope binning assays are performed in a classical sandwich assay format whereby a solution antibody (analyte) is tested for binding to its antigen that is first captured via an immobilized antibody (ligand) because an inverted sandwiching response is observed when an analyte displaces a ligand, signifying the antigen's unusually rapid dissociation from its ligand. In addition to classifying antibodies within a panel in terms of their ability to block or sandwich pair with one another, displacement provides a hybrid mechanism of competition. Using high-throughput epitope binning studies we demonstrate that displacements can be observed on any target, if the antibody panel contains appropriate epitope diversity. Unidirectional displacements occurring between disparate-affinity antibodies can generate apparent asymmetries in a cross-blocking experiment, confounding their interpretation. However, examining competition across a wide enough concentration range will often reveal that these displacements are reversible. Displacement provides a gentle and efficient way of eluting antigen from an otherwise high affinity binding partner which can be leveraged in designing reagents or therapeutic antibodies with unique properties.

Interferometric measurement of displacements and displacement velocities for nondestructive quality control

NASA Astrophysics Data System (ADS)

Shpeĭzman, V. V.; Peschanskaya, N. N.

2007-07-01

It is shown that the interferometric measurement of small displacements and small-displacement velocities can be used to determine internal stresses or the stresses induced by an applied load in solids and to control structural changes in them. The interferometric method based on the measurement of the reaction of a solid to a small perturbation in its state of stress is applied to determine stresses from the deviation of the reaction to perturbations from that in the standard stress-free case. For structural control, this method is employed to study the specific features of the characteristics of microplastic deformation that appear after material treatment or operation and manifest themselves in the temperature and force dependences of the rate of a small inelastic strain.

Nonclassicality of Photon-Added Displaced Thermal State via Quantum Phase-Space Distributions

NASA Astrophysics Data System (ADS)

Zhang, Ran; Meng, Xiang-Guo; Du, Chuan-Xun; Wang, Ji-Suo

2018-02-01

We introduce a new kind of nonclassical mixed state generated by adding arbitrary photons to a displaced thermal state, i.e., the photon-added displaced thermal state (PADTS), and obtain the normalization factor, which is simply related to two-variable Hermite polynomials. We also discuss the nonclassicality of the PADTS by considering quantum phase-space distributions. The results indicate that the value of the photon count statistics is maximum when the number of detected photons is equal to the number of added photons, and that the photon-added operation has a similar modulation effect with increasing displacement. Moreover, the negative volume of the Wigner function for the PADTS takes a maximal value for a specific photon-added number.

Finger displacement in Parkinson disease: up? down? sideways?

PubMed

Lieberman, Abraham; Dhall, Rohit; Salins, Naomi; Sadreddin, Arshia; Moguel-Cobos, Guillermo; Karis, John; Krishnamurthi, Narayanan

2014-05-01

We previously reported that patients with tremor preponderant Parkinson disease (PD) displayed upward or lateral displacement of their more tremulous finger when they pointed both their index fingers at a target and closed their eyes for 15 seconds. In this study, we examined the phenomenon in 104 PD patients: 72 patients without tremor and 32 with minimal tremor to see if the displacement is related to the disease or the tremor. Sixty-eight of the 72 patients without tremor, 94%, exhibited finger displacement suggesting the phenomenon is related to the disease. None of the 104 patients were demented: mini-mental status examination (MMSE) score 29.0 ± 0. 75. Ninety patients displayed upward displacement (56 patients) or lateral or medial displacement (34 patients). MMSE score of the 90 patients: 29.2 ± 0.74 with no score < 28. Eight patients (6 without tremor) displayed downward displacement. MMSE score of the 8 patients: 27.5 ± 0.35 with 5 having MMSE score of 27. Although not significant the results suggest that patients with downward displacement and lower MMSE score may be evolving a dementia. Upward displacement with eyes closed for 15 seconds requires an ability to "remember" the position of the finger in space and to alter tone to overcome gravity. Downward displacement implies an inability to "remember" the position of the finger in space an inability to overcome the effects of gravity. This may be more likely in patients who are evolving a dementia. Two patients, with PD-like symptoms, and specific anatomical abnormalities are also presented as they illustrate the anatomy of finger displacement.

Kinetic modeling of benzodiazepine receptor binding with PET and high specific activity [(11)C]Iomazenil in healthy human subjects.

PubMed

Bremner, J D; Horti, A; Staib, L H; Zea-Ponce, Y; Soufer, R; Charney, D S; Baldwin, R

2000-01-01

Quantitation of the PET benzodiazepine receptor antagonist, [(11)C]Iomazenil, using low specific activity radioligand was recently described. The purpose of this study was to quantitate benzodiazepine receptor binding in human subjects using PET and high specific activity [(11)C]Iomazenil. Six healthy human subjects underwent PET imaging following a bolus injection of high specific activity (>100 Ci/mmol) [(11)C]iomazenil. Arterial samples were collected at multiple time points after injection for measurement of unmetabolized total and nonprotein-bound parent compound in plasma. Time activity curves of radioligand concentration in brain and plasma were analyzed using two and three compartment model. Kinetic rate constants of transfer of radioligand between plasma, nonspecifically bound brain tissue, and specifically bound brain tissue compartments were fitted to the model. Values for fitted kinetic rate constants were used in the calculation of measures of benzodiazepine receptor binding, including binding potential (the ratio of receptor density to affinity), and product of BP and the fraction of free nonprotein-bound parent compound (V(3)'). Use of the three compartment model improved the goodness of fit in comparison to the two compartment model. Values for kinetic rate constants and measures of benzodiazepine receptor binding, including BP and V(3)', were similar to results obtained with the SPECT radioligand [(123)I]iomazenil, and a prior report with low specific activity [(11)C]Iomazenil. Kinetic modeling using the three compartment model with PET and high specific activity [(11)C]Iomazenil provides a reliable measure of benzodiazepine receptor binding. Synapse 35:68-77, 2000. Published 2000 Wiley-Liss, Inc.

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

Pradhan, P., E-mail: pppradhan77@gmail.com

We derive various important thermodynamic relations of the inner and outer horizons in the background of the Taub–NUT (Newman–Unti–Tamburino) black hole in four-dimensional Lorentzian geometry. We compare these properties with the properties of the Reissner–Nordström black hole. We compute the area product, area sum, area subtraction, and area division of black hole horizons. We show that they all are not universal quantities. Based on these relations, we compute the area bound of all horizons. From the area bound, we derive an entropy bound and an irreducible mass bound for both horizons. We further study the stability of such black holesmore » by computing the specific heat for both horizons. It is shown that due to the negative specific heat, the black hole is thermodynamically unstable. All these calculations might be helpful in understanding the nature of the black hole entropy (both interior and exterior) at the microscopic level.« less

Dynamic behaviors of water contained in calcium-silicate-hydrate gel at different temperatures studied by quasi-elastic neutron scattering spectroscopy

NASA Astrophysics Data System (ADS)

Yi, Zhou; Deng, Pei-Na; Zhang, Li-Li; Li, Hua

2016-10-01

The dynamic behaviors of water contained in calcium-silicate-hydrate (C-S-H) gel with different water content values from 10% to 30% (by weight), are studied by using an empirical diffusion model (EDM) to analyze the experimental data of quasi-elastic neutron scattering (QENS) spectra at measured temperatures ranging from 230 K to 280 K. In the study, the experimental QENS spectra with the whole Q-range are considered. Several important parameters including the bound/immobile water elastic coefficient A, the bound water index BWI, the Lorentzian with a half-width at half-maximum (HWHM) Γ 1(Q) and Γ 2(Q), the self-diffusion coefficients D t1 and D t2 of water molecules, the average residence times τ 01 and τ 02, and the proton mean squared displacement (MSD) are obtained. The results show that the QENS spectra can be fitted very well not only for small Q (≤ 1 Å-1) but also for large Q. The bound/immobile water fraction in a C-S-H gel sample can be shown by the fitted BWI. The distinction between bound/immobile and mobile water, which includes confined water and ultra-confined water, can be seen by the fitted MSD. All the MSD tend to be the smallest value below 0.25 Å2 (the MSD of bound/immobile water) as the Q increases to 1.9 Å-1, no matter what the temperature and water content are. Furthermore, by the abrupt changes of the fitted values of D t1, τ 01, and Γ 1(Q), a crossover temperature at 250 K, namely the liquid-to-crystal-like transition temperature, can be identified for confined water in large gel pores (LGPs) and/or small gel pores (SGPs) contained in the C-S-H gel sample with 30% water content.