The effect of surface tension on steadily translating bubbles in an unbounded Hele-Shaw cell

PubMed Central

2017-01-01

New numerical solutions to the so-called selection problem for one and two steadily translating bubbles in an unbounded Hele-Shaw cell are presented. Our approach relies on conformal mapping which, for the two-bubble problem, involves the Schottky-Klein prime function associated with an annulus. We show that a countably infinite number of solutions exist for each fixed value of dimensionless surface tension, with the bubble shapes becoming more exotic as the solution branch number increases. Our numerical results suggest that a single solution is selected in the limit that surface tension vanishes, with the scaling between the bubble velocity and surface tension being different to the well-studied problems for a bubble or a finger propagating in a channel geometry. PMID:28588410

Strong γ-ray emission from neutron unbound states populated in β-decay: Impact on (n,γ) cross-section estimates

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

Tain, J. L.; Guadilla, V.; Valencia, E.

Total absorption gamma-ray spectroscopy is used to measure accurately the intensity of γ emission from neutron-unbound states populated in the β-decay of delayed-neutron emitters. From the comparison of this intensity with the intensity of neutron emission one can deduce information on the (n,γ) cross section for unstable neutron-rich nuclei of interest in r process abundance calculations. A surprisingly large γ branching was observed for a number of isotopes. Here, the results are compared with Hauser-Feshbach calculations and discussed.

Strong γ-ray emission from neutron unbound states populated in β-decay: Impact on (n,γ) cross-section estimates

DOE PAGES

Tain, J. L.; Guadilla, V.; Valencia, E.; ...

2017-09-13

Total absorption gamma-ray spectroscopy is used to measure accurately the intensity of γ emission from neutron-unbound states populated in the β-decay of delayed-neutron emitters. From the comparison of this intensity with the intensity of neutron emission one can deduce information on the (n,γ) cross section for unstable neutron-rich nuclei of interest in r process abundance calculations. A surprisingly large γ branching was observed for a number of isotopes. Here, the results are compared with Hauser-Feshbach calculations and discussed.

Nematode development after removal of egg cytoplasm: absence of localized unbound determinants.

PubMed

Laufer, J S; von Ehrenstein, G

1981-01-23

Embryos of Caenorhabditis elegans develop into fertile adults after cell fragments, containing presumptive cytoplasm of somatic and germ line precursors, are extruded from uncleaved eggs or early blastomeres through laser-induced holes in the eggshells. This suggests that the determinate development of this worm is not dependent on the prelocalization of determinants in specific regions of the egg cytoplasm.

The lift force on a drop in unbounded plane Poiseuille flow

NASA Technical Reports Server (NTRS)

Wohl, P. R.

1976-01-01

The lift force on a deformable liquid sphere moving in steady, plane Poiseuille-Stokes flow and subjected to an external body force is calculated. The results are obtained by seeking a solution to Stokes' equations for the motion of the liquids inside and outside the slightly perturbed sphere surface, as expansions valid for small values of the ratio of the Weber number to the Reynolds number. When the ratio of the drop and external fluid viscosities is small, the lift exerted on a neutrally buoyant drop is found to be approximately one-tenth of the magnitude of the force reported by Wohl and Rubinow acting on the same drop in unbounded Poiseuille flow in a tube. The resultant trajectory of the drop is calculated and displayed as a function of the external body force.

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

PubMed Central

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

2013-01-01

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

Trivelpiece-Gould modes in a uniform unbounded plasma

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

Stenzel, R. L.; Urrutia, J. M.

Trivelpiece-Gould (TG) modes originally described electrostatic surface waves on an axially magnetized cylindrical plasma column. Subsequent studies of electromagnetic waves in such plasma columns revealed two modes, a predominantly magnetic helicon mode (H) and the mixed magnetic and electrostatic Trivelpiece-Gould modes (TG). The latter are similar to whistler modes near the oblique cyclotron resonance in unbounded plasmas. The wave propagation in cylindrical geometry is assumed to be paraxial while the modes exhibit radial standing waves. The present work shows that TG modes also arise in a uniform plasma without radial standing waves. It is shown experimentally that oblique cyclotron resonancemore » arises in large mode number helicons. Their azimuthal wave number far exceeds the axial wave number which creates whistlers near the oblique cyclotron resonance. Cyclotron damping absorbs the TG mode and can energize electrons in the center of a plasma column rather than the edge of conventional TG modes. The angular orbital field momentum can produce new perpendicular wave-particle interactions.« less

Measurement of plasma unbound unconjugated bilirubin.

PubMed

Ahlfors, C E

2000-03-15

A method is described for measuring the unconjugated fraction of the unbound bilirubin concentration in plasma by combining the peroxidase method for determining unbound bilirubin with a diazo method for measuring conjugated and unconjugated bilirubin. The accuracy of the unbound bilirubin determination is improved by decreasing sample dilution, eliminating interference by conjugated bilirubin, monitoring changes in bilirubin concentration using diazo derivatives, and correcting for rate-limiting dissociation of bilirubin from albumin. The unbound unconjugated bilirubin concentration by the combined method in plasma from 20 jaundiced newborns was significantly greater than and poorly correlated with the unbound bilirubin determined by the existing peroxidase method (r = 0.7), possibly due to differences in sample dilution between the methods. The unbound unconjugated bilirubin was an unpredictable fraction of the unbound bilirubin in plasma samples from patients with similar total bilirubin concentrations but varying levels of conjugated bilirubin. A bilirubin-binding competitor was readily detected at a sample dilution typically used for the combined test but not at the dilution used for the existing peroxidase method. The combined method is ideally suited to measuring unbound unconjugated bilirubin in jaundiced human newborns or animal models of kernicterus. Copyright 2000 Academic Press.

Single-particle and collective motion in unbound deformed 39Mg

NASA Astrophysics Data System (ADS)

Fossez, K.; Rotureau, J.; Michel, N.; Liu, Quan; Nazarewicz, W.

2016-11-01

Background: Deformed neutron-rich magnesium isotopes constitute a fascinating territory where the interplay between collective rotation and single-particle motion is strongly affected by the neutron continuum. The unbound f p -shell nucleus 39Mg is an ideal candidate to study this interplay. Purpose: In this work, we predict the properties of low-lying resonant states of 39Mg, using a suite of realistic theoretical approaches rooted in the open quantum system framework. Method: To describe the spectrum and decay modes of 39Mg we use the conventional shell model, Gamow shell model, resonating group method, density matrix renormalization group method, and the nonadiabatic particle-plus-rotor model formulated in the Berggren basis. Results: The unbound ground state of 39Mg is predicted to be either a Jπ=7/2 - state or a 3/2 - state. A narrow Jπ=7/2 - ground-state candidate exhibits a resonant structure reminiscent of that of its one-neutron halo neighbor 37Mg, which is dominated by the f7 /2 partial wave at short distances and a p3 /2 component at large distances. A Jπ=3/2 - ground-state candidate is favored by the large deformation of the system. It can be associated with the 1/2 -[321 ] Nilsson orbital dominated by the ℓ =1 wave; hence its predicted width is large. The excited Jπ=1/2 - and 5 /2- states are expected to be broad resonances, while the Jπ=9/2 - and 11/2 - members of the ground-state rotational band are predicted to have very small neutron decay widths. Conclusion: We demonstrate that the subtle interplay between deformation, shell structure, and continuum coupling can result in a variety of excitations in an unbound nucleus just outside the neutron drip line.

Erratum: The 2.27 day period of WR-134 (HD 191765)

NASA Astrophysics Data System (ADS)

McCandliss, Stephan R.; Bohannan, Bruce; Robert, Carmelle; Moffat, Anthony F. J.

1994-11-01

The original temporal analysis of a 12 night spectral timeseries of Wolf-Rayet (WR)-134 has been found to be flawed and a re-analysis shows that the line profile variations are indeed periodic. When combined with a 4 night timeseries taken 45 days earlier, a period near 2.27 d is found in periodograms of the He II lambda 5412 line centroid, rms line width, and line skew variations. When the emission line residuals are ordered as a function of phase, a sinuous feature appears to 'snake' about the line center with an amplitude of +/-500 km/s. This is approximately equal to 20 larger than the line centroid amplitude; the calculation of which is heavily weighted by static portions of the line profile. In addition to the 'snake,' emission residuals appear that move away from line center on unbound trajectories and are thought to result from the interaction of a periodic driver with the unstable flow of the radiation driven wind.

Erratum: The 2.27 day period of WR-134 (HD 191765)

NASA Technical Reports Server (NTRS)

Mccandliss, Stephan R.; Bohannan, Bruce; Robert, Carmelle; Moffat, Anthony F. J.

1994-01-01

The original temporal analysis of a 12 night spectral timeseries of Wolf-Rayet (WR)-134 has been found to be flawed and a re-analysis shows that the line profile variations are indeed periodic. When combined with a 4 night timeseries taken 45 days earlier, a period near 2.27 d is found in periodograms of the He II lambda 5412 line centroid, rms line width, and line skew variations. When the emission line residuals are ordered as a function of phase, a sinuous feature appears to 'snake' about the line center with an amplitude of +/-500 km/s. This is approximately equal to 20 larger than the line centroid amplitude; the calculation of which is heavily weighted by static portions of the line profile. In addition to the 'snake,' emission residuals appear that move away from line center on unbound trajectories and are thought to result from the interaction of a periodic driver with the unstable flow of the radiation driven wind.

Helicon and Trivelpiece-Gould modes in uniform unbounded plasmas

NASA Astrophysics Data System (ADS)

Stenzel, R. L.; Urrutia, J. M.

2016-10-01

Helicon modes are whistler modes with angular orbital momentum caused by phase rotation in addition to the axial phase propagation. Although these modes have been associated with whistler eigenmodes in bounded plasma columns, they do exist in unbounded plasmas. Experiments in a large laboratory plasma show the wave excitation with phased antenna arrays, the wave field topology and the propagation of helicons. Low frequency whistlers can have two modes with different wavelengths at a given frequency, called helicons and Trivelpiece-Gould modes. The latter are whistler modes near the oblique cyclotron resonance. The oblique propagation is due to short radial wavelengths near the boundary. In unbounded plasmas, the oblique propagation arises from short azimuthal wavelengths. This has been observed in high-mode number helicons (e.g., m = 8). It creates wave absorption in the center of the helicon mode. The strong absorption of the wave can heat electrons and create perpendicular wave-particle interactions. These results may be of interest in space plasmas for scattering of energetic electrons and in helicon plasma sources for plasma processing and thruster applications. Work supported by NSF/DOE.

Electromagnetic fields and potentials generated by massless charged particles

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

Azzurli, Francesco, E-mail: francesco.azzurli@gmail.com; Lechner, Kurt, E-mail: lechner@pd.infn.it; INFN, Sezione di Padova, Via F. Marzolo, 8, 35131 Padova

2014-10-15

We provide for the first time the exact solution of Maxwell’s equations for a massless charged particle moving on a generic trajectory at the speed of light. In particular we furnish explicit expressions for the vector potential and the electromagnetic field, which were both previously unknown, finding that they entail different physical features for bounded and unbounded trajectories. With respect to the standard Liénard–Wiechert field the electromagnetic field acquires singular δ-like contributions whose support and dimensionality depend crucially on whether the motion is (a) linear, (b) accelerated unbounded, (c) accelerated bounded. In the first two cases the particle generates amore » planar shock-wave-like electromagnetic field traveling along a straight line. In the second and third cases the field acquires, in addition, a δ-like contribution supported on a physical singularity-string attached to the particle. For generic accelerated motions a genuine radiation field is also present, represented by a regular principal-part type distribution diverging on the same singularity-string. - Highlights: • First exact solution of Maxwell’s equations for massless charges in arbitrary motion. • Explicit expressions of electromagnetic fields and potentials. • Derivations are rigorous and based on distribution theory. • The form of the field depends heavily on whether the motion is bounded or unbounded. • The electromagnetic field contains unexpected Dirac-delta-function contributions.« less

Neutron unbound states in 28 Ne and 25 F

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

Smith, J. K.; Baumann, T.; Brown, B. A.

2012-11-01

Unbound states in Ne-28 and F-25 were populated in the reaction of a 102 MeV/nucleon Na-29 beam on a beryllium target. The measured decay energy of 32(22) keV in the Ne-27+n system corresponds to an unbound excited state in Ne-28 at 3.86(11) MeV. This is the first measured unbound state of Ne-28. The decay energy of the F-24+n system was measured as 300(170) keV. This places the second measured unbound state of F-25 at 4.66(17) MeV.

Population pharmacokinetics of unbound hydrocortisone in critically ill neonates and infants with vasopressor-resistant hypotension.

PubMed

Vezina, Heather E; Ng, Chee M; Vazquez, Delia M; Barks, John D; Bhatt-Mehta, Varsha

2014-07-01

To determine the population pharmacokinetics of unbound hydrocortisone in critically ill neonates and infants receiving IV hydrocortisone for treatment of vasopressor-resistant hypotension and to identify patient-specific sources of pharmacokinetic variability. Prospective observational cohort study. Level 3 neonatal ICU. Sixty-two critically ill neonates and infants receiving IV hydrocortisone as part of standard of care for the treatment of vasopressor-resistant hypotension: median gestational age 28 weeks (range, 23-41), median weight 1.2 kg (range, 0.5-4.4), and 29 females. None. Unbound baseline cortisol and postdose hydrocortisone concentrations measured from blood samples being drawn for routine laboratory tests. A one-compartment model best described the data. Allometric weight and postmenstrual age were significant covariates on unbound hydrocortisone clearance and volume of distribution. Final population estimates for clearance, volume of distribution, and baseline cortisol concentration were 20.2 L/hr, 244 L, and 1.37 ng/mL, respectively. Using the median weight and postmenstrual age of our subjects (i.e., 1.2 kg and 28 wk) in the final model, the typical unbound hydrocortisone clearance and volume of distribution were 1.0 L/hr and 4.2 L, respectively. The typical half-life for unbound hydrocortisone was 2.9 hours. A sharp and continuous increase in unbound hydrocortisone clearance was observed at 35 weeks postmenstrual age. We report the first pharmacokinetic data for unbound hydrocortisone, the pharmacologically active moiety, in critically ill neonates and infants with vasopressor-resistant hypotension. Unbound hydrocortisone clearance increased with body weight and was faster in children with an older postmenstrual age. Unbound hydrocortisone clearance increased sharply at 35 weeks postmenstrual age and continued to mature thereafter. This study lays the groundwork for evaluating unbound hydrocortisone exposure-response relationships and drawing definitive conclusions about the dosing of IV hydrocortisone in critically ill neonates and infants with vasopressor-resistant hypotension.

Population pharmacokinetics of unbound hydrocortisone in critically ill neonates and infants with vasopressor-resistant hypotension

PubMed Central

Vezina, Heather E.; Ng, Chee M.; Vazquez, Delia M.; Barks, John D.; Bhatt-Mehta, Varsha

2014-01-01

Objective To determine the population pharmacokinetics of unbound hydrocortisone (HC) in critically ill neonates and infants receiving intravenous HC for treatment of vasopressor-resistant hypotension and to identify patient-specific sources of pharmacokinetic variability. Design Prospective observational cohort study. Setting Level 3 neonatal intensive care unit. Patients Sixty-two critically ill neonates and infants receiving intravenous HC as part of standard of care for the treatment of vasopressor-resistant hypotension: median gestational age 28 weeks (range, 23 to 41), median weight 1.2 kg (range, 0.5 to 4.4), 29 females. Interventions None. Measurements Unbound baseline cortisol and post-dose HC concentrations measured from blood samples being drawn for routine laboratory tests. Main Results A one compartment model best described the data. Allometric weight and postmenstrual age (PMA) were significant covariates on unbound HC clearance (CL) and volume of distribution (V). Final population estimates for CL, V, and baseline cortisol concentration were 20.2 L/h, 244 L, and 1.37 ng/mL, respectively. Using the median weight and PMA of our subjects (i.e. 1.2 kg and 28 weeks) in the final model, the typical unbound HC CL and V were 1.0 L/h and 4.2 L, respectively. The typical half-life for unbound HC was 2.9 hours. A sharp and continuous increase in unbound HC CL was observed at 35 weeks PMA. Conclusions We report the first pharmacokinetic data for unbound HC, the pharmacologically active moiety, in critically ill neonates and infants with vasopressor-resistant hypotension. Unbound HC CL increased with body weight and was faster in children with an older PMA. Unbound HC CL increased sharply at 35 weeks PMA and continued to mature thereafter. This study lays the groundwork for evaluating unbound HC exposure-response relationships and drawing definitive conclusions about the dosing of intravenous HC in critically-ill neonates and infants with vasopressor-resistant hypotension. PMID:24797719

Interference-free Micro/nanoparticle Cell Engineering by Use of High-Throughput Microfluidic Separation.

PubMed

Yeo, David C; Wiraja, Christian; Zhou, Yingying; Tay, Hui Min; Xu, Chenjie; Hou, Han Wei

2015-09-23

Engineering cells with active-ingredient-loaded micro/nanoparticles is becoming increasingly popular for imaging and therapeutic applications. A critical yet inadequately addressed issue during its implementation concerns the significant number of particles that remain unbound following the engineering process, which inadvertently generate signals and impart transformative effects onto neighboring nontarget cells. Here we demonstrate that those unbound micro/nanoparticles remaining in solution can be efficiently separated from the particle-labeled cells by implementing a fast, continuous, and high-throughput Dean flow fractionation (DFF) microfluidic device. As proof-of-concept, we applied the DFF microfluidic device for buffer exchange to sort labeled suspension cells (THP-1) from unbound fluorescent dye and dye-loaded micro/nanoparticles. Compared to conventional centrifugation, the depletion efficiency of free dyes or particles was improved 20-fold and the mislabeling of nontarget bystander cells by free particles was minimized. The microfluidic device was adapted to further accommodate heterogeneous-sized mesenchymal stem cells (MSCs). Complete removal of unbound nanoparticles using DFF led to the usage of engineered MSCs without exerting off-target transformative effects on the functional properties of neighboring endothelial cells. Apart from its effectiveness in removing free particles, this strategy is also efficient and scalable. It could continuously process cell solutions with concentrations up to 10(7) cells·mL(-1) (cell densities commonly encountered during cell therapy) without observable loss of performance. Successful implementation of this technology is expected to pave the way for interference-free clinical application of micro/nanoparticle engineered cells.

Simplified and Yet Turing Universal Spiking Neural P Systems with Communication on Request.

PubMed

Wu, Tingfang; Bîlbîe, Florin-Daniel; Păun, Andrei; Pan, Linqiang; Neri, Ferrante

2018-04-02

Spiking neural P systems are a class of third generation neural networks belonging to the framework of membrane computing. Spiking neural P systems with communication on request (SNQ P systems) are a type of spiking neural P system where the spikes are requested from neighboring neurons. SNQ P systems have previously been proved to be universal (computationally equivalent to Turing machines) when two types of spikes are considered. This paper studies a simplified version of SNQ P systems, i.e. SNQ P systems with one type of spike. It is proved that one type of spike is enough to guarantee the Turing universality of SNQ P systems. Theoretical results are shown in the cases of the SNQ P system used in both generating and accepting modes. Furthermore, the influence of the number of unbounded neurons (the number of spikes in a neuron is not bounded) on the computation power of SNQ P systems with one type of spike is investigated. It is found that SNQ P systems functioning as number generating devices with one type of spike and four unbounded neurons are Turing universal.

Proton decay of 73Rb

NASA Astrophysics Data System (ADS)

Rogers, Andrew; Anderson, C.; Barney, J.; Estee, J.; Lynch, W. G.; Manfredi, J.; Setiawan, H.; Showalter, R. H.; Sweany, S.; Tangwancharoen, S.; Tsang, M. B.; Winkelbauer, J. R.; Brown, K. W.; Elson, J. M.; Pruitt, C.; Sobotka, L. G.; Chajecki, Z.; Lee, J.

2017-09-01

Properties of nuclei beyond the proton drip-line are important for mass models, nuclear structure, and astrophysics. Weakly-bound or proton-unbound nuclei near the rp-process waiting points, such as the unbound Tz = -1/2 nucleus 73Rb, play a critical role in constraining calculations and observations of type I x-ray bursts. For instance, the rp process is greatly slowed near 72Kr (N = Z) due to its relatively long β-decay half life and inhibited proton capture. This waiting point, however, may be bypassed by sequential 2p-capture through 73Rb -a reaction which is sensitive to the 73Rb proton separation energy, Sp. Using invariant-mass spectroscopy, we have performed an experiment at NSCL to measure the decay of 73Rb ->p+72Kr in an attempt to directly determine Sp (73Rb) . Analysis of reconstructed proton-emission spectra and decay signatures will be discussed. This work is supported by the U.S. DOE Office of Nuclear Physics, Award No. DE-FG02-94ER40848.

Metabolic studies of an orally active platinum anticancer drug by liquid chromatography-electrospray ionization mass spectrometry.

PubMed

Poon, G K; Raynaud, F I; Mistry, P; Odell, D E; Kelland, L R; Harrap, K R; Barnard, C F; Murrer, B A

1995-09-29

Bis(acetato)amminedichloro(cyclohexylamine) platinum(IV) (JM216) is a new orally administered platinum complex with antitumor properties, and is currently undergoing phase II clinical trials. When JM216 was incubated with human plasma ultrafiltrate, 93% of the platinum species were protein-bound and 7% were unbound. The unbound platinum complexes in the ultrafiltrates of human plasma were analysed using a liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method. Apart from the parent drug, four metabolites were identified and characterised. These include JM118 [amminedichloro(cyclohexylamine) platinum(II)], JM383 [bis(acetato)ammine(cyclohexylamine)dihydroxo platinum(IV)] and the two isomers JM559 and JM518 [bis(acetato)amminechloro(cyclohexylamine) hydroxo platinum(IV)]. Their elemental compositions were determined by accurate mass measurement during the LC analysis, to confirm their identities. Quantitation of these metabolites by off-line LC atomic absorption spectroscopy demonstrated that JM118 is the major metabolite in plasma from patients receiving JM216 treatment.

Self-adjointness of deformed unbounded operators

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

Much, Albert

2015-09-15

We consider deformations of unbounded operators by using the novel construction tool of warped convolutions. By using the Kato-Rellich theorem, we show that unbounded self-adjoint deformed operators are self-adjoint if they satisfy a certain condition. This condition proves itself to be necessary for the oscillatory integral to be well-defined. Moreover, different proofs are given for self-adjointness of deformed unbounded operators in the context of quantum mechanics and quantum field theory.

Dynamical decoupling of unbounded Hamiltonians

NASA Astrophysics Data System (ADS)

Arenz, Christian; Burgarth, Daniel; Facchi, Paolo; Hillier, Robin

2018-03-01

We investigate the possibility to suppress interactions between a finite dimensional system and an infinite dimensional environment through a fast sequence of unitary kicks on the finite dimensional system. This method, called dynamical decoupling, is known to work for bounded interactions, but physical environments such as bosonic heat baths are usually modeled with unbounded interactions; hence, here, we initiate a systematic study of dynamical decoupling for unbounded operators. We develop a sufficient decoupling criterion for arbitrary Hamiltonians and a necessary decoupling criterion for semibounded Hamiltonians. We give examples for unbounded Hamiltonians where decoupling works and the limiting evolution as well as the convergence speed can be explicitly computed. We show that decoupling does not always work for unbounded interactions and we provide both physically and mathematically motivated examples.

f-lacunary statistical convergence of order (α, β)

NASA Astrophysics Data System (ADS)

Sengul, Hacer; Isik, Mahmut; Et, Mikail

2017-09-01

The main purpose of this paper is to introduce the concepts of f-lacunary statistical convergence of order (α, β) and strong f-lacunary summability of order (α, β) of sequences of real numbers for 0 <α ≤ β ≤ 1, where f is an unbounded modulus.

Shock/vortex interaction and vortex-breakdown modes

NASA Technical Reports Server (NTRS)

Kandil, Osama A.; Kandil, H. A.; Liu, C. H.

1992-01-01

Computational simulation and study of shock/vortex interaction and vortex-breakdown modes are considered for bound (internal) and unbound (external) flow domains. The problem is formulated using the unsteady, compressible, full Navier-Stokes (NS) equations which are solved using an implicit, flux-difference splitting, finite-volume scheme. For the bound flow domain, a supersonic swirling flow is considered in a configured circular duct and the problem is solved for quasi-axisymmetric and three-dimensional flows. For the unbound domain, a supersonic swirling flow issued from a nozzle into a uniform supersonic flow of lower Mach number is considered for quasi-axisymmetric and three-dimensional flows. The results show several modes of breakdown; e.g., no-breakdown, transient single-bubble breakdown, transient multi-bubble breakdown, periodic multi-bubble multi-frequency breakdown and helical breakdown.

Population pharmacokinetics of phenytoin in critically ill children.

PubMed

Hennig, Stefanie; Norris, Ross; Tu, Quyen; van Breda, Karin; Riney, Kate; Foster, Kelly; Lister, Bruce; Charles, Bruce

2015-03-01

The objective was to study the population pharmacokinetics of bound and unbound phenytoin in critically ill children, including influences on the protein binding profile. A population pharmacokinetic approach was used to analyze paired protein-unbound and total phenytoin plasma concentrations (n = 146 each) from 32 critically ill children (0.08-17 years of age) who were admitted to a pediatric hospital, primarily intensive care unit. The pharmacokinetics of unbound and bound phenytoin and the influence of possible influential covariates were modeled and evaluated using visual predictive checks and bootstrapping. The pharmacokinetics of protein-unbound phenytoin was described satisfactorily by a 1-compartment model with first-order absorption in conjunction with a linear partition coefficient parameter to describe the binding of phenytoin to albumin. The partitioning coefficient describing protein binding and distribution to bound phenytoin was estimated to be 8.22. Nonlinear elimination of unbound phenytoin was not supported in this patient group. Weight, allometrically scaled for clearance and volume of distribution for the unbound and bound compartments, and albumin concentration significantly influenced the partition coefficient for protein binding of phenytoin. The population model can be applied to estimate the fraction of unbound phenytoin in critically ill children given an individual's albumin concentration. © 2014, The American College of Clinical Pharmacology.

Helicon waves in uniform plasmas. II. High m numbers

NASA Astrophysics Data System (ADS)

Stenzel, R. L.; Urrutia, J. M.

2015-09-01

Helicons are whistler modes with azimuthal wave numbers. They have been studied in solids and plasmas where boundaries play a role. The present work shows that very similar modes exist in unbounded gaseous plasmas. Instead of boundaries, the antenna properties determine the topology of the wave packets. The simplest antenna is a magnetic loop which excites m = 0 or m = 1 helicons depending on whether the dipole moment is aligned parallel or perpendicular to the ambient background magnetic field B0. While these low order helicons have been described by J. M. Urrutia and R. L. Stenzel ["Helicon modes in uniform plasmas. I. Low m modes," Phys. Plasmas 22, 092111 (2015)], the present work focuses on high order modes up to m = 8. These are excited by antenna arrays forming magnetic multipoles. Their wave magnetic field has been measured in space and time in a large and uniform laboratory plasma free of boundary effects. The observed wave topology exhibits m pairs of unique field line spirals which may have inspired the name "helicon" to this mode. All field lines converge into these nested spirals which propagate like corkscrews along B0. The field lines near the axis of helicons are perpendicular to B0 and circularly polarized as in parallel whistlers. Helical antennas couple to these transverse fields but not to the spiral fields of helicons. Using a circular antenna array of phased m = 0 loops, right or left rotating or non-rotating multipole antenna fields are generated. They excite m < 0 and m > 0 modes, showing that the plasma supports both modes equally well. The poor excitation of m < 0 modes is a characteristic of loops with dipole moment across B0. The radiation efficiency of multipole antennas has been found to decrease with m.

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

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

Volkov, N. B.; Zubarev, N. M., E-mail: nick@iep.uran.ru; Zubareva, O. V.

Exact solutions are obtained for the problem of an equilibrium configuration of an uncharged cylindrical jet of a conducting liquid in a transverse electric field. The transverse cross section of the jet moving between two planar electrodes is deformed under the action of electrostatic forces (capillary forces play a stabilizing role). According to the solutions obtained, the initially circular cross section of the jet may be significantly (formally, unboundedly) stretched along the lines of forces of the field, and the boundaries of the jet asymptotically approach the electrodes.

Exploration of Toeplitz-like matrices with unbounded symbols is not a purely academic journey

NASA Astrophysics Data System (ADS)

Böttcher, A.; Garoni, C.; Serra-Capizzano, S.

2017-11-01

It is often asked why Toeplitz-like matrices with unbounded symbols are worth studying. This paper gives an answer by presenting several concrete problems that motivate such studies. It surveys the central results of the theory of Generalized Locally Toeplitz (GLT) sequences in a self-contained tool-kit fashion, and gives a new extension from bounded Riemann integrable functions to unbounded almost everywhere continuous functions. The emergence of unbounded symbols is illustrated by local grid refinements in finite difference and finite element discretizations and also by preconditioning strategies. Bibliography: 40 titles.

Traveling-wave solutions in continuous chains of unidirectionally coupled oscillators

NASA Astrophysics Data System (ADS)

Glyzin, S. D.; Kolesov, A. Yu; Rozov, N. Kh

2017-12-01

Proposed is a mathematical model of a continuous annular chain of unidirectionally coupled generators given by certain nonlinear advection-type hyperbolic boundary value problem. Such problems are constructed by a limit transition from annular chains of unidirectionally coupled ordinary differential equations with an unbounded increase in the number of links. It is shown that any preassigned finite number of stable periodic motions of the traveling-wave type can coexist in the model.

Kinetic rate constant prediction supports the conformational selection mechanism of protein binding.

PubMed

Moal, Iain H; Bates, Paul A

2012-01-01

The prediction of protein-protein kinetic rate constants provides a fundamental test of our understanding of molecular recognition, and will play an important role in the modeling of complex biological systems. In this paper, a feature selection and regression algorithm is applied to mine a large set of molecular descriptors and construct simple models for association and dissociation rate constants using empirical data. Using separate test data for validation, the predicted rate constants can be combined to calculate binding affinity with accuracy matching that of state of the art empirical free energy functions. The models show that the rate of association is linearly related to the proportion of unbound proteins in the bound conformational ensemble relative to the unbound conformational ensemble, indicating that the binding partners must adopt a geometry near to that of the bound prior to binding. Mirroring the conformational selection and population shift mechanism of protein binding, the models provide a strong separate line of evidence for the preponderance of this mechanism in protein-protein binding, complementing structural and theoretical studies.

The Role of Automatic Indexing in Access Control: A Modular View

ERIC Educational Resources Information Center

Hartson, H. Rex

1974-01-01

A model which relates the access control and indexing functions. The model is based on concept protection which allows a practically unbounded number of levels (subsets) of protection without requiring a fixed hierarchy among the levels. This protection is offered independently for each of the user operations allowed. (Author)

Cryptic binding sites on proteins: definition, detection, and druggability.

PubMed

Vajda, Sandor; Beglov, Dmitri; Wakefield, Amanda E; Egbert, Megan; Whitty, Adrian

2018-05-22

Many proteins in their unbound structures lack surface pockets appropriately sized for drug binding. Hence, a variety of experimental and computational tools have been developed for the identification of cryptic sites that are not evident in the unbound protein but form upon ligand binding, and can provide tractable drug target sites. The goal of this review is to discuss the definition, detection, and druggability of such sites, and their potential value for drug discovery. Novel methods based on molecular dynamics simulations are particularly promising and yield a large number of transient pockets, but it has been shown that only a minority of such sites are generally capable of binding ligands with substantial affinity. Based on recent studies, current methodology can be improved by combining molecular dynamics with fragment docking and machine learning approaches. Copyright © 2018 Elsevier Ltd. All rights reserved.

A rapid procedure for measurement of the free testosterone fraction in human plasma using the centria radioimmunoassay centrifugal analyzer.

PubMed

Schwarz, S; Boyd, J

1981-01-01

Following the incubation of plasma with a tracer amount of tritiated testosterone, the reaction mixture is separated into a sex hormone-binding globulin bound and an unbound fraction of radioligand using DEAE-cellulose columns placed in the incubator-separator module of the Centria radioimmunoassay centrifugal analyzer. Neural Tris-buffer elutes unbound steroid from the matrix, while acidic Tris-buffer can remove the protein-bound fraction in a subsequent step. Complementary and thus qualitatively equal results are obtained when counting either eluate. Comparison of this technique with an ammonium sulfate precipitation method showed high correlation. Free testosterone indices as determined by the Centria modification in a number of prepuberal children, normal men and women, as well as pregnant and hirsute women similar to those previously reported.

Limited value of the urinary phenytoin metabolic ratio for the assessment of cytochrome P4502C9 activity in vivo

PubMed Central

TASSANEEYAKUL, WICHITTRA; BIRKETT, DONALD J.; PASS, MICHAEL C.; MINERS, JOHN O.

1996-01-01

Relationships between the ratio of p-hydroxyphenytoin (p-HPPH), the major metabolite of phenytoin, to unchanged phenytoin excreted in urine (the urinary metabolic ratio or MR) were compared with a number of indices of the metabolic clearances of phenytoin and tolbutamide published previously for seventeen subjects separately administered these known cytochrome P4502C9 (CYP2C9) substrates. Significant correlations (rs=0.50–0.60, P<0.05) were observed between the phenytoin MR, derived from either 0–24 or 24–48 h urine collections, and inverse areas under the plasma unbound concentration-time curves (measured over various time intervals) of phenytoin and with plasma unbound tolbutamide clearance. Significant correlations (rs =0.59–0.74) were also observed between the phenytoin MRs and metabolic unbound clearances for p-hydroxyphenytoin formation. Despite the significant correlations, variability in tolbutamide and phenytoin metabolic clearance parameters tended to account for <50% of the variability in phenytoin MR. Correlations between the renal clearance of phenytoin and the phenytoin MRs suggest that variability in the renal clearance of unchanged drug limits the usefulness of the phenytoin MR for the investigation of factors influencing CYP2C9 activity in vivo. PMID:8971435

Monte Carlo replica-exchange based ensemble docking of protein conformations.

PubMed

Zhang, Zhe; Ehmann, Uwe; Zacharias, Martin

2017-05-01

A replica-exchange Monte Carlo (REMC) ensemble docking approach has been developed that allows efficient exploration of protein-protein docking geometries. In addition to Monte Carlo steps in translation and orientation of binding partners, possible conformational changes upon binding are included based on Monte Carlo selection of protein conformations stored as ordered pregenerated conformational ensembles. The conformational ensembles of each binding partner protein were generated by three different approaches starting from the unbound partner protein structure with a range spanning a root mean square deviation of 1-2.5 Å with respect to the unbound structure. Because MC sampling is performed to select appropriate partner conformations on the fly the approach is not limited by the number of conformations in the ensemble compared to ensemble docking of each conformer pair in ensemble cross docking. Although only a fraction of generated conformers was in closer agreement with the bound structure the REMC ensemble docking approach achieved improved docking results compared to REMC docking with only the unbound partner structures or using docking energy minimization methods. The approach has significant potential for further improvement in combination with more realistic structural ensembles and better docking scoring functions. Proteins 2017; 85:924-937. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Note on a modified return period scale for upper-truncated unbounded flood distributions

NASA Astrophysics Data System (ADS)

Bardsley, Earl

2017-01-01

Probability distributions unbounded to the right often give good fits to annual discharge maxima. However, all hydrological processes are in reality constrained by physical upper limits, though not necessarily well defined. A result of this contradiction is that for sufficiently small exceedance probabilities the unbounded distributions anticipate flood magnitudes which are impossibly large. This raises the question of whether displayed return period scales should, as is current practice, have some given number of years, such as 500 years, as the terminating rightmost tick-point. This carries the implication that the scale might be extended indefinitely to the right with a corresponding indefinite increase in flood magnitude. An alternative, suggested here, is to introduce a sufficiently high upper truncation point to the flood distribution and modify the return period scale accordingly. The rightmost tick-mark then becomes infinity, corresponding to the upper truncation point discharge. The truncation point is likely to be set as being above any physical upper bound and the return period scale will change only slightly over all practical return periods of operational interest. The rightmost infinity tick point is therefore proposed, not as an operational measure, but rather to signal in flood plots that the return period scale does not extend indefinitely to the right.

Unbound particles in dark matter halos

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

Behroozi, Peter S.; Wechsler, Risa H.; Loeb, Abraham, E-mail: behroozi@stanford.edu, E-mail: aloeb@cfa.harvard.edu, E-mail: rwechsler@stanford.edu

2013-06-01

We investigate unbound dark matter particles in halos by tracing particle trajectories in a simulation run to the far future (a = 100). We find that the traditional sum of kinetic and potential energies is a very poor predictor of which dark matter particles will eventually become unbound from halos. We also study the mass fraction of unbound particles, which increases strongly towards the edges of halos, and decreases significantly at higher redshifts. We discuss implications for dark matter detection experiments, precision calibrations of the halo mass function, the use of baryon fractions to constrain dark energy, and searches formore » intergalactic supernovae.« less

Unbound particles in dark matter halos

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

Behroozi, Peter S.; Loeb, Abraham; Wechsler, Risa H.

2013-06-13

We investigate unbound dark matter particles in halos by tracing particle trajectories in a simulation run to the far future (a = 100). We find that the traditional sum of kinetic and potential energies is a very poor predictor of which dark matter particles will eventually become unbound from halos. We also study the mass fraction of unbound particles, which increases strongly towards the edges of halos, and decreases significantly at higher redshifts. We discuss implications for dark matter detection experiments, precision calibrations of the halo mass function, the use of baryon fractions to constrain dark energy, and searches formore » intergalactic supernovae.« less

Spectroscopy at the two-proton drip line: Excited states in 158W

NASA Astrophysics Data System (ADS)

Joss, D. T.; Page, R. D.; Herzán, A.; Donosa, L.; Uusitalo, J.; Carroll, R. J.; Darby, I. G.; Andgren, K.; Cederwall, B.; Eeckhaudt, S.; Grahn, T.; Greenlees, P. T.; Hadinia, B.; Jakobsson, U.; Jones, P. M.; Julin, R.; Juutinen, S.; Leino, M.; Leppanen, A.-P.; Nyman, M.; O'Donnell, D.; Pakarinen, J.; Rahkila, P.; Sandzelius, M.; Sarén, J.; Scholey, C.; Seweryniak, D.; Simpson, J.; Sorri, J.

2017-09-01

Excited states have been identified in the heaviest known even-Z N = 84 isotone 158W, which lies in a region of one-proton emitters and the two-proton drip line. The observation of γ-ray transitions feeding the ground state establishes the excitation energy of the yrast 6+ state confirming the spin-gap nature of the α-decaying 8+ isomer. The 8+ isomer is also expected to be unbound to two-proton emission but no evidence for this decay mode was observed. An upper limit for the two-proton decay branch has been deduced as b2p ≤ 0.17% at the 90% confidence level. The possibility of observing two-proton emission from multiparticle isomers in nearby nuclides is considered.

Factors influencing palmitoyl-CoA oxidation by rat liver peroxisomal fractions. Substrate concentration, organelle integrity and ATP.

PubMed Central

Thomas, J; Debeer, L J; De Schepper, P J; Mannaerts, G P

1980-01-01

1. The first dehydrogenation step of peroxisomal beta-oxidation involves the reduction of O2 to H2O2. Production rates of H2O2 and acetyl units by purified rat liver peroxisomes oxidizing palmitoyl-CoA were equal, indicating that H2O2 production is a reliable index for the release of acetyl units during peroxisomal fatty-acid oxidation. 2. Measurements of H2O2 and acid-soluble oxidation products during [1-14C]palmitoyl-CoA oxidation by purified peroxisomes revealed that the number of acetyl units released per molecule of palmitoyl-CoA oxidized rapidly decreased with increasing unbound palmitoyl-CoA concentrations. Structural damage to the peroxisomes caused by detergents or other treatments also decreased the number of acetyl units released. Under conditions where oxidation proceeded linearly with time the theoretical maximum of 5 acetyl units released per molecule of palmitoyl-CoA oxidized [Lazarow (1978) J. Biol. Chem. 253, 1522--1528] was never reached. 3. Expressed in terms of acetyl units produced and measured at low unbound-palmitoyl-CoA concentrations, mitochondrial oxidation was 10--20-fold higher than peroxisomal oxidation. 4. ATP stimulated peroxisomal palmitoyl-CoA oxidation approx. 2-fold. The ATP effect required the presence of Mg2+ and was lost when peroxisomal membranes were disrupted by Triton X-100 or high concentrations of unbound palmitoyl-CoA. 5. Disruption of peroxisomes by detergents, freeze--thawing, osmotic or mechanical treatment did not stimulate palmitoyl-CoA oxidation in the presence of ATP, indicating that peroxisomal fatty-acid-CoA oxidation was not latent. In the absence of ATP, Triton X-100 stimulated peroxisomal palmitoyl-CoA oxidation approx. 2-fold. PMID:7470063

A limited sampling model for estimation of total and unbound mycophenolic acid (MPA) area under the curve (AUC) in hematopoietic cell transplantation (HCT).

PubMed

Ng, Juki; Rogosheske, John; Barker, Juliet; Weisdorf, Daniel; Jacobson, Pamala A

2006-06-01

Renal transplant patients with suboptimal mycophenolic acid (MPA) areas under the curves (AUCs) are at greater risk of acute rejection. In hematopoietic cell transplantation, a low MPA AUC is also associated with a higher incidence of acute graft versus host disease. Therefore, a limited sampling model was developed and validated to simultaneously estimate total and unbound MPA AUC0-12 in hematopoietic cell transplantation patients. Intensive pharmacokinetic sampling was performed at steady state between days 3 to 7 posttransplant in 73 adult subjects while receiving prophylactic mycophenolate mofetil 1 g per 12 hours orally or intravenously plus cyclosporine. Total and unbound MPA plasma concentrations were measured, and total and unbound AUC0-12 was determined using noncompartmental analysis. Regression analysis was then performed to build IV and PO, total and unbound AUC0-12 models from the first 34 subjects. The predictive performance of these models was tested in the next 39 subjects. Trough concentrations poorly estimate observed total and unbound AUC0-12 (r<0.48). A model with 3 concentrations (2-, 4-, and 6-hour post start of infusion) best estimated observed total and unbound AUC0-12 after IV dosing (r>0.99). Oral total and unbound AUC0-12 was more difficult to estimate and required at least 4 concentrations (0-, 1-, 2-, and 6-hour post dose) in the model (r>0.85). The predictive performance of the final models was good. Eighty-three percent of IV and 70% of PO AUC0-12 predictions fell within +/-20% of the observed values without significant bias. Trough MPA concentrations do not accurately describe MPA AUC0-12. Three intravenous (2-, 4-, 6-hour post start of infusion) or 4 oral (0-, 1-, 2-, and 6-hour post dose) MPA plasma concentrations measured over a 12-hour dosing interval will estimate the total and unbound AUC0-12 nearly as well as intensive pharmacokinetic sampling with good precision and low bias. This approach simplifies AUC0-12 targeting of MPA post hematopoietic cell transplantation.

The quantitative effect of serum albumin, serum urea, and valproic acid on unbound phenytoin concentrations in children.

PubMed

ter Heine, Rob; van Maarseveen, Erik M; van der Westerlaken, Monique M L; Braun, Kees P J; Koudijs, Suzanne M; Berg, Maarten J Ten; Malingré, Mirte M

2014-06-01

Dosing of phenytoin is difficult in children because of its variable pharmacokinetics and protein binding. Possible covariates for this protein binding have mostly been univariately investigated in small, and often adult, adult populations. We conducted a study to identify and quantify these covariates in children. We extracted data on serum phenytoin concentrations, albumin, triglycerides, urea, total bilirubin and creatinine concentrations and data on coadministration of valproic acid or carbamazepine in 186 children. Using nonlinear mixed effects modeling the effects of covariates on the unbound phenytoin fraction were investigated. Serum albumin, serum urea concentrations, and concomitant valproic acid use significantly influenced the unbound phenytoin fraction. For clinical practice, we recommend that unbound phenytoin concentrations are measured routinely. However, if this is impossible, we suggest to use our model to calculate the unbound concentration. In selected children, close treatment monitoring and dose reductions should be considered to prevent toxicity. © The Author(s) 2013.

The spectral theorem for quaternionic unbounded normal operators based on the S-spectrum

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

Alpay, Daniel, E-mail: dany@math.bgu.ac.il; Kimsey, David P., E-mail: dpkimsey@gmail.com; Colombo, Fabrizio, E-mail: fabrizio.colombo@polimi.it

In this paper we prove the spectral theorem for quaternionic unbounded normal operators using the notion of S-spectrum. The proof technique consists of first establishing a spectral theorem for quaternionic bounded normal operators and then using a transformation which maps a quaternionic unbounded normal operator to a quaternionic bounded normal operator. With this paper we complete the foundation of spectral analysis of quaternionic operators. The S-spectrum has been introduced to define the quaternionic functional calculus but it turns out to be the correct object also for the spectral theorem for quaternionic normal operators. The lack of a suitable notion ofmore » spectrum was a major obstruction to fully understand the spectral theorem for quaternionic normal operators. A prime motivation for studying the spectral theorem for quaternionic unbounded normal operators is given by the subclass of unbounded anti-self adjoint quaternionic operators which play a crucial role in the quaternionic quantum mechanics.« less

Is the Kerr black hole a super accelerator?

NASA Astrophysics Data System (ADS)

Krasnikov, S.; Skvortsova, M. V.

2018-02-01

A number of long-standing puzzles, such as the origin of extreme-energy cosmic rays, could perhaps be solved if we found a mechanism for effectively transferring energy from black holes to particles and, correspondingly, accelerating the latter to (unboundedly, as long as we neglect the back reaction) large velocities. As of today the only such candidate mechanism in the case of the nonextreme Kerr black hole is colliding a particle that freely falls from infinity with a particle whose trajectory is subject to some special requirements to fulfil which it has to be suitably corrected by auxiliary collisions. In the present paper we prove that—at least when the relevant particles move in the equatorial plane and experience a single correcting collision—this mechanism does not work too. The energy of the final collision becomes unboundedly high only when the energies of the incoming particles do.

On the linear stability of compressible plane Couette flow

NASA Technical Reports Server (NTRS)

Duck, Peter W.; Erlebacher, Gordon; Hussaini, M. Yousuff

1991-01-01

The linear stability of compressible plane Couette flow is investigated. The correct and proper basic velocity and temperature distributions are perturbed by a small amplitude normal mode disturbance. The full small amplitude disturbance equations are solved numerically at finite Reynolds numbers, and the inviscid limit of these equations is then investigated in some detail. It is found that instability can occur, although the stability characteristics of the flow are quite different from unbounded flows. The effects of viscosity are also calculated, asymptotically, and shown to have a stabilizing role in all the cases investigated. Exceptional regimes to the problem occur when the wavespeed of the disturbances approaches the velocity of either of the walls, and these regimes are also analyzed in some detail. Finally, the effect of imposing radiation-type boundary conditions on the upper (moving) wall (in place of impermeability) is investigated, and shown to yield results common to both bounded and unbounded flows.

Analysis of backward error recovery for concurrent processes with recovery blocks

NASA Technical Reports Server (NTRS)

Shin, K. G.; Lee, Y. H.

1982-01-01

Three different methods of implementing recovery blocks (RB's). These are the asynchronous, synchronous, and the pseudo recovery point implementations. Pseudo recovery points so that unbounded rollback may be avoided while maintaining process autonomy are proposed. Probabilistic models for analyzing these three methods under standard assumptions in computer performance analysis, i.e., exponential distributions for related random variables were developed. The interval between two successive recovery lines for asynchronous RB's mean loss in computation power for the synchronized method, and additional overhead and rollback distance in case PRP's are used were estimated.

Convexity of level lines of Martin functions and applications

NASA Astrophysics Data System (ADS)

Gallagher, A.-K.; Lebl, J.; Ramachandran, K.

2018-01-01

Let Ω be an unbounded domain in R× Rd. A positive harmonic function u on Ω that vanishes on the boundary of Ω is called a Martin function. In this note, we show that, when Ω is convex, the superlevel sets of a Martin function are also convex. As a consequence we obtain that if in addition Ω has certain symmetry with respect to the t-axis, and partial Ω is sufficiently flat, then the maximum of any Martin function along a slice Ω \\cap ({t}× R^d) is attained at (t, 0).

Development of a Simple and Rapid Method to Measure the Free Fraction of Tacrolimus in Plasma Using Ultrafiltration and LC-MS/MS.

PubMed

Stienstra, Nicolaas A; Sikma, Maaike A; van Dapperen, Anouk L; de Lange, Dylan W; van Maarseveen, Erik M

2016-12-01

Tacrolimus is an immunosuppressant mainly used in the prophylaxis of solid organ transplant rejection. Therapeutic drug monitoring of tacrolimus is essential for avoiding toxicity related to overexposure and transplant rejection from underexposure. Previous studies suggest that unbound tacrolimus concentrations in the plasma may serve as a better predictor of tacrolimus-associated nephrotoxicity and neurotoxicity compared to tacrolimus concentration in whole blood. Monitoring the plasma concentrations of unbound tacrolimus might be of interest in preventing tacrolimus-related toxicity. Therefore, the aim was to develop a method for the measurement of total and unbound tacrolimus concentrations in plasma. The sample preparation for the determination of the plasma concentrations of unbound tacrolimus consisted of an easy-to-use ultrafiltration method followed by solid-phase extraction. To determine the total concentration of tacrolimus in plasma, a simple method based on protein precipitation was developed. The extracts were injected into a Thermo Scientific HyPurity C18 column using gradient elution. The analytes were detected by liquid chromatography-tandem mass spectrometry with positive ionization. The method was validated over a linear range of 1.00-200 ng/L for unbound tacrolimus concentrations in plasma and 100-3200 ng/L for total plasma concentrations. The lower limit of quantification was 1.00 ng/L in ultrafiltrate and 100 ng/L in plasma. The inaccuracy and imprecision for the determination of unbound tacrolimus concentrations in ultrafiltrate and plasma showed a maximum coefficients of variation (CV) of 11.7% and a maximum bias of 3.8%. A rapid and easy method based on ultrafiltration and liquid chromatography-tandem mass spectrometry was established to measure the total and unbound tacrolimus concentrations in plasma. This method can facilitate further investigations on the relationship between plasma concentrations of unbound tacrolimus and clinical outcomes in transplant recipients.

Dynamics of flexible fibers and vesicles in Poiseuille flow at low Reynolds number.

PubMed

Farutin, Alexander; Piasecki, Tomasz; Słowicka, Agnieszka M; Misbah, Chaouqi; Wajnryb, Eligiusz; Ekiel-Jeżewska, Maria L

2016-09-21

The dynamics of flexible fibers and vesicles in unbounded planar Poiseuille flow at low Reynolds number is shown to exhibit similar basic features, when their equilibrium (moderate) aspect ratio is the same and vesicle viscosity contrast is relatively high. Tumbling, lateral migration, accumulation and shape evolution of these two types of flexible objects are analyzed numerically. The linear dependence of the accumulation position on relative bending rigidity, and other universal scalings are derived from the local shear flow approximation.

Buffering effect in continuous chains of unidirectionally coupled generators

NASA Astrophysics Data System (ADS)

Glyzin, S. D.; Kolesov, A. Yu.; Rozov, N. Kh.

2014-11-01

We propose a mathematical model of a continuous annular chain of unidirectionally coupled generators given by some nonlinear advection-type hyperbolic boundary value problem. Such problems are constructed by a limit transition from annular chains of unidirectionally coupled ordinary differential equations with an unbounded increase in the number of links. We find that a certain buffering phenomenon is realized in our boundary value problem. Namely, we show that any preassigned finite number of stable periodic motions of the traveling-wave type can coexist in the model.

Transition and mixing in axisymmetric jets and vortex rings

NASA Technical Reports Server (NTRS)

Allen, G. A., Jr.; Cantwell, B. J.

1986-01-01

A class of impulsively started, axisymmetric, laminar jets produced by a time dependent joint source of momentum are considered. These jets are different flows, each initially at rest in an unbounded fluid. The study is conducted at three levels of detail. First, a generalized set of analytic creeping flow solutions are derived with a method of flow classification. Second, from this set, three specific creeping flow solutions are studied in detail: the vortex ring, the round jet, and the ramp jet. This study involves derivation of vorticity, stream function, entrainment diagrams, and evolution of time lines through computer animation. From entrainment diagrams, critical points are derived and analyzed. The flow geometry is dictated by the properties and location of critical points which undergo bifurcation and topological transformation (a form of transition) with changing Reynolds number. Transition Reynolds numbers were calculated. A state space trajectory was derived describing the topological behavior of these critical points. This state space derivation yielded three states of motion which are universal for all axisymmetric jets. Third, the axisymmetric round jet is solved numerically using the unsteady laminar Navier Stokes equations. These equations were shown to be self similar for the round jet. Numerical calculations were performed up to a Reynolds number of 30 for a 60x60 point mesh. Animations generated from numerical solution showed each of the three states of motion for the round jet, including the Re = 30 case.

Complicated asymptotic behavior of solutions for porous medium equation in unbounded space

NASA Astrophysics Data System (ADS)

Wang, Liangwei; Yin, Jingxue; Zhou, Yong

2018-05-01

In this paper, we find that the unbounded spaces Yσ (RN) (0 < σ <2/m-1 ) can provide the work spaces where complicated asymptotic behavior appears in the solutions of the Cauchy problem of the porous medium equation. To overcome the difficulties caused by the nonlinearity of the equation and the unbounded solutions, we establish the propagation estimates, the growth estimates and the weighted L1-L∞ estimates for the solutions.

Long-term Ultraviolet Monitoring of a Tidal Disruption Event at only 90 Mpc

NASA Astrophysics Data System (ADS)

Maksym, W. Peter; Cenko, Bradley; Eracleous, Michael; Keel, William C.; Irwin, Jimmy; Sigurdsson, Steinn; Fruchter, Andrew; Gezari, Suvi; Bogdanovic, Tamara; Roth, Katherine

2018-01-01

At only 90 Mpc, ASASSN-14li is one of the nearest tidal disruption events (TDEs) to permit high-quality multi-wavelength monitoring, and is the first TDE with ultraviolet spectroscopic observations between Lyman alpha and Mg II λ2800Å. We present results from a continued long-term ultraviolet monitoring campaign with the Hubble Space Telescope. Prior observations had showed an array of broad emission lines common to Seyferts. Surpisingly, however, uncommon lines such as He II λ1640Å, N III] λ1750Å and N IV] λ1486Å had been enhanced, whereas others such as C III] λ1909Å and Mg II λ2800Å are notably absent. Our campaign shows contnued continuum emission accompanied by the gradual disappearance of broad line emission, which may indicate the gradual disappearance of a TDE wind as the accretion rate declines to sub-critical levels. Variability of the semi-forbidden lines supports stimulation by the TDE. A continued absence of low-ionization lines like Mg II in our monitoring may constrain the presence of ionized unbound material at large radii.

On Identifying the Sound Sources in a Turbulent Flow

NASA Technical Reports Server (NTRS)

Goldstein, M. E.

2008-01-01

A space-time filtering approach is used to divide an unbounded turbulent flow into its radiating and non-radiating components. The result is then used to clarify a number of issues including the possibility of identifying the sources of the sound in such flows. It is also used to investigate the efficacy of some of the more recent computational approaches.

Pressure Distributions About Finite Wedges in Bounded and Unbounded Subsonic Streams

NASA Technical Reports Server (NTRS)

Donoughe, Patrick L; Prasse, Ernst I

1953-01-01

An analytical investigation of incompressible flow about wedges was made to determine effects of tunnel-wedge ratio and wedge angle on the wedge pressure distributions. The region of applicability of infinite wedge-type velocity distribution was examined for finite wedges. Theoretical and experimental pressure coefficients for various tunnel-wedge ratios, wedge angles, and subsonic Mach numbers were compared.

Procedural uncertainties of Proctor compaction tests applied on MSWI bottom ash.

PubMed

Izquierdo, Maria; Querol, Xavier; Vazquez, Enric

2011-02-28

MSWI bottom ash is a well-graded highly compactable material that can be used as a road material in unbound pavements. Achieving the compactness assumed in the design of the pavement is of primary concern to ensure long term structural stability. Regulations on road construction in a number of EU countries rely on standard tests originally developed for natural aggregates, which may not be appropriate to accurately assess MSWI bottom ash. This study is intended to assist in consistently assessing MSWI bottom ash compaction by means of the Proctor method. This test is routinely applied to address unbound road materials and suggests two methods. Compaction parameters show a marked procedural dependency due to the particle morphology and weak particle strength of ash. Re-compacting a single batch sample to determine Proctor curves is a common practise that turns out to overvalue optimum moisture contents and maximum dry densities. This could result in wet-side compactions not meeting stiffness requirements. Inaccurate moisture content measurements during testing may also induce erroneous determinations of compaction parameters. The role of a number of physical properties of MSWI bottom ash in compaction is also investigated. Copyright © 2011 Elsevier B.V. All rights reserved.

Carprofen pharmacokinetics in plasma and in control and inflamed canine tissue fluid using in vivo ultrafiltration.

PubMed

Messenger, K M; Wofford, J A; Papich, M G

2016-02-01

Measurement of unbound drug concentrations at their sites of action is necessary for accurate PK/PD modeling. The objective of this study was to determine the unbound concentration of carprofen in canine interstitial fluid (ISF) using in vivo ultrafiltration and to compare pharmacokinetic parameters of free carprofen concentrations between inflamed and control tissue sites. We hypothesized that active concentrations of carprofen would exhibit different dispositions in ISF between inflamed vs. normal tissues. Bilateral ultrafiltration probes were placed subcutaneously in six healthy Beagle dogs 12 h prior to induction of inflammation. Two milliliters of either 2% carrageenan or saline control was injected subcutaneously at each probe site, 12 h prior to intravenous carprofen (4 mg/kg) administration. Plasma and ISF samples were collected at regular intervals for 72 h, and carprofen concentrations were determined using HPLC. Prostaglandin E2 (PGE2 ) concentrations were quantified in ISF using ELISA. Unbound carprofen concentrations were higher in ISF compared with predicted unbound plasma drug concentrations. Concentrations were not significantly higher in inflamed ISF compared with control ISF. Compartmental modeling was used to generate pharmacokinetic parameter estimates, which were not significantly different between sites. Terminal half-life (T½) was longer in the ISF compared with plasma. PGE2 in ISF decreased following administration of carprofen. In vivo ultrafiltration is a reliable method to determine unbound carprofen in ISF, and that disposition of unbound drug into tissue is much higher than predicted from unbound drug concentration in plasma. However, concentrations and pharmacokinetic parameter estimates are not significantly different in inflamed vs. un-inflamed tissues. © 2015 John Wiley & Sons Ltd.

Effect of protein binding on unbound atazanavir and darunavir cerebrospinal fluid concentrations.

PubMed

Delille, Cecile A; Pruett, Sarah T; Marconi, Vincent C; Lennox, Jeffrey L; Armstrong, Wendy S; Arrendale, Richard F; Sheth, Anandi N; Easley, Kirk A; Acosta, Edward P; Vunnava, Aswani; Ofotokun, Ighovwerha

2014-09-01

HIV-1 protease inhibitors (PIs) exhibit different protein binding affinities and achieve variable plasma and tissue concentrations. Degree of plasma protein binding may impact central nervous system penetration. This cross-sectional study assessed cerebrospinal fluid (CSF) unbound PI concentrations, HIV-1 RNA, and neopterin levels in subjects receiving either ritonavir-boosted darunavir (DRV), 95% plasma protein bound, or atazanavir (ATV), 86% bound. Unbound PI trough concentrations were measured using rapid equilibrium dialysis and liquid chromatography/tandem mass spectrometry. Plasma and CSF HIV-1 RNA and neopterin were measured by Ampliprep/COBAS® Taqman® 2.0 assay (Roche) and enzyme-linked immunosorbent assay (ALPCO), respectively. CSF/plasma unbound drug concentration ratio was higher for ATV, 0.09 [95% confidence interval (CI) 0.06-0.12] than DRV, 0.04 (95%CI 0.03-0.06). Unbound CSF concentrations were lower than protein adjusted wild-type inhibitory concentration-50 (IC50 ) in all ATV and 1 DRV-treated subjects (P < 0.001). CSF HIV-1 RNA was detected in 2/15 ATV and 4/15 DRV subjects (P = 0.65). CSF neopterin levels were low and similar between arms. ATV relative to DRV had higher CSF/plasma unbound drug ratio. Low CSF HIV-1 RNA and neopterin suggest that both regimens resulted in CSF virologic suppression and controlled inflammation. © 2014, The American College of Clinical Pharmacology.

Effect of Protein Binding on Unbound Atazanavir and Darunavir Cerebrospinal Fluid Concentrations

PubMed Central

Delille, Cecile A.; Pruett, Sarah T.; Marconi, Vincent C.; Lennox, Jeffrey L.; Armstrong, Wendy S.; Arrendale, Richard F.; Sheth, Anandi N.; Easley, Kirk A.; Acosta, Edward P.; Vunnava, Aswani; Ofotokun, Ighovwerha

2015-01-01

HIV-1 protease inhibitors (PIs) exhibit different protein binding affinities and achieve variable plasma and tissue concentrations. Degree of plasma protein binding may impact central nervous system penetration. This cross-sectional study assessed cerebrospinal fluid (CSF) unbound PI concentrations, HIV-1 RNA, and neopterin levels in subjects receiving either ritonavir-boosted darunavir (DRV), 95% plasma protein bound, or atazanavir (ATV), 86% bound. Unbound PI trough concentrations were measured using rapid equilibrium dialysis and liquid chromatography/tandem mass spectrometry. Plasma and CSF HIV-1 RNA and neopterin were measured by Ampliprep/COBAS® Taqman® 2.0 assay (Roche) and enzyme-linked immunosorbent assay (ALPCO), respectively. CSF/plasma unbound drug concentration ratio was higher for ATV, 0.09 [95% confidence interval (CI) 0.06–0.12] than DRV, 0.04 (95%CI 0.03–0.06). Unbound CSF concentrations were lower than protein adjusted wild-type inhibitory concentration-50 (IC50) in all ATV and 1 DRV-treated subjects (P < 0.001). CSF HIV-1 RNA was detected in 2/15 ATV and 4/15 DRV subjects (P = 0.65). CSF neopterin levels were low and similar between arms. ATV relative to DRV had higher CSF/plasma unbound drug ratio. Low CSF HIV-1 RNA and neopterin suggest that both regimens resulted in CSF virologic suppression and controlled inflammation. PMID:24691856

Unbound Bilirubin and Auditory Neuropathy Spectrum Disorder in Late Preterm and Term Infants with Severe Jaundice

PubMed Central

Amin, Sanjiv B; Wang, Hongyue; Laroia, Nirupama; Orlando, Mark

2016-01-01

Objective To evaluate if unbound bilirubin is a better predictor of auditory neuropathy spectrum disorder (ANSD) than total serum bilirubin (TSB) or the bilirubin albumin molar ratio (BAMR) in late preterm and term neonates with severe jaundice (TSB ≥ 20 mg/dL or TSB that met exchange transfusion criteria). Study design Infants ≥ 34 weeks gestational age with severe jaundice during the first two weeks of life were eligible for the prospective observational study. A comprehensive auditory evaluation was performed within 72 hours of peak TSB. ANSD was defined as absent or abnormal auditory brainstem evoked response waveform morphology at 80 decibel click intensity in the presence of normal outer hair cell function. TSB, serum albumin, and unbound bilirubin were measured using the colorimetric, bromocresol green, and modified peroxidase method, respectively. Results Five of 44 infants developed ANSD. By logistic regression, peak unbound bilirubin but not peak TSB or peak BAMR was associated with ANSD (odds ratio 4.6, 95% CI: 1.6-13.5, p = 0.002). On comparing receiver operating characteristic curves, the area under the curve (AUC) for unbound bilirubin (0.92) was significantly greater (p = 0.04) compared with the AUC for TSB (0.50) or BAMR (0.62). Conclusions Unbound bilirubin is a more sensitive and specific predictor of ANSD than TSB or BAMR in late preterm and term infants with severe jaundice. PMID:26952116

Blood collection techniques, heparin and quinidine protein binding.

PubMed

Kessler, K M; Leech, R C; Spann, J F

1979-02-01

With the use of glass syringes without heparin and all glass equipment, the percent of unbound quinidine was measured by ultrafiltration and a double-extraction assay method after addition of 2 microgram/ml of quinidine sulfate. Compared to the all-glass method, collection of blood using Vacutainers resulted in an erroneous and variable decrease in quinidine binding related to blood to rubber-stopper contact. With glass, the unbound quinidine fraction was (mean +/- standard error) 10 +/- 1% in 10 normal volunteers, 8.5 +/- 1.5% in 10 patients with congestive heart failure, and 11 +/- 2% in 11 patients with chronic renal failure (although in 8 of the latter 11 patients the percent of unbound quinidine was 4 or more standard errors from the mean of the normal group). During cardiac catheterization, patients had markedly elevated unbound quinidine fractions: 24 +/- 2% (p less than 0.001). This abnormality coincided with the addition of heparin in vivo and was less apparent after the addition of up to 10 U/ml of heparin in vitro (120% and 29% increase in unbound quinidine fractions, respectively). Quinidine binding should be measured with all glass or equivalent equipment.

BIAS: A Regional Management of Underwater Sound in the Baltic Sea.

PubMed

Sigray, Peter; Andersson, Mathias; Pajala, Jukka; Laanearu, Janek; Klauson, Aleksander; Tegowski, Jaroslaw; Boethling, Maria; Fischer, Jens; Tougaard, Jakob; Wahlberg, Magnus; Nikolopoulos, Anna; Folegot, Thomas; Matuschek, Rainer; Verfuss, Ursula

2016-01-01

Management of the impact of underwater sound is an emerging concern worldwide. Several countries are in the process of implementing regulatory legislations. In Europe, the Marine Strategy Framework Directive was launched in 2008. This framework addresses noise impacts and the recommendation is to deal with it on a regional level. The Baltic Sea is a semienclosed area with nine states bordering the sea. The number of ships is one of the highest in Europe. Furthermore, the number of ships is estimated to double by 2030. Undoubtedly, due to the unbound character of noise, an efficient management of sound in the Baltic Sea must be done on a regional scale. In line with the European Union directive, the Baltic Sea Information on the Acoustic Soundscape (BIAS) project was established to implement Descriptor 11 of the Marine Strategy Framework Directive in the Baltic Sea region. BIAS will develop tools, standards, and methodologies that will allow for cross-border handling of data and results, measure sound in 40 locations for 1 year, establish a seasonal soundscape map by combining measured sound with advanced three-dimensional modeling, and, finally, establish standards for measuring continuous sound. Results from the first phase of BIAS are presented here, with an emphasis on standards and soundscape mapping as well as the challenges related to regional handling.

Power-rate synchronization of coupled genetic oscillators with unbounded time-varying delay.

PubMed

Alofi, Abdulaziz; Ren, Fengli; Al-Mazrooei, Abdullah; Elaiw, Ahmed; Cao, Jinde

2015-10-01

In this paper, a new synchronization problem for the collective dynamics among genetic oscillators with unbounded time-varying delay is investigated. The dynamical system under consideration consists of an array of linearly coupled identical genetic oscillators with each oscillators having unbounded time-delays. A new concept called power-rate synchronization, which is different from both the asymptotical synchronization and the exponential synchronization, is put forward to facilitate handling the unbounded time-varying delays. By using a combination of the Lyapunov functional method, matrix inequality techniques and properties of Kronecker product, we derive several sufficient conditions that ensure the coupled genetic oscillators to be power-rate synchronized. The criteria obtained in this paper are in the form of matrix inequalities. Illustrative example is presented to show the effectiveness of the obtained results.

Production of N(+)-asterisk from N2 + hnu - Effective EUV emission yields from laboratory and dayglow data

NASA Technical Reports Server (NTRS)

Meier, R. R.; Samson, James A. R.; Chung, Y.; Lee, E.-M.; He, Z.-X.

1991-01-01

Photodissociative ionization of N2 into the unbound N2(+) H 2Sigma-g(+) state is identified as the parentage of a number of N(+) and N-excited states that contribute to the u.v. dayglow. Yields have been obtained for the production of extreme ultraviolet emission lines of N(+) and N from a laboratory experiment using a broadband synchrotron radiation source with fluorescence spectroscopy. The yields are termed 'effective', in that they are constant percentages of the H state cross section. These are compared wih effective yields needed to reproduce N II 1085 and 916 A lines from four dayglow observations using a model of solar energy deposition and photoelectron production and loss in the earth's thermosphere. The 1085 A effective yield measured in the laboratory (18 percent) agrees with that from the dayglow data (average of 17 percent) to well within experimental uncertainties. Thus, it is concluded that photodissociative ionization of N2 is the primary source of the N II 1085 A dayglow. However, there is an order of magnitude discrepancy among the various dayglow observations of the 1085/916 intensity ratio, only one of which is consistent with the laboratory observation of 4.4. Neither contamination by other dayglow features nor atmospheric extinction can account for the disparities. Laboratory measurements of N2 and O2 absorption cross sections at these wavelengths are also reported.

Local quantum transformations requiring infinite rounds of classical communication.

PubMed

Chitambar, Eric

2011-11-04

In this Letter, we investigate the number of measurement and communication rounds needed to implement certain tasks by local quantum operations and classical communication (LOCC), a relatively unexplored topic. To demonstrate the possible strong dependence on the round number, we consider the problem of converting three-qubit entanglement into two-qubit form, specifically in the random distillation setting of [Phys. Rev. Lett. 98, 260501 (2007)]. We find that the number of LOCC rounds needed for a transformation can depend on the amount of entanglement distilled. In fact, for a wide range of transformations, the required number of rounds is infinite (unbounded). This represents the first concrete example of a task needing an infinite number of rounds to implement.

21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1113 Bilirubin (total and unbound) in the neonate test system. (a...

21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1113 Bilirubin (total and unbound) in the neonate test system. (a...

21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1113 Bilirubin (total and unbound) in the neonate test system. (a...

21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1113 Bilirubin (total and unbound) in the neonate test system. (a...

21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1113 Bilirubin (total and unbound) in the neonate test system. (a...

Unbound Bilirubin and Auditory Neuropathy Spectrum Disorder in Late Preterm and Term Infants with Severe Jaundice.

PubMed

Amin, Sanjiv B; Wang, Hongyue; Laroia, Nirupama; Orlando, Mark

2016-06-01

This study evaluates whether unbound bilirubin is a better predictor of auditory neuropathy spectrum disorder (ANSD) than total serum bilirubin (TSB) or the bilirubin:albumin molar ratio (BAMR) in late preterm and term neonates with severe jaundice (TSB ≥20 mg/dL or TSB that met exchange transfusion criteria). Infants ≥34 weeks' gestation with severe jaundice during the first 2 weeks of life were eligible for the prospective observational study. A comprehensive auditory evaluation was performed within 72 hours of peak TSB. ANSD was defined as absent or abnormal auditory brainstem evoked response waveform morphology at 80-decibel click intensity in the presence of normal outer hair cell function. TSB, serum albumin, and unbound bilirubin were measured using the colorimetric, bromocresol green, and modified peroxidase method, respectively. Five of 44 infants developed ANSD. By logistic regression, peak unbound bilirubin but not peak TSB or peak BAMR was associated with ANSD (OR, 4.6; 95% CI, 1.6-13.5; P = .002). On comparing receiver operating characteristic curves, the area under the curve for unbound bilirubin (0.92) was significantly greater (P = .04) compared with the area under the curve for TSB (0.50) or BAMR (0.62). Unbound bilirubin is a more sensitive and specific predictor of ANSD than TSB or BAMR in late preterm and term infants with severe jaundice. Copyright © 2016 Elsevier Inc. All rights reserved.

Helicon waves in uniform plasmas. II. High m numbers

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

Stenzel, R. L.; Urrutia, J. M.

2015-09-15

Helicons are whistler modes with azimuthal wave numbers. They have been studied in solids and plasmas where boundaries play a role. The present work shows that very similar modes exist in unbounded gaseous plasmas. Instead of boundaries, the antenna properties determine the topology of the wave packets. The simplest antenna is a magnetic loop which excites m = 0 or m = 1 helicons depending on whether the dipole moment is aligned parallel or perpendicular to the ambient background magnetic field B{sub 0}. While these low order helicons have been described by J. M. Urrutia and R. L. Stenzel [“Helicon modes in uniform plasmas.more » I. Low m modes,” Phys. Plasmas 22, 092111 (2015)], the present work focuses on high order modes up to m = 8. These are excited by antenna arrays forming magnetic multipoles. Their wave magnetic field has been measured in space and time in a large and uniform laboratory plasma free of boundary effects. The observed wave topology exhibits m pairs of unique field line spirals which may have inspired the name “helicon” to this mode. All field lines converge into these nested spirals which propagate like corkscrews along B{sub 0}. The field lines near the axis of helicons are perpendicular to B{sub 0} and circularly polarized as in parallel whistlers. Helical antennas couple to these transverse fields but not to the spiral fields of helicons. Using a circular antenna array of phased m = 0 loops, right or left rotating or non-rotating multipole antenna fields are generated. They excite m < 0 and m > 0 modes, showing that the plasma supports both modes equally well. The poor excitation of m < 0 modes is a characteristic of loops with dipole moment across B{sub 0}. The radiation efficiency of multipole antennas has been found to decrease with m.« less

Coexistence of bounded and unbounded motions in a bouncing ball model

NASA Astrophysics Data System (ADS)

Marò, Stefano

2013-05-01

We consider the model describing the vertical motion of a ball falling with constant acceleration on a wall and elastically reflected. The wall is supposed to move in the vertical direction according to a given periodic function f. We apply the Aubry-Mather theory to the generating function in order to prove the existence of bounded motions with prescribed mean time between the bounces. As the existence of unbounded motions is known, it is possible to find a class of functions f that allow both bounded and unbounded motions.

Boundary Approximation Methods for Sloving Elliptic Problems on Unbounded Domains

NASA Astrophysics Data System (ADS)

Li, Zi-Cai; Mathon, Rudolf

1990-08-01

Boundary approximation methods with partial solutions are presented for solving a complicated problem on an unbounded domain, with both a crack singularity and a corner singularity. Also an analysis of partial solutions near the singular points is provided. These methods are easy to apply, have good stability properties, and lead to highly accurate solutions. Hence, boundary approximation methods with partial solutions are recommended for the treatment of elliptic problems on unbounded domains provided that piecewise solution expansions, in particular, asymptotic solutions near the singularities and infinity, can be found.

Tension-dependent structural deformation alters single-molecule transition kinetics.

PubMed

Sudhanshu, B; Mihardja, S; Koslover, E F; Mehraeen, S; Bustamante, C; Spakowitz, A J

2011-02-01

We analyze the response of a single nucleosome to tension, which serves as a prototypical biophysical measurement where tension-dependent deformation alters transition kinetics. We develop a statistical-mechanics model of a nucleosome as a wormlike chain bound to a spool, incorporating fluctuations in the number of bases bound, the spool orientation, and the conformations of the unbound polymer segments. With the resulting free-energy surface, we perform dynamic simulations that permit a direct comparison with experiments. This simple approach demonstrates that the experimentally observed structural states at nonzero tension are a consequence of the tension and that these tension-induced states cease to exist at zero tension. The transitions between states exhibit substantial deformation of the unbound polymer segments. The associated deformation energy increases with tension; thus, the application of tension alters the kinetics due to tension-induced deformation of the transition states. This mechanism would arise in any system where the tether molecule is deformed in the transition state under the influence of tension.

Tension-dependent structural deformation alters single-molecule transition kinetics

PubMed Central

Sudhanshu, B.; Mihardja, S.; Koslover, E. F.; Mehraeen, S.; Bustamante, C.; Spakowitz, A. J.

2011-01-01

We analyze the response of a single nucleosome to tension, which serves as a prototypical biophysical measurement where tension-dependent deformation alters transition kinetics. We develop a statistical-mechanics model of a nucleosome as a wormlike chain bound to a spool, incorporating fluctuations in the number of bases bound, the spool orientation, and the conformations of the unbound polymer segments. With the resulting free-energy surface, we perform dynamic simulations that permit a direct comparison with experiments. This simple approach demonstrates that the experimentally observed structural states at nonzero tension are a consequence of the tension and that these tension-induced states cease to exist at zero tension. The transitions between states exhibit substantial deformation of the unbound polymer segments. The associated deformation energy increases with tension; thus, the application of tension alters the kinetics due to tension-induced deformation of the transition states. This mechanism would arise in any system where the tether molecule is deformed in the transition state under the influence of tension. PMID:21245354

Use of Inert Gases and Carbon Monoxide to Study the Possible Influence of Countercurrent Exchange on Passive Absorption from the Small Bowel

PubMed Central

Bond, John H.; Levitt, David G.; Levitt, Michael D.

1974-01-01

The purpose of the present study was to quantitate the influence of countercurrent exchange on passive absorption of highly diffusible substances from the small intestine of the rabbit. The absorption of carbon monoxide, which is tightly bound to hemoglobin and therefore cannot exchange, was compared to the absorption of four unbound gases (H2, He, CH4, and 133Xe), which should exchange freely. The degree to which the observed absorption of the unbound gases falls below that predicted from CO absorption should provide a quantitative measure of countercurrent exchange. CO uptake at high luminal Pco is flow-limited and, assuming that villus and central hemoglobin concentrations are equal, the flow that equilibrates with CO (Fco) was calculated to equal 7.24 ml/min/100 g. The observed absorption rate of the unbound gases was from two to four times greater than would have been predicted had their entire uptake been accounted for by equilibration with Fco. This is the opposite of what would occur if countercurrent exchange retarded absorption of the unbound gases. The unbound gases have both flow- and diffusion-limited components, and Fco should account for only the fraction of absorption that is flow limited. A simple model of perfusion and diffusion made it possible to calculate the fraction of the total uptake of unbound gases that was flow limited. This fraction of the total observed absorption rate was still about 1.8 times greater than predicted by CO absorption. A possible explanation for this discrepancy is that plasma skimming reduces the hemoglobin of villus blood to about 60% of that of central blood. Thus, Fco is actually about 1.7 times greater than initially calculated, and with this correction, there is close agreement between the predicted and observed rates of absorption of each of the unbound gases. We conclude that countercurrent exchange does not influence passive absorption under the conditions of this study. PMID:4436431

Exposure to Total and Protein-Unbound Rifampin Is Not Affected by Malnutrition in Indonesian Tuberculosis Patients

PubMed Central

Ruslami, R.; Later-Nijland, H.; Mooren, F.; Teulen, M.; Apriani, L.; Koenderink, J. B.; Russel, F. G.; Burger, D. M.; Alisjahbana, B.; Wieringa, F.; van Crevel, R.; Aarnoutse, R. E.

2015-01-01

Nutritional status may have a profound impact on the pharmacokinetics of drugs, yet only few data are available for tuberculosis (TB) drugs. As malnutrition occurs frequently among TB patients, we assessed the effect of malnutrition on the steady-state pharmacokinetics of total and protein-unbound rifampin during the intensive phase of TB treatment. In a descriptive pharmacokinetic study in Bandung, Indonesia, patients received a fixed standard rifampin dose of 450 mg once daily during the intensive phase of TB treatment. A full pharmacokinetic curve for rifampin was recorded, and total and unbound concentrations of rifampin were analyzed in all samples. Rifampin pharmacokinetic parameters were compared between severely malnourished (BMI of <16.0 kg/m2), malnourished (BMI of <18.5 kg/m2), and well-nourished (BMI of ≥18.5 kg/m2) individuals. No difference in total and protein-unbound pharmacokinetic parameters between severely malnourished (n = 7), malnourished (n = 11), and well-nourished (n = 25) patients could be demonstrated. In addition, no significant correlation between BMI and exposure (area under the concentration-time curve from 0 to 24 h [AUC0–24] and maximum concentration of drug in serum [Cmax]) was found. Females had significantly higher total AUC0–24 (geometric mean, 59.2 versus 48.2 h · mg/liter; P = 0.02) and higher unbound AUC0–24 (geometric mean, 6.2 versus 4.8 h · mg/liter; P = 0.02) than males. Overall, a marked 2-fold interindividual variation in the free fraction was observed (7.6 to 15.0%; n = 36). Nutritional status and BMI do not appear to have a major effect on total and protein-unbound pharmacokinetic parameters of rifampin in Indonesian subjects. The large interindividual variability in the free fraction of rifampin suggests that protein-unbound rather than total rifampin concentrations should preferably be used to study exposure-response relationships. PMID:25801554

Exposure–effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis

PubMed Central

Abd Rahman, Azrin N; Tett, Susan E; Abdul Gafor, Halim A; McWhinney, Brett C; Staatz, Christine E

2015-01-01

Aims The aim was to examine relationships between total and unbound mycophenolic acid (MPA) and prednisolone exposure and clinical outcomes in patients with lupus nephritis. Methods Six blood samples were drawn pre- and at 1, 2, 4, 6 and 8 h post-dose and total and unbound MPA and prednisolone pre-dose (C0), maximum concentration (Cmax) and area under the concentration–time curve (AUC) were determined using non-compartmental analysis in 25 patients. The analyses evaluated drug exposures in relation to treatment response since starting MPA and drug-related adverse events. Results Dose-normalized AUC varied 10-, 8-, 7- and 19-fold for total MPA, unbound MPA, total prednisolone and unbound prednisolone, respectively. Median values (95% CI) of total MPA AUC(0,8 h) (21.5 [15.0, 42.0] vs. 11.2 [4.8, 30.0] mg l–1 h, P= 0.048) and Cmax (11.9 [6.7, 26.3] vs. 6.1 [1.6, 9.2] mg l–1, P = 0.016) were significantly higher in responders than non-responders. Anaemia was significantly associated with higher total (37.8 [14.1, 77.5] vs. 18.5 [11.7, 32.7] mg l–1 h, P = 0.038) and unbound MPA AUC(0,12 h) (751 [214, 830] vs. 227 [151, 389] mg l–1 h, P = 0.004). Unbound prednisolone AUC(0,24 h) was significantly higher in patients with Cushingoid appearance (unbound: 1372 [1242, 1774] vs. 846 [528, 1049] nmol l–1 h, P = 0.019) than in those without. Poorer treatment response was observed in patients with lowest tertile exposure to both total MPA and prednisolone as compared with patients with middle and higher tertile exposure (17% vs. 74%, P = 0.023). Conclusions This study suggests a potential role for therapeutic drug monitoring in individualizing immunosuppressant therapy in patients with lupus nephritis. PMID:25959850

Exposure-effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis.

PubMed

Abd Rahman, Azrin N; Tett, Susan E; Abdul Gafor, Halim A; McWhinney, Brett C; Staatz, Christine E

2015-11-01

The aim was to examine relationships between total and unbound mycophenolic acid (MPA) and prednisolone exposure and clinical outcomes in patients with lupus nephritis. Six blood samples were drawn pre- and at 1, 2, 4, 6 and 8 h post-dose and total and unbound MPA and prednisolone pre-dose (C0 ), maximum concentration (Cmax ) and area under the concentration-time curve (AUC) were determined using non-compartmental analysis in 25 patients. The analyses evaluated drug exposures in relation to treatment response since starting MPA and drug-related adverse events. Dose-normalized AUC varied 10-, 8-, 7- and 19-fold for total MPA, unbound MPA, total prednisolone and unbound prednisolone, respectively. Median values (95% CI) of total MPA AUC(0,8 h) (21.5 [15.0, 42.0] vs. 11.2 [4.8, 30.0] mg l(-1) h, P= 0.048) and Cmax (11.9 [6.7, 26.3] vs. 6.1 [1.6, 9.2] mg l(-1) , P = 0.016) were significantly higher in responders than non-responders. Anaemia was significantly associated with higher total (37.8 [14.1, 77.5] vs. 18.5 [11.7, 32.7] mg l(-1) h, P = 0.038) and unbound MPA AUC(0,12 h) (751 [214, 830] vs. 227 [151, 389] mg l(-1) h, P = 0.004). Unbound prednisolone AUC(0,24 h) was significantly higher in patients with Cushingoid appearance (unbound: 1372 [1242, 1774] vs. 846 [528, 1049] nmol l(-1) h, P = 0.019) than in those without. Poorer treatment response was observed in patients with lowest tertile exposure to both total MPA and prednisolone as compared with patients with middle and higher tertile exposure (17% vs. 74%, P = 0.023). This study suggests a potential role for therapeutic drug monitoring in individualizing immunosuppressant therapy in patients with lupus nephritis. © 2015 The British Pharmacological Society.

Walking at the drip line

NASA Astrophysics Data System (ADS)

Bonaccorso, Angela

2015-02-01

Among exotic nuclei those at the drip line which are unstable against neutron emission are particularly interesting because they convey information on the nuclear force in the most extreme situations. Strictly speaking they are not ''nuclei" but they exist thanks to long living resonances between a neutron and a bound ''core" nucleus. Adding one more neutron they become bound and are called "borromean". Being particularly exotic they have attracted much attention in past years, see for example Refs.[1, 2, 3]. One very challenging example is 13Be whose level ordering has been discussed in a large number of papers in which it has been studied by transfer [4] and fragmentation experiments [5]-[11], or it has been discussed theoretically[12]-[19]. Although projectile fragmentation spectra show evident similarities, the interpretations of data all differ from each other. In this paper we argue that a way trough the problem could be to try to establish first, or at the same time, the quite elusive "nature" of the second s-state in the Beryllium isotopes with A=9-14. On the other hand there are other recent neutron removal experiments leading to nuclei unstable by one or more proton emissions [20], and thus somewhat mirror to borromean nuclei, performed with nuclei close to the proton drip line. It has been shown that by taking in coincidence all (charged) particles but the removed neutron, reconstructing the invariant mass and gating on the ground state peak, it is possible to obtain the longitudinal momentum distribution of the unbound "core". One can link it to the original wave function of the bound orbital and thus determine the initial neutron angular momentum from the shape of the distribution and the initial occupation probability from the absolute removal cross section. Then it is clear that modern experiments and theories are able to study unstable nuclei with the same degree of accuracy as stable nuclei. Such a line of research offers a great potential for numerous further studies beyond the drip line.

Determination of total and unbound concentrations of lopinavir in plasma using liquid chromatography-tandem mass spectrometry and ultrafiltration methods.

PubMed

Illamola, S M; Labat, L; Benaboud, S; Tubiana, R; Warszawski, J; Tréluyer, J M; Hirt, D

2014-08-15

Lopinavir is an HIV protease inhibitor with high protein binding (98-99%) in human plasma. This study was designed to develop an ultrafiltration method to measure the unbound concentrations of lopinavir overcoming the non-specific binding issue. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of total concentrations of lopinavir in plasma was developed and validated, and an adaptation was also optimized and validated for the determination of unbound concentrations. The chromatographic separation was performed with a C18 column (100 mm × 2.1mm i.d., 5 μm particle size) using a mobile phase containing deionized water with formic acid, and acetonitrile, with gradient elution at a flow-rate of 350 μL min(-1). Identification of the compounds was performed by multiple reaction monitoring, using electrospray ionization in positive ion mode. The method was validated over a clinical range of 0.01-1 μg/mL for human plasma ultrafiltrate and 0.1-15 μg/mL in human plasma. The inter and intra-assay accuracies and precisions were between 0.23% and 11.37% for total lopinavir concentrations, and between 3.50% and 13.30% for plasma ultrafiltrate (unbound concentration). The ultrafiltration method described allows an accurate separation of the unbound fraction of lopinavir, circumscribing the loss of drug by nonspecific binding (NSB), and the validated LC-MS/MS methodology proposed is suitable for the determination of total and unbound concentrations of lopinavir in clinical practice. Copyright © 2014 Elsevier B.V. All rights reserved.

Stationary transport processes with unbounded collision operators

NASA Astrophysics Data System (ADS)

Greenberg, William; van der Mee, C. V. M.

1984-01-01

An abstract Hilbert space equation is studied, which models many of the stationary, one-dimensional transport equations with partial-range boundary conditions. In particular, the collision term may be unbounded and nondissipative. A complete existence and uniqueness theory is presented.

Accretion Rate: An Axis Of Agn Unification

NASA Astrophysics Data System (ADS)

Trump, Jonathan R.; Impey, C. D.; Kelly, B. C.

2011-01-01

We show how accretion rate governs the physical properties of broad-line, narrow-line, and lineless active galactic nuclei (AGNs). We avoid the systematic errors plaguing previous studies of AGN accretion rate by using accurate accretion luminosities from well-sampled multiwavelength SEDs from the Cosmic Evolution Survey (COSMOS), and accurate black hole masses derived from virial scaling relations (for broad-line AGNs) or host-AGN relations (for narrow-line and lineless AGNs). In general, broad emission lines are present only at the highest accretion rates (L/L_Edd>0.01), and these rapidly accreting AGNs are observed as broad-line AGNs or possibly as obscured narrow-line AGNs. Narrow-line and lineless AGNs at lower specific accretion rates (L/L_Edd<0.01) are unobscured and yet lack a broad line region. The disappearance of the broad emission lines is caused by an expanding radiatively inefficient accretion flow (RIAF) at the inner radius of the accretion disk. The presence of the RIAF also drives L/L_Edd<0.01 narrow-line and lineless AGNs to be 10-100 times more radio-luminous than broad-line AGNs, since the unbound nature of the RIAF means it is easier to form a radio outflow. The IR torus signature also tends to become weaker or disappear from L/L_Edd<0.01 AGNs, although there may be additional mid-IR synchrotron emission associated with the RIAF. Together these results suggest that specific accretion rate is an important physical "axis" of AGN unification, described by a simple model.

Seasonal variations in the moduli of unbound pavement layers.

DOT National Transportation Integrated Search

2006-07-01

The in situ moduli of unbound pavement materials vary on a seasonal basis as a function of temperature and moisture conditions. : Knowledge of these variations is required for accurate prediction of pavement life for pavement design and other pavemen...

Effect of drainage in unbound aggregate bases on flexible pavement performance.

DOT National Transportation Integrated Search

2009-03-01

The main objective of this study is to optimize the gradation of Mexican limestone aggregate for use as an unbound drainable base material that has adequate permeability while staying structurally stable during the construction time and the pavement...

Determination of resilient properties of unbound materials with repeated load triaxial and diametral test systems.

DOT National Transportation Integrated Search

1981-12-01

Repeated load diametral test systems are experiencing increased use to determine resilient properties of asphalt concrete and admixture stabilized materials; they have not been used extensively to determine the resilient properties of unbound materia...

Resilient moduli of typical Missouri soils and unbound granular base materials.

DOT National Transportation Integrated Search

2009-01-01

The objective of this project was to determine the resilient moduli for common Missouri subgrade soils and typical unbound granular base materials in accordance with the AASHTO T 307 test method. The results allow Missouri Department of Transportatio...

Verifying Multi-Agent Systems via Unbounded Model Checking

NASA Technical Reports Server (NTRS)

Kacprzak, M.; Lomuscio, A.; Lasica, T.; Penczek, W.; Szreter, M.

2004-01-01

We present an approach to the problem of verification of epistemic properties in multi-agent systems by means of symbolic model checking. In particular, it is shown how to extend the technique of unbounded model checking from a purely temporal setting to a temporal-epistemic one. In order to achieve this, we base our discussion on interpreted systems semantics, a popular semantics used in multi-agent systems literature. We give details of the technique and show how it can be applied to the well known train, gate and controller problem. Keywords: model checking, unbounded model checking, multi-agent systems

Resilient moduli of typical Missouri soils and unbound granular base materials

DOT National Transportation Integrated Search

2008-03-01

The objective of this project is to accurately determine the resilient moduli for common Missouri subgrade soils and unbound granular base materials in accordance with the AASHTO T 307 test method. The test results included moduli data from 27 common...

Measurement of seasonal changes and spatial variations in pavement unbound base and subgrade properties.

DOT National Transportation Integrated Search

2009-01-01

Soils often undergo cyclic wetting/drying, but there is very limited research on unsaturated : soils subjected to variations in moisture content. More specifically, field moisture variation : over time in highway unbound bases and subgrade soils is a...

Unbounded and revocable hierarchical identity-based encryption with adaptive security, decryption key exposure resistant, and short public parameters

PubMed Central

Wang, Baosheng; Tao, Jing

2018-01-01

Revocation functionality and hierarchy key delegation are two necessary and crucial requirements to identity-based cryptosystems. Revocable hierarchical identity-based encryption (RHIBE) has attracted a lot of attention in recent years, many RHIBE schemes have been proposed but shown to be either insecure or bounded where they have to fix the maximum hierarchical depth of RHIBE at setup. In this paper, we propose a new unbounded RHIBE scheme with decryption key exposure resilience and with short public system parameters, and prove our RHIBE scheme to be adaptively secure. Our system model is scalable inherently to accommodate more levels of user adaptively with no adding workload or restarting the system. By carefully designing the hybrid games, we overcome the subtle obstacle in applying the dual system encryption methodology for the unbounded and revocable HIBE. To the best of our knowledge, this is the first construction of adaptively secure unbounded RHIBE scheme. PMID:29649326

Plasma protein binding of phenytoin in 100 epileptic patients.

PubMed Central

Peterson, G M; McLean, S; Aldous, S; Von Witt, R J; Millingen, K S

1982-01-01

The plasma protein binding of phenytoin was investigated in 100 epileptic patients, using equilibrium dialysis at 37 degrees C. The unbound fractions of phenytoin in plasma formed a skewed distribution, with a range of 9.7 to 24.7% and a median value of 12.3%. Most (80%) patients appeared to form one group with free phenytoin fractions from 9.7 to 14.5%, while the remainder formed a group with elevated free fractions (greater than 14.5%). Total and unbound plasma concentrations of phenytoin were strongly correlated (r=0.95, P less than 0.0001). There was a weak correlation between increasing age and the unbound phenytoin fraction (r=0.28, P less than 0.01). The results indicate that measurement of the total phenytoin concentration in plasma should usually provide a reliable index of anticonvulsant effect. However, determination of the unbound phenytoin fraction would be beneficial in the management of those patients in whom this fraction may be elevated, due to interacting drugs or biochemical abnormalities. PMID:7104186

Unbound bilirubin measurements by a novel probe in preterm infants.

PubMed

Hegyi, Thomas; Kleinfeld, Alan; Huber, Andrew; Weinberger, Barry; Memon, Naureen; Shih, Weichung; Carayannopoulos, Mary; Oh, William

2018-03-12

Hyperbilirubinemia occurs in over 80% of newborns and severe bilirubin toxicity can lead to neurological dysfunction and death, especially in preterm infants. Currently, the risk of bilirubin toxicity is assessed by measuring the levels of total serum bilirubin (TSB), which are used to direct treatments including immunoglobulin administration, phototherapy, and exchange transfusion. However, free, unbound bilirubin levels (Bf) predict the risk of bilirubin neurotoxicity more accurately than TSB. To examine Bf levels in preterm infants and determine the frequency with which they exceed reported neurotoxic thresholds. One hundred thirty preterm infants (BW 500-2000 g; GA 23-34 weeks) were enrolled and Bf levels measured during the first week of life by the fluorescent Bf sensor BL22P1B11-Rh. TSB and plasma albumin were measured by standard techniques. Bilirubin-albumin dissociation constants (K d ) were calculated based on Bf and plasma albumin. Five hundred eighty samples were measured during the first week of life, with an overall mean Bf of 13.6 ± 9.0 nM. A substantial number of measurements exceeded potential toxic thresholds levels as reported in the literature. The correlation between Bf and TSB was statistically significant (r 2 0.17), but this weak relationship was lost at high Bf levels. Infants <28-week gestations had more hearing screening failures than infants ≥28-week gestation. Unbound (free) bilirubin values are extremely variable during the first week of life in preterm infants. A significant proportion of these values exceeded reported neurotoxic thresholds.

On the Magnetic Shield for a Vlasov-Poisson Plasma

NASA Astrophysics Data System (ADS)

Caprino, Silvia; Cavallaro, Guido; Marchioro, Carlo

2017-12-01

We study the screening of a bounded body Γ against the effect of a wind of charged particles, by means of a shield produced by a magnetic field which becomes infinite on the border of Γ . The charged wind is modeled by a Vlasov-Poisson plasma, the bounded body by a torus, and the external magnetic field is taken close to the border of Γ . We study two models: a plasma composed by different species with positive or negative charges, and finite total mass of each species, and another made of many species of the same sign, each having infinite mass. We investigate the time evolution of both systems, showing in particular that the plasma particles cannot reach the body. Finally we discuss possible extensions to more general initial data. We show also that when the magnetic lines are straight lines, (that imposes an unbounded body), the previous results can be improved.

Protein Binding of Lopinavir and Ritonavir During Four Phases of Pregnancy: Implications for Treatment Guidelines

PubMed Central

Patterson, Kristine B.; Dumond, Julie B.; Prince, Heather A.; Jenkins, Amanda J.; Scarsi, Kimberly K.; Wang, Ruili; Malone, Stephanie; Hudgens, Michael G.; Kashuba, Angela DM.

2013-01-01

Objective To investigate the intraindividual pharmacokinetics of total (protein bound + unbound) and unbound lopinavir/ritonavir (LPV/RTV) and to assess whether the pediatric formulation (100mg/25mg) can overcome any pregnancy-associated changes. Design Prospective longitudinal pharmacokinetic (PK) study Methods HIV-infected pregnant antiretroviral therapy-naïve and experienced women receiving LPV/RTV 400mg/100mg tablets twice daily. Intensive PK evaluations were performed at 20–24 weeks (PK1), 30 weeks (PK2) followed by empiric dose increase using the pediatric formulation (100mg/25mg twice daily), 32 weeks (PK3), and 8 weeks postpartum (PK4). Results Twelve women completed pre-specified PK evaluations. Median (range) age was 28 (1–35) years and baseline BMI was 32 (19–41) kg/m2. During pregnancy, total area under the time concentration (AUC0–12hr) for LPV was significantly lower than postpartum [PK1, PK2 or PK3 vs. PK4, p= 0.005]. Protein unbound LPV AUC0–12hr remained unchanged during pregnancy [PK1: 1.6 (1.3–1.9) vs. PK2: 1.6 (1.3–1.9) µg*hr/mL, p=0.4] despite a 25% dose increase [PK2 vs. PK3: 1.8 (1.3–2.1) µg*hr/mL, p=0.5]. Protein unbound LPV predose concentrations (C12h) did not significantly change despite dose increase [PK2: 0.10 (0.08–0.15) vs. PK3: 0.12 (0.10–0.15) µg/mL, p=0.09]. Albumin and LPV AUC0–12h fraction unbound were correlated (rs=0.3, p=0.03). Conclusions Total LPV exposure was significantly decreased throughout pregnancy despite the increased dose. However, the exposure of unbound LPV did not change significantly regardless of trimester or dose. Predose concentrations of unbound LPV were not affected by the additional dose and were 70-fold greater than the minimum efficacy concentration. These findings suggest dose adjustments may not be necessary in all HIV-infected pregnant women. PMID:23221983

Generalized Categorial Grammar for Unbounded Dependencies Recovery

ERIC Educational Resources Information Center

Nguyen, Luan Viet

2014-01-01

Accurate recovery of predicate-argument dependencies is vital for interpretation tasks like information extraction and question answering, and unbounded dependencies may account for a significant portion of the dependencies in any given text. This thesis describes a Generalized Categorial Grammar (GCG) which, like other categorial grammars,…

Quantum Markov Semigroups with Unbounded Generator and Time Evolution of the Support Projection of a State

NASA Astrophysics Data System (ADS)

Gliouez, Souhir; Hachicha, Skander; Nasroui, Ikbel

We characterize the support projection of a state evolving under the action of a quantum Markov semigroup with unbounded generator represented in the generalized GKSL form and a quantum version of the classical Lévy-Austin-Ornstein theorem.

Probability Distributions over Cryptographic Protocols

DTIC Science & Technology

2009-06-01

Artificial Immune Algorithm . . . . . . . . . . . . . . . . . . . 9 3 Design Decisions 11 3.1 Common Ground...creation algorithm for unbounded distribution . . . . . . . 24 4.2 Message creation algorithm for unbounded naive distribution . . . . 24 4.3 Protocol...creation algorithm for intended-run distributions . . . . . . 26 4.4 Protocol and message creation algorithm for realistic distribution . . 32 ix THIS

Triadic Closure in Configuration Models with Unbounded Degree Fluctuations

NASA Astrophysics Data System (ADS)

van der Hofstad, Remco; van Leeuwaarden, Johan S. H.; Stegehuis, Clara

2018-01-01

The configuration model generates random graphs with any given degree distribution, and thus serves as a null model for scale-free networks with power-law degrees and unbounded degree fluctuations. For this setting, we study the local clustering c(k), i.e., the probability that two neighbors of a degree-k node are neighbors themselves. We show that c(k) progressively falls off with k and the graph size n and eventually for k=Ω (√{n}) settles on a power law c(k)˜ n^{5-2τ }k^{-2(3-τ )} with τ \\in (2,3) the power-law exponent of the degree distribution. This fall-off has been observed in the majority of real-world networks and signals the presence of modular or hierarchical structure. Our results agree with recent results for the hidden-variable model and also give the expected number of triangles in the configuration model when counting triangles only once despite the presence of multi-edges. We show that only triangles consisting of triplets with uniquely specified degrees contribute to the triangle counting.

Investigation of finite element: ABC methods for electromagnetic field simulation. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Chatterjee, A.; Volakis, John L.; Nguyen, J.

1994-01-01

The mechanics of wave propagation in the presence of obstacles is of great interest in many branches of engineering and applied mathematics like electromagnetics, fluid dynamics, geophysics, seismology, etc. Such problems can be broadly classified into two categories: the bounded domain or the closed problem and the unbounded domain or the open problem. Analytical techniques have been derived for the simpler problems; however, the need to model complicated geometrical features, complex material coatings and fillings, and to adapt the model to changing design parameters have inevitably tilted the balance in favor of numerical techniques. The modeling of closed problems presents difficulties primarily in proper meshing of the interior region. However, problems in unbounded domains pose a unique challenge to computation, since the exterior region is inappropriate for direct implementation of numerical techniques. A large number of solutions have been proposed but only a few have stood the test of time and experiment. The goal of this thesis is to develop an efficient and reliable partial differential equation technique to model large three dimensional scattering problems in electromagnetics.

Helicon waves in uniform plasmas. IV. Bessel beams, Gendrin beams, and helicons

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

Urrutia, J. M.; Stenzel, R. L.

Electromagnetic waves in the low frequency whistler mode regime are investigated experimentally and by digital data superposition. The radiation from a novel circular antenna array is shown to produce highly collimated helicon beams in a uniform unbounded plasma. The differences to Bessel beams in free space are remarked upon. Low divergence beams arise from the parallel group velocity of whistlers with phase velocity either along the guide field or at the Gendrin angle. Waves with angular momentum are produced by phasing the array in the circular direction. The differences in the field topologies for positive and negative modes numbers aremore » shown. It is also shown that in uniform plasmas, the radial amplitude profile of the waves depends on the antenna field topology. Thus, there are no helicon “eigenmodes” with radial Bessel function profiles in uniform plasmas. It is pointed out that phase measurements in helicon devices indicate radial wave propagation which is inconsistent with helicon eigenmode theory based on paraxial wave propagation. Trivelpiece-Gould modes also exist in uniform unbounded plasmas.« less

A Floating Cylinder on an Unbounded Bath

NASA Astrophysics Data System (ADS)

Chen, Hanzhe; Siegel, David

2018-03-01

In this paper, we reconsider a circular cylinder horizontally floating on an unbounded reservoir in a gravitational field directed downwards, which was studied by Bhatnagar and Finn (Phys Fluids 18(4):047103, 2006). We follow their approach but with some modifications. We establish the relation between the total energy E_T relative to the undisturbed state and the total force F_T , that is, F_T = -dE_T/dh , where h is the height of the center of the cylinder relative to the undisturbed fluid level. There is a monotone relation between h and the wetting angle φ _0 . We study the number of equilibria, the floating configurations and their stability for all parameter values. We find that the system admits at most two equilibrium points for arbitrary contact angle γ , the one with smaller φ _0 is stable and the one with larger φ _0 is unstable. Since the one-sided solution can be translated horizontally, the fluid interfaces may intersect. We show that the stable equilibrium point never lies in the intersection region, while the unstable equilibrium point may lie in the intersection region.

Bridging the Semantic Gap Between Heterogeneous Modeling Formalisms and FMI

DTIC Science & Technology

2014-04-25

Naval Research Laboratory (NRL #N0013-12-1-G015), and the following companies: Bosch, National Instruments, and Toyota ). 1 of contract, these two...but only on the interconnections of the FMUs in the network). To our knowledge , the question how to create FMUs has not been formally addressed. This...unbounded length. The main characteristic of SDF is that the number of tokens that each actor consumes from its input queues and produces to its output

Approximation methods for control of structural acoustics models with piezoceramic actuators

NASA Astrophysics Data System (ADS)

Banks, H. T.; Fang, W.; Silcox, R. J.; Smith, R. C.

1993-01-01

The active control of acoustic pressure in a 2-D cavity with a flexible boundary (a beam) is considered. Specifically, this control is implemented via piezoceramic patches on the beam which produces pure bending moments. The incorporation of the feedback control in this manner leads to a system with an unbounded input term. Approximation methods in this manner leads to a system with an unbounded input term. Approximation methods in this manner leads to a system with an unbounded input team. Approximation methods in the context of linear quadratic regulator (LQR) state space control formulation are discussed and numerical results demonstrating the effectiveness of this approach in computing feedback controls for noise reduction are presented.

The damped wave equation with unbounded damping

NASA Astrophysics Data System (ADS)

Freitas, Pedro; Siegl, Petr; Tretter, Christiane

2018-06-01

We analyze new phenomena arising in linear damped wave equations on unbounded domains when the damping is allowed to become unbounded at infinity. We prove the generation of a contraction semigroup, study the relation between the spectra of the semigroup generator and the associated quadratic operator function, the convergence of non-real eigenvalues in the asymptotic regime of diverging damping on a subdomain, and we investigate the appearance of essential spectrum on the negative real axis. We further show that the presence of the latter prevents exponential estimates for the semigroup and turns out to be a robust effect that cannot be easily canceled by adding a positive potential. These analytic results are illustrated by examples.

Global solutions to the electrodynamic two-body problem on a straight line

NASA Astrophysics Data System (ADS)

Bauer, G.; Deckert, D.-A.; Dürr, D.; Hinrichs, G.

2017-06-01

The classical electrodynamic two-body problem has been a long standing open problem in mathematics. For motion constrained to the straight line, the interaction is similar to that of the two-body problem of classical gravitation. The additional complication is the presence of unbounded state-dependent delays in the Coulomb forces due to the finiteness of the speed of light. This circumstance renders the notion of local solutions meaningless, and therefore, straightforward ODE techniques cannot be applied. Here, we study the time-symmetric case, i.e., the Fokker-Schwarzschild-Tetrode (FST) equations, comprising both advanced and retarded delays. We extend the technique developed in Deckert and Hinrichs (J Differ Equ 260:6900-6929, 2016), where existence of FST solutions was proven on the half line, to ensure global existence—a result that had been obtained by Bauer (Ein Existenzsatz für die Wheeler-Feynman-Elektrodynamik, Herbert Utz Verlag, München, 1997). Due to the novel technique, the presented proof is shorter and more transparent but also relies on the idea to employ asymptotic data to characterize solutions.

"University Unbound" Rebounds: Can MOOCs "Educate" as Well as Train?

ERIC Educational Resources Information Center

McCully, George

2012-01-01

In the days since NEBHE convened hundreds of educators and opinion leaders in Boston for the "University Unbound" conference, people have received a surge of reactions including the one from George McCully, founder of the "Catalogue for Philanthropy." NEBHE has begun focusing the attention of New England institutions on the…

Unbound free fatty acids from preterm infants treated with intralipid decouples unbound from total bilirubin potentially making phototherapy ineffective.

PubMed

Hegyi, Thomas; Kathiravan, Suganya; Stahl, Gary E; Huber, Andrew H; Kleinfeld, Alan

2013-01-01

Extremely low birth weight (ELBW; <1,000 g) infants have poor outcomes, often compromised by bilirubin neurotoxicity. We measured unbound bilirubin (Bf) and unbound free fatty acid (FFAu) levels in 5 ELBW infants in a trial examining the effects of pharmacologic ductal closure on infants treated with Intralipid infusion (3 g/kg/day). The levels for all infants (mean ± SD) were: total serum bilirubin (TSB) 4.6 ± 1.7 mg/dl, FFAu 376 ± 496 nM, and Bf 42 ± 30 nM. Of the 3 infants who died, 2 had TSB <5.9 mg/dl but FFAu >580 nM and Bf >75 nM. Multiple regression revealed a major effect on Bf levels due to FFAu, indicating that Intralipid elevated levels of FFAu and Bf. Indomethacin or ibuprofen reduced Bf levels, most likely by reducing FFAu levels through lipase inhibition. Because displacement of Bf by FFAu decouples Bf from TSB, phototherapy may not reduce the risk of bilirubin or FFAu toxicity in Intralipid-treated ELBW infants. Copyright © 2013 S. Karger AG, Basel.

Spermatozoa with high mitochondrial membrane potential and low tyrosine phosphorylation preferentially bind to oviduct explants in the water buffalo (Bubalus bubalis).

PubMed

Saraf, Kaustubh Kishor; Kumaresan, Arumugam; Chhillar, Shivani; Nayak, Samiksha; Lathika, Sreela; Datta, Tirtha Kumar; Gahlot, Subhash Chand; Karan, Prabha; Verma, Kiran; Mohanty, Tushar Kumar

2017-05-01

Although it is understood that spermatozoa are subjected to selection processes to form a functional sperm reservoir in the oviduct, the mechanism remains obscure. With the aim to understand the sperm selection process in the oviduct, in the present in vitro study, we analyzed mitochondrial membrane potential and tyrosine phosphorylation status in oviduct-explants bound and unbound spermatozoa. Frozen semen from Murrah buffalo bulls (n=10) used under progeny testing programme were utilized for the study. Oviduct explants were prepared by overnight culture of epithelial cells in TCM- 199 and washed spermatozoa were added to the oviduct explants and incubated for 4h. Mitochondrial membrane potential (MMP) and tyrosine phosphorylation status of bound and unbound spermatozoa were assessed at 1h and 4h of incubation. The proportion of spermatozoa with high MMP was significantly higher (P<0.001) among the bound spermatozoa (range 84.67-96.56%) compared to unbound (range 8.70-21.03%) spermatozoa. The proportion of tyrosine phosphorylated spermatozoa was significantly higher (P<0.001) among unbound population as compared to bound population. The proportion of spermatozoa displaying tyrosine phosphorylation at acrosomal area was significantly (P<0.05) lower in bound sperm population compared to unbound population. It was inferred that spermatozoa with high MMP and low tyrosine phosphorylation were preferred for oviduct-explants binding in the buffalo. Copyright © 2017 Elsevier B.V. All rights reserved.

Population approach to analyze the pharmacokinetics of free and total lopinavir in HIV-infected pregnant women and consequences for dose adjustment.

PubMed

Fauchet, Floris; Treluyer, Jean-Marc; Illamola, Silvia M; Pressiat, Claire; Lui, Gabrielle; Valade, Elodie; Mandelbrot, Laurent; Lechedanec, Jerome; Delmas, Sandrine; Blanche, Stéphane; Warszawski, Josiane; Urien, Saik; Tubiana, Roland; Hirt, Déborah

2015-09-01

The aims of this study were to describe the unbound and total lopinavir (LPV) pharmacokinetics in pregnant women in order to evaluate if a dosing adjustment is necessary during pregnancy. Lopinavir placental transfer is described, and several genetic covariates were tested to explain its variability. A total of 400 maternal, 79 cord blood, and 48 amniotic fluid samples were collected from 208 women for LPV concentration determinations and pharmacokinetics analysis. Among the maternal LPV concentrations, 79 samples were also used to measure the unbound LPV concentrations. Population pharmacokinetics models were developed by using NONMEM software. Two models were developed to describe (i) unbound and total LPV pharmacokinetics and (ii) LPV placental transfer. The pharmacokinetics was best described by a one-compartment model with first-order absorption and elimination. A pregnancy effect was found on maternal clearance (39% increase), whereas the treatment group (monotherapy versus triple therapy) or the genetic polymorphisms did not explain the pharmacokinetics or placental transfer of LPV. Efficient unbound LPV concentrations in nonpregnant women were similar to those measured during the third trimester of pregnancy. Our study showed a 39% increase of maternal total LPV clearance during pregnancy, whereas unbound LPV concentrations were similar to those simulated in nonpregnant women. The genetic polymorphisms selected did not influence the LPV pharmacokinetics or placental transfer. Thus, we suggest that the LPV dosage should not be increased during pregnancy. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Population Approach To Analyze the Pharmacokinetics of Free and Total Lopinavir in HIV-Infected Pregnant Women and Consequences for Dose Adjustment

PubMed Central

Treluyer, Jean-Marc; Illamola, Silvia M.; Pressiat, Claire; Lui, Gabrielle; Valade, Elodie; Mandelbrot, Laurent; Lechedanec, Jerome; Delmas, Sandrine; Blanche, Stéphane; Warszawski, Josiane; Urien, Saik; Tubiana, Roland; Hirt, Déborah

2015-01-01

The aims of this study were to describe the unbound and total lopinavir (LPV) pharmacokinetics in pregnant women in order to evaluate if a dosing adjustment is necessary during pregnancy. Lopinavir placental transfer is described, and several genetic covariates were tested to explain its variability. A total of 400 maternal, 79 cord blood, and 48 amniotic fluid samples were collected from 208 women for LPV concentration determinations and pharmacokinetics analysis. Among the maternal LPV concentrations, 79 samples were also used to measure the unbound LPV concentrations. Population pharmacokinetics models were developed by using NONMEM software. Two models were developed to describe (i) unbound and total LPV pharmacokinetics and (ii) LPV placental transfer. The pharmacokinetics was best described by a one-compartment model with first-order absorption and elimination. A pregnancy effect was found on maternal clearance (39% increase), whereas the treatment group (monotherapy versus triple therapy) or the genetic polymorphisms did not explain the pharmacokinetics or placental transfer of LPV. Efficient unbound LPV concentrations in nonpregnant women were similar to those measured during the third trimester of pregnancy. Our study showed a 39% increase of maternal total LPV clearance during pregnancy, whereas unbound LPV concentrations were similar to those simulated in nonpregnant women. The genetic polymorphisms selected did not influence the LPV pharmacokinetics or placental transfer. Thus, we suggest that the LPV dosage should not be increased during pregnancy. PMID:26149996

Population Pharmacokinetic Modeling of the Unbound Levofloxacin Concentrations in Rat Plasma and Prostate Tissue Measured by Microdialysis

PubMed Central

Hurtado, Felipe K.; Weber, Benjamin; Derendorf, Hartmut; Hochhaus, Guenther

2014-01-01

Levofloxacin is a broad-spectrum fluoroquinolone used in the treatment of both acute and chronic bacterial prostatitis. Currently, the treatment of bacterial prostatitis is still difficult, especially due to the poor distribution of many antimicrobials into the prostate, thus preventing the drug to reach effective interstitial concentrations at the infection site. Newer fluoroquinolones show a greater penetration into the prostate. In the present study, we compared the unbound levofloxacin prostate concentrations measured by microdialysis to those in plasma after a 7-mg/kg intravenous bolus dose to Wistar rats. Plasma and dialysate samples were analyzed using a validated high-pressure liquid chromatography-fluorescence method. Both noncompartmental analysis (NCA) and population-based compartmental modeling (NONMEM 6) were performed. Unbound prostate tissue concentrations represented 78% of unbound plasma levels over a period of 12 h by comparing the extent of exposure (unbound AUC0–∞) of 6.4 and 4.8 h·μg/ml in plasma and tissue, respectively. A three-compartment model with simultaneous passive diffusion and saturable distribution kinetics from the prostate to the central compartment gave the best results in terms of curve fitting, precision of parameter estimates, and model stability. The following parameter values were estimated by the population model: V1 (0.38 liter; where V1 represents the volume of the central compartment), CL (0.22 liter/h), k12 (2.27 h−1), k21 (1.44 h−1), k13 (0.69 h−1), Vmax (7.19 μg/h), kM (0.35 μg/ml), V3/fuprostate (0.05 liter; where fuprostate represents the fraction unbound in the prostate), and k31 (3.67 h−1). The interindividual variability values for V1, CL, Vmax, and kM were 21, 37, 42, and 76%, respectively. Our results suggest that levofloxacin is likely to be substrate for efflux transporters in the prostate. PMID:24217697

Search for unbound 15Be states in the 3 n +12Be channel

NASA Astrophysics Data System (ADS)

Kuchera, A. N.; Spyrou, A.; Smith, J. K.; Baumann, T.; Christian, G.; DeYoung, P. A.; Finck, J. E.; Frank, N.; Jones, M. D.; Kohley, Z.; Mosby, S.; Peters, W. A.; Thoennessen, M.

2015-01-01

Background: 15Be is expected to have low-lying 3 /2+ and 5 /2+ states. A first search did not find the 3 /2+ [A. Spyrou et al., Phys. Rev. C 84, 044309 (2011), 10.1103/PhysRevC.84.044309]; however, a resonance in 15Be was populated in a second attempt and determined to be unbound with respect to 14Be by 1.8(1) MeV with a tentative spin-parity assignment of 5 /2+ [J. Snyder et al., Phys. Rev. C 88, 031303(R) (2013), 10.1103/PhysRevC.88.031303]. Purpose: Search for the predicted 15Be 3 /2+ state in the three-neutron decay channel. Method: A two-proton removal reaction from a 55 MeV/u 17C beam was used to populate neutron-unbound states in 15Be. The two-, three-, and four-body decay energies of the 12Be + neutron(s) detected in coincidence were reconstructed using invariant mass spectroscopy. Monte Carlo simulations were performed to extract the resonance and decay properties from the observed spectra. Results: The low-energy regions of the decay energy spectra can be described with the first excited unbound state of 14Be (Ex=1.54 MeV, Er=0.28 MeV). Including a state in 15Be that decays through the first excited 14Be state slightly improves the fit at higher energies though the cross section is small. Conclusions: A 15Be component is not needed to describe the data. If the 3 /2+ state in 15Be is populated, the decay by three-neutron emission through 14Be is weak, ≤11 % up to 4 MeV. In the best fit, 15Be is unbound with respect to 12Be by 1.4 MeV (unbound with respect to 14Be by 2.66 MeV) with a strength of 7 % .

Identification of p53 unbound to T-antigen in human cells transformed by simian virus 40 T-antigen.

PubMed

O'Neill, F J; Hu, Y; Chen, T; Carney, H

1997-02-27

In several clones of SV40-transformed human cells, we investigated the relative amounts of large T-Antigen (T-Ag) and p53 proteins, both unbound and associated within complexes, with the goal of identifying changes associated with transformation and immortalization. Cells were transformed by wild type (wt) T-Ag, a functionally temperature sensitive T-Ag (tsA58) and other T-Ag variants. Western analysis showed that while most of the T-Ag was ultimately bound by p53, most of the p53 remained unbound to T-Ag. Unbound p53 remained in the supernatant after a T-Ag immunoprecipitation and p53 was present in two to fourfold excess of T-Ag. In one transformant there was five to tenfold more p53 than T-Ag. p53 was present in transformants in amounts at least 200-fold greater than in untransformed human cells. In wt and variant T-Ag transformants, including those generated with tsA58 T-Ag, large amounts of unbound p53 were present in both pre-crisis and immortal cells and when the cells were grown at permissive or non-permissive temperatures. We also found that in transformants produced by tsA58, an SV40/JCV chimeric T-Ag and other variants, T-Ag appeared to form a complex with p53 slowly perhaps because one or both proteins matured slowly. The presence in transformed human cells of large amounts of unbound p53 and in excess of T-Ag suggests that sequestration of p53 by T-Ag, resulting from complex formation, is required neither for morphological transformation nor immortalization of human cells. Rather, these results support the proposal that high levels of p53, the T-Ag/p53 complexes, or other biochemical event(s), lead to transformation and immortalization of human cells by T-Ag.

Short-term memory binding deficits in Alzheimer's disease.

PubMed

Parra, Mario A; Abrahams, Sharon; Fabi, Katia; Logie, Robert; Luzzi, Simona; Della Sala, Sergio

2009-04-01

Alzheimer's disease impairs long term memories for related events (e.g. faces with names) more than for single events (e.g. list of faces or names). Whether or not this associative or 'binding' deficit is also found in short-term memory has not yet been explored. In two experiments we investigated binding deficits in verbal short-term memory in Alzheimer's disease. Experiment 1: 23 patients with Alzheimer's disease and 23 age and education matched healthy elderly were recruited. Participants studied visual arrays of objects (six for healthy elderly and four for Alzheimer's disease patients), colours (six for healthy elderly and four for Alzheimer's disease patients), unbound objects and colours (three for healthy elderly and two for Alzheimer's disease patients in each of the two categories), or objects bound with colours (three for healthy elderly and two for Alzheimer's disease patients). They were then asked to recall the items verbally. The memory of patients with Alzheimer's disease for objects bound with colours was significantly worse than for single or unbound features whereas healthy elderly's memory for bound and unbound features did not differ. Experiment 2: 21 Alzheimer's disease patients and 20 matched healthy elderly were recruited. Memory load was increased for the healthy elderly group to eight items in the conditions assessing memory for single or unbound features and to four items in the condition assessing memory for the binding of these features. For Alzheimer's disease patients the task remained the same. This manipulation permitted the performance to be equated across groups in the conditions assessing memory for single or unbound features. The impairment in Alzheimer's disease patients in recalling bound objects reported in Experiment 1 was replicated. The binding cost was greater than that observed in the healthy elderly group, who did not differ in their performance for bound and unbound features. Alzheimer's disease grossly impairs the mechanisms responsible for holding integrated objects in verbal short-term memory.

Impact of fraction unbound, CYP3A, and CYP2D6 in vivo activities, and other potential covariates to the clearance of tramadol enantiomers in patients with neuropathic pain.

PubMed

de Moraes, Natália V; Lauretti, Gabriela R; Coelho, Eduardo B; Godoy, Ana Leonor P C; Neves, Daniel V; Lanchote, Vera L

2016-04-01

The pharmacokinetics of tramadol is characterized by a large interindividual variability, which is partially attributed to polymorphic CYP2D6 metabolism. The contribution of CYP3A, CYP2B6, fraction unbound, and other potential covariates remains unknown. This study aimed to investigate the contribution of in vivo activities of cytochrome P450 (CYP) 2D6 and 3A as well as other potential covariates (CYP2B6 genotype to the SNP g.15631G>T, fraction unbound, age, body weight, creatinine clearance) to the enantioselective pharmacokinetics of tramadol. Thirty patients with neuropathic pain and phenotyped as CYP2D6 extensive metabolizers were treated with a single oral dose of 100 mg tramadol. Multiple linear regressions were performed to determine the contribution of CYP activities and other potential covariates to the clearance of tramadol enantiomers. The apparent total clearances were 44.9 (19.1-102-2) L/h and 55.2 (14.8-126.0) L/h for (+)- and (-)-tramadol, respectively [data presented as median (minimum-maximum)]. Between 79 and 83% of the overall variation in apparent clearance of tramadol enantiomers was explained by fraction unbound, CYP2D6, and CYP3A in vivo activities and body weight. Fraction unbound explained 47 and 41% of the variation in clearance of (+)-tramadol and (-)-tramadol, respectively. Individually, CYP2D6 and CYP3A activities were shown to have moderate contribution on clearance of tramadol enantiomers (11-16% and 11-18%, respectively). In conclusion, factors affecting fraction unbound of drugs (such as hyperglycemia or co-administration of drugs highly bound to plasma proteins) should be monitored, because this parameter dominates the elimination of tramadol enantiomers. © 2015 Société Française de Pharmacologie et de Thérapeutique.

Black hole field theory with a firewall in two spacetime dimensions

NASA Astrophysics Data System (ADS)

Ho, C. T. Marco; Su, Daiqin; Mann, Robert B.; Ralph, Timothy C.

2016-10-01

We propose that the vacuum state of a scalar field around a black hole is a modified Unruh vacuum. In (1 +1 ) dimensions, we show that a free-faller close to such an horizon can be modeled as an inertial observer in a modified Minkowski vacuum. The modification allows for information-leaking correlations at high frequencies. Using a Gaussian detector centered at k0, we find that the expectation value of the number operator for a detector crossing the horizon is proportional to 1 /|k0|, implying that the free-faller will observe unbounded numbers of high-energy photons, i.e. a firewall.

A Unified Conformational Selection and Induced Fit Approach to Protein-Peptide Docking

PubMed Central

Trellet, Mikael; Melquiond, Adrien S. J.; Bonvin, Alexandre M. J. J.

2013-01-01

Protein-peptide interactions are vital for the cell. They mediate, inhibit or serve as structural components in nearly 40% of all macromolecular interactions, and are often associated with diseases, making them interesting leads for protein drug design. In recent years, large-scale technologies have enabled exhaustive studies on the peptide recognition preferences for a number of peptide-binding domain families. Yet, the paucity of data regarding their molecular binding mechanisms together with their inherent flexibility makes the structural prediction of protein-peptide interactions very challenging. This leaves flexible docking as one of the few amenable computational techniques to model these complexes. We present here an ensemble, flexible protein-peptide docking protocol that combines conformational selection and induced fit mechanisms. Starting from an ensemble of three peptide conformations (extended, a-helix, polyproline-II), flexible docking with HADDOCK generates 79.4% of high quality models for bound/unbound and 69.4% for unbound/unbound docking when tested against the largest protein-peptide complexes benchmark dataset available to date. Conformational selection at the rigid-body docking stage successfully recovers the most relevant conformation for a given protein-peptide complex and the subsequent flexible refinement further improves the interface by up to 4.5 Å interface RMSD. Cluster-based scoring of the models results in a selection of near-native solutions in the top three for ∼75% of the successfully predicted cases. This unified conformational selection and induced fit approach to protein-peptide docking should open the route to the modeling of challenging systems such as disorder-order transitions taking place upon binding, significantly expanding the applicability limit of biomolecular interaction modeling by docking. PMID:23516555

A unified conformational selection and induced fit approach to protein-peptide docking.

PubMed

Trellet, Mikael; Melquiond, Adrien S J; Bonvin, Alexandre M J J

2013-01-01

Protein-peptide interactions are vital for the cell. They mediate, inhibit or serve as structural components in nearly 40% of all macromolecular interactions, and are often associated with diseases, making them interesting leads for protein drug design. In recent years, large-scale technologies have enabled exhaustive studies on the peptide recognition preferences for a number of peptide-binding domain families. Yet, the paucity of data regarding their molecular binding mechanisms together with their inherent flexibility makes the structural prediction of protein-peptide interactions very challenging. This leaves flexible docking as one of the few amenable computational techniques to model these complexes. We present here an ensemble, flexible protein-peptide docking protocol that combines conformational selection and induced fit mechanisms. Starting from an ensemble of three peptide conformations (extended, a-helix, polyproline-II), flexible docking with HADDOCK generates 79.4% of high quality models for bound/unbound and 69.4% for unbound/unbound docking when tested against the largest protein-peptide complexes benchmark dataset available to date. Conformational selection at the rigid-body docking stage successfully recovers the most relevant conformation for a given protein-peptide complex and the subsequent flexible refinement further improves the interface by up to 4.5 Å interface RMSD. Cluster-based scoring of the models results in a selection of near-native solutions in the top three for ∼75% of the successfully predicted cases. This unified conformational selection and induced fit approach to protein-peptide docking should open the route to the modeling of challenging systems such as disorder-order transitions taking place upon binding, significantly expanding the applicability limit of biomolecular interaction modeling by docking.

Generation Unbound: Drifting into Sex and Parenthood without Marriage

ERIC Educational Resources Information Center

Sawhill, Isabel V.

2014-01-01

Over half of all births to young adults in the United States now occur outside of marriage, and many are unplanned. The result is increased poverty and inequality for children. The left argues for more social support for unmarried parents; the right argues for a return to traditional marriage. In "Generation Unbound," Isabel V. Sawhill…

Semistable extremal ground states for nonlinear evolution equations in unbounded domains

NASA Astrophysics Data System (ADS)

Rodríguez-Bernal, Aníbal; Vidal-López, Alejandro

2008-02-01

In this paper we show that dissipative reaction-diffusion equations in unbounded domains posses extremal semistable ground states equilibria, which bound asymptotically the global dynamics. Uniqueness of such positive ground state and their approximation by extremal equilibria in bounded domains is also studied. The results are then applied to the important case of logistic equations.

Repulsive Effect for Unbound High Energy Particles Along Rotation Axis in Kerr-Taub-NUT Spacetime

NASA Astrophysics Data System (ADS)

Zhang, Lu; Chen, Song-Bai

2018-04-01

We have investigated the acceleration of the unbound high energy particles moving along the rotation axis in the Kerr-Taub-NUT spacetime, and then study the dependence of the repulsive effects on the NUT charge for the particles in the spacetime. Whether the repulsive effects with the NUT charge become stronger depends on the Carter constant, the position and velocity of the particles themselves. We also present numerically the changes of the observable velocity and acceleration with the NUT charge for the unbound particles in the Kerr-Taub-NUT spacetime. Supported by the Scientific Research Fund of Hunan Provincial Education Department under Grant No. 17A124, and the Construct Program of Key Disciplines in Hunan Province

Melanin targeting for intracellular drug delivery: Quantification of bound and free drug in retinal pigment epithelial cells.

PubMed

Rimpelä, Anna-Kaisa; Hagström, Marja; Kidron, Heidi; Urtti, Arto

2018-05-31

Melanin binding affects drug distribution and retention in pigmented ocular tissues, thereby affecting drug response, duration of activity and toxicity. Therefore, it is a promising possibility for drug targeting and controlled release in the pigmented cells and tissues. Intracellular unbound drug concentrations determine pharmacological and toxicological actions, but analyses of unbound vs. total drug concentrations in pigmented cells are lacking. We studied intracellular binding and cellular drug uptake in pigmented retinal pigment epithelial cells and in non-pigmented ARPE-19 cells with five model drugs (chloroquine, propranolol, timolol, diclofenac, methotrexate). The unbound drug fractions in pigmented cells were 0.00016-0.73 and in non-pigmented cells 0.017-1.0. Cellular uptake (i.e. distribution ratio Kp), ranged from 1.3 to 6300 in pigmented cells and from 1.0 to 25 in non-pigmented cells. Values for intracellular bioavailability, F ic , were similar in both cells types (although larger variation in pigmented cells). In vitro melanin binding parameters were used to predict intracellular unbound drug fraction and cell uptake. Comparison of predictions with experimental data indicates that other factors (e.g. ion-trapping, lipophilicity-related binding to other cell components) also play a role. Melanin binding is a major factor that leads to cellular uptake and unbound drug fractions of a range of 3-4 orders of magnitude indicating that large reservoirs of melanin bound drug can be generated in the cells. Understanding melanin binding has important implications on retinal drug targeting, efficacy and toxicity. Copyright © 2017. Published by Elsevier B.V.

Different Formulations of the Orthogonal Array Problem and Their Symmetries

DTIC Science & Technology

2014-06-19

t). Note that OAP(k, s, t, λ) is a polytope not an unbounded polyhedron because it can be embedded inside the hypercube [0, λ]m. Theorem 5. The OAP(k...3.1) is a facet since otherwise OAP(k, s, t, λ) would be an unbounded polyhedron . Then there exists Ny ∈ Rm satisfying all but the 28 facet defining

Weak Compactness and Control Measures in the Space of Unbounded Measures

PubMed Central

Brooks, James K.; Dinculeanu, Nicolae

1972-01-01

We present a synthesis theorem for a family of locally equivalent measures defined on a ring of sets. This theorem is then used to exhibit a control measure for weakly compact sets of unbounded measures. In addition, the existence of a local control measure for locally strongly bounded vector measures is proved by means of the synthesis theorem. PMID:16591980

Analysis of Unbound Aggregate Layer Deformation Behavior from Full Scale Aircraft Gear Loading with Wander

ERIC Educational Resources Information Center

Donovan, Phillip Raymond

2009-01-01

This study focuses on the analysis of the behavior of unbound aggregates to offset wheel loads. Test data from full-scale aircraft gear loading conducted at the National Airport Pavement Test Facility (NAPTF) by the Federal Aviation Administration (FAA) are used to investigate the effects of wander (offset loads) on the deformation behavior of…

Critical behavior in a stochastic model of vector mediated epidemics

NASA Astrophysics Data System (ADS)

Alfinito, E.; Beccaria, M.; Macorini, G.

2016-06-01

The extreme vulnerability of humans to new and old pathogens is constantly highlighted by unbound outbreaks of epidemics. This vulnerability is both direct, producing illness in humans (dengue, malaria), and also indirect, affecting its supplies (bird and swine flu, Pierce disease, and olive quick decline syndrome). In most cases, the pathogens responsible for an illness spread through vectors. In general, disease evolution may be an uncontrollable propagation or a transient outbreak with limited diffusion. This depends on the physiological parameters of hosts and vectors (susceptibility to the illness, virulence, chronicity of the disease, lifetime of the vectors, etc.). In this perspective and with these motivations, we analyzed a stochastic lattice model able to capture the critical behavior of such epidemics over a limited time horizon and with a finite amount of resources. The model exhibits a critical line of transition that separates spreading and non-spreading phases. The critical line is studied with new analytical methods and direct simulations. Critical exponents are found to be the same as those of dynamical percolation.

Critical behavior in a stochastic model of vector mediated epidemics.

PubMed

Alfinito, E; Beccaria, M; Macorini, G

2016-06-06

The extreme vulnerability of humans to new and old pathogens is constantly highlighted by unbound outbreaks of epidemics. This vulnerability is both direct, producing illness in humans (dengue, malaria), and also indirect, affecting its supplies (bird and swine flu, Pierce disease, and olive quick decline syndrome). In most cases, the pathogens responsible for an illness spread through vectors. In general, disease evolution may be an uncontrollable propagation or a transient outbreak with limited diffusion. This depends on the physiological parameters of hosts and vectors (susceptibility to the illness, virulence, chronicity of the disease, lifetime of the vectors, etc.). In this perspective and with these motivations, we analyzed a stochastic lattice model able to capture the critical behavior of such epidemics over a limited time horizon and with a finite amount of resources. The model exhibits a critical line of transition that separates spreading and non-spreading phases. The critical line is studied with new analytical methods and direct simulations. Critical exponents are found to be the same as those of dynamical percolation.

Predicting protein complex geometries with a neural network.

PubMed

Chae, Myong-Ho; Krull, Florian; Lorenzen, Stephan; Knapp, Ernst-Walter

2010-03-01

A major challenge of the protein docking problem is to define scoring functions that can distinguish near-native protein complex geometries from a large number of non-native geometries (decoys) generated with noncomplexed protein structures (unbound docking). In this study, we have constructed a neural network that employs the information from atom-pair distance distributions of a large number of decoys to predict protein complex geometries. We found that docking prediction can be significantly improved using two different types of polar hydrogen atoms. To train the neural network, 2000 near-native decoys of even distance distribution were used for each of the 185 considered protein complexes. The neural network normalizes the information from different protein complexes using an additional protein complex identity input neuron for each complex. The parameters of the neural network were determined such that they mimic a scoring funnel in the neighborhood of the native complex structure. The neural network approach avoids the reference state problem, which occurs in deriving knowledge-based energy functions for scoring. We show that a distance-dependent atom pair potential performs much better than a simple atom-pair contact potential. We have compared the performance of our scoring function with other empirical and knowledge-based scoring functions such as ZDOCK 3.0, ZRANK, ITScore-PP, EMPIRE, and RosettaDock. In spite of the simplicity of the method and its functional form, our neural network-based scoring function achieves a reasonable performance in rigid-body unbound docking of proteins. Proteins 2010. (c) 2009 Wiley-Liss, Inc.

Centromere Size and Its Relationship to Haploid Formation in Plants.

PubMed

Wang, Na; Dawe, R Kelly

2018-03-05

Wide species crosses often result in uniparental genome elimination and visible failures in centromere function. Crosses involving lines with mutated forms of the CENH3 histone variant that organizes the centromere/kinetochore interface have been shown to have similar effects, inducing haploids at high frequencies. Here, we propose a simple centromere size model that endeavors to explain both observations. It is based on the idea of a quantitative centromere architecture where each centromere in an individual is the same size, and the average size is dictated by a natural equilibrium between bound and unbound CENH3 (and its chaperones or binding proteins). While centromere size is determined by the cellular milieu, centromere positions are heritable and defined by the interactions of a small set of proteins that bind to both DNA and CENH3. Lines with defective or mutated CENH3 have a lower loading capacity and support smaller centromeres. In cases where a line with small or defective centromeres is crossed to a line with larger or normal centromeres, the smaller/defective centromeres are selectively degraded or not maintained, resulting in chromosome loss from the small-centromere parent. The model is testable and generalizable, and helps to explain the counterintuitive observation that inducer lines do not induce haploids when crossed to themselves. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

Accelerated testing for studying pavement design and performance (FY 2001) : evaluation of the performance of permeable and semi-permeable unbound granular bases under Portland Cement Concrete Pavement (PCCP) slabs and alternate load transfer devices for

DOT National Transportation Integrated Search

2003-11-01

The objectives of this research are to determine the effect of unbound drainable base types on the performance of PCCP and the efficiency of fiber-reinforced polymer (FRP) dowels, compared to epoxy coated steel dowels, when retrofitted to re-establis...

Unbalanced Nature, Unbounded Bodies, and Unlimited Technology: Ecocriticism and Karen Traviss' Wess'har Series

ERIC Educational Resources Information Center

Sullivan, Heather I.

2010-01-01

While nature is often claimed to be a space of harmonized balance or an antidote to the chaos of the modern world, we need a more grounded assessment of nature as endlessly changing and much less predictable than we like to assume. In this essay, I explore Karen Traviss' provocative exploration of unbalanced nature and unbounded bodies in her…

Altered disposition and effect of lerisetron in rats with elevated alpha 1-acid glycoprotein levels.

PubMed

Jauregizar, N; Calvo, R; Suarez, E; Quintana, A; Raczka, E; Lukas, J C

2001-06-01

To examine the effect of changes in plasma alpha1-acid glycoprotein (AAG) levels on the pharmacokinetics (PK) and pharmacodynamics (PD) of lerisetron, a novel serotonin 5-HT3 receptor antagonist, in the rat. After subcutaneous administration of turpentine oil, AAG was significantly elevated compared with controls. The PK of unchanged lerisetron (UL; high-performance liquid chromatography with radioactivity monitoring) and total lerisetron (TL; unchanged + changed, scintillation counting) was characterized post intravenous (i.v.) 14C lerisetron (50 microg/kg) in control and turpentine oil pretreated rats. The PK (0-180 min) was described by a two-compartmental model. Protein binding of lerisetron in vitro was measured using an ultrafiltration technique. The effect of lerisetron (5 microg/kg, i.v.) over 180 min was measured in anesthetized rats (control and pretreated) with the Bezold-Jarisch reflex (inhibition of bradycardia after 16 microg/kg serotonin i.v.) as the endpoint. PD parameters were estimated by sigmoid Emax models. The unbound fraction was significantly diminished in pretreated rats (mean +/- SEM) (6.60 +/- 1.23% vs. control 14.4 +/- 1.40%, P < 0.05). Volume of distribution (V) and clearance for UL and TL were significantly decreased when compared to the controls (P < 0.0001 for UL and P < 0.05 for TL). Plasma clearance based on unbound concentration for UL did not differ between groups but the unbound V and steady-state unbound V remained decreased (P < 0.05 and P < 0.0001). Pretreated rats showed a significantly diminished drug effect: the area under the E-t curve over 180 min was (mean +/- SEM) 5,189 +/- 657.7 in control animals vs. 3,486 +/- 464.4 in the pretreated group (P < 0.05). The EC50 (concentration at half maximum effect) for UL and TL were increased in pretreated rats and were not compensated when the unbound concentration was used. An increase in AAG causes alterations in the PK and PD of lerisetron, and because this is not compensated with the unbound concentration, we suggest that mechanisms not linked to protein binding may be involved.

Cryptanalysis of Chatterjee-Sarkar Hierarchical Identity-Based Encryption Scheme at PKC 06

NASA Astrophysics Data System (ADS)

Park, Jong Hwan; Lee, Dong Hoon

In 2006, Chatterjee and Sarkar proposed a hierarchical identity-based encryption (HIBE) scheme which can support an unbounded number of identity levels. This property is particularly useful in providing forward secrecy by embedding time components within hierarchical identities. In this paper we show that their scheme does not provide the claimed property. Our analysis shows that if the number of identity levels becomes larger than the value of a fixed public parameter, an unintended receiver can reconstruct a new valid ciphertext and decrypt the ciphertext using his or her own private key. The analysis is similarly applied to a multi-receiver identity-based encryption scheme presented as an application of Chatterjee and Sarkar's HIBE scheme.

BP-Dock: A Flexible Docking Scheme for Exploring Protein–Ligand Interactions Based on Unbound Structures

PubMed Central

Bolia, Ashini; Gerek, Z. Nevin; Ozkan, S. Banu

2016-01-01

Molecular docking serves as an important tool in modeling protein–ligand interactions. However, it is still challenging to incorporate overall receptor flexibility, especially backbone flexibility, in docking due to the large conformational space that needs to be sampled. To overcome this problem, we developed a novel flexible docking approach, BP-Dock (Backbone Perturbation-Dock) that can integrate both backbone and side chain conformational changes induced by ligand binding through a multi-scale approach. In the BP-Dock method, we mimic the nature of binding-induced events as a first-order approximation by perturbing the residues along the protein chain with a small Brownian kick one at a time. The response fluctuation profile of the chain upon these perturbations is computed using the perturbation response scanning method. These response fluctuation profiles are then used to generate binding-induced multiple receptor conformations for ensemble docking. To evaluate the performance of BP-Dock, we applied our approach on a large and diverse data set using unbound structures as receptors. We also compared the BP-Dock results with bound and unbound docking, where overall receptor flexibility was not taken into account. Our results highlight the importance of modeling backbone flexibility in docking for recapitulating the experimental binding affinities, especially when an unbound structure is used. With BP-Dock, we can generate a wide range of binding site conformations realized in nature even in the absence of a ligand that can help us to improve the accuracy of unbound docking. We expect that our fast and efficient flexible docking approach may further aid in our understanding of protein–ligand interactions as well as virtual screening of novel targets for rational drug design. PMID:24380381

Distribution of lacosamide in the rat brain assessed by in vitro slice technique.

PubMed

Gáll, Zsolt; Vancea, Szende

2018-01-01

Lacosamide is a newer anticonvulsant and is the only one that enhances the slow inactivation of voltage gated sodium channels. It is also claimed to have disease-modifying potential, but its pharmacokinetic properties have been much less discussed in the literature. In rats, lacosamide shows restricted distribution to tissues, and the brain-to-plasma partition coefficient (K p ) is only 0.553. In this study, the brain disposition of lacosamide was evaluated in rat brains, and its neuropharmacokinetic parameters (i.e., protein binding and intracellular accumulation) were assessed using in vitro methods. Brain slice experiments and brain homogenate binding studies were performed for several drugs acting on the central nervous system, and drugs were assayed by using a liquid chromatography-mass spectrometry system. By applying a combined approach, it was found that (1) the unbound volume of distribution in the brain for lacosamide (V u,brain  = 1.37) was lower than that of other classical anticonvulsants; (2) the unbound fraction of lacosamide in the brain (0.899) was slightly lower than its unbound fraction in plasma (0.96); (3) the unbound intracellular-to-extracellular concentration ratio of lacosamide was 1.233, meaning that lacosamide was accumulated in the intracellular space because of its physicochemical properties and zwitterionic structure; and (4) the unbound brain-to-plasma concentration ratio of lacosamide was lower than the total brain-to-plasma concentration ratio (K p,uu,brain  = 0.42 vs. K p  = 0.553). In conclusion, the limited brain distribution of lacosamide is not related to its nonspecific protein-binding capacity; rather, an active transport mechanism across the blood-brain barrier may be involved, which reduces the anticonvulsant and/or antiepileptogenic actions of this drug.

Quenching methods for background reduction in luminescence-based probe-target binding assays

DOEpatents

Cai, Hong [Los Alamos, NM; Goodwin, Peter M [Los Alamos, NM; Keller, Richard A [Los Alamos, NM; Nolan, Rhiannon L [Santa Fe, NM

2007-04-10

Background luminescence is reduced from a solution containing unbound luminescent probes, each having a first molecule that attaches to a target molecule and having an attached luminescent moiety, and luminescent probe/target adducts. Quenching capture reagent molecules are formed that are capable of forming an adduct with the unbound luminescent probes and having an attached quencher material effective to quench luminescence of the luminescent moiety. The quencher material of the capture reagent molecules is added to a solution of the luminescent probe/target adducts and binds in a proximity to the luminescent moiety of the unbound luminescent probes to quench luminescence from the luminescent moiety when the luminescent moiety is exposed to exciting illumination. The quencher capture reagent does not bind to probe molecules that are bound to target molecules and the probe/target adduct emission is not quenched.

Study of Structure and Small-Scale Fragmentation in TMC-1

NASA Technical Reports Server (NTRS)

Langer, W. D.; Velusamy, T.; Kuiper, T. B.; Levin, S.; Olsen, E.; Migenes, V.

1995-01-01

Large-scale C(sup 18)O maps show that the Taurus molecular cloud 1 (TMC-1) has numerous cores located along a ridge which extends about 12 minutes by at least 35 minutes. The cores traced by C(sup 18)O are about a few arcminutes (0.1-0.2 pc) in extent, typically contain about 0.5-3 solar mass, and are probably gravitationally bound. We present a detailed study of the small-scale fragmentary structure of one of these cores, called core D, within TMC-1 using very high spectral and spatial resolution maps of CCS and CS. The CCS lines are excellent tracers for investigating the density, temperature, and velocity structure in dense cores. The high spectral resolution, 0.008 km /s, data consist mainly of single-dish, Nyquist-sampled maps of CCS at 22 GHz with 45 sec spatial resolution taken with NASA's 70 m DSN antenna at Goldstone. The high spatial resolution spectral line maps were made with the Very Large Array (9 sec resolution) at 22 GHz and with the OVRO millimeter array in CCS and CS at 93 GHz and 98 GHz, respectively, with 6 sec resolution. These maps are supplemented with single-dish observations of CCS and CC(sup 34)S spectra at 33 GHz using a NASA 34 m DSN antenna, CCS 93 GHz, C(sup 34)S (2-1), and C(sup 18)O (1-0) single-dish observations made with the AT&T Bell Laboratories 7 m antenna. Our high spectral and spatial CCS and CS maps show that core D is highly fragmented. The single-dish CCS observations map out several clumps which range in size from approx. 45 sec to 90 sec (0.03-0.06 pc). These clumps have very narrow intrinsic line widths, 0.11-0.25 km/s, slightly larger than the thermal line width for CCS at 10 K, and masses about 0.03-0.2 solar mass. Interferometer observations of some of these clumps show that they have considerable additional internal structure, consisting of several condensations ranging in size from approx. 10 sec- 30 sec (0.007-0.021 pc), also with narrow line widths. The mass of these smallest fragments is of order 0.01 solar mass. These small-scale structures traced by CCS appear to be gravitationally unbound by a large factor. Most of these objects have masses that fall below those of the putative proto-brown dwarfs (approx. less than 0.1 solar mass). The presence of many small gravitationally unbound clumps suggests that fragmentation mechanisms other than a purely Jeans gravitational instability may be important for the dynamics of these cold dense cores.

Chandrasekhar equations for infinite dimensional systems. Part 2: Unbounded input and output case

NASA Technical Reports Server (NTRS)

Ito, Kazufumi; Powers, Robert K.

1987-01-01

A set of equations known as Chandrasekhar equations arising in the linear quadratic optimal control problem is considered. In this paper, we consider the linear time-invariant system defined in Hilbert spaces involving unbounded input and output operators. For a general class of such systems, the Chandrasekhar equations are derived and the existence, uniqueness, and regularity of the results of their solutions established.

Convergence of the flow of a chemically reacting gaseous mixture to incompressible Euler equations in a unbounded domain

NASA Astrophysics Data System (ADS)

Kwon, Young-Sam

2017-12-01

The flow of chemically reacting gaseous mixture is associated with a variety of phenomena and processes. We study the combined quasineutral and inviscid limit from the flow of chemically reacting gaseous mixture governed by Poisson equation to incompressible Euler equations with the ill-prepared initial data in the unbounded domain R^2× T. Furthermore, the convergence rates are obtained.

Ubiquitin dynamics in complexes reveal molecular recognition mechanisms beyond induced fit and conformational selection.

PubMed

Peters, Jan H; de Groot, Bert L

2012-01-01

Protein-protein interactions play an important role in all biological processes. However, the principles underlying these interactions are only beginning to be understood. Ubiquitin is a small signalling protein that is covalently attached to different proteins to mark them for degradation, regulate transport and other functions. As such, it interacts with and is recognised by a multitude of other proteins. We have conducted molecular dynamics simulations of ubiquitin in complex with 11 different binding partners on a microsecond timescale and compared them with ensembles of unbound ubiquitin to investigate the principles of their interaction and determine the influence of complex formation on the dynamic properties of this protein. Along the main mode of fluctuation of ubiquitin, binding in most cases reduces the conformational space available to ubiquitin to a subspace of that covered by unbound ubiquitin. This behaviour can be well explained using the model of conformational selection. For lower amplitude collective modes, a spectrum of zero to almost complete coverage of bound by unbound ensembles was observed. The significant differences between bound and unbound structures are exclusively situated at the binding interface. Overall, the findings correspond neither to a complete conformational selection nor induced fit scenario. Instead, we introduce a model of conformational restriction, extension and shift, which describes the full range of observed effects.

Metronidazole and hydroxymetronidazole central nervous system distribution: 1. microdialysis assessment of brain extracellular fluid concentrations in patients with acute brain injury.

PubMed

Frasca, Denis; Dahyot-Fizelier, Claire; Adier, Christophe; Mimoz, Olivier; Debaene, Bertrand; Couet, William; Marchand, Sandrine

2014-01-01

The distribution of metronidazole in the central nervous system has only been described based on cerebrospinal fluid data. However, extracellular fluid (ECF) concentrations may better predict its antimicrobial effect and/or side effects. We sought to explore by microdialysis brain ECF metronidazole distribution in patients with acute brain injury. Four brain-injured patients monitored by cerebral microdialysis received 500 mg of metronidazole over 0.5 h every 8 h. Brain dialysates and blood samples were collected at steady state over 8 h. Probe recoveries were evaluated by in vivo retrodialysis in each patient for metronidazole. Metronidazole and OH-metronidazole were assayed by high-pressure liquid chromatography, and a noncompartmental pharmacokinetic analysis was performed. Probe recovery was equal to 78.8% ± 1.3% for metronidazole in patients. Unbound brain metronidazole concentration-time curves were delayed compared to unbound plasma concentration-time curves but with a mean metronidazole unbound brain/plasma AUC0-τ ratio equal to 102% ± 19% (ranging from 87 to 124%). The unbound plasma concentration-time profiles for OH-metronidazole were flat, with mean average steady-state concentrations equal to 4.0 ± 0.7 μg ml(-1). This microdialysis study describes the steady-state brain distribution of metronidazole in patients and confirms its extensive distribution.

Quantum communication complexity advantage implies violation of a Bell inequality

PubMed Central

Buhrman, Harry; Czekaj, Łukasz; Grudka, Andrzej; Horodecki, Michał; Horodecki, Paweł; Markiewicz, Marcin; Speelman, Florian; Strelchuk, Sergii

2016-01-01

We obtain a general connection between a large quantum advantage in communication complexity and Bell nonlocality. We show that given any protocol offering a sufficiently large quantum advantage in communication complexity, there exists a way of obtaining measurement statistics that violate some Bell inequality. Our main tool is port-based teleportation. If the gap between quantum and classical communication complexity can grow arbitrarily large, the ratio of the quantum value to the classical value of the Bell quantity becomes unbounded with the increase in the number of inputs and outputs. PMID:26957600

A fast numerical method for the valuation of American lookback put options

NASA Astrophysics Data System (ADS)

Song, Haiming; Zhang, Qi; Zhang, Ran

2015-10-01

A fast and efficient numerical method is proposed and analyzed for the valuation of American lookback options. American lookback option pricing problem is essentially a two-dimensional unbounded nonlinear parabolic problem. We reformulate it into a two-dimensional parabolic linear complementary problem (LCP) on an unbounded domain. The numeraire transformation and domain truncation technique are employed to convert the two-dimensional unbounded LCP into a one-dimensional bounded one. Furthermore, the variational inequality (VI) form corresponding to the one-dimensional bounded LCP is obtained skillfully by some discussions. The resulting bounded VI is discretized by a finite element method. Meanwhile, the stability of the semi-discrete solution and the symmetric positive definiteness of the full-discrete matrix are established for the bounded VI. The discretized VI related to options is solved by a projection and contraction method. Numerical experiments are conducted to test the performance of the proposed method.

On the definition of the time evolution operator for time-independent Hamiltonians in non-relativistic quantum mechanics

NASA Astrophysics Data System (ADS)

Amaku, Marcos; Coutinho, Francisco A. B.; Masafumi Toyama, F.

2017-09-01

The usual definition of the time evolution operator e-i H t /ℏ=∑n=0∞1/n ! (-i/ℏHt ) n , where H is the Hamiltonian of the system, as given in almost every book on quantum mechanics, causes problems in some situations. The operators that appear in quantum mechanics are either bounded or unbounded. Unbounded operators are not defined for all the vectors (wave functions) of the Hilbert space of the system; when applied to some states, they give a non-normalizable state. Therefore, if H is an unbounded operator, the definition in terms of the power series expansion does not make sense because it may diverge or result in a non-normalizable wave function. In this article, we explain why this is so and suggest, as an alternative, another definition used by mathematicians.

Quantum critical charge response from higher derivatives in holography

NASA Astrophysics Data System (ADS)

Witczak-Krempa, William

2014-04-01

We extend the range of possibilities for the charge response in the quantum critical regime in 2 + 1D using holography, and compare them with field theory and recent quantum Monte Carlo results. We show that a family of (infinitely many) higher derivative terms in the gravitational bulk leads to behavior far richer than what was previously obtained. For example, we prove that the conductivity becomes unbounded, undermining previously obtained constraints. We further find a nontrivial and infinite set of theories that have a self-dual conductivity. Particle-vortex or S duality plays a key role; notably, it maps theories with a finite number of bulk terms to ones with an infinite number. Many properties, such as sum rules and stability conditions, are proven.

Exploring high dimensional free energy landscapes: Temperature accelerated sliced sampling

NASA Astrophysics Data System (ADS)

Awasthi, Shalini; Nair, Nisanth N.

2017-03-01

Biased sampling of collective variables is widely used to accelerate rare events in molecular simulations and to explore free energy surfaces. However, computational efficiency of these methods decreases with increasing number of collective variables, which severely limits the predictive power of the enhanced sampling approaches. Here we propose a method called Temperature Accelerated Sliced Sampling (TASS) that combines temperature accelerated molecular dynamics with umbrella sampling and metadynamics to sample the collective variable space in an efficient manner. The presented method can sample a large number of collective variables and is advantageous for controlled exploration of broad and unbound free energy basins. TASS is also shown to achieve quick free energy convergence and is practically usable with ab initio molecular dynamics techniques.

Unbounded boundaries and shifting baselines: Estuaries and coastal seas in a rapidly changing world

NASA Astrophysics Data System (ADS)

Little, S.; Spencer, K. L.; Schuttelaars, H. M.; Millward, G. E.; Elliott, M.

2017-11-01

This Special Issue of Estuarine, Coastal and Shelf Science presents contributions from ECSA 55; an international symposium organised by the Estuarine and Coastal Sciences Association (ECSA) and Elsevier on the broad theme of estuaries and coastal seas in times of intense change. The objectives of the SI are to synthesise, hypothesise and illustrate the impacts of global change on estuaries and coastal seas through learning lessons from the past, discussing the current and forecasting for the future. It is highlighted here that establishing impacts and assigning cause to the many pressures of global change is and will continue to be a formidable challenge in estuaries and coastal seas, due in part to: (1) their complexity and unbounded nature; (2) difficulties distinguishing between human-induced changes and natural variations and; (3) multiple pressures and effects. The contributing authors have explored a number of these issues over a range of disciplines. The complexity and connectivity of estuaries and coastal seas have been investigated through studies of physicochemical and ecological components, whilst the human imprint on the environment has been identified through a series of predictive, contemporary, historical and palaeo approaches. The impact of human activities has been shown to occur over a range of spatial and temporal scales, requiring the development of integrated management approaches. These 30 articles provide an important contribution to our understanding and assessment of the impacts of global change. The authors highlight methods for essential management/mitigation of the consequences of global change and provide a set of directions, ideas and observations for future work. These include the need to consider: (1) the cumulative, synergistic and antagonistic effects of multiple pressures; (2) the importance of unbounded boundaries and connectivity across the aquatic continuum; (3) the value of combining cross-disciplinary palaeo, contemporary and future modelling studies and; (4) the importance of shifting baselines on ecosystem functioning and the future provision of ecosystem services.

Structure of the exotic 9He nucleus from the no-core shell model with continuum

NASA Astrophysics Data System (ADS)

Vorabbi, Matteo; Calci, Angelo; Navrátil, Petr; Kruse, Michael K. G.; Quaglioni, Sofia; Hupin, Guillaume

2018-03-01

Background: The exotic 9He nucleus, which presents one of the most extreme neutron-to-proton ratios, belongs to the N =7 isotonic chain famous for the phenomenon of ground-state parity inversion with decreasing number of protons. Consequently, it would be expected to have an unnatural (positive) parity ground state similar to 11Be and 10Li. Despite many experimental and theoretical investigations, its structure remains uncertain. Apart from the fact that it is unbound, other properties including the spin and parity of its ground state, and the very existence of additional low-lying resonances are still a matter of debate. Purpose: In this work, we study the properties of 9He by analyzing the n +8He continuum in the context of the ab initio no-core shell model with continuum (NCSMC) formalism with chiral nucleon-nucleon interactions as the only input. Methods: The NCSMC is a state-of-the-art approach for the ab initio description of light nuclei. With its capability to predict properties of bound states, resonances, and scattering states in a unified framework, the method is particularly well suited for the study of unbound nuclei such as 9He. Results: Our analysis produces an unbound 9He nucleus. Two resonant states are found at the energies of ˜1 and ˜3.5 MeV, respectively, above the n +8He breakup threshold. The first state has a spin-parity assignment of Jπ=1/2 - and can be associated with the ground state of 9He, while the second, broader state has a spin parity of 3/2 -. No resonance is found in the 1/2 + channel, only a very weak attraction. Conclusions: We find that the 9He ground-state resonance has a negative parity and thus breaks the parity-inversion mechanism found in the 11Be and 10Li nuclei of the same N =7 isotonic chain.

Unbound Young Stellar Systems: Star Formation on the Loose

NASA Astrophysics Data System (ADS)

Gouliermis, Dimitrios A.

2018-07-01

Unbound young stellar systems, the loose ensembles of physically related young bright stars, trace the typical regions of recent star formation in galaxies. Their morphologies vary from small few pc-size associations of newly formed stars to enormous few kpc-size complexes composed of stars few 100 Myr old. These stellar conglomerations are located within the disks and along the spiral arms and rings of star-forming disk galaxies, and they are the active star-forming centers of dwarf and starburst galaxies. Being associated with star-forming regions of various sizes, these stellar structures trace the regions where stars form at various length- and timescales, from compact clusters to whole galactic disks. Stellar associations, the prototypical unbound young systems, and their larger counterparts, stellar aggregates, and stellar complexes, have been the focus of several studies for quite a few decades, with special interest on their demographics, classification, and structural morphology. The compiled surveys of these loose young stellar systems demonstrate that the clear distinction of these systems into well-defined classes is not as straightforward as for stellar clusters, due to their low densities, asymmetric shapes and variety in structural parameters. These surveys also illustrate that unbound stellar structures follow a clear hierarchical pattern in the clustering of their stars across various scales. Stellar associations are characterized by significant sub-structure with bound stellar clusters being their most compact parts, while associations themselves are the brighter denser parts of larger stellar aggregates and stellar complexes, which are members of larger super-structures up to the scale of a whole star-forming galaxy. This structural pattern, which is usually characterized as self-similar or fractal, appears to be identical to that of star-forming giant molecular clouds and interstellar gas, driven mainly by turbulence cascade. In this short review, I make a concise compilation of our understanding of unbound young stellar systems across various environments in the local universe, as it is developed during the last 60 years. I present a factual assessment of the clustering behavior of star formation, as revealed from the assembling pattern of stars across loose stellar structures and its relation to the interstellar medium and the environmental conditions. I also provide a consistent account of the processes that possibly play important role in the formation of unbound stellar systems, compiled from both theoretical and observational investigations on the field.

Structure of 10 N in 9 C+p resonance scattering

DOE PAGES

Hooker, J.; Rogachev, G. V.; Goldberg, V. Z.; ...

2017-03-17

We studied the structure of exotic nucleus 10N using 9C+p resonance scattering. Two ℓ=0 resonances were found to be the lowest states in 10N. Furthermore, the ground state of 10N is unbound with respect to proton decay by 2.2(2) or 1.9(2) MeV depending on the 2 -or 1 -spin-parity assignment, and the first excited state is unbound by 2.8(2) MeV.

Super-Penrose process due to collisions inside ergosphere

NASA Astrophysics Data System (ADS)

Zaslavskii, O. B.

If two particles collide inside the ergosphere, the energy in the center of mass frame can be made unbound provided at least one of particles has a large negative angular momentum [A. A. Grib and Yu. V. Pavlov, Europhys. Lett. 101 (2013) 20004]. We show that the same condition can give rise to unbounded Killing energy of debris at infinity, i.e. super-Penrose process. Proximity of the point of collision to the black hole horizon is not required.

The Incidence of Sixteenth Century Cosmic Models in Modern Texts

NASA Astrophysics Data System (ADS)

Maene, S. A.; Best, J. S.; Usher, P. D.

1999-12-01

In the sixteenth century, the bounded cosmological models of Copernicus (1543) and Tycho Brahe (1588), and the unbounded model of Thomas Digges (1576), vied with the bounded geocentric model of Ptolemy (c. 140 AD). The work of the philosopher Giordano Bruno in 1584 lent further support to the Digges model. Despite the eventual acceptance of the unbounded universe, analysis of over 100 modern introductory astronomy texts reveals that these early unbounded models are mentioned infrequently. The ratio of mentions of Digges' model to Copernicus' model has the surprisingly low value of R = 0.08. The philosophical speculation of Bruno receives mention more than twice as often (R = 0.17). The expectation that these early unbounded models warrant inclusion in astronomy texts is supported both by modern hindsight and by the literature of the time. In Shakespeare's "Hamlet" of c. 1601, Prince Hamlet suffers from two transformations. According to the cosmic allegorical model, one transformation changes the bounded geocentricism of Ptolemy to the bounded heliocentricism of Copernicus, while the other completes the change to Digges' model of the infinite universe of suns. This interpretation and the modern world view suggest that both transformations should receive equal mention and thus that the ratio R in introductory texts should be close to unity. This work was supported in part by the NASA West Virginia Space Grant Consortium.

Metronidazole and Hydroxymetronidazole Central Nervous System Distribution: 1. Microdialysis Assessment of Brain Extracellular Fluid Concentrations in Patients with Acute Brain Injury

PubMed Central

Frasca, Denis; Dahyot-Fizelier, Claire; Adier, Christophe; Mimoz, Olivier; Debaene, Bertrand; Couet, William

2014-01-01

The distribution of metronidazole in the central nervous system has only been described based on cerebrospinal fluid data. However, extracellular fluid (ECF) concentrations may better predict its antimicrobial effect and/or side effects. We sought to explore by microdialysis brain ECF metronidazole distribution in patients with acute brain injury. Four brain-injured patients monitored by cerebral microdialysis received 500 mg of metronidazole over 0.5 h every 8 h. Brain dialysates and blood samples were collected at steady state over 8 h. Probe recoveries were evaluated by in vivo retrodialysis in each patient for metronidazole. Metronidazole and OH-metronidazole were assayed by high-pressure liquid chromatography, and a noncompartmental pharmacokinetic analysis was performed. Probe recovery was equal to 78.8% ± 1.3% for metronidazole in patients. Unbound brain metronidazole concentration-time curves were delayed compared to unbound plasma concentration-time curves but with a mean metronidazole unbound brain/plasma AUC0–τ ratio equal to 102% ± 19% (ranging from 87 to 124%). The unbound plasma concentration-time profiles for OH-metronidazole were flat, with mean average steady-state concentrations equal to 4.0 ± 0.7 μg ml−1. This microdialysis study describes the steady-state brain distribution of metronidazole in patients and confirms its extensive distribution. PMID:24277041

A multi-layered active target for the study of neutron-unbound nuclides at NSCL

NASA Astrophysics Data System (ADS)

Freeman, Jessica; Gueye, Paul; Redpath, Thomas; MoNA Collaboration

2017-01-01

The characteristics of neutron-unbound nuclides were investigated using a multi-layered Si/Be active target designed for use with the MoNA/LISA setup at the National Superconducting Cyclotron (NSCL). The setup consists of the MoNA/LISA arrays (for neutron detection) and a superconducting sweeper magnet (for charged separation) to identify products following the decay of neutron unbound states. The segmented target consisted of three 700 mg/cm2 beryllium targets and four 0.14 mm thick 62x62 mm2 silicon detectors. As a commissioning experiment for the target the decay of two-neutron unbound 26O populated in a one-proton removal reaction from a radioactive 27F beam was performed. The 27F secondary radioactive beam from the NSCL's Coupled Cyclotron Facility was produced from the fragmentation of a 140 MeV/u 48Ca beam incident on a thick beryllium target and then cleanly selected by the A1900 fragment separator. The energy loss and position spectra of the incoming beam and reaction products were used to calibrate the Silicon detectors to within 1.5% in both energy and position. A dedicated Geant4 model of the target was developed to simulate the energy loss within the target. A description of the experimental setup, simulation work, and energy and position calibration will be presented. DoE/NNSA - DE-NA0000979.

On one-dimensional compressible Navier-Stokes equations for a reacting mixture in unbounded domains

NASA Astrophysics Data System (ADS)

Li, Siran

2017-10-01

In this paper we consider the one-dimensional Navier-Stokes system for a heat-conducting, compressible reacting mixture which describes the dynamic combustion of fluids of mixed kinds on unbounded domains. This model has been discussed on bounded domains by Chen (SIAM J Math Anal 23:609-634, 1992) and Chen-Hoff-Trivisa (Arch Ration Mech Anal 166:321-358, 2003), among others, in which the reaction rate function is a discontinuous function obeying the Arrhenius' law of thermodynamics. We prove the global existence of weak solutions to this model on one-dimensional unbounded domains with large initial data in H^1. Moreover, the large-time behaviour of the weak solution is identified. In particular, the uniform-in-time bounds for the temperature and specific volume have been established via energy estimates. For this purpose we utilise techniques developed by Kazhikhov-Shelukhin (cf. Kazhikhov in Siber Math J 23:44-49, 1982; Solonnikov and Kazhikhov in Annu Rev Fluid Mech 13:79-95, 1981) and refined by Jiang (Commun Math Phys 200:181-193, 1999, Proc R Soc Edinb Sect A 132:627-638, 2002), as well as a crucial estimate in the recent work by Li-Liang (Arch Ration Mech Anal 220:1195-1208, 2016). Several new estimates are also established, in order to treat the unbounded domain and the reacting terms.

Production of insulin-like growth factor binding proteins by small-cell lung cancer cell lines

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

Jaques, G.; Kiefer, P.; Rotsch, M.

1989-10-01

Conditioned serum-free media (CM) from small-cell lung cancer (SCLC) cell lines were examined for the presence of insulin-like growth-factor-binding proteins (IGF-BP). 6/9 SCLC cell lines secreted binding proteins with high affinity for IGFs. When ({sup 125}I)IGF-1 or ({sup 125}I)IGF-II was incubated with the CMs, complexes of tracer with proteins could be demonstrated by gel filtration, by precipitation with polyethylenglycol, and after adsorption of unbound tracer with activated charcoal. Analysis of binding data according to the method of Scatchard resulted in linear plots for IGF-I and IGF-II. Cross-linking of ({sup 125}I)IGF-I or ({sup 125}I)IGF-II to the CMs followed by sodium dodecylmore » sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under nonreducing conditions revealed the presence of IGF-BPs with molecular masses in the range of 24-32 kDa. Northern blot hybridization with an IGF-BP cDNA probe encoding a low-molecular-weight IGF-BP from a human placenta cDNA library and Western blot analysis with a corresponding polyclonal antibody showed no expression of this gene. These data demonstrate that SCLC cell lines release IGF-BPs in culture supernatants, which differ from IGF-BPs detected in liver and placenta. These IGF-BPs might be important mediators in the autocrine/paracrine growth regulation of IGFs in SCLC.« less

From Quantum Fields to Local Von Neumann Algebras

NASA Astrophysics Data System (ADS)

Borchers, H. J.; Yngvason, Jakob

The subject of the paper is an old problem of the general theory of quantized fields: When can the unbounded operators of a Wightman field theory be associated with local algebras of bounded operators in the sense of Haag? The paper reviews and extends previous work on this question, stressing its connections with a noncommutive generalization of the classical Hamburger moment problem. Necessary and sufficient conditions for the existence of a local net of von Neumann algebras corresponding to a given Wightman field are formulated in terms of strengthened versions of the usual positivity property of Wightman functionals. The possibility that the local net has to be defined in an enlarged Hilbert space cannot be ruled out in general. Under additional hypotheses, e.g., if the field operators obey certain energy bounds, such an extension of the Hilbert space is not necessary, however. In these cases a fairly simple condition for the existence of a local net can be given involving the concept of “central positivity” introduced by Powers. The analysis presented here applies to translationally covariant fields with an arbitrary number of components, whereas Lorentz covariance is not needed. The paper contains also a brief discussion of an approach to noncommutative moment problems due to Dubois-Violette, and concludes with some remarks on modular theory for algebras of unbounded operators.

NEUTRINO-DRIVEN WINDS IN THE AFTERMATH OF A NEUTRON STAR MERGER: NUCLEOSYNTHESIS AND ELECTROMAGNETIC TRANSIENTS

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

Martin, D.; Perego, A.; Arcones, A.

2015-11-01

We present a comprehensive nucleosynthesis study of the neutrino-driven wind in the aftermath of a binary neutron star merger. Our focus is the initial remnant phase when a massive central neutron star is present. Using tracers from a recent hydrodynamical simulation, we determine total masses and integrated abundances to characterize the composition of unbound matter. We find that the nucleosynthetic yields depend sensitively on both the life time of the massive neutron star and the polar angle. Matter in excess of up to 9 × 10{sup −3} M{sub ⊙} becomes unbound until ∼200 ms. Due to electron fractions of Y{submore » e} ≈ 0.2–0.4, mainly nuclei with mass numbers A < 130 are synthesized, complementing the yields from the earlier dynamic ejecta. Mixing scenarios with these two types of ejecta can explain the abundance pattern in r-process enriched metal-poor stars. Additionally, we calculate heating rates for the decay of the freshly produced radioactive isotopes. The resulting light curve peaks in the blue band after about 4 hr. Furthermore, high opacities due to heavy r-process nuclei in the dynamic ejecta lead to a second peak in the infrared after 3–4 days.« less

Calculation of Relative Binding Free Energy in the Water-Filled Active Site of Oligopeptide-Binding Protein A.

PubMed

Maurer, Manuela; de Beer, Stephanie B A; Oostenbrink, Chris

2016-04-15

The periplasmic oligopeptide binding protein A (OppA) represents a well-known example of water-mediated protein-ligand interactions. Here, we perform free-energy calculations for three different ligands binding to OppA, using a thermodynamic integration approach. The tripeptide ligands share a high structural similarity (all have the sequence KXK), but their experimentally-determined binding free energies differ remarkably. Thermodynamic cycles were constructed for the ligands, and simulations conducted in the bound and (freely solvated) unbound states. In the unbound state, it was observed that the difference in conformational freedom between alanine and glycine leads to a surprisingly slow convergence, despite their chemical similarity. This could be overcome by increasing the softness parameter during alchemical transformations. Discrepancies remained in the bound state however, when comparing independent simulations of the three ligands. These difficulties could be traced to a slow relaxation of the water network within the active site. Fluctuations in the number of water molecules residing in the binding cavity occur mostly on a timescale larger than the simulation time along the alchemical path. After extensive simulations, relative binding free energies that were converged to within thermal noise could be obtained, which agree well with available experimental data.

Calculation of Relative Binding Free Energy in the Water-Filled Active Site of Oligopeptide-Binding Protein A

PubMed Central

Maurer, Manuela; de Beer, Stephanie B. A.; Oostenbrink, Chris

2018-01-01

The periplasmic oligopeptide binding protein A (OppA) represents a well-known example of water-mediated protein-ligand interactions. Here, we perform free-energy calculations for three different ligands binding to OppA, using a thermodynamic integration approach. The tripeptide ligands share a high structural similarity (all have the sequence KXK), but their experimentally-determined binding free energies differ remarkably. Thermodynamic cycles were constructed for the ligands, and simulations conducted in the bound and (freely solvated) unbound states. In the unbound state, it was observed that the difference in conformational freedom between alanine and glycine leads to a surprisingly slow convergence, despite their chemical similarity. This could be overcome by increasing the softness parameter during alchemical transformations. Discrepancies remained in the bound state however, when comparing independent simulations of the three ligands. These difficulties could be traced to a slow relaxation of the water network within the active site. Fluctuations in the number of water molecules residing in the binding cavity occur mostly on a timescale larger than the simulation time along the alchemical path. After extensive simulations, relative binding free energies that were converged to within thermal noise could be obtained, which agree well with available experimental data. PMID:27092480

Influence of Clinical Status on the Association Between Plasma Total and Unbound Bilirubin and Death or Adverse Neurodevelopmental Outcomes in Extremely Low Birth Weight Infants

PubMed Central

Oh, William; Stevenson, David K.; Tyson, Jon E.; Morris, Brenda H.; Ahlfors, Charles E.; Bender, G. Jesse; Wong, Ronald J.; Perritt, Rebecca; Vohr, Betty R.; Van Meurs, Krista P.; Vreman, Hendrik J.; Das, Abhik; Phelps, Dale L.; O’Shea, T. Michael; Higgins, Rosemary D.

2010-01-01

Objectives To assess the influence of clinical status on the association between total plasma bilirubin and unbound bilirubin on death or adverse neurodevelopmental outcomes at 18–22 months corrected age in extremely low birth weight infants. Method Total plasma biirubin and unbound biirubin were measured in 1,101 extremely low birth weight infants at 5±1 day of age. Clinical criteria were used to classify infants as clinically stable or unstable. Survivors were examined at 18–22 months corrected age by certified examiners. Outcome variables were death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death prior to follow-up. For all outcomes, the interaction between bilirubin variables and clinical status was assessed in logistic regression analyses adjusted for multiple risk factors. Results Regardless of clinical status, an increasing level of unbound bilirubin was associated with higher rates of death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss and death before follow-up. Total plasma bilirubin values were directly associated with death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death before follow-up in unstable infants, but not in stable infants. An inverse association between total plasma bilirubin and death or cerebral palsy was found in stable infants. Conclusions In extremely low birth weight infants, clinical status at 5 days of age affects the association between total plasma and unbound bilirubin and death or adverse neurodevelopmental outcomes at 18–22 months of corrected age. An increasing level of UB is associated a higher risk of death or adverse neurodevelopmental outcomes regardless of clinical status. Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants. PMID:20105142

Effect of racemic ibuprofen dose on the magnitude and duration of platelet cyclo-oxygenase inhibition: relationship between inhibition of thromboxane production and the plasma unbound concentration of S(+)-ibuprofen.

PubMed

Evans, A M; Nation, R L; Sansom, L N; Bochner, F; Somogyi, A A

1991-02-01

1. Four healthy male subjects received racemic ibuprofen (200, 400, 800 and 1200 mg), orally, on four occasions, 2 weeks apart, according to a four-way Latin-square design, in order to investigate the influence of increasing dose of ibuprofen on the magnitude and duration of its antiplatelet effect as well as on the relationship between such effect and drug concentration. 2. The antiplatelet effect of ibuprofen was assessed by measuring the inhibition of platelet thromboxane B2 (TXB2) generation during the controlled clotting of whole blood. The plasma unbound concentration of S(+)-ibuprofen, the enantiomer shown in an in vitro study to be responsible for the inhibitory effect of platelet TXB2 generation, was measured using an enantioselective method. 3. The maximum percentage inhibition of TXB2 generation increased significantly with dose from a mean +/- s.d. of 93.4 +/- 1.2% after the 200 mg dose to 98.8 +/- 0.3% after the 1200 mg dose, and there was an increase with dose in the duration of inhibition of TXB2 generation. The effect of ibuprofen on platelet TXB2 generation was transient and mirrored the time-course of unbound S(+)-ibuprofen in plasma; on all but one of the 16 occasions, serum TXB2 concentrations returned to at least within 10% of the pretreatment concentrations within 24 h of ibuprofen administration. 4. For each subject, the relationship between the percentage inhibition of TXB2 generation and the unbound concentration of S(+)-ibuprofen in plasma was modelled according to a sigmoidal Emax equation. The mean plasma unbound concentration of S(+)-ibuprofen required to inhibit platelet TXB2 generation by 50% (EC50) was 9.8 +/- 1.0 micrograms l-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Green’s Functions for an Anisotropic Medium: Part 1. Unbounded Case

DTIC Science & Technology

1993-12-01

AA 2 - x • , - a or b (41a) td A -2 A-- ’ -L x " " - , -a or b (41b) 13 4. DISCUSSION Having now derived the DGF of the unbounded biaxially...B 2 A3 121/3 b s- - + (_ + )A + [ (_ L_1/ + - (A13) A - 1 (3q - b) (Al4a) (3q B - -L (-2b 3 + 9bq + 27r) (Al4b) q - Ac - 4d (Al5a) r - - Ad 2 + 4bd - C

Polyhedral sweeping processes with unbounded nonconvex-valued perturbation

NASA Astrophysics Data System (ADS)

Tolstonogov, A. A.

2017-12-01

A polyhedral sweeping process with a multivalued perturbation whose values are nonconvex unbounded sets is studied in a separable Hilbert space. Polyhedral sweeping processes do not satisfy the traditional assumptions used to prove existence theorems for convex sweeping processes. We consider the polyhedral sweeping process as an evolution inclusion with subdifferential operators depending on time. The widely used assumption of Lipschitz continuity for the multivalued perturbation term is replaced by a weaker notion of (ρ - H) Lipschitzness. The existence of solutions is proved for this sweeping process.

Sound-absorbing slabs and structures based on granular materials (bound and unbound). [energy absorbing efficiency of porous material

NASA Technical Reports Server (NTRS)

Petre-Lazar, S.; Popeea, G.

1974-01-01

Sound absorbing slabs and structures made up of bound or unbound granular materials are considered and how to manufacture these elements at the building site. The raw material is a single grain powder (sand, expanded blast furnace slag, etc.) that imparts to the end products an apparent porosity of 25-45% and an energy dissipation within the structure leading to absorption coefficients that can be compared with those of mineral wool and urethane.

Localized basis sets for unbound electrons in nanoelectronics.

PubMed

Soriano, D; Jacob, D; Palacios, J J

2008-02-21

It is shown how unbound electron wave functions can be expanded in a suitably chosen localized basis sets for any desired range of energies. In particular, we focus on the use of Gaussian basis sets, commonly used in first-principles codes. The possible usefulness of these basis sets in a first-principles description of field emission or scanning tunneling microscopy at large bias is illustrated by studying a simpler related phenomenon: The lifetime of an electron in a H atom subjected to a strong electric field.

Critical behavior in a stochastic model of vector mediated epidemics

PubMed Central

Alfinito, E.; Beccaria, M.; Macorini, G.

2016-01-01

The extreme vulnerability of humans to new and old pathogens is constantly highlighted by unbound outbreaks of epidemics. This vulnerability is both direct, producing illness in humans (dengue, malaria), and also indirect, affecting its supplies (bird and swine flu, Pierce disease, and olive quick decline syndrome). In most cases, the pathogens responsible for an illness spread through vectors. In general, disease evolution may be an uncontrollable propagation or a transient outbreak with limited diffusion. This depends on the physiological parameters of hosts and vectors (susceptibility to the illness, virulence, chronicity of the disease, lifetime of the vectors, etc.). In this perspective and with these motivations, we analyzed a stochastic lattice model able to capture the critical behavior of such epidemics over a limited time horizon and with a finite amount of resources. The model exhibits a critical line of transition that separates spreading and non-spreading phases. The critical line is studied with new analytical methods and direct simulations. Critical exponents are found to be the same as those of dynamical percolation. PMID:27264105

Mass of the H Dibaryon

NASA Astrophysics Data System (ADS)

Shanahan, P. E.; Thomas, A. W.; Young, R. D.

2011-08-01

Recent lattice QCD calculations have reported evidence for the existence of a bound state with strangeness -2 and baryon number 2 at quark masses somewhat higher than the physical values. By developing a description of the dependence of this binding energy on the up, down and strange quark masses that allows a controlled chiral extrapolation, we explore the hypothesis that this state is to be identified with the H dibaryon. Taking as input the recent results of the HAL and NPLQCD Collaborations, we show that the H dibaryon is likely to be unbound by 13±14MeV at the physical point.

Diphytanyl glycerol ether distributions in sediments of the Orca Basin

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

Pease, T.K.; VanVleet, E.S.; Barre, J.S.

1992-09-01

Archaebacterially produced diphytanyl glycerol ether (DPGE) was examined in core sediments from the Orca Basin, an anoxic hypersaline basin in the northwestern Gulf of Mexico, to observe its spatial variability and potential origin. A differential extraction protocol was employed to quantify the isopranyl glycerol ethers associated with unbound, intermediate-bound, and kerogen-bound lipid fractions. Archaebacterial lipids were evident at all depths for the unbound and intermediate-bound fractions. Concentrations of DPGE ranged from 0.51 to 2.91 [mu]g/g dry sediment at the surface and showed secondary maxima deeper in basin sediments. Intermediate-bound DPGE concentrations exhibited an inverse relationship to unbound DPGE concentrations. Kerogen-boundmore » DPGE concentrations were normally below detection limits. Earlier studies describing the general homogeneity of lipid components within the overlying brine and at the brine/seawater interface suggest that the large-scale sedimentary DPGE variations observed in this study result from spatial and temporal variations in in-situ production by methanogenic or extremely halophilic archaebacteria.« less

Uptake and metabolism of cisplatin by rat kidney.

PubMed

Safirstein, R; Miller, P; Guttenplan, J B

1984-05-01

Cisplatin, an effective antineoplastic agent, is toxic to the kidney. Since the kidney's vulnerability to cisplatin may originate in its ability to accumulate and retain platinum to a greater degree than other organs, we studied the characteristics of the renal accumulation of platinum and investigated the nature of intracellular platinum. Cisplatin and ethylenediamminedichloroplatinum, nephrotoxic and antineoplastic liganded platinum compounds, were concentrated in rat renal cortical slices fivefold above medium concentration. Platinum uptake was energy- and temperature-dependent and could be inhibited by drugs which inhibit base transport. The organic anions para-aminohippurate and pyrazinoate did not reduce renal slice platinum uptake. Unbound platinum in the blood and urine was predominantly cisplatin but unbound platinum in kidney cytosol was not. This latter compound, in contrast to cisplatin, was not active as a mutagen. These studies suggest that the kidney accumulates platinum in part by transport or specific binding to the base transport system in the kidney and biotransforms it intracellularly. Unbound platinum in the cell is not cisplatin and may no longer be toxic.

Realistic noise-tolerant randomness amplification using finite number of devices.

PubMed

Brandão, Fernando G S L; Ramanathan, Ravishankar; Grudka, Andrzej; Horodecki, Karol; Horodecki, Michał; Horodecki, Paweł; Szarek, Tomasz; Wojewódka, Hanna

2016-04-21

Randomness is a fundamental concept, with implications from security of modern data systems, to fundamental laws of nature and even the philosophy of science. Randomness is called certified if it describes events that cannot be pre-determined by an external adversary. It is known that weak certified randomness can be amplified to nearly ideal randomness using quantum-mechanical systems. However, so far, it was unclear whether randomness amplification is a realistic task, as the existing proposals either do not tolerate noise or require an unbounded number of different devices. Here we provide an error-tolerant protocol using a finite number of devices for amplifying arbitrary weak randomness into nearly perfect random bits, which are secure against a no-signalling adversary. The correctness of the protocol is assessed by violating a Bell inequality, with the degree of violation determining the noise tolerance threshold. An experimental realization of the protocol is within reach of current technology.

Realistic noise-tolerant randomness amplification using finite number of devices

NASA Astrophysics Data System (ADS)

Brandão, Fernando G. S. L.; Ramanathan, Ravishankar; Grudka, Andrzej; Horodecki, Karol; Horodecki, Michał; Horodecki, Paweł; Szarek, Tomasz; Wojewódka, Hanna

2016-04-01

Randomness is a fundamental concept, with implications from security of modern data systems, to fundamental laws of nature and even the philosophy of science. Randomness is called certified if it describes events that cannot be pre-determined by an external adversary. It is known that weak certified randomness can be amplified to nearly ideal randomness using quantum-mechanical systems. However, so far, it was unclear whether randomness amplification is a realistic task, as the existing proposals either do not tolerate noise or require an unbounded number of different devices. Here we provide an error-tolerant protocol using a finite number of devices for amplifying arbitrary weak randomness into nearly perfect random bits, which are secure against a no-signalling adversary. The correctness of the protocol is assessed by violating a Bell inequality, with the degree of violation determining the noise tolerance threshold. An experimental realization of the protocol is within reach of current technology.

Realistic noise-tolerant randomness amplification using finite number of devices

PubMed Central

Brandão, Fernando G. S. L.; Ramanathan, Ravishankar; Grudka, Andrzej; Horodecki, Karol; Horodecki, Michał; Horodecki, Paweł; Szarek, Tomasz; Wojewódka, Hanna

2016-01-01

Randomness is a fundamental concept, with implications from security of modern data systems, to fundamental laws of nature and even the philosophy of science. Randomness is called certified if it describes events that cannot be pre-determined by an external adversary. It is known that weak certified randomness can be amplified to nearly ideal randomness using quantum-mechanical systems. However, so far, it was unclear whether randomness amplification is a realistic task, as the existing proposals either do not tolerate noise or require an unbounded number of different devices. Here we provide an error-tolerant protocol using a finite number of devices for amplifying arbitrary weak randomness into nearly perfect random bits, which are secure against a no-signalling adversary. The correctness of the protocol is assessed by violating a Bell inequality, with the degree of violation determining the noise tolerance threshold. An experimental realization of the protocol is within reach of current technology. PMID:27098302

Conformational Heterogeneity of Unbound Proteins Enhances Recognition in Protein-Protein Encounters.

PubMed

Pallara, Chiara; Rueda, Manuel; Abagyan, Ruben; Fernández-Recio, Juan

2016-07-12

To understand cellular processes at the molecular level we need to improve our knowledge of protein-protein interactions, from a structural, mechanistic, and energetic point of view. Current theoretical studies and computational docking simulations show that protein dynamics plays a key role in protein association and support the need for including protein flexibility in modeling protein interactions. Assuming the conformational selection binding mechanism, in which the unbound state can sample bound conformers, one possible strategy to include flexibility in docking predictions would be the use of conformational ensembles originated from unbound protein structures. Here we present an exhaustive computational study about the use of precomputed unbound ensembles in the context of protein docking, performed on a set of 124 cases of the Protein-Protein Docking Benchmark 3.0. Conformational ensembles were generated by conformational optimization and refinement with MODELLER and by short molecular dynamics trajectories with AMBER. We identified those conformers providing optimal binding and investigated the role of protein conformational heterogeneity in protein-protein recognition. Our results show that a restricted conformational refinement can generate conformers with better binding properties and improve docking encounters in medium-flexible cases. For more flexible cases, a more extended conformational sampling based on Normal Mode Analysis was proven helpful. We found that successful conformers provide better energetic complementarity to the docking partners, which is compatible with recent views of binding association. In addition to the mechanistic considerations, these findings could be exploited for practical docking predictions of improved efficiency.

Approximate Model Checking of PCTL Involving Unbounded Path Properties

NASA Astrophysics Data System (ADS)

Basu, Samik; Ghosh, Arka P.; He, Ru

We study the problem of applying statistical methods for approximate model checking of probabilistic systems against properties encoded as PCTL formulas. Such approximate methods have been proposed primarily to deal with state-space explosion that makes the exact model checking by numerical methods practically infeasible for large systems. However, the existing statistical methods either consider a restricted subset of PCTL, specifically, the subset that can only express bounded until properties; or rely on user-specified finite bound on the sample path length. We propose a new method that does not have such restrictions and can be effectively used to reason about unbounded until properties. We approximate probabilistic characteristics of an unbounded until property by that of a bounded until property for a suitably chosen value of the bound. In essence, our method is a two-phase process: (a) the first phase is concerned with identifying the bound k 0; (b) the second phase computes the probability of satisfying the k 0-bounded until property as an estimate for the probability of satisfying the corresponding unbounded until property. In both phases, it is sufficient to verify bounded until properties which can be effectively done using existing statistical techniques. We prove the correctness of our technique and present its prototype implementations. We empirically show the practical applicability of our method by considering different case studies including a simple infinite-state model, and large finite-state models such as IPv4 zeroconf protocol and dining philosopher protocol modeled as Discrete Time Markov chains.

Severe valproic acid intoxication: case study on the unbound fraction and the applicability of extracorporeal elimination.

PubMed

van den Broek, Marcel P H; Sikma, Maaike A; Ververs, Tessa F; Meulenbelt, Jan

2009-12-01

Among anticonvulsants, valproic acid (VPA) is cited as the most frequent cause of unintentional and intentional intoxications. Symptoms of VPA intoxication are diverse and are related to VPA plasma concentration. Although total plasma concentrations of less than 450 mg/l produce limited toxicity, severe intoxications (>850 mg/l) can induce coma and are ultimately life threatening. A 32-year-old comatose woman was admitted to the ICU at our hospital; she suffered from hypotension, respiratory depression, hypoglycaemia, sinus bradycardia, hyperammonaemia, metabolic acidosis, and her core body temperature was 33.7 degrees C. The total VPA plasma concentration was 1244 mg/l with an increased unbound fraction of 85%. After we administered multiple doses of activated charcoal, she underwent continuous veno-venous haemofiltration to reduce the plasma VPA concentration. As the total concentration decreased, the unbound fraction also decreased. Within 20 h of admission, the patient made a full recovery. In cases of VPA intoxication, protein-binding saturation and drug characteristics render extracorporeal elimination, an effective technique for eliminating the unbound drug. Its application should be considered, depending on clinical symptoms, VPA concentration (>300 mg/l), albumin concentration and ammonia concentration (>400 micromol/l). The application of this technique should be weighed against its risks. This case illustrates the clinical significance of applying continuous veno-venous haemofiltration in VPA intoxication because of protein-binding saturation, and suggests when extracorporeal elimination should be considered.

Numerical simulation of high Reynolds number bubble motion

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

McLaughlin, J.B.

This paper presents the results of numerical simulations of bubble motion. All the results are for single bubbles in unbounded fluids. The liquid phase is quiescent except for the motion created by the bubble, which is axisymmetric. The main focus of the paper is on bubbles that are of order 1 mm in diameter in water. Of particular interest is the effect of surfactant molecules on bubble motion. Results for the {open_quotes}insoluble surfactant{close_quotes} model will be presented. These results extend research by other investigators to finite Reynolds numbers. The results indicate that, by assuming complete coverage of the bubble surface,more » one obtains good agreement with experimental observations of bubble motion in tap water. The effect of surfactant concentration on the separation angle is discussed.« less

The Resolved Stellar Populations in the LEGUS Galaxies1

NASA Astrophysics Data System (ADS)

Sabbi, E.; Calzetti, D.; Ubeda, L.; Adamo, A.; Cignoni, M.; Thilker, D.; Aloisi, A.; Elmegreen, B. G.; Elmegreen, D. M.; Gouliermis, D. A.; Grebel, E. K.; Messa, M.; Smith, L. J.; Tosi, M.; Dolphin, A.; Andrews, J. E.; Ashworth, G.; Bright, S. N.; Brown, T. M.; Chandar, R.; Christian, C.; Clayton, G. C.; Cook, D. O.; Dale, D. A.; de Mink, S. E.; Dobbs, C.; Evans, A. S.; Fumagalli, M.; Gallagher, J. S., III; Grasha, K.; Herrero, A.; Hunter, D. A.; Johnson, K. E.; Kahre, L.; Kennicutt, R. C.; Kim, H.; Krumholz, M. R.; Lee, J. C.; Lennon, D.; Martin, C.; Nair, P.; Nota, A.; Östlin, G.; Pellerin, A.; Prieto, J.; Regan, M. W.; Ryon, J. E.; Sacchi, E.; Schaerer, D.; Schiminovich, D.; Shabani, F.; Van Dyk, S. D.; Walterbos, R.; Whitmore, B. C.; Wofford, A.

2018-03-01

The Legacy ExtraGalactic UV Survey (LEGUS) is a multiwavelength Cycle 21 Treasury program on the Hubble Space Telescope. It studied 50 nearby star-forming galaxies in 5 bands from the near-UV to the I-band, combining new Wide Field Camera 3 observations with archival Advanced Camera for Surveys data. LEGUS was designed to investigate how star formation occurs and develops on both small and large scales, and how it relates to the galactic environments. In this paper we present the photometric catalogs for all the apparently single stars identified in the 50 LEGUS galaxies. Photometric catalogs and mosaicked images for all filters are available for download. We present optical and near-UV color–magnitude diagrams for all the galaxies. For each galaxy we derived the distance from the tip of the red giant branch. We then used the NUV color–magnitude diagrams to identify stars more massive than 14 M ⊙, and compared their number with the number of massive stars expected from the GALEX FUV luminosity. Our analysis shows that the fraction of massive stars forming in star clusters and stellar associations is about constant with the star formation rate. This lack of a relation suggests that the timescale for evaporation of unbound structures is comparable or longer than 10 Myr. At low star formation rates this translates to an excess of mass in clustered environments as compared to model predictions of cluster evolution, suggesting that a significant fraction of stars form in unbound systems. Based on observations with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by AURA Inc., under NASA contract NAS 5-26555.

A fast immersed boundary method for external incompressible viscous flows using lattice Green's functions

NASA Astrophysics Data System (ADS)

Liska, Sebastian; Colonius, Tim

2017-02-01

A new parallel, computationally efficient immersed boundary method for solving three-dimensional, viscous, incompressible flows on unbounded domains is presented. Immersed surfaces with prescribed motions are generated using the interpolation and regularization operators obtained from the discrete delta function approach of the original (Peskin's) immersed boundary method. Unlike Peskin's method, boundary forces are regarded as Lagrange multipliers that are used to satisfy the no-slip condition. The incompressible Navier-Stokes equations are discretized on an unbounded staggered Cartesian grid and are solved in a finite number of operations using lattice Green's function techniques. These techniques are used to automatically enforce the natural free-space boundary conditions and to implement a novel block-wise adaptive grid that significantly reduces the run-time cost of solutions by limiting operations to grid cells in the immediate vicinity and near-wake region of the immersed surface. These techniques also enable the construction of practical discrete viscous integrating factors that are used in combination with specialized half-explicit Runge-Kutta schemes to accurately and efficiently solve the differential algebraic equations describing the discrete momentum equation, incompressibility constraint, and no-slip constraint. Linear systems of equations resulting from the time integration scheme are efficiently solved using an approximation-free nested projection technique. The algebraic properties of the discrete operators are used to reduce projection steps to simple discrete elliptic problems, e.g. discrete Poisson problems, that are compatible with recent parallel fast multipole methods for difference equations. Numerical experiments on low-aspect-ratio flat plates and spheres at Reynolds numbers up to 3700 are used to verify the accuracy and physical fidelity of the formulation.

Dynamics of proteins aggregation. I. Universal scaling in unbounded media

NASA Astrophysics Data System (ADS)

Zheng, Size; Javidpour, Leili; Shing, Katherine S.; Sahimi, Muhammad

2016-10-01

It is well understood that in some cases proteins do not fold correctly and, depending on their environment, even properly-folded proteins change their conformation spontaneously, taking on a misfolded state that leads to protein aggregation and formation of large aggregates. An important factor that contributes to the aggregation is the interactions between the misfolded proteins. Depending on the aggregation environment, the aggregates may take on various shapes forming larger structures, such as protein plaques that are often toxic. Their deposition in tissues is a major contributing factor to many neuro-degenerative diseases, such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and prion. This paper represents the first part in a series devoted to molecular simulation of protein aggregation. We use the PRIME, a meso-scale model of proteins, together with extensive discontinuous molecular dynamics simulation to study the aggregation process in an unbounded fluid system, as the first step toward MD simulation of the same phenomenon in crowded cellular environments. Various properties of the aggregates have been computed, including dynamic evolution of aggregate-size distribution, mean aggregate size, number of peptides that contribute to the formation of β sheets, number of various types of hydrogen bonds formed in the system, radius of gyration of the aggregates, and the aggregates' diffusivity. We show that many of such quantities follow dynamic scaling, similar to those for aggregation of colloidal clusters. In particular, at long times the mean aggregate size S(t) grows with time as, S(t) ˜ tz, where z is the dynamic exponent. To our knowledge, this is the first time that the qualitative similarity between aggregation of proteins and colloidal aggregates has been pointed out.

Climate Change Impacts on Transportation; Groundwater Elevation, Road Performance, and Robust Adaptation

NASA Astrophysics Data System (ADS)

Kirshen, P. H.; Knott, J. F.; Ray, P.; Elshaer, M.; Daniel, J.; Jacobs, J. M.

2016-12-01

Transportation climate change vulnerability and adaptation studies have primarily focused on surface-water flooding from sea-level rise (SLR); little attention has been given to the effects of climate change and SLR on groundwater and subsequent impacts on the unbound foundation layers of coastal-road infrastructure. The magnitude of service-life reduction depends on the height of the groundwater in the unbound pavement materials, the pavement structure itself, and the loading. Using a steady-state groundwater model, and a multi-layer elastic pavement evaluation model, the strain changes in the layers can be determined as a function of parameter values and the strain changes translated into failure as measured by number of loading cycles to failure. For a section of a major coastal road in New Hampshire, future changes in sea-level, precipitation, temperature, land use, and groundwater pumping are characterized by deep uncertainty. Parameters that describe the groundwater system such as hydraulic conductivity can be probabilistically described while road characteristics are assumed to be deterministic. To understand the vulnerability of this road section, a bottom-up planning approach was employed over time where the combinations of parameter values that cause failure were determined and their plausibility of their occurring was analyzed. To design a robust adaptation strategy that will function reasonably well in the present and the future given the large number of uncertain parameter values, performance of adaptation options were investigated. Adaptation strategies that were considered include raising the road, load restrictions, increasing pavement layer thicknesses, replacing moisture-sensitive materials with materials that are not moisture sensitive, improving drainage systems, and treatment of the underlying materials.

Exact Solution to Stationary Onset of Convection Due to Surface Tension Variation in a Multicomponent Fluid Layer With Interfacial Deformation

NASA Technical Reports Server (NTRS)

Skarda, J. Raymond Lee; McCaughan, Frances E.

1998-01-01

Stationary onset of convection due to surface tension variation in an unbounded multicomponent fluid layer is considered. Surface deformation is included and general flux boundary conditions are imposed on the stratifying agencies (temperature/composition) disturbance equations. Exact solutions are obtained to the general N-component problem for both finite and infinitesimal wavenumbers. Long wavelength instability may coexist with a finite wavelength instability for certain sets of parameter values, often referred to as frontier points. For an impermeable/insulated upper boundary and a permeable/conductive lower boundary, frontier boundaries are computed in the space of Bond number, Bo, versus Crispation number, Cr, over the range 5 x 10(exp -7) less than or equal to Bo less than or equal to 1. The loci of frontier points in (Bo, Cr) space for different values of N, diffusivity ratios, and, Marangoni numbers, collapsed to a single curve in (Bo, D(dimensional variable)Cr) space, where D(dimensional variable) is a Marangoni number weighted diffusivity ratio.

HIV envelope glycoprotein imaged at high resolution | Center for Cancer Research

Cancer.gov

The outer surface of the human immunodeficiency virus (HIV) is surrounded by an envelope studded with spike-shaped glycoproteins called Env that help the deadly virus identify, bind, and infect cells. When unbound, Env exists in a “closed” conformational state. Upon binding with target cells, such as CD4+ T cells, the protein transitions to an “open” configuration. Given that Env is the only viral protein expressed on HIV’s surface, knowing its detailed structure—especially in the unbound state—may be critical for designing antibodies and vaccines against HIV.

Euclidean supergravity

NASA Astrophysics Data System (ADS)

de Wit, Bernard; Reys, Valentin

2017-12-01

Supergravity with eight supercharges in a four-dimensional Euclidean space is constructed at the full non-linear level by performing an off-shell time-like reduction of five-dimensional supergravity. The resulting four-dimensional theory is realized off-shell with the Weyl, vector and tensor supermultiplets and a corresponding multiplet calculus. Hypermultiplets are included as well, but they are themselves only realized with on-shell supersymmetry. We also briefly discuss the non-linear supermultiplet. The off-shell reduction leads to a full understanding of the Euclidean theory. A complete multiplet calculus is presented along the lines of the Minkowskian theory. Unlike in Minkowski space, chiral and anti-chiral multiplets are real and supersymmetric actions are generally unbounded from below. Precisely as in the Minkowski case, where one has different formulations of Poincaré supergravity upon introducing different compensating supermultiplets, one can also obtain different versions of Euclidean supergravity.

Probing Extragalactic Planets Using Quasar Microlensing

NASA Astrophysics Data System (ADS)

Dai, Xinyu; Guerras, Eduardo

2018-02-01

Previously, planets have been detected only in the Milky Way galaxy. Here, we show that quasar microlensing provides a means to probe extragalactic planets in the lens galaxy, by studying the microlensing properties of emission close to the event horizon of the supermassive black hole of the background quasar, using the current generation telescopes. We show that a population of unbound planets between stars with masses ranging from Moon to Jupiter masses is needed to explain the frequent Fe Kα line energy shifts observed in the gravitationally lensed quasar RXJ 1131–1231 at a lens redshift of z = 0.295 or 3.8 billion lt-yr away. We constrain the planet mass-fraction to be larger than 0.0001 of the halo mass, which is equivalent to 2000 objects ranging from Moon to Jupiter mass per main-sequence star.

Development of a hydrological model for simulation of runoff from catchments unbounded by ridge lines

NASA Astrophysics Data System (ADS)

Vema, Vamsikrishna; Sudheer, K. P.; Chaubey, I.

2017-08-01

Watershed hydrological models are effective tools for simulating the hydrological processes in the watershed. Although there are a plethora of hydrological models, none of them can be directly applied to make water conservation decisions in irregularly bounded areas that do not confirm to topographically defined ridge lines. This study proposes a novel hydrological model that can be directly applied to any catchment, with or without ridge line boundaries. The model is based on the water balance concept, and a linear function concept to approximate the cross-boundary flow from upstream areas to the administrative catchment under consideration. The developed model is tested in 2 watersheds - Riesel Experimental Watershed and a sub-basin of Cedar Creek Watershed in Texas, USA. Hypothetical administrative catchments that did not confirm to the location of ridge lines were considered for verifying the efficacy of the model for hydrologic simulations. The linear function concept used to account the cross boundary flow was based on the hypothesis that the flow coming from outside the boundary to administrative area was proportional to the flow generated in the boundary grid cell. The model performance was satisfactory with an NSE and r2 of ≥0.80 and a PBIAS of <25 in all the cases. The simulated hydrographs for the administrative catchments of the watersheds were in good agreement with the observed hydrographs, indicating a satisfactory performance of the model in the administratively bounded areas.

Stellar dynamics in E+E pairs of galaxies. 2: Simulations and interpretation

NASA Astrophysics Data System (ADS)

Combes, F.; Rampazzo, R.; Bonfanti, P. P.; Prugniel, P.; Sulentic, J. W.

1995-05-01

We have presented in a companion article a kinematic study of three E+E galaxy pairs, NGC741/742, 1587/1588 (CPG 99) and 2672/2673 (CPG 175). We find some evidence for perturbed velocity dispersion profiles. These perturbation features are now reported for 14 galaxies in the literature. They occur, or require observations for detection, at large radii where the S/N in the data is low. While observations of individual galaxies are sometimes uncertain, the large number of objects where such features are suspected gives confidence that they are real. These perturbations can be attributed to projection effects contamination along the line of sight, or directly to the tidal interaction. We report the results of several self-gravitating simulations of unbound pairs in an effort to better understand these perturbations another generic features of close E+E pairs reported in the literature. The models frequently show off-center envelopes created by the asymmetry of tidal forces during interpenetrating encounters. The envelopes last for a few 108 yrs, which explains the frequency of such features in observed pairs. This phenomenon is stronger in the self-gravitating simulations than in the MTBA runs. U-shaped (and an equal number of inverse U shaped velocity profiles are seen in the simulations, a result of ablation in the outer envelopes. Simulations including inner galaxy rotation also preserve this feature, irrespective of the spin vector direction in each galaxy. U-shape velocity structure is found to be a robust indicator of the ongoing interaction. All simulations show evidence for enhanced velocity dispersion between the galaxies even in the case of simple superposition of two non interacting objects. We therefore conclude that this cannot be considered an unambiguous indicator of the interaction.

Bridging Enzymatic Structure Function via Mechanics: A Coarse-Grain Approach.

PubMed

Sacquin-Mora, S

2016-01-01

Flexibility is a central aspect of protein function, and ligand binding in enzymes involves a wide range of structural changes, ranging from large-scale domain movements to small loop or side-chain rearrangements. In order to understand how the mechanical properties of enzymes, and the mechanical variations that are induced by ligand binding, relate to enzymatic activity, we carried out coarse-grain Brownian dynamics simulations on a set of enzymes whose structures in the unbound and ligand-bound forms are available in the Protein Data Bank. Our results show that enzymes are remarkably heterogeneous objects from a mechanical point of view and that the local rigidity of individual residues is tightly connected to their part in the protein's overall structure and function. The systematic comparison of the rigidity of enzymes in their unbound and bound forms highlights the fact that small conformational changes can induce large mechanical effects, leading to either more or less flexibility depending on the enzyme's architecture and the location of its ligand-biding site. These mechanical variations target a limited number of specific residues that occupy key locations for enzymatic activity, and our approach thus offers a mean to detect perturbation-sensitive sites in enzymes, where the addition or removal of a few interactions will lead to important changes in the proteins internal dynamics. © 2016 Elsevier Inc. All rights reserved.

Structural deformation upon protein-protein interaction: A structural alphabet approach

PubMed Central

Martin, Juliette; Regad, Leslie; Lecornet, Hélène; Camproux, Anne-Claude

2008-01-01

Background In a number of protein-protein complexes, the 3D structures of bound and unbound partners significantly differ, supporting the induced fit hypothesis for protein-protein binding. Results In this study, we explore the induced fit modifications on a set of 124 proteins available in both bound and unbound forms, in terms of local structure. The local structure is described thanks to a structural alphabet of 27 structural letters that allows a detailed description of the backbone. Using a control set to distinguish induced fit from experimental error and natural protein flexibility, we show that the fraction of structural letters modified upon binding is significantly greater than in the control set (36% versus 28%). This proportion is even greater in the interface regions (41%). Interface regions preferentially involve coils. Our analysis further reveals that some structural letters in coil are not favored in the interface. We show that certain structural letters in coil are particularly subject to modifications at the interface, and that the severity of structural change also varies. These information are used to derive a structural letter substitution matrix that summarizes the local structural changes observed in our data set. We also illustrate the usefulness of our approach to identify common binding motifs in unrelated proteins. Conclusion Our study provides qualitative information about induced fit. These results could be of help for flexible docking. PMID:18307769

Structural deformation upon protein-protein interaction: a structural alphabet approach.

PubMed

Martin, Juliette; Regad, Leslie; Lecornet, Hélène; Camproux, Anne-Claude

2008-02-28

In a number of protein-protein complexes, the 3D structures of bound and unbound partners significantly differ, supporting the induced fit hypothesis for protein-protein binding. In this study, we explore the induced fit modifications on a set of 124 proteins available in both bound and unbound forms, in terms of local structure. The local structure is described thanks to a structural alphabet of 27 structural letters that allows a detailed description of the backbone. Using a control set to distinguish induced fit from experimental error and natural protein flexibility, we show that the fraction of structural letters modified upon binding is significantly greater than in the control set (36% versus 28%). This proportion is even greater in the interface regions (41%). Interface regions preferentially involve coils. Our analysis further reveals that some structural letters in coil are not favored in the interface. We show that certain structural letters in coil are particularly subject to modifications at the interface, and that the severity of structural change also varies. These information are used to derive a structural letter substitution matrix that summarizes the local structural changes observed in our data set. We also illustrate the usefulness of our approach to identify common binding motifs in unrelated proteins. Our study provides qualitative information about induced fit. These results could be of help for flexible docking.

A multiscale approach to simulating the conformational properties of unbound multi-C₂H₂ zinc finger proteins.

PubMed

Liu, Lei; Wade, Rebecca C; Heermann, Dieter W

2015-09-01

The conformational properties of unbound multi-Cys2 His2 (mC2H2) zinc finger proteins, in which zinc finger domains are connected by flexible linkers, are studied by a multiscale approach. Three methods on different length scales are utilized. First, atomic detail molecular dynamics simulations of one zinc finger and its adjacent flexible linker confirmed that the zinc finger is more rigid than the flexible linker. Second, the end-to-end distance distributions of mC2H2 zinc finger proteins are computed using an efficient atomistic pivoting algorithm, which only takes excluded volume interactions into consideration. The end-to-end distance distribution gradually changes its profile, from left-tailed to right-tailed, as the number of zinc fingers increases. This is explained by using a worm-like chain model. For proteins of a few zinc fingers, an effective bending constraint favors an extended conformation. Only for proteins containing more than nine zinc fingers, is a somewhat compacted conformation preferred. Third, a mesoscale model is modified to study both the local and the global conformational properties of multi-C2H2 zinc finger proteins. Simulations of the CCCTC-binding factor (CTCF), an important mC2H2 zinc finger protein for genome spatial organization, are presented. © 2015 Wiley Periodicals, Inc.

Structure of the exotic He 9 nucleus from the no-core shell model with continuum

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

Vorabbi, Matteo; Calci, Angelo; Navratil, Petr

2018-03-13

Here, the exotic 9He nucleus, which presents one of the most extreme neutron-to-proton ratios, belongs to the N = 7 isotonic chain famous for the phenomenon of ground-state parity inversion with decreasing number of protons. Consequently, it would be expected to have an unnatural (positive) parity ground state similar to 11Be and 10Li. Despite many experimental and theoretical investigations, its structure remains uncertain. Apart from the fact that it is unbound, other properties including the spin and parity of its ground state, and the very existence of additional low-lying resonances are still a matter of debate

On the measurement of airborne, angular-dependent sound transmission through supercritical bars.

PubMed

Shaw, Matthew D; Anderson, Brian E

2012-10-01

The coincidence effect is manifested by maximal sound transmission at angles at which trace wave number matching occurs. Coincidence effect theory is well-defined for unbounded thin plates using plane-wave excitation. However, experimental results for finite bars are known to diverge from theory near grazing angles. Prior experimental work has focused on pulse excitation. An experimental setup has been developed to observe coincidence using continuous- wave excitation and phased-array methods. Experimental results with an aluminum bar exhibit maxima at the predicted angles, showing that coincidence is observable using continuous waves. Transmission near grazing angles is seen to diverge from infinite plate theory.

Science-based Region-of-Interest Image Compression

NASA Technical Reports Server (NTRS)

Wagstaff, K. L.; Castano, R.; Dolinar, S.; Klimesh, M.; Mukai, R.

2004-01-01

As the number of currently active space missions increases, so does competition for Deep Space Network (DSN) resources. Even given unbounded DSN time, power and weight constraints onboard the spacecraft limit the maximum possible data transmission rate. These factors highlight a critical need for very effective data compression schemes. Images tend to be the most bandwidth-intensive data, so image compression methods are particularly valuable. In this paper, we describe a method for prioritizing regions in an image based on their scientific value. Using a wavelet compression method that can incorporate priority information, we ensure that the highest priority regions are transmitted with the highest fidelity.

Resistance of Soil-Bound Prions to Rumen Digestion

PubMed Central

Saunders, Samuel E.; Bartelt-Hunt, Shannon L.; Bartz, Jason C.

2012-01-01

Before prion uptake and infection can occur in the lower gastrointestinal system, ingested prions are subjected to anaerobic digestion in the rumen of cervids and bovids. The susceptibility of soil-bound prions to rumen digestion has not been evaluated previously. In this study, prions from infectious brain homogenates as well as prions bound to a range of soils and soil minerals were subjected to in vitro rumen digestion, and changes in PrP levels were measured via western blot. Binding to clay appeared to protect noninfectious hamster PrPc from complete digestion, while both unbound and soil-bound infectious PrPSc proved highly resistant to rumen digestion. In addition, no change in intracerebral incubation period was observed following active rumen digestion of unbound hamster HY TME prions and HY TME prions bound to a silty clay loam soil. These results demonstrate that both unbound and soil-bound prions readily survive rumen digestion without a reduction in infectivity, further supporting the potential for soil-mediated transmission of chronic wasting disease (CWD) and scrapie in the environment. PMID:22937149

From localization to anomalous diffusion in the dynamics of coupled kicked rotors

NASA Astrophysics Data System (ADS)

Notarnicola, Simone; Iemini, Fernando; Rossini, Davide; Fazio, Rosario; Silva, Alessandro; Russomanno, Angelo

2018-02-01

We study the effect of many-body quantum interference on the dynamics of coupled periodically kicked systems whose classical dynamics is chaotic and shows an unbounded energy increase. We specifically focus on an N -coupled kicked rotors model: We find that the interplay of quantumness and interactions dramatically modifies the system dynamics, inducing a transition between energy saturation and unbounded energy increase. We discuss this phenomenon both numerically and analytically through a mapping onto an N -dimensional Anderson model. The thermodynamic limit N →∞ , in particular, always shows unbounded energy growth. This dynamical delocalization is genuinely quantum and very different from the classical one: Using a mean-field approximation, we see that the system self-organizes so that the energy per site increases in time as a power law with exponent smaller than 1. This wealth of phenomena is a genuine effect of quantum interference: The classical system for N ≥2 always behaves ergodically with an energy per site linearly increasing in time. Our results show that quantum mechanics can deeply alter the regularity or ergodicity properties of a many-body-driven system.

Hot Spots in a Network of Functional Sites

PubMed Central

Ozbek, Pemra; Soner, Seren; Haliloglu, Turkan

2013-01-01

It is of significant interest to understand how proteins interact, which holds the key phenomenon in biological functions. Using dynamic fluctuations in high frequency modes, we show that the Gaussian Network Model (GNM) predicts hot spot residues with success rates ranging between S 8–58%, C 84–95%, P 5–19% and A 81–92% on unbound structures and S 8–51%, C 97–99%, P 14–50%, A 94–97% on complex structures for sensitivity, specificity, precision and accuracy, respectively. High specificity and accuracy rates with a single property on unbound protein structures suggest that hot spots are predefined in the dynamics of unbound structures and forming the binding core of interfaces, whereas the prediction of other functional residues with similar dynamic behavior explains the lower precision values. The latter is demonstrated with the case studies; ubiquitin, hen egg-white lysozyme and M2 proton channel. The dynamic fluctuations suggest a pseudo network of residues with high frequency fluctuations, which could be plausible for the mechanism of biological interactions and allosteric regulation. PMID:24023934

When Is It Important to Measure Unbound Drug in Evaluating Nanomedicine Pharmacokinetics?

PubMed Central

Stern, Stephan T.; Stevens, David M.

2016-01-01

Nanoformulations have become important tools for modifying drug disposition, be it from the perspective of enabling prolonged drug release, protecting the drug molecule from metabolism, or achieving targeted delivery. When examining the in vivo pharmacokinetic properties of these formulations, most investigations either focus on systemic concentrations of total (encapsulated plus unencapsulated) drug, or concentrations of encapsulated and unencapsulated drug. However, it is rare to find studies that differentiate between protein-bound and unbound (free) forms of the unencapsulated drug. In light of the unique attributes of these formulations, we cannot simply assume it appropriate to rely upon the protein-binding properties of the traditionally formulated or legacy drug when trying to define the pharmacokinetic or pharmacokinetic/pharmacodynamic characteristics of these nanoformulations. Therefore, this commentary explores reasons why it is important to consider not only unencapsulated drug, but also the portion of unencapsulated drug that is not bound to plasma proteins. Specifically, we highlight those situations when it may be necessary to include measurement of unencapsulated, unbound drug concentrations as part of the nanoformulation pharmacokinetic evaluation. PMID:27670412

Determination of Unbound Partition Coefficient and in Vitro-in Vivo Extrapolation for SLC13A Transporter-Mediated Uptake.

PubMed

Riccardi, Keith; Li, Zhenhong; Brown, Janice A; Gorgoglione, Matthew F; Niosi, Mark; Gosset, James; Huard, Kim; Erion, Derek M; Di, Li

2016-10-01

Unbound partition coefficient (Kpuu) is important to an understanding of the asymmetric free drug distribution of a compound between cells and medium in vitro, as well as between tissue and plasma in vivo, especially for transporter-mediated processes. Kpuu was determined for a set of compounds from the SLC13A family that are inhibitors and substrates of transporters in hepatocytes and transporter-transfected cell lines. Enantioselectivity was observed, with (R)-enantiomers achieving much higher Kpuu (>4) than the (S)-enantiomers (<1) in human hepatocytes and SLC13A5-transfected human embryonic 293 cells. The intracellular free drug concentration correlated directly with in vitro pharmacological activity rather than the nominal concentration in the assay because of the high Kpuu mediated by SLC13A5 transporter uptake. Delivery of the diacid PF-06649298 directly or via hydrolysis of the ethyl ester prodrug PF-06757303 resulted in quite different Kpuu values in human hepatocytes (Kpuu of 3 for diacid versus 59 for prodrug), which was successfully modeled on the basis of passive diffusion, active uptake, and conversion rate from ester to diacid using a compartmental model. Kpuu values changed with drug concentrations; lower values were observed at higher concentrations possibly owing to a saturation of transporters. Michaelis-Menten constant (Km) of SLC13A5 was estimated to be 24 μM for PF-06649298 in human hepatocytes. In vitro Kpuu obtained from rat suspension hepatocytes supplemented with 4% fatty acid free bovine serum albumin showed good correlation with in vivo Kpuu of liver-to-plasma, illustrating the potential of this approach to predict in vivo Kpuu from in vitro systems. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Erosive Hit-and-Run Impact Events: Debris Unbound

NASA Astrophysics Data System (ADS)

Sarid, Gal; Stewart, Sarah T.; Leinhardt, Zoë M.

2016-01-01

Erosive collisions among planetary embryos in the inner solar system can lead to multiple remnant bodies, varied in mass, composition and residual velocity. Some of the smaller, unbound debris may become available to seed the main asteroid belt. The makeup of these collisionally produced bodies is different from the canonical chondritic composition, in terms of rock/iron ratio and may contain further shock-processed material. Having some of the material in the asteroid belt owe its origin from collisions of larger planetary bodies may help in explaining some of the diversity and oddities in composition of different asteroid groups.

A Semi-linear Backward Parabolic Cauchy Problem with Unbounded Coefficients of Hamilton–Jacobi–Bellman Type and Applications to Optimal Control

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

Addona, Davide, E-mail: d.addona@campus.unimib.it

2015-08-15

We obtain weighted uniform estimates for the gradient of the solutions to a class of linear parabolic Cauchy problems with unbounded coefficients. Such estimates are then used to prove existence and uniqueness of the mild solution to a semi-linear backward parabolic Cauchy problem, where the differential equation is the Hamilton–Jacobi–Bellman equation of a suitable optimal control problem. Via backward stochastic differential equations, we show that the mild solution is indeed the value function of the controlled equation and that the feedback law is verified.

LQR Control of Shell Vibrations Via Piezoceramic Actuators

NASA Technical Reports Server (NTRS)

delRosario, R. C. H.; Smith, R. C.

1997-01-01

A model-based Linear Quadratic Regulator (LQR) method for controlling vibrations in cylindrical shells is presented. Surface-mounted piezo-ceramic patches are employed as actuators which leads to unbounded control input operators. Modified Donnell-Mushtari shell equations incorporating strong or Kelvin-Voigt damping are used to model the system. The model is then abstractly formulated in terms of sesquilinear forms. This provides a framework amenable for proving model well-posedness and convergence of LQR gains using analytic semigroup results combined with LQR theory for unbounded input operators. Finally, numerical examples demonstrating the effectiveness of the method are presented.

Provably unbounded memory advantage in stochastic simulation using quantum mechanics

NASA Astrophysics Data System (ADS)

Garner, Andrew J. P.; Liu, Qing; Thompson, Jayne; Vedral, Vlatko; Gu, mile

2017-10-01

Simulating the stochastic evolution of real quantities on a digital computer requires a trade-off between the precision to which these quantities are approximated, and the memory required to store them. The statistical accuracy of the simulation is thus generally limited by the internal memory available to the simulator. Here, using tools from computational mechanics, we show that quantum processors with a fixed finite memory can simulate stochastic processes of real variables to arbitrarily high precision. This demonstrates a provable, unbounded memory advantage that a quantum simulator can exhibit over its best possible classical counterpart.

A computational method for the Helmholtz equation in unbounded domains based on the minimization of an integral functional

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

Ciraolo, Giulio, E-mail: g.ciraolo@math.unipa.it; Gargano, Francesco, E-mail: gargano@math.unipa.it; Sciacca, Vincenzo, E-mail: sciacca@math.unipa.it

2013-08-01

We study a new approach to the problem of transparent boundary conditions for the Helmholtz equation in unbounded domains. Our approach is based on the minimization of an integral functional arising from a volume integral formulation of the radiation condition. The index of refraction does not need to be constant at infinity and may have some angular dependency as well as perturbations. We prove analytical results on the convergence of the approximate solution. Numerical examples for different shapes of the artificial boundary and for non-constant indexes of refraction will be presented.

Holography for a De Sitter-Esque geometry

NASA Astrophysics Data System (ADS)

Anninos, Dionysios; de Buyl, Sophie; Detournay, Stéphane

2011-05-01

Warped dS3 arises as a solution to topologically massive gravity (TMG) with positive cosmological constant +1/ ℓ 2 and Chern-Simons coefficient 1/ μ in the region μ 2 ℓ 2 < 27. It is given by a real line fibration over two-dimensional de Sitter space and is equivalent to the rotating Nariai geometry at fixed polar angle. We study the thermodynamic and asymptotic structure of a family of geometries with warped dS3 asymptotics. Interestingly, these solutions have both a cosmological horizon and an internal one, and their entropy is unbounded from above unlike black holes in regular de Sitter space. The asymptotic symmetry group resides at future infinity and is given by a semi-direct product of a Virasoro algebra and a current algebra. The right moving central charge vanishes when μ 2 ℓ 2 = 27/5. We discuss the possible holographic interpretation of these de Sitter-esque spacetimes.

Disappearance kinetics of solutes from synovial fluid after intra-articular injection.

PubMed Central

Owen, S G; Francis, H W; Roberts, M S

1994-01-01

1. Five rheumatoid patients with a knee joint effusion participated in the study. An aqueous solution (0.1 to 0.2 ml) containing paracetamol, salicylate, diclofenac and [125I]-albumin was injected into a given joint to yield target concentrations of approximately 20 micrograms ml-1 for diclofenac, salicylate and paracetamol and 10(8) counts ml-1 for [125I]-albumin. 2. Paracetamol, salicylate and diclofenac were analysed in synovial fluid by h.p.l.c. [125I]-albumin was analysed using gamma counting. 3. The clearances (+/- s.d.) obtained for the solutes were [125I]-albumin (0.0053 +/- 0.0019 l h-1), diclofenac (0.0096 +/- 0.0061 l h-1), salicylate (0.024 +/- 0.022 l h-1) and paracetamol (0.055 +/- 0.041 l h-1). The corresponding fractions unbound of these solutes in synovial fluid were 0.0, < or = 0.01, 0.34 +/- 0.09 and 0.85 +/- 0.10, respectively. 4. Diffusion of unbound solute through the synovium is estimated to account for (+/- s.d.) 0.52 +/- 0.08, 0.87 +/- 0.06 and 0.99 +/- 0.01 of the total clearance of diclofenac, salicylate and paracetamol from the joint space, respectively. The remaining proportion of clearance is accounted for by efflux of solute bound to albumin. 5. An expression for the ratio of synovial fluid to total plasma concentrations after systemic administration was developed to include both diffusion of unbound solute and albumin flux. Most solutes appear to satisfy the conditions in which this expression reduces to the limiting case where the unbound concentration of the solute is identical in the synovial fluid and plasma under steady state conditions. PMID:7833225

Clinical pharmacokinetics of unbound docetaxel: role of polysorbate 80 and serum proteins.

PubMed

Loos, Walter J; Baker, Sharyn D; Verweij, Jaap; Boonstra, Joke G; Sparreboom, Alex

2003-10-01

Our objectives were to study the extent of docetaxel binding to plasma in the presence and absence of its excipient, polysorbate 80 (Tween 80; Imperial Chemical Industries PLC, London, United Kingdom), in vitro and to evaluate the pharmacokinetics of unbound docetaxel in vivo. Equilibrium dialysis was used for determination of the fraction unbound (f(u)) docetaxel and was applied to study the pharmacokinetic behavior of unbound docetaxel in 23 patients with cancer receiving an intravenous infusion of the drug formulated in polysorbate 80 (Taxotere; Aventis Pharma SA, Vitry-sur-Seine Cedex, France). Polysorbate 80, added at clinically relevant concentrations (up to 1.0 microL/mL), increased f(u) in vitro by 13% (7.84% +/- 0.0752% versus 6.95% +/- 0.0678%, P <.00001). Similarly, f(u) calculated on the basis of the observed area under the plasma concentration-time curve (AUC) values [f(u)(AUC)] in vivo was 12% higher than f(u) in pretreatment samples [f(u)(pre)] (6.00% +/- 1.03% versus 5.49% +/- 1.01%, P =.038). Of various serum proteins evaluated, only alpha(1)-acid glycoprotein was significantly related to f(u) (P <.0018), with higher f(u) in the presence of lower protein levels. Total docetaxel clearance was related to alpha(1)-acid glycoprotein (R(2) = 0.13, P =.058), f(u)(pre) (R(2) = 0.15, P =.039), and f(u)(AUC) (R(2) = 0.29, P =.0048). This study demonstrates that the plasma binding of docetaxel is influenced by both alpha(1)-acid glycoprotein and its formulation vehicle. Further investigation is required to resolve the potential clinical significance of these observations.

Effect of multiple dosing of ketoconazole on pharmacokinetics of midazolam, a cytochrome P-450 3A substrate in beagle dogs.

PubMed

Kuroha, Masanori; Azumano, Akinori; Kuze, Yoji; Shimoda, Minoru; Kokue, Eiichi

2002-01-01

To evaluate effects of multiple dosing of ketoconazole (KTZ) on hepatic CYP3A, the pharmacokinetics of intravenous midazolam (MDZ, 0.5 mg/kg) before and during multiple dosing of KTZ were investigated in beagle dogs. KTZ tablets were given orally to dogs (n = 4) for 30 days (200 mg b.i.d.). With coadministration of KTZ, t(1/2beta) of MDZ were significantly increased both on day 1 (2-fold) and on day 30 (3-fold). Total body clearance (CL(tot)) of MDZ declined gradually during the first 5 days after the start of KTZ treatment, and thereafter CL(tot) appeared to reach a plateau phase (one-fourth), depending on plasma KTZ concentrations. The effects of KTZ on the biotransformation of MDZ were also investigated using dog liver microsomes (n = 5). The K(i) values of KTZ for MDZ 1'-hydroxylation and 4-hydroxylation were 0.0237 and 0.111 microM, respectively, indicating that KTZ extensively inhibits hepatic CYP3A activity in dogs. CL(tot) values estimated from in vitro K(i) values corrected by unbound fraction of KTZ and unbound concentrations of the drug in plasma were consistent with in vivo CL(tot) of MDZ. The results in this study suggest that KTZ treatment is necessary until plasma concentrations of the drug reach a steady state to evaluate the effect of multiple dosing of the drug on hepatic CYP3A in vivo. In addition, it is suggested that K(i) values corrected by unbound fraction of KTZ and unbound concentrations of the drug in plasma enable precise in vitro-in vivo scaling.

Steady-state pharmacokinetics of (R)- and (S)-methadone in methadone maintenance patients

PubMed Central

Foster, David J R; Somogyi, Andrew A; Dyer, Kyle R; White, Jason M; Bochner, Felix

2000-01-01

Aims To investigate the steady-state pharmacokinetics of (R)- and (S)-methadone in a methadone maintenance population. Methods Eighteen patients recruited from a public methadone maintenance program underwent an interdosing interval pharmacokinetic study. Plasma and urine samples were collected and analysed for methadone and its major metabolite (EDDP) using stereoselective h.p.l.c. Methadone plasma protein binding was examined using ultrafiltration, and plasma α1-acid glycoprotein concentrations were quantified by radial immunoassay. Results (R)-methadone had a significantly (P < 0.05) greater unbound fraction (mean 173%) and total renal clearance (182%) compared with (S)-methadone, while maximum measured plasma concentrations (83%) and apparent partial clearance of methadone to EDDP (76%) were significantly (P < 0.001) lower. When protein binding was considered (R)-methadone plasma clearance of the unbound fraction (59%) and apparent partial intrinsic clearance to EDDP (44%) were significantly (P < 0.01) lower than for (S)-methadone, while AUCτSS, (167%) was significantly (P < 0.001) greater. There were no significant (P > 0.2) differences between the methadone enantiomers for AUCτSS, steady-state plasma clearance, trough plasma concentrations and unbound renal clearance. Patients excreted significantly (P < 0.0001) more (R)-methadone and (S)-EDDP than the corresponding enantiomers. Considerable interindividual variability was observed for the pharmacokinetic parameters, with coefficients of variation of up to 70%. Conclusions Steady-state pharmacokinetics of unbound methadone are stereoselective, and there is large interindividual variability consistent with CYP3A4 mediated metabolism to the major metabolite EDDP; the variability did not obscure a significant dose-plasma concentration relationship. Stereoselective differences in the pharmacokinetics of methadone may have important implications for pharmacokinetic-pharmacodynamic modelling but is unlikely to be important for therapeutic drug monitoring of methadone, in the setting of opioid dependence. PMID:11069437

Hepatic cyst penetration of cefazolin in patients receiving aspiration sclerotherapy.

PubMed

Lantinga, M A; Wijnands, T F M; Te Morsche, R H M; de Sévaux, R G L; Kuipers, S; Allegaert, K; Burger, D; Drenth, J P H

2016-09-01

Hepatic cyst infection is a potentially severe complication in cystic disease. Treatment demands effective antibiotic concentrations within the infected cyst. The aim of this study was to use elective hepatic cyst drainage as a unique pharmacokinetic model to investigate whether cefazolin, a first-generation cephalosporin, is able to penetrate hepatic cysts. Patients scheduled to undergo percutaneous aspiration sclerotherapy of a symptomatic non-infected, non-neoplastic hepatic cyst were eligible for this study. All participants received a single perioperative prophylactic dose of cefazolin (1000 mg, intravenously). We collected blood and cyst fluid samples to determine total and unbound cefazolin concentrations using HPLC. The primary outcome was hepatic cyst penetration, expressed as the ratio (%) of unbound concentration of cefazolin in cyst fluid to plasma (both in mg/L). We included eight patients [male = 25%, median age = 60 years (IQR 54-75), median estimated glomerular filtration rate = 97 mL/min/1.73 m(2) (IQR 67-102) and median serum albumin = 40 g/L (IQR 37-40)]. We detected low concentrations of unbound cefazolin in cyst fluid (≤1.0 mg/L). The median plasma unbound cefazolin peak level (immediately after cefazolin administration) was 36.6 mg/L (IQR 23.7-54.1) and the level at the time of cyst fluid aspiration was 16.1 mg/L (IQR 13.0-20.1). In total, the hepatic cyst penetration of free cefazolin was only 2.2% (IQR 0.7-5.2). We developed a study model to investigate the penetration of antibiotics into hepatic cysts. Cefazolin did not reach adequate intracystic concentrations. Future studies should explore alternatives. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Effects of Soybean Lipid Infusion on Unbound Free Fatty Acids and Unbound Bilirubin in Preterm Infants.

PubMed

Hegyi, Thomas; Kleinfeld, Alan; Huber, Andrew; Weinberger, Barry; Memon, Naureen; Shih, Weichung Joe; Carayannopoulos, Mary; Oh, William

2017-05-01

To assess the effects of a soybean lipid emulsion infusions on levels of unbound (free) bilirubin (Bf) and unbound free fatty acids (FFAu) as well as changes in Bf and total serum bilirubin (TSB) during phototherapy in infants born preterm. Ninety-seven infants born preterm (birth weight: 500-2000 g; gestational age: 23-34 weeks) were enrolled to investigate the effect of 0, 1, 2, and 3 g/kg/d of intralipid infusion on Bf and FFAu. Pre- and postphototherapy TSB, FFAu, and Bf also were analyzed in 91 infants to assess the effects of phototherapy. FFAu levels were measured with the fluorescent probe ADIFAB2 and Bf by the fluorescent Bf sensor BL22P1B11-Rh during intralipid infusion and at start and end of phototherapy. TSB and plasma albumin were measured by the diazo and bromcresol green techniques, respectively. Bilirubin-albumin dissociation constants were calculated based on Bf and plasma albumin. Bf and FFAu increased with increasing intralipid dosage across all gestational ages. TSB and Bf were correlated significantly when infants received 0 or 1 g/kg/d of intralipid but not at greater doses of intralipid (2 and 3 g/kg/d). Although phototherapy effectively reduced both TSB and Bf in the total phototherapy group (by 32% and 12%, respectively), it reduced TSB, but not Bf, in infants less than 28 weeks of gestation. Increasing intralipid doses result in increasing FFAu levels, which are associated with increased Bf independent of TSB. In infants born extremely preterm (<28 weeks of gestation), phototherapy effectively reduces TSB but not Bf. Copyright © 2016 Elsevier Inc. All rights reserved.

Posaconazole in Human Serum: a Greater Pharmacodynamic Effect than Predicted by the Non-Protein-Bound Serum Concentration ▿

PubMed Central

Lignell, Anders; Löwdin, Elisabeth; Cars, Otto; Chryssanthou, Erja; Sjölin, Jan

2011-01-01

It is generally accepted that only the unbound fraction of a drug is pharmacologically active. Posaconazole is an antifungal agent with a protein binding of 98 to 99%. Taking into account the degree of protein binding, plasma levels in patients, and MIC levels of susceptible strains, it can be assumed that the free concentration of posaconazole sometimes will be too low to exert the expected antifungal effect. The aim was therefore to test the activity of posaconazole in serum in comparison with that of the calculated unbound concentrations in protein-free media. Significant differences (P < 0.05) from the serum control were found at serum concentrations of posaconazole of 1.0 and 0.10 mg/liter, with calculated free concentrations corresponding to 1× MIC and 0.1× MIC, respectively, against one Candida lusitaniae strain selected for proof of principle. In RPMI 1640, the corresponding calculated unbound concentration of 0.015 mg/liter resulted in a significant effect, whereas that of 0.0015 mg/liter did not. Also, against seven additional Candida strains tested, there was an effect of the low posaconazole concentration in serum, in contrast to the results in RPMI 1640. Fluconazole, a low-grade-protein-bound antifungal, was used for comparison at corresponding concentrations in serum and RPMI 1640. No effect was observed at the serum concentration, resulting in a calculated unbound concentration of 0.1× MIC. In summary, there was a substantially greater pharmacodynamic effect of posaconazole in human serum than could be predicted by the non-protein-bound serum concentration. A flux from serum protein-bound to fungal lanosterol 14α-demethylase-bound posaconazole is suggested. PMID:21502622

Revisiting atenolol as a low passive permeability marker.

PubMed

Chen, Xiaomei; Slättengren, Tim; de Lange, Elizabeth C M; Smith, David E; Hammarlund-Udenaes, Margareta

2017-10-31

Atenolol, a hydrophilic beta blocker, has been used as a model drug for studying passive permeability of biological membranes such as the blood-brain barrier (BBB) and the intestinal epithelium. However, the extent of S-atenolol (the active enantiomer) distribution in brain has never been evaluated, at equilibrium, to confirm that no transporters are involved in its transport at the BBB. To assess whether S-atenolol, in fact, depicts the characteristics of a low passive permeable drug at the BBB, a microdialysis study was performed in rats to monitor the unbound concentrations of S-atenolol in brain extracellular fluid (ECF) and plasma during and after intravenous infusion. A pharmacokinetic model was developed, based on the microdialysis data, to estimate the permeability clearance of S-atenolol into and out of brain. In addition, the nonspecific binding of S-atenolol in brain homogenate was evaluated using equilibrium dialysis. The steady-state ratio of unbound S-atenolol concentrations in brain ECF to that in plasma (i.e., K p,uu,brain ) was 3.5% ± 0.4%, a value much less than unity. The unbound volume of distribution in brain (V u, brain ) of S-atenolol was also calculated as 0.69 ± 0.10 mL/g brain, indicating that S-atenolol is evenly distributed within brain parenchyma. Lastly, equilibrium dialysis showed limited nonspecific binding of S-atenolol in brain homogenate with an unbound fraction (f u,brain ) of 0.88 ± 0.07. It is concluded, based on K p,uu,brain being much smaller than unity, that S-atenolol is actively effluxed at the BBB, indicating the need to re-consider S-atenolol as a model drug for passive permeability studies of BBB transport or intestinal absorption.

Alkali Halide Opacity in Brown Dwarf and Cool Stellar Atmospheres: A Study of Lithium Chloride

NASA Astrophysics Data System (ADS)

Kirby, K.; Weck, P. F.; Schweitzer, A.; Stancil, P. C.; Hauschildt, P. H.

2003-12-01

Recent thermochemical equilibrium calculations have revealed the important role played by lithium chloride in the lithium chemistry of cool dwarf atmospheres (K. Lodders 1999, ApJ 519, 793). Indeed, LiCl appears to be the dominant Li-bearing gas over an extended domain of the (P,T) diagram, typically for temperatures below 1500 K. LiCl has a large dipole moment in its ground electronic state which can give rise to intense rovibrational line spectra. In addition, LiCl can make dipole transitions to several low-lying unbound excited states, causing dissociation of the molecule. For these reasons, LiCl may be a significant source of line and continuum opacity in brown dwarf and cool stellar atmospheres. In this work, we report calculations of complete lists of line oscillator strengths and photodissociation cross sections for the low-lying electronic states of LiCl. We have performed single- and double-excitation configuration interaction calculations using the ALCHEMY ab initio package (Mc Lean et al. 1991, MOTECC 91, Elsevier, Leiden) and obtained the potential curves and the corresponding dipole transition moment functions between the X 1Σ ^+ ground state and the B 1Σ ^+ and A 1Π excited states. The resulting line oscillator strengths and molecular photodissociation cross sections have been included in the PHOENIX stellar atmosphere code (Hauschildt & Baron 1999, J. Comput. App. Math. 102, 41). The new models, calculated using spherical geometry for all gravities considered, also incorporate our latest database of nearly 670 million molecular lines, and updated equations of state (EOS). This work was supported in part by NSF grants AST-9720704 and AST-0086246, NASA grants NAG5-8425, NAG5-9222, and NAG5-10551 as well as NASA/JPL grant 961582.

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

Moon, Chang-Bum, E-mail: cbmoon@hoseo.edu

This paper outlines the new physics possibilities that fall within the field of nuclear structure and astrophysics based on experiments with radioactive ion beams at the future Rare Isotope Beams Accelerator facility in Korea. This ambitious multi-beam facility has both an Isotope Separation On Line (ISOL) and fragmentation capability to produce rare isotopes beams (RIBs) and will be capable of producing and accelerating beams of wide range mass of nuclides with energies of a few to hundreds MeV per nucleon. The large dynamic range of reaccelerated RIBs will allow the optimization in each nuclear reaction case with respect to crossmore » section and channel opening. The low energy RIBs around Coulomb barrier offer nuclear reactions such as elastic resonance scatterings, one or two particle transfers, Coulomb multiple-excitations, fusion-evaporations, and direct capture reactions for the study of the very neutron-rich and proton-rich nuclides. In contrast, the high energy RIBs produced by in-flight fragmentation with reaccelerated ions from the ISOL enable to explore the study of neutron drip lines in intermediate mass regions. The proposed studies aim at investigating the exotic nuclei near and beyond the nucleon drip lines, and to explore how nuclear many-body systems change in such extreme regions by addressing the following topics: the evolution of shell structure in areas of extreme proton to neutron imbalance; the study of the weak interaction in exotic decay schemes such as beta-delayed two-neutron or two-proton emission; the change of isospin symmetry in isobaric mirror nuclei at the drip lines; two protons or two neutrons radioactivity beyond the drip lines; the role of the continuum states including resonant states above the particle-decay threshold in exotic nuclei; and the effects of nuclear reaction rates triggered by the unbound proton-rich nuclei on nuclear astrophysical processes.« less

Isomer spectroscopy using RI beam

NASA Astrophysics Data System (ADS)

Odahara, Atsuko

2009-10-01

We have studied systematically high-spin oblate shape isomers in the N=83 isotones, which have revealed the characteristics of nuclear structure, such as the preserving pairing interactions at high-spin states, decrease of Z=64 proton shell gap energy as the decrease of proton number from 64 to 60 and so on. Recently, it became possible to search for isomers by the secondary fusion reaction at high-spin states in nuclei, which could not be populated by the stable beam and stable target, using RCNP RI beam line at Osaka University. RI beams enable us to study high-spin states in nuclei in wide mass region. By using the RI beams delivered by RIBF and the high-efficiency γ-ray detection system GRETINA, it will be possible to investigate nuclei far from the stability line. Single-particle energies and nucleon-nucleon interactions of these nuclei close to drip line are expected to be the test ground of nuclear models, such as shell structures. We have a plan to search for isomers with half lives of ˜μsec to ˜msec and to explore the decay mechanism of isomers in the proton-rich nuclei along N=Z line with 80< A<100. Moreover we try to search for nuclei beyond the proton drip line, which could be defined that isomeric states would be bound by the centrifugal potential although the ground states would be unbound against the proton emission. Isomers are expected to reveal the following characteristics of these nuclei. (1) Existence of isomers could prove the magicity of N=Z=50 and the large neutron-proton interaction, as one of the candidates of isomers is spin-gap isomer which is caused by the lowering of excitation energies resulting from the stretch coupling of spins of high-j (g9/2) holes of the ^100Sn core. (2) Isomers could prove the nuclear deformation which is caused by the evolution of shell structure. One of spin-gap isomers in ^94Ag was reported to have large prolate deformation. (3) This mass region is on the way of the rapid proton (rp) synthesis pass. Recently, neutrino reactions in the super novae were reported to play a role of the synthesis of the rp-process nuclei. In the case of no path or slow down of rp process, isomers could contribute to synthesis of rp-nuclei with larger Z, although the production rates of isomers are small.

Population PKPD modeling of BACE1 inhibitor-induced reduction in Aβ levels in vivo and correlation to in vitro potency in primary cortical neurons from mouse and guinea pig.

PubMed

Janson, Juliette; Eketjäll, Susanna; Tunblad, Karin; Jeppsson, Fredrik; Von Berg, Stefan; Niva, Camilla; Radesäter, Ann-Cathrin; Fälting, Johanna; Visser, Sandra A G

2014-03-01

The aims were to quantify the in vivo time-course between the oral dose, the plasma and brain exposure and the inhibitory effect on Amyloid β (Aβ) in brain and cerebrospinal fluid, and to establish the correlation between in vitro and in vivo potency of novel β-secretase (BACE1) inhibitors. BACE1-mediated inhibition of Aβ was quantified in in vivo dose- and/or time-response studies and in vitro in SH-SY5Y cells, N2A cells, and primary cortical neurons (PCN). An indirect response model with inhibition on Aβ production rate was used to estimate unbound in vivo IC 50 in a population pharmacokinetic-pharmacodynamic modeling approach. Estimated in vivo inhibitory potencies varied between 1 and 1,000 nM. The turnover half-life of Aβ40 in brain was predicted to be 0.5 h in mouse and 1 h in guinea pig. An excellent correlation between PCN and in vivo potency was observed. Moreover, a strong correlation in potency was found between human SH-SY5Y cells and mouse PCN, being 4.5-fold larger in SH-SY5Y cells. The strong in vivo-in vitro correlation increased the confidence in using human cell lines for screening and optimization of BACE1 inhibitors. This can optimize the design and reduce the number of preclinical in vivo effect studies.

Two-dimensional turbulent flow chromatography coupled on-line to liquid chromatography-mass spectrometry for solution-based ligand screening against multiple proteins.

PubMed

Zhou, Jian-Liang; An, Jing-Jing; Li, Ping; Li, Hui-Jun; Jiang, Yan; Cheng, Jie-Fei

2009-03-20

We present herein a novel bioseparation/chemical analysis strategy for protein-ligand screening and affinity ranking in compound mixtures, designed to increase screening rates and improve sensitivity and ruggedness in performance. The strategy is carried out by combining on-line two-dimensional turbulent flow chromatography (2D-TFC) with liquid chromatography-mass spectrometry (LC-MS), and accomplished through the following steps: (1) a reversed-phase TFC stage to separate the protein/ligand complex from the unbound free molecules, (2) an on-line dissociation process to release the bound ligands from the complexes, and (3) a second mixed-mode cation-exchange/reversed-phase TFC stage to trap the bound ligands and to remove the proteins and salts, followed by LC-MS analysis for identification and determination of the binding affinities. The technique can implement an ultra-fast isolation of protein/ligand complex with the retention time of a complex peak in about 5s, and on-line prepare the "clean" sample to be directly compatible with the LC-MS analysis. The improvement in performance of this 2D-TFC/LC-MS approach over the conventional approach has been demonstrated by determining affinity-selected ligands of the target proteins acetylcholinesterase and butyrylcholinesterase from a small library with known binding affinities and a steroidal alkaloid library composed of structurally similar compounds. Our results show that 2D-TFC/LC-MS is a generic and efficient tool for high-throughput screening of ligands with low-to-high binding affinities, and structure-activity relationship evaluation.

Global stabilization analysis of inertial memristive recurrent neural networks with discrete and distributed delays.

PubMed

Wang, Leimin; Zeng, Zhigang; Ge, Ming-Feng; Hu, Junhao

2018-05-02

This paper deals with the stabilization problem of memristive recurrent neural networks with inertial items, discrete delays, bounded and unbounded distributed delays. First, for inertial memristive recurrent neural networks (IMRNNs) with second-order derivatives of states, an appropriate variable substitution method is invoked to transfer IMRNNs into a first-order differential form. Then, based on nonsmooth analysis theory, several algebraic criteria are established for the global stabilizability of IMRNNs under proposed feedback control, where the cases with both bounded and unbounded distributed delays are successfully addressed. Finally, the theoretical results are illustrated via the numerical simulations. Copyright © 2018 Elsevier Ltd. All rights reserved.

Optimal discrete-time LQR problems for parabolic systems with unbounded input: Approximation and convergence

NASA Technical Reports Server (NTRS)

Rosen, I. G.

1988-01-01

An abstract approximation and convergence theory for the closed-loop solution of discrete-time linear-quadratic regulator problems for parabolic systems with unbounded input is developed. Under relatively mild stabilizability and detectability assumptions, functional analytic, operator techniques are used to demonstrate the norm convergence of Galerkin-based approximations to the optimal feedback control gains. The application of the general theory to a class of abstract boundary control systems is considered. Two examples, one involving the Neumann boundary control of a one-dimensional heat equation, and the other, the vibration control of a cantilevered viscoelastic beam via shear input at the free end, are discussed.

On local strong solutions to the three-dimensional nonhomogeneous incompressible magnetohydrodynamic equations with density-dependent viscosity and vacuum

NASA Astrophysics Data System (ADS)

Song, Sisi

2018-04-01

This paper concerns the three-dimensional nonhomogeneous incompressible magnetohydrodynamic equations with density-dependent viscosity and vacuum on Ω \\subset R^3. The domain Ω \\subset R^3 is a general connected smooth one, either bounded or unbounded. In particular, the initial density can have compact support when Ω is unbounded. First, we obtain the local existence and uniqueness of strong solution to the three-dimensional nonhomogeneous incompressible magnetohydrodynamic equations without any compatibility condition assumed on the initial data. Then, we also prove the continuous dependence of strong solution on the initial data under an additional compatibility condition.

Optimal fixed-finite-dimensional compensator for Burgers' equation with unbounded input/output operators

NASA Technical Reports Server (NTRS)

Burns, John A.; Marrekchi, Hamadi

1993-01-01

The problem of using reduced order dynamic compensators to control a class of nonlinear parabolic distributed parameter systems was considered. Concentration was on a system with unbounded input and output operators governed by Burgers' equation. A linearized model was used to compute low-order-finite-dimensional control laws by minimizing certain energy functionals. Then these laws were applied to the nonlinear model. Standard approaches to this problem employ model/controller reduction techniques in conjunction with linear quadratic Gaussian (LQG) theory. The approach used is based on the finite dimensional Bernstein/Hyland optimal projection theory which yields a fixed-finite-order controller.

Approximation methods for control of acoustic/structure models with piezoceramic actuators

NASA Technical Reports Server (NTRS)

Banks, H. T.; Fang, W.; Silcox, R. J.; Smith, R. C.

1991-01-01

The active control of acoustic pressure in a 2-D cavity with a flexible boundary (a beam) is considered. Specifically, this control is implemented via piezoceramic patches on the beam which produces pure bending moments. The incorporation of the feedback control in this manner leads to a system with an unbounded input term. Approximation methods in this manner leads to a system with an unbounded input term. Approximation methods in the context of linear quadratic regulator (LQR) state space control formulation are discussed and numerical results demonstrating the effectiveness of this approach in computing feedback controls for noise reduction are presented.

Use of recycled aggregates from construction and demolition waste in geotechnical applications: A literature review.

PubMed

Cardoso, Rafaela; Silva, Rui Vasco; Brito, Jorge de; Dhir, Ravindra

2016-03-01

The use of recycled aggregates (RA) in construction constitutes a significant step towards a more sustainable society and also creates a new market opportunity to be exploited. In recent years, several case-studies have emerged in which RA were used in Geotechnical applications, such as filling materials and in unbound pavement layers. This paper presents a review of the most important physical properties of different types of RA and their comparison with natural aggregates (NA), and how these properties affect their hydraulic and mechanical behaviour when compacted. Specifically, the effects of compaction on grading size distribution curves and density are analysed, as well as the consequences of particle crushing on the resilient modulus, CBR and permeability. The paper also contains an analysis of the influence of incorporating different RA types on the performance of unbound road pavement layers as compared with those built with NA by means of the International Roughness Index and deflection values. The results collected from the literature indicate that the performance of most RA is comparable to that of NA and can be used in unbound pavement layers or in other applications requiring compaction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Plasma concentrations of fentanyl with subcutaneous infusion in palliative care patients.

PubMed

Miller, R S; Peterson, G M; Abbott, F; Maddocks, I; Parker, D; McLean, S

1995-12-01

1. Plasma concentrations of fentanyl were measured by g.c. in 20 patients (median age: 75 years and range: 54-86 years; eight females) in palliative care receiving the drug by continuous s.c. infusion (median rate: 1200 micrograms day-1 and range: 100-5000 micrograms day-1). 2. The infusion rate was significantly related to the duration of therapy (Spearman rho = 0.56, P < 0.05). The total steady-state plasma concentrations of fentanyl ranged between 0.1 and 9 ng ml-1, with a median of 1 ng ml-1. The unbound fraction of fentanyl in the plasma ranged from 17.8 to 44.4%, with a median value of 33.6%. Infusion rates and both total and unbound plasma concentrations of fentanyl were correlated (Spearman rho = 0.92, P < 0.05 in each case). Even with standardization for dosage, there was an eightfold variation in total plasma concentrations and 3.5-fold variation in unbound plasma concentrations of fentanyl. 3. There is considerable inter-patient variability in the pharmacokinetics of fentanyl with s.c. infusion in the palliative care setting, which necessitates careful titration of dosage according to individual clinical response.

Effect of fat content and homogenization under conventional or ultra-high-pressure conditions on interactions between proteins in rennet curds.

PubMed

Zamora, A; Trujillo, A J; Armaforte, E; Waldron, D S; Kelly, A L

2012-09-01

The objective of this study was to investigate the influence of conventional and ultra-high-pressure homogenization on interactions between proteins within drained rennet curds. The effect of fat content of milk (0.0, 1.8, or 3.6%) and homogenization treatment on dissociation of proteins by different chemical agents was thus studied. Increasing the fat content of raw milk increased levels of unbound whey proteins and calcium-bonded caseins in curds; in contrast, hydrophobic interactions and hydrogen bonds were inhibited. Both homogenization treatments triggered the incorporation of unbound whey proteins in the curd, and of caseins through ionic bonds involving calcium salts. Conventional homogenization-pasteurization enhanced interactions between caseins through hydrogen bonds and hydrophobic interactions. In contrast, ultra-high-pressure homogenization impaired hydrogen bonding, led to the incorporation of both whey proteins and caseins through hydrophobic interactions and increased the amount of unbound caseins. Thus, both homogenization treatments provoked changes in the protein interactions within rennet curds; however, the nature of the changes depended on the homogenization conditions. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Interpreting Tacrolimus Concentrations During Pregnancy and Postpartum

PubMed Central

Hebert, Mary F.; Zheng, Songmao; Hays, Karen; Shen, Danny D.; Davis, Connie L.; Umans, Jason G.; Miodovnik, Menachem; Thummel, Kenneth E.; Easterling, Thomas R.

2012-01-01

Summary Pregnancy following solid organ transplantation, although considered high risk for maternal, fetal and neonatal complications, has been quite successful. Tacrolimus pharmacokinetic changes during pregnancy make interpretation of whole blood trough concentrations particularly challenging. There are multiple factors that can increase the fraction of unbound tacrolimus, including but not limited to low albumin concentration and low RBC count. The clinical titration of dosage to maintain whole blood tacrolimus trough concentrations in the usual therapeutic range can lead to elevated unbound concentrations and possibly toxicity in pregnant women with anemia and hypoalbuminemia. Measurement of plasma or unbound tacrolimus concentrations for pregnant women might better reflect the active form of the drug, though these are technically-challenging and often unavailable in usual clinical practice. Tacrolimus crosses the placenta with in utero exposure being approximately 71% of maternal blood concentrations. The lower fetal blood concentrations are likely due to active efflux transport of tacrolimus from the fetus toward the mother by placental P-glycoprotein. To date, tacrolimus has not been linked to congenital malformations, but can cause reversible nephrotoxicity and hyperkalemia in the newborn. In contrast, very small amounts of tacrolimus are excreted in the breast milk and are unlikely to elicit adverse effects in the nursing infant. PMID:23274970

Unbound or distant planetary mass population detected by gravitational microlensing.

PubMed

2011-05-19

Since 1995, more than 500 exoplanets have been detected using different techniques, of which 12 were detected with gravitational microlensing. Most of these are gravitationally bound to their host stars. There is some evidence of free-floating planetary-mass objects in young star-forming regions, but these objects are limited to massive objects of 3 to 15 Jupiter masses with large uncertainties in photometric mass estimates and their abundance. Here, we report the discovery of a population of unbound or distant Jupiter-mass objects, which are almost twice (1.8(+1.7)(-0.8)) as common as main-sequence stars, based on two years of gravitational microlensing survey observations towards the Galactic Bulge. These planetary-mass objects have no host stars that can be detected within about ten astronomical units by gravitational microlensing. However, a comparison with constraints from direct imaging suggests that most of these planetary-mass objects are not bound to any host star. An abrupt change in the mass function at about one Jupiter mass favours the idea that their formation process is different from that of stars and brown dwarfs. They may have formed in proto-planetary disks and subsequently scattered into unbound or very distant orbits.

A nonlocal spatial model for Lyme disease

NASA Astrophysics Data System (ADS)

Yu, Xiao; Zhao, Xiao-Qiang

2016-07-01

This paper is devoted to the study of a nonlocal and time-delayed reaction-diffusion model for Lyme disease with a spatially heterogeneous structure. In the case of a bounded domain, we first prove the existence of the positive steady state and a threshold type result for the disease-free system, and then establish the global dynamics for the model system in terms of the basic reproduction number. In the case of an unbound domain, we obtain the existence of the disease spreading speed and its coincidence with the minimal wave speed. At last, we use numerical simulations to verify our analytic results and investigate the influence of model parameters and spatial heterogeneity on the disease infection risk.

Electrostatics in protein–protein docking

PubMed Central

Heifetz, Alexander; Katchalski-Katzir, Ephraim; Eisenstein, Miriam

2002-01-01

A novel geometric-electrostatic docking algorithm is presented, which tests and quantifies the electrostatic complementarity of the molecular surfaces together with the shape complementarity. We represent each molecule to be docked as a grid of complex numbers, storing information regarding the shape of the molecule in the real part and information regarding the electrostatic character of the molecule in the imaginary part. The electrostatic descriptors are derived from the electrostatic potential of the molecule. Thus, the electrostatic character of the molecule is represented as patches of positive, neutral, or negative values. The potential for each molecule is calculated only once and stored as potential spheres adequate for exhaustive rotation/translation scans. The geometric-electrostatic docking algorithm is applied to 17 systems, starting form the structures of the unbound molecules. The results—in terms of the complementarity scores of the nearly correct solutions, their ranking in the lists of sorted solutions, and their statistical uniqueness—are compared with those of geometric docking, showing that the inclusion of electrostatic complementarity in docking is very important, in particular in docking of unbound structures. Based on our results, we formulate several "good electrostatic docking rules": The geometric-electrostatic docking procedure is more successful than geometric docking when the potential patches are large and when the potential extends away from the molecular surface and protrudes into the solvent. In contrast, geometric docking is recommended when the electrostatic potential around the molecules to be docked appears homogenous, that is, with a similar sign all around the molecule. PMID:11847280

Competitive binding experiments can reduce the false positive results of affinity-based ultrafiltration-HPLC: A case study for identification of potent xanthine oxidase inhibitors from Perilla frutescens extract.

PubMed

Wang, Zhiqiang; Kwon, Shin Hwa; Hwang, Seung Hwan; Kang, Young-Hee; Lee, Jae-Yong; Lim, Soon Sung

2017-03-24

The purpose of this study was to assess the possibility of using competitive binding experiments with ultrafiltration-HPLC analysis to identify potent xanthine oxidase (XO) inhibitors from the Perilla frutescens extract as an attempt to reduce the number of false positive results. To isolate the enzyme-ligand complex from unbound compounds, the P. frutescens extract was either incubated in the absence of XO, in the presence of XO, or with the active site blocked XO before the ultrafiltration was performed. Allopurinaol was used as the XO active site blocker. The unbound compounds were subjected to HPLC analysis. The degree of total binding (TBD) and degree of specific binding (SBD) of each compound were calculated using the peak areas. TBD represents the binding affinities of compounds from the P. frutescens extract for the XO binding site. SBD represents the XO competitive binding between allopurinol and ligands from the extract samples. Two criteria were applied to select putative targets that could help avoid false positives. These include TBD>30% and SBD>10%. Using that approach, kaempferol-3-O-rutinoside, rosmarinic acid, methyl-rosmarinic acid, apigenin, and 4',5,7-trimethoxyflavone were identified, from total 11 compounds, as potent XO inhibitors. Finally, apigenin, 4',5,7-trimethoxyflavone, and luteolin were XO inhibitors verified through an XO inhibition assay and structural simulation of the complex. These results showed that the newly developed strategy has the advantage that the number of targets identified via ultrafiltration-HPLC can be narrowed from many false positives. However, not all false positives can be eliminated with this approach. Some potent inhibitors might also be excluded with the use of this method. The limitations of this method are also discussed herein. Copyright © 2017 Elsevier B.V. All rights reserved.

Chaos and nonlinear dynamics of single-particle orbits in a magnetotaillike magnetic field

NASA Technical Reports Server (NTRS)

Chen, J.; Palmadesso, P. J.

1986-01-01

The properties of charged-particle motion in Hamiltonian dynamics are studied in a magnetotaillike magnetic field configuration. It is shown by numerical integration of the equation of motion that the system is generally nonintegrable and that the particle motion can be classified into three distinct types of orbits: bounded integrable orbits, unbounded stochastic orbits, and unbounded transient orbits. It is also shown that different regions of the phase space exhibit qualitatively different responses to external influences. The concept of 'differential memory' in single-particle distributions is proposed. Physical implications for the dynamical properties of the magnetotail plasmas and the possible generation of non-Maxwellian features in the distribution functions are discussed.

Fast immersed interface Poisson solver for 3D unbounded problems around arbitrary geometries

NASA Astrophysics Data System (ADS)

Gillis, T.; Winckelmans, G.; Chatelain, P.

2018-02-01

We present a fast and efficient Fourier-based solver for the Poisson problem around an arbitrary geometry in an unbounded 3D domain. This solver merges two rewarding approaches, the lattice Green's function method and the immersed interface method, using the Sherman-Morrison-Woodbury decomposition formula. The method is intended to be second order up to the boundary. This is verified on two potential flow benchmarks. We also further analyse the iterative process and the convergence behavior of the proposed algorithm. The method is applicable to a wide range of problems involving a Poisson equation around inner bodies, which goes well beyond the present validation on potential flows.

Accretion Rate and the Physical Nature of Unobscured Active Galaxies

NASA Astrophysics Data System (ADS)

Trump, Jonathan R.; Impey, Christopher D.; Kelly, Brandon C.; Civano, Francesca; Gabor, Jared M.; Diamond-Stanic, Aleksandar M.; Merloni, Andrea; Urry, C. Megan; Hao, Heng; Jahnke, Knud; Nagao, Tohru; Taniguchi, Yoshi; Koekemoer, Anton M.; Lanzuisi, Giorgio; Liu, Charles; Mainieri, Vincenzo; Salvato, Mara; Scoville, Nick Z.

2011-05-01

We show how accretion rate governs the physical properties of a sample of unobscured broad-line, narrow-line, and lineless active galactic nuclei (AGNs). We avoid the systematic errors plaguing previous studies of AGN accretion rates by using accurate intrinsic accretion luminosities (L int) from well-sampled multiwavelength spectral energy distributions from the Cosmic Evolution Survey, and accurate black hole masses derived from virial scaling relations (for broad-line AGNs) or host-AGN relations (for narrow-line and lineless AGNs). In general, broad emission lines are present only at the highest accretion rates (L int/L Edd > 10-2), and these rapidly accreting AGNs are observed as broad-line AGNs or possibly as obscured narrow-line AGNs. Narrow-line and lineless AGNs at lower specific accretion rates (L int/L Edd < 10-2) are unobscured and yet lack a broad-line region. The disappearance of the broad emission lines is caused by an expanding radiatively inefficient accretion flow (RIAF) at the inner radius of the accretion disk. The presence of the RIAF also drives L int/L Edd < 10-2 narrow-line and lineless AGNs to have ratios of radio-to-optical/UV emission that are 10 times higher than L int/L Edd > 10-2 broad-line AGNs, since the unbound nature of the RIAF means it is easier to form a radio outflow. The IR torus signature also tends to become weaker or disappear from L int/L Edd < 10-2 AGNs, although there may be additional mid-IR synchrotron emission associated with the RIAF. Together, these results suggest that specific accretion rate is an important physical "axis" of AGN unification, as described by a simple model. Based on observations with the XMM-Newton satellite, an ESA science mission with instruments and contributions directly funded by ESA member states and NASA; the Magellan telescope, operated by the Carnegie Observatories; the ESO Very Large Telescope; and the MMT Observatory, a joint facility of the University of Arizona and the Smithsonian Institution; the Subaru Telescope, operated by the National Astronomical Observatory of Japan; and the NASA/ESA Hubble Space Telescope, operated at the Space Telescope Science Institute, which is operated by AURA Inc., under NASA contract NAS 5-26555.

Gamma Decay of Unbound Neutron-Hole States in 133Sn

NASA Astrophysics Data System (ADS)

Vaquero, V.; Jungclaus, A.; Doornenbal, P.; Wimmer, K.; Gargano, A.; Tostevin, J. A.; Chen, S.; Nácher, E.; Sahin, E.; Shiga, Y.; Steppenbeck, D.; Taniuchi, R.; Xu, Z. Y.; Ando, T.; Baba, H.; Garrote, F. L. Bello; Franchoo, S.; Hadynska-Klek, K.; Kusoglu, A.; Liu, J.; Lokotko, T.; Momiyama, S.; Motobayashi, T.; Nagamine, S.; Nakatsuka, N.; Niikura, M.; Orlandi, R.; Saito, T.; Sakurai, H.; Söderström, P. A.; Tveten, G. M.; Vajta, Zs.; Yalcinkaya, M.

2017-05-01

Excited states in the nucleus 133Sn, with one neutron outside the double magic 132Sn core, were populated following one-neutron knockout from a 134Sn beam on a carbon target at relativistic energies at the Radioactive Isotope Beam Factory at RIKEN. Besides the γ rays emitted in the decay of the known neutron single-particle states in 133Sn additional γ strength in the energy range 3.5-5.5 MeV was observed for the first time. Since the neutron-separation energy of 133Sn is low, Sn=2.402 (4 ) MeV , this observation provides direct evidence for the radiative decay of neutron-unbound states in this nucleus. The ability of electromagnetic decay to compete successfully with neutron emission at energies as high as 3 MeV above threshold is attributed to a mismatch between the wave functions of the initial and final states in the latter case. These findings suggest that in the region southeast of 132Sn nuclear structure effects may play a significant role in the neutron versus γ competition in the decay of unbound states. As a consequence, the common neglect of such effects in the evaluation of the neutron-emission probabilities in calculations of global β -decay properties for astrophysical simulations may have to be reconsidered.

Multiple μ-stability of neural networks with unbounded time-varying delays.

PubMed

Wang, Lili; Chen, Tianping

2014-05-01

In this paper, we are concerned with a class of recurrent neural networks with unbounded time-varying delays. Based on the geometrical configuration of activation functions, the phase space R(n) can be divided into several Φη-type subsets. Accordingly, a new set of regions Ωη are proposed, and rigorous mathematical analysis is provided to derive the existence of equilibrium point and its local μ-stability in each Ωη. It concludes that the n-dimensional neural networks can exhibit at least 3(n) equilibrium points and 2(n) of them are μ-stable. Furthermore, due to the compatible property, a set of new conditions are presented to address the dynamics in the remaining 3(n)-2(n) subset regions. As direct applications of these results, we can get some criteria on the multiple exponential stability, multiple power stability, multiple log-stability, multiple log-log-stability and so on. In addition, the approach and results can also be extended to the neural networks with K-level nonlinear activation functions and unbounded time-varying delays, in which there can store (2K+1)(n) equilibrium points, (K+1)(n) of them are locally μ-stable. Numerical examples are given to illustrate the effectiveness of our results. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Study on Pharmacokinetics of Bosentan with Systems Modeling, Part 1: Translating Systemic Plasma Concentration to Liver Exposure in Healthy Subjects.

PubMed

Li, Rui; Niosi, Mark; Johnson, Nathaniel; Tess, David A; Kimoto, Emi; Lin, Jian; Yang, Xin; Riccardi, Keith A; Ryu, Sangwoo; El-Kattan, Ayman F; Maurer, Tristan S; Tremaine, Larry M; Di, Li

2018-04-01

Understanding liver exposure of hepatic transporter substrates in clinical studies is often critical, as it typically governs pharmacodynamics, drug-drug interactions, and toxicity for certain drugs. However, this is a challenging task since there is currently no easy method to directly measure drug concentration in the human liver. Using bosentan as an example, we demonstrate a new approach to estimate liver exposure based on observed systemic pharmacokinetics from clinical studies using physiologically based pharmacokinetic modeling. The prediction was verified to be both accurate and precise using sensitivity analysis. For bosentan, the predicted pseudo steady-state unbound liver-to-unbound systemic plasma concentration ratio was 34.9 (95% confidence interval: 4.2, 50). Drug-drug interaction (i.e., CYP3A and CYP2B6 induction) and inhibition of hepatic transporters (i.e., bile salt export pump, multidrug resistance-associated proteins, and sodium-taurocholate cotransporting polypeptide) were predicted based on the estimated unbound liver tissue or plasma concentrations. With further validation and refinement, we conclude that this approach may serve to predict human liver exposure and complement other methods involving tissue biopsy and imaging. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Formal Definitions of Unbounded Evolution and Innovation Reveal Universal Mechanisms for Open-Ended Evolution in Dynamical Systems.

PubMed

Adams, Alyssa; Zenil, Hector; Davies, Paul C W; Walker, Sara Imari

2017-04-20

Open-ended evolution (OEE) is relevant to a variety of biological, artificial and technological systems, but has been challenging to reproduce in silico. Most theoretical efforts focus on key aspects of open-ended evolution as it appears in biology. We recast the problem as a more general one in dynamical systems theory, providing simple criteria for open-ended evolution based on two hallmark features: unbounded evolution and innovation. We define unbounded evolution as patterns that are non-repeating within the expected Poincare recurrence time of an isolated system, and innovation as trajectories not observed in isolated systems. As a case study, we implement novel variants of cellular automata (CA) where the update rules are allowed to vary with time in three alternative ways. Each is capable of generating conditions for open-ended evolution, but vary in their ability to do so. We find that state-dependent dynamics, regarded as a hallmark of life, statistically out-performs other candidate mechanisms, and is the only mechanism to produce open-ended evolution in a scalable manner, essential to the notion of ongoing evolution. This analysis suggests a new framework for unifying mechanisms for generating OEE with features distinctive to life and its artifacts, with broad applicability to biological and artificial systems.

Matrix effect on leaching of Bisphenol A diglycidyl ether (BADGE) from epoxy resin based inner lacquer of aluminium tubes into semi-solid dosage forms.

PubMed

Lipke, Uwe; Haverkamp, Jan Boris; Zapf, Thomas; Lipperheide, Cornelia

2016-04-01

To study the impact of different semi-solid dosage form components on the leaching of Bisphenol A (BPA) and Bisphenol A diglycidyl ether (BADGE) from the epoxy resin-based inner lacquer of aluminium tubes, the tubes were filled with different matrix preparations and stored at an elevated temperature. Despite compliance with the European Standards EN 15348 and EN 15766 on porosity and polymerisation of internal coatings of aluminium tubes, the commercially available tubes used in the study contained an increased amount of polymerisation residues, such as unbound BPA, BADGE and BADGE derivatives in the lacquer, as determined by acetonitrile extraction. Storage of Macrogol ointments in these tubes resulted in an almost quantitative migration of the unbound polymerisation residues from the coating into the ointment. In addition, due to alterations observed in the RP-HPLC chromatograms of the matrix spiked with BADGE and BADGE derivatives it is supposed that the leachates can react with formulation components. The contamination of the medicinal product by BPA, BADGE and BADGE derivatives can be precluded by using aluminium tubes with an internal lacquer with a low degree of unbound polymerisation residues. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Investigational agents for the treatment of growth hormone-insensitivity syndrome.

PubMed

Kemp, Stephen F; Thrailkill, Kathryn M

2006-04-01

Growth hormone-insensitivity syndrome (GHIS) is usually caused by mutations in the growth hormone receptor. Recombinant IGF-I has been used to treat GHIS either alone (mecasermin) or in combination with IGF-binding protein (IGFBP)-3 (mecasermin rinfabate). IGF-I increases the growth velocity of children with IGF deficiency, which is either as a result of GHIS or an IGF-I gene deletion. Hypoglycaemia has been reported with administration of unbound IGF-I and, in addition, the serum half-life of unbound IGF-I is shorter when administered to patients with GHIS (who have low serum concentrations of its binding protein IGFBP-3) than when administered to normal volunteers or to patients with an IGF-I gene deletion (but normal IGFBP-3 levels). The IGF-I-IGFBP-3 combination was developed to prolong the half-life and counteract the acute adverse events (particularly hypoglycaemia) that are associated with administration of IGF-I. It seems that the IGF-I-IGFBP-3 combination has a longer half-life in patients with GHIS than unbound IGF-I, with fewer reports of adverse events (including hypoglycaemia) when administered to patients with diabetes. There are no studies comparing the efficacy of mecasermin with mecasermin rinfabate; both drugs have been shown to be effective but cannot be differentiated in terms of efficacy.

Determination of total and unbound warfarin and warfarin alcohols in human plasma by high performance liquid chromatography with fluorescence detection.

PubMed

Lomonaco, Tommaso; Ghimenti, Silvia; Piga, Isabella; Onor, Massimo; Melai, Bernardo; Fuoco, Roger; Di Francesco, Fabio

2013-11-01

Two analytical procedures are presented for the determination of the total content and unbound fraction of both warfarin and warfarin alcohols in human plasma. Chromatographic separation was carried out in isocratic conditions at 25°C on a C-18 reversed-phase column with a mobile phase consisting of a 70% buffer phosphate 25mM at pH=7, 25% methanol and 5% acetonitrile at a flow rate of 1.2mL/min. Fluorescence detection was performed at 390nm (excitation wavelength 310nm). Neither method showed any detectable interference or matrix effect. Inter-day recovery of the total warfarin and warfarin alcohols at a concentration level of 1000ng/mL was 89±3% and 73±3%, respectively, whereas for their unbound fraction (at a concentration level of 10ng/mL) was 66±8% and 90±7%, respectively. The intra- and inter-day precision (assessed as relative standard deviation) was <10% for both methods. The limits of detection were 0.4 and 0.2ng/mL for warfarin and warfarin alcohols, respectively. The methods were successfully applied to a pooled plasma sample obtained from 69 patients undergoing warfarin therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

Gamma Decay of Unbound Neutron-Hole States in ^{133}Sn.

PubMed

Vaquero, V; Jungclaus, A; Doornenbal, P; Wimmer, K; Gargano, A; Tostevin, J A; Chen, S; Nácher, E; Sahin, E; Shiga, Y; Steppenbeck, D; Taniuchi, R; Xu, Z Y; Ando, T; Baba, H; Garrote, F L Bello; Franchoo, S; Hadynska-Klek, K; Kusoglu, A; Liu, J; Lokotko, T; Momiyama, S; Motobayashi, T; Nagamine, S; Nakatsuka, N; Niikura, M; Orlandi, R; Saito, T; Sakurai, H; Söderström, P A; Tveten, G M; Vajta, Zs; Yalcinkaya, M

2017-05-19

Excited states in the nucleus ^{133}Sn, with one neutron outside the double magic ^{132}Sn core, were populated following one-neutron knockout from a ^{134}Sn beam on a carbon target at relativistic energies at the Radioactive Isotope Beam Factory at RIKEN. Besides the γ rays emitted in the decay of the known neutron single-particle states in ^{133}Sn additional γ strength in the energy range 3.5-5.5 MeV was observed for the first time. Since the neutron-separation energy of ^{133}Sn is low, S_{n}=2.402(4)  MeV, this observation provides direct evidence for the radiative decay of neutron-unbound states in this nucleus. The ability of electromagnetic decay to compete successfully with neutron emission at energies as high as 3 MeV above threshold is attributed to a mismatch between the wave functions of the initial and final states in the latter case. These findings suggest that in the region southeast of ^{132}Sn nuclear structure effects may play a significant role in the neutron versus γ competition in the decay of unbound states. As a consequence, the common neglect of such effects in the evaluation of the neutron-emission probabilities in calculations of global β-decay properties for astrophysical simulations may have to be reconsidered.

PPI4DOCK: large scale assessment of the use of homology models in free docking over more than 1000 realistic targets.

PubMed

Yu, Jinchao; Guerois, Raphaël

2016-12-15

Protein-protein docking methods are of great importance for understanding interactomes at the structural level. It has become increasingly appealing to use not only experimental structures but also homology models of unbound subunits as input for docking simulations. So far we are missing a large scale assessment of the success of rigid-body free docking methods on homology models. We explored how we could benefit from comparative modelling of unbound subunits to expand docking benchmark datasets. Starting from a collection of 3157 non-redundant, high X-ray resolution heterodimers, we developed the PPI4DOCK benchmark containing 1417 docking targets based on unbound homology models. Rigid-body docking by Zdock showed that for 1208 cases (85.2%), at least one correct decoy was generated, emphasizing the efficiency of rigid-body docking in generating correct assemblies. Overall, the PPI4DOCK benchmark contains a large set of realistic cases and provides new ground for assessing docking and scoring methodologies. Benchmark sets can be downloaded from http://biodev.cea.fr/interevol/ppi4dock/ CONTACT: guerois@cea.frSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Nonlinear diffusion equations as asymptotic limits of Cahn-Hilliard systems on unbounded domains via Cauchy's criterion

NASA Astrophysics Data System (ADS)

Fukao, Takeshi; Kurima, Shunsuke; Yokota, Tomomi

2018-05-01

This paper develops an abstract theory for subdifferential operators to give existence and uniqueness of solutions to the initial-boundary problem (P) for the nonlinear diffusion equation in an unbounded domain $\\Omega\\subset\\mathbb{R}^N$ ($N\\in{\\mathbb N}$), written as \\[ \\frac{\\partial u}{\\partial t} + (-\\Delta+1)\\beta(u) = g \\quad \\mbox{in}\\ \\Omega\\times(0, T), \\] which represents the porous media, the fast diffusion equations, etc., where $\\beta$ is a single-valued maximal monotone function on $\\mathbb{R}$, and $T>0$. Existence and uniqueness for (P) were directly proved under a growth condition for $\\beta$ even though the Stefan problem was excluded from examples of (P). This paper completely removes the growth condition for $\\beta$ by confirming Cauchy's criterion for solutions of the following approximate problem (P)$_{\\varepsilon}$ with approximate parameter $\\varepsilon>0$: \\[ \\frac{\\partial u_{\\varepsilon}}{\\partial t} + (-\\Delta+1)(\\varepsilon(-\\Delta+1)u_{\\varepsilon} + \\beta(u_{\\varepsilon}) + \\pi_{\\varepsilon}(u_{\\varepsilon})) = g \\quad \\mbox{in}\\ \\Omega\\times(0, T), \\] which is called the Cahn--Hilliard system, even if $\\Omega \\subset \\mathbb{R}^N$ ($N \\in \\mathbb{N}$) is an unbounded domain. Moreover, it can be seen that the Stefan problem is covered in the framework of this paper.

Discovery of 72Rb: A Nuclear Sandbank Beyond the Proton Drip Line

NASA Astrophysics Data System (ADS)

Suzuki, H.; Sinclair, L.; Söderström, P.-A.; Lorusso, G.; Davies, P.; Ferreira, L. S.; Maglione, E.; Wadsworth, R.; Wu, J.; Xu, Z. Y.; Nishimura, S.; Doornenbal, P.; Ahn, D. S.; Browne, F.; Fukuda, N.; Inabe, N.; Kubo, T.; Lubos, D.; Patel, Z.; Rice, S.; Shimizu, Y.; Takeda, H.; Baba, H.; Estrade, A.; Fang, Y.; Henderson, J.; Isobe, T.; Jenkins, D.; Kubono, S.; Li, Z.; Nishizuka, I.; Sakurai, H.; Schury, P.; Sumikama, T.; Watanabe, H.; Werner, V.

2017-11-01

In this Letter, the observation of two previously unknown isotopes is presented for the first time: 72Rb with 14 observed events and 77Zr with one observed event. From the nonobservation of the less proton-rich nucleus 73Rb, we derive an upper limit for the ground-state half-life of 81 ns, consistent with the previous upper limit of 30 ns. For 72Rb, we have measured a half-life of 103(22) ns. This observation of a relatively long-lived odd-odd nucleus, 72Rb, with a less exotic odd-even neighbor, 73Rb, being unbound shows the diffuseness of the proton drip line and the possibility of sandbanks to exist beyond it. The 72Rb half-life is consistent with a 5+→5 /2- proton decay with an energy of 800-900 keV, in agreement with the atomic mass evaluation proton-separation energy as well as results from the finite-range droplet model and shell model calculations using the GXPF1A interaction. However, we cannot explicitly exclude the possibility of a proton transition between 9+(72Rb)→9 /2+ (71Kr) isomeric states with a broken mirror symmetry. These results imply that 72Kr is a strong waiting point in x-ray burst r p -process scenarios.

Feedback in the Antennae Galaxies (NGC 4038/9): I. High-Resolution Infrared Spectroscopy of Winds from Super Star Clusters

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

Gilbert, A; Graham, J

2007-06-05

We present high-resolution (R {approx} 24,600) near-IR spectroscopy of the youngest super star clusters (SSCs) in the prototypical starburst merger, the Antennae Galaxies. These SSCs are young (3-7 Myr old) and massive (10{sup 5}-10{sup 7} M{sub {circle_dot}} for a Kroupa IMF) and their spectra are characterized by broad, extended Brackett {gamma} emission, so we refer to them as emission-line clusters (ELCs) to distinguish them from older SSCs. The Br {gamma} lines of most ELCs have supersonic widths (60-110 km s{sup -1} FWHM) and non-Gaussian wings whose velocities exceed the clusters escape velocities. This high-velocity unbound gas is flowing out inmore » winds that are powered by the clusters massive O and W-R stars over the course of at least several crossing times. The large sizes of some ELCs relative to those of older SSCs may be due to expansion caused by these outflows; many of the ELCs may not survive as bound stellar systems, but rather dissipate rapidly into the field population. The observed tendency of older ELCs to be more compact than young ones is consistent with the preferential survival of the most concentrated clusters at a given age.« less

The nu-process

NASA Technical Reports Server (NTRS)

Woosley, S. E.; Hartmann, D. H.; Hoffman, R. D.; Haxton, W. C.

1990-01-01

As the core of a massive star collapses to form a neutron star, the flux of neutrinos in the overlying shells of heavy elements becomes so great that, despite the small cross section, substantial nuclear transmutation is induced. Neutrinos excite heavy elements and even helium to particle unbound levels. The evaporation of a single neutron or proton, and the back reaction of these nucleons on other species present, significantly alters the outcome of traditional nucleosynthesis calculations leading to a new process: nu-nucleosynthesis. Modifications to traditional hydrostatic and explosive varieties of helium, carbon, neon, oxygen, and silicon burning are considered. The results show that a large number of rare isotopes, including many of the odd-Z nuclei from boron through copper, owe much of their present abundance in nature to this process.

Properties of Coulomb crystals: rigorous results.

PubMed

Cioslowski, Jerzy

2008-04-28

Rigorous equalities and bounds for several properties of Coulomb crystals are presented. The energy e(N) per particle pair is shown to be a nondecreasing function of the particle number N for all clusters described by double-power-law pairwise-additive potentials epsilon(r) that are unbound at both r-->0 and r-->infinity. A lower bound for the ratio of the mean reciprocal crystal radius and e(N) is derived. The leading term in the asymptotic expression for the shell capacity that appears in the recently introduced approximate model of Coulomb crystals is obtained, providing in turn explicit large-N asymptotics for e(N) and the mean crystal radius. In addition, properties of the harmonic vibrational spectra are investigated, producing an upper bound for the zero-point energy.

Nonparametric weighted stochastic block models

NASA Astrophysics Data System (ADS)

Peixoto, Tiago P.

2018-01-01

We present a Bayesian formulation of weighted stochastic block models that can be used to infer the large-scale modular structure of weighted networks, including their hierarchical organization. Our method is nonparametric, and thus does not require the prior knowledge of the number of groups or other dimensions of the model, which are instead inferred from data. We give a comprehensive treatment of different kinds of edge weights (i.e., continuous or discrete, signed or unsigned, bounded or unbounded), as well as arbitrary weight transformations, and describe an unsupervised model selection approach to choose the best network description. We illustrate the application of our method to a variety of empirical weighted networks, such as global migrations, voting patterns in congress, and neural connections in the human brain.

A Novel Fluorescence-Labeled Curcumin Conjugate: Synthesis, Evaluation And Imaging On Human Cell Lines.

PubMed

Sheikh, Sumbla; Sturzu, Alexander; Kalbacher, Hubert; Nagele, Thomas; Weidenmaier, Christopher; Horger, Marius; Schwentner, Christian; Ernemann, Ulrike; Heckl, Stefan

2018-04-05

Curcumin, as the main ingredient of the curcuma spice has increasingly become the target of scientific research. The turmeric root which the spice is obtained from has been widely used in traditional medicine and scientific studies found anti-inflammatory, anti-cancer, anti-angiogenic effects as well as antibacterial properties for curcumin. Recently, curcumin has gathered interest as potential therapeutic agent in the research on Alzheimer's disease. A consistent problem in the investigative and therapeutic applications of curcumin is its poor solubility in aqueous solutions. In the present study we synthesized a conjugate of curcumin, the amino acid lysine and the fluorescent dye fluorescein. This conjugate was soluble in cell culture medium and facilitated the examination of curcumin with fluorescence imaging methods. We studied the cell growth impact of unmodified curcumin on seven different human cell lines and then analyzed the uptake and cellular localization of our curcumin conjugate with confocal laser scanning imaging and flow cytometry on the seven cell lines. We found that unbound curcumin inhibited cell growth in vitro and was not taken up into the cells. The curcumin conjugate was internalized into the cell cytoplasm in a dot-like pattern and cellular uptake correlated with cell membrane damage which was measured using propidium iodide. The CAL-72 osteosarcoma cell exhibited 3-4fold increased conjugate uptake and a strong uniform fluorescein staining in addition to the dot-like pattern observed in all cell lines. In conclusion we successfully synthesized a novel water-soluble fluorescent curcumin conjugate which showed a strong preference for CAL-72 osteosarcoma cells in vitro. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Rosetta FlexPepDock ab-initio: simultaneous folding, docking and refinement of peptides onto their receptors.

PubMed

Raveh, Barak; London, Nir; Zimmerman, Lior; Schueler-Furman, Ora

2011-04-29

Flexible peptides that fold upon binding to another protein molecule mediate a large number of regulatory interactions in the living cell and may provide highly specific recognition modules. We present Rosetta FlexPepDock ab-initio, a protocol for simultaneous docking and de-novo folding of peptides, starting from an approximate specification of the peptide binding site. Using the Rosetta fragments library and a coarse-grained structural representation of the peptide and the receptor, FlexPepDock ab-initio samples efficiently and simultaneously the space of possible peptide backbone conformations and rigid-body orientations over the receptor surface of a given binding site. The subsequent all-atom refinement of the coarse-grained models includes full side-chain modeling of both the receptor and the peptide, resulting in high-resolution models in which key side-chain interactions are recapitulated. The protocol was applied to a benchmark in which peptides were modeled over receptors in either their bound backbone conformations or in their free, unbound form. Near-native peptide conformations were identified in 18/26 of the bound cases and 7/14 of the unbound cases. The protocol performs well on peptides from various classes of secondary structures, including coiled peptides with unusual turns and kinks. The results presented here significantly extend the scope of state-of-the-art methods for high-resolution peptide modeling, which can now be applied to a wide variety of peptide-protein interactions where no prior information about the peptide backbone conformation is available, enabling detailed structure-based studies and manipulation of those interactions. © 2011 Raveh et al.

Rosetta FlexPepDock ab-initio: Simultaneous Folding, Docking and Refinement of Peptides onto Their Receptors

PubMed Central

Raveh, Barak; London, Nir; Zimmerman, Lior; Schueler-Furman, Ora

2011-01-01

Flexible peptides that fold upon binding to another protein molecule mediate a large number of regulatory interactions in the living cell and may provide highly specific recognition modules. We present Rosetta FlexPepDock ab-initio, a protocol for simultaneous docking and de-novo folding of peptides, starting from an approximate specification of the peptide binding site. Using the Rosetta fragments library and a coarse-grained structural representation of the peptide and the receptor, FlexPepDock ab-initio samples efficiently and simultaneously the space of possible peptide backbone conformations and rigid-body orientations over the receptor surface of a given binding site. The subsequent all-atom refinement of the coarse-grained models includes full side-chain modeling of both the receptor and the peptide, resulting in high-resolution models in which key side-chain interactions are recapitulated. The protocol was applied to a benchmark in which peptides were modeled over receptors in either their bound backbone conformations or in their free, unbound form. Near-native peptide conformations were identified in 18/26 of the bound cases and 7/14 of the unbound cases. The protocol performs well on peptides from various classes of secondary structures, including coiled peptides with unusual turns and kinks. The results presented here significantly extend the scope of state-of-the-art methods for high-resolution peptide modeling, which can now be applied to a wide variety of peptide-protein interactions where no prior information about the peptide backbone conformation is available, enabling detailed structure-based studies and manipulation of those interactions. PMID:21572516

Particle decay of proton-unbound levels in N 12

DOE PAGES

Chipps, K. A.; Pain, S. D.; Greife, U.; ...

2017-04-24

Transfer reactions are a useful tool for studying nuclear structure, particularly in the regime of low level densities and strong single-particle strengths. Additionally, transfer reactions can populate levels above particle decay thresholds, allowing for the possibility of studying the subsequent decays and furthering our understanding of the nuclei being probed. In particular, the decay of loosely bound nuclei such as 12 N can help inform and improve structure models.The purpose of this paper is to learn about the decay of excited states in 12 N , to more generally inform nuclear structure models, particularly in the case of particle-unbound levelsmore » in low-mass systems which are within the reach of state-of-the-art ab initio calculations.« less

Competing decay modes of a high-spin isomer in the proton-unbound nucleus ¹⁵⁸Ta*

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

Carroll, R. J.; Page, R. D.; Joss, D. T.

2015-01-01

An isomeric state at high spin and excitation energy was recently observed in the proton-unbound nucleus 158Ta. This state was observed to decay by both α and γ decay modes. The large spin change required to decay via γ-ray emission incurs a lifetime long enough for α decay to compete. The α decay has an energy of 8644(11) keV, which is among the highest observed in the region, a partial half-life of 440(70) μs and changes the spin by 11ℏ. In this study, additional evidence supporting the assignment of this α decay to the high-spin isomer in 158Ta will bemore » presented.« less

Approximation of discrete-time LQG compensators for distributed systems with boundary input and unbounded measurement

NASA Technical Reports Server (NTRS)

Gibson, J. S.; Rosen, I. G.

1987-01-01

The approximation of optimal discrete-time linear quadratic Gaussian (LQG) compensators for distributed parameter control systems with boundary input and unbounded measurement is considered. The approach applies to a wide range of problems that can be formulated in a state space on which both the discrete-time input and output operators are continuous. Approximating compensators are obtained via application of the LQG theory and associated approximation results for infinite dimensional discrete-time control systems with bounded input and output. Numerical results for spline and modal based approximation schemes used to compute optimal compensators for a one dimensional heat equation with either Neumann or Dirichlet boundary control and pointwise measurement of temperature are presented and discussed.

Structure and Active Stie Residues of Pg1D, an N-Acetyltransferase from the Bacillosamine Synthetic Pathway Required for N-Glycan Synthesis in Campylobacter jejuni

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

Rangarajan,E.; Ruane, K.; Sulea, T.

2008-01-01

Campylobacter jejuni is highly unusual among bacteria in forming N-linked glycoproteins. The heptasaccharide produced by its pgl system is attached to protein Asn through its terminal 2, 4-diacetamido-2, 4,6-trideoxy-d-Glc (QuiNAc4NAc or N, N'-diacetylbacillosamine) moiety. The crucial, last part of this sugar's synthesis is the acetylation of UDP-2-acetamido-4-amino-2, 4,6-trideoxy-d-Glc by the enzyme PglD, with acetyl-CoA as a cosubstrate. We have determined the crystal structures of PglD in CoA-bound and unbound forms, refined to 1.8 and 1.75 Angstroms resolution, respectively. PglD is a trimer of subunits each comprised of two domains, an N-terminal {alpha}/{beta}-domain and a C-terminal left-handed {beta}-helix. Few structural differencesmore » accompany CoA binding, except in the C-terminal region following the {beta}-helix (residues 189-195), which adopts an extended structure in the unbound form and folds to extend the {beta}-helix upon binding CoA. Computational molecular docking suggests a different mode of nucleotide-sugar binding with respect to the acetyl-CoA donor, with the molecules arranged in an 'L-shape', compared with the 'in-line' orientation in related enzymes. Modeling indicates that the oxyanion intermediate would be stabilized by the NH group of Gly143', with His125' the most likely residue to function as a general base, removing H+ from the amino group prior to nucleophilic attack at the carbonyl carbon of acetyl-CoA. Site-specific mutations of active site residues confirmed the importance of His125', Glu124', and Asn118. We conclude that Asn118 exerts its function by stabilizing the intricate hydrogen bonding network within the active site and that Glu124' may function to increase the pKa of the putative general base, His125'.« less

A novel nanobody-based target module for retargeting of T lymphocytes to EGFR-expressing cancer cells via the modular UniCAR platform

PubMed Central

Albert, Susann; Arndt, Claudia; Feldmann, Anja; Bachmann, Dominik; Koristka, Stefanie; Ludwig, Florian; Ziller-Walter, Pauline; Kegler, Alexandra; Gärtner, Sebastian; Schmitz, Marc; Ehninger, Armin; Cartellieri, Marc; Ehninger, Gerhard; Pietzsch, Hans-Jürgen; Steinbach, Jörg; Bachmann, Michael

2017-01-01

ABSTRACT Recent treatments of leukemias with chimeric antigen receptor (CAR) expressing T cells underline their impressive therapeutic potential. However, once adoptively transferred into patients, there is little scope left to shut them down after elimination of tumor cells or in case adverse side effects occur. This becomes of special relevance if they are directed against commonly expressed tumor associated antigens (TAAs) such as receptors of the ErbB family. To overcome this limitation, we recently established a modular CAR platform technology termed UniCAR. UniCARs are not directed against TAAs but instead against a unique peptide epitope on engineered recombinant targeting modules (TMs), which guide them to the target. In the absence of a TM UniCAR T cells are inactive. Thus an interruption of any UniCAR activity requires an elimination of unbound TM and the TM complexed with UniCAR T cells. Elimination of the latter one requires a disassembly of the UniCAR-TM complexes. Here, we describe a first nanobody (nb)-based TM directed against EGFR. The novel TM efficiently retargets UniCAR T cells to EGFR positive tumors and mediates highly efficient target-specific and target-dependent tumor cell lysis both in vitro and in vivo. After radiolabeling of the novel TM with 64Cu and 68Ga, we analyzed its biodistribution and clearance as well as the stability of the UniCAR-TM complexes. As expected unbound TM is rapidly eliminated while the elimination of the TM complexed with UniCAR T cells is delayed. Nonetheless, we show that UniCAR-TM complexes dissociate in vitro and in vivo in a concentration-dependent manner in line with the concept of a repeated stop and go retargeting of tumor cells via the UniCAR technology. PMID:28507794

A dynamically collapsing core and a precursor of a core in a filament supported by turbulent and magnetic pressures

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

Furuya, Ray S.; Kitamura, Yoshimi; Shinnaga, Hiroko, E-mail: rsf@tokushima-u.ac.jp, E-mail: kitamura@isas.jaxa.jp, E-mail: hiroko.shinnaga@nao.ac.jp

2014-10-01

To study physical properties of the natal filament gas around the cloud core harboring an exceptionally young low-mass protostar GF 9-2, we carried out J = 1-0 line observations of {sup 12}CO, {sup 13}CO, and C{sup 18}O molecules using the Nobeyama 45 m telescope. The mapping area covers ∼ one-fifth of the whole filament. Our {sup 13}CO and C{sup 18}O maps clearly demonstrate that the core formed at the local density maxima of the filament, and the internal motions of the filament gas are totally governed by turbulence with Mach number of ∼2. We estimated the scale height of themore » filament to be H = 0.3-0.7 pc, yielding the central density of n {sub c} = 800-4200 cm{sup –3}. Our analysis adopting an isothermal cylinder model shows that the filament is supported by the turbulent and magnetic pressures against the radial and axial collapse due to self-gravity. Since both the dissipation timescales of the turbulence and the transverse magnetic fields can be comparable to the free-fall time of the filament gas of 10{sup 6} yr, we conclude that the local decay of the supersonic turbulence and magnetic fields made the filament gas locally unstable, hence making the core collapse. Furthermore, we newly detected a gas condensation with velocity width enhancement to ∼0.3 pc southwest of the GF 9-2 core. The condensation has a radius of ∼0.15 pc and an LTE mass of ∼5 M {sub ☉}. Its internal motion is turbulent with Mach number of ∼3, suggesting a gravitationally unbound state. Considering the uncertainties in our estimates, however, we propose that the condensation is a precursor of a cloud core, which would have been produced by the collision of the two gas components identified in the filament.« less

Killing (absorption) versus survival in random motion

NASA Astrophysics Data System (ADS)

Garbaczewski, Piotr

2017-09-01

We address diffusion processes in a bounded domain, while focusing on somewhat unexplored affinities between the presence of absorbing and/or inaccessible boundaries. For the Brownian motion (Lévy-stable cases are briefly mentioned) model-independent features are established of the dynamical law that underlies the short-time behavior of these random paths, whose overall lifetime is predefined to be long. As a by-product, the limiting regime of a permanent trapping in a domain is obtained. We demonstrate that the adopted conditioning method, involving the so-called Bernstein transition function, works properly also in an unbounded domain, for stochastic processes with killing (Feynman-Kac kernels play the role of transition densities), provided the spectrum of the related semigroup operator is discrete. The method is shown to be useful in the case, when the spectrum of the generator goes down to zero and no isolated minimal (ground state) eigenvalue is in existence, like in the problem of the long-term survival on a half-line with a sink at origin.

The Chaplygin Sleigh with Parametric Excitation: Chaotic Dynamics and Nonholonomic Acceleration

NASA Astrophysics Data System (ADS)

Bizyaev, Ivan A.; Borisov, Alexey V.; Mamaev, Ivan S.

2017-12-01

This paper is concerned with the Chaplygin sleigh with time-varying mass distribution (parametric excitation). The focus is on the case where excitation is induced by a material point that executes periodic oscillations in a direction transverse to the plane of the knife edge of the sleigh. In this case, the problem reduces to investigating a reduced system of two first-order equations with periodic coefficients, which is similar to various nonlinear parametric oscillators. Depending on the parameters in the reduced system, one can observe different types of motion, including those accompanied by strange attractors leading to a chaotic (diffusion) trajectory of the sleigh on the plane. The problem of unbounded acceleration (an analog of Fermi acceleration) of the sleigh is examined in detail. It is shown that such an acceleration arises due to the position of the moving point relative to the line of action of the nonholonomic constraint and the center of mass of the platform. Various special cases of existence of tensor invariants are found.

Nuclear structure beyond the neutron drip line. The lowest energy states in 9He via their T=5/2 isobaric analogs in 9Li

DOE PAGES

Uberseder, E.; Rogachev, G. V.; Goldberg, V. Z.; ...

2016-03-01

The level structure of the very neutron rich and unbound 9He nucleus has been the subject of significant experimental and theoretical study. Many recent works have claimed that the two lowest energy 9He states exist with spins J π=1/2 +and Jπ=1/2 -and widths on the order of 100–200 keV. These find-ings cannot be reconciled with our contemporary understanding of nuclear structure. Our present work is the first high-resolution study with low statistical uncertainty of the relevant excitation energy range in the 8He+n system, performed via a search for the T =5/2 isobaric analog states in 9Li populated through 8He+p elasticmore » scattering. Moreover, the present data show no indication of any narrow structures. Instead, we find evidence for a broad J π=1/2 +state in 9He located approximately 3 MeV above the neutron decay threshold.« less

Discovery of a parsec-scale bipolar nebula around MWC 349A

NASA Astrophysics Data System (ADS)

Gvaramadze, V. V.; Menten, K. M.

2012-05-01

We report the discovery of a bipolar nebula around the peculiar emission-line star MWC 349A using archival Spitzer Space Telescope 24 μm data. The nebula extends over several arcminutes (up to 5 pc) and has the same orientation and geometry as the well-known subarcsecond-scale (~400 times smaller) bipolar radio nebula associated with this star. We discuss the physical relationship between MWC 349A and the nearby B0 III star MWC 349B and propose that both stars were members of a hierarchical triple system, which was ejected from the core of the Cyg OB2 association several Myr ago and recently was dissolved into a binary system (now MWC 349A) and a single unbound star (MWC 349B). Our proposal implies that MWC 349A is an evolved massive star (likely a luminous blue variable) in a binary system with a low-mass star. A possible origin of the bipolar nebula around MWC 349A is discussed.

Rigorously modeling self-stabilizing fault-tolerant circuits: An ultra-robust clocking scheme for systems-on-chip.

PubMed

Dolev, Danny; Függer, Matthias; Posch, Markus; Schmid, Ulrich; Steininger, Andreas; Lenzen, Christoph

2014-06-01

We present the first implementation of a distributed clock generation scheme for Systems-on-Chip that recovers from an unbounded number of arbitrary transient faults despite a large number of arbitrary permanent faults. We devise self-stabilizing hardware building blocks and a hybrid synchronous/asynchronous state machine enabling metastability-free transitions of the algorithm's states. We provide a comprehensive modeling approach that permits to prove, given correctness of the constructed low-level building blocks, the high-level properties of the synchronization algorithm (which have been established in a more abstract model). We believe this approach to be of interest in its own right, since this is the first technique permitting to mathematically verify, at manageable complexity, high-level properties of a fault-prone system in terms of its very basic components. We evaluate a prototype implementation, which has been designed in VHDL, using the Petrify tool in conjunction with some extensions, and synthesized for an Altera Cyclone FPGA.

Dynamics in atomic signaling games.

PubMed

Fox, Michael J; Touri, Behrouz; Shamma, Jeff S

2015-07-07

We study an atomic signaling game under stochastic evolutionary dynamics. There are a finite number of players who repeatedly update from a finite number of available languages/signaling strategies. Players imitate the most fit agents with high probability or mutate with low probability. We analyze the long-run distribution of states and show that, for sufficiently small mutation probability, its support is limited to efficient communication systems. We find that this behavior is insensitive to the particular choice of evolutionary dynamic, a property that is due to the game having a potential structure with a potential function corresponding to average fitness. Consequently, the model supports conclusions similar to those found in the literature on language competition. That is, we show that efficient languages eventually predominate the society while reproducing the empirical phenomenon of linguistic drift. The emergence of efficiency in the atomic case can be contrasted with results for non-atomic signaling games that establish the non-negligible possibility of convergence, under replicator dynamics, to states of unbounded efficiency loss. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rigorously modeling self-stabilizing fault-tolerant circuits: An ultra-robust clocking scheme for systems-on-chip☆

PubMed Central

Dolev, Danny; Függer, Matthias; Posch, Markus; Schmid, Ulrich; Steininger, Andreas; Lenzen, Christoph

2014-01-01

We present the first implementation of a distributed clock generation scheme for Systems-on-Chip that recovers from an unbounded number of arbitrary transient faults despite a large number of arbitrary permanent faults. We devise self-stabilizing hardware building blocks and a hybrid synchronous/asynchronous state machine enabling metastability-free transitions of the algorithm's states. We provide a comprehensive modeling approach that permits to prove, given correctness of the constructed low-level building blocks, the high-level properties of the synchronization algorithm (which have been established in a more abstract model). We believe this approach to be of interest in its own right, since this is the first technique permitting to mathematically verify, at manageable complexity, high-level properties of a fault-prone system in terms of its very basic components. We evaluate a prototype implementation, which has been designed in VHDL, using the Petrify tool in conjunction with some extensions, and synthesized for an Altera Cyclone FPGA. PMID:26516290

An investigation of acetylcholine released in skeletal muscle and protein unbound drug released in blood based on the pyridostigmine bromide (pretreatment drug) sustained-release pellets by microdialysis technique in the rabbit model.

PubMed

Huang, Yuh-Tyng; Cheng, Chun-Jen; Lai, Tsun-Fwu; Tsai, Tong-Rong; Tsai, Tung-Hu; Chuo, Wen-Ho; Cham, Thau-Ming

2007-04-18

Pyridostigmine bromide (PB) is a reversible acetylcholinesterase inhibitor that has been used as a pretreatment drug for "Soman" nerve gas poisoning in combat to increase survival. The once-daily PB-sustained-release (SR) pellets were developed by extrusion-spheronization and fluid-bed methods in our laboratory, which was followed by zero-order release mechanism. The results showed that the released concentration of acetylcholine (ACh) in skeletal muscle and the released concentration of protein unbound drug in blood were determined by microdialysis technique to have significant differences (P<0.05) among the three dosage forms (IV injection, commercial IR tablets and the PB-SR pellet). The released concentrations of ACh and protein unbound drug for PB-SR pellets were slower than IV injection and commercial IR tablets; this phenomenon indicating that the retention period of drug efficacy in vivo for PB-SR pellet was longer than the others, that is to say, the PB-SR pellets provided with SR effect in vivo as well. We believe that once-daily administered PB-SR pellets would improve limitations of post-exposure antidotes, decrease the frequency of administration and enhance the retention period of drug efficacy in vivo for personnel exposed to contamination situations in wars or terrorist attacks in the future.

Revisiting hypervelocity stars after Gaia DR2

NASA Astrophysics Data System (ADS)

Boubert, D.; Guillochon, J.; Hawkins, K.; Ginsburg, I.; Evans, N. W.; Strader, J.

2018-06-01

Hypervelocity stars are intriguing rare objects traveling at speeds large enough to be unbound from the Milky Way. Several mechanisms have been proposed for producing them, including the interaction of the Galaxy's super-massive black hole (SMBH) with a binary; rapid mass-loss from a companion to a star in a short-period binary; the tidal disruption of an infalling galaxy and finally ejection from the Large Magellanic Cloud. While previously discovered high-velocity early-type stars are thought to be the result of an interaction with the SMBH, the origin of high-velocity late type stars is ambiguous. The second data release of Gaia (DR2) enables a unique opportunity to resolve this ambiguity and determine whether any late-type candidates are truly unbound from the Milky Way. In this paper, we utilize the new proper motion and velocity information available from DR2 to re-evaluate a collection of historical data compiled on the newly-created Open Fast Stars Catalog. We find that almost all previously-known high-velocity late-type stars are most likely bound to the Milky Way. Only one late-type object (LAMOST J115209.12+120258.0) is unbound from the Galaxy. Performing integrations of orbital histories, we find that this object cannot have been ejected from the Galactic centre and thus may be either debris from the disruption of a satellite galaxy or a disc runaway.

The effect of tenidap sodium on the disposition and plasma protein binding of phenytoin in healthy male volunteers

PubMed Central

Blum, R. A.; Schentag, J. J.; Gardner, M. J.; Wilner, K. D.

1995-01-01

1 The effects of tenidap sodium 120 mg day-1 at steady state and placebo on the plasma protein binding and pharmacokinetics of phenytoin were compared in this randomised, double-blind, placebo-controlled, parallel-group study, involving 12 healthy young men, conducted over 34 days. 2 Single oral doses of phenytoin 200 mg were given on days 1-3 and 29-31, and intravenous phenytoin, 250 mg infused over 20 min, was given on days 4 and 32. Tenidap (120 mg day-1), or matching placebo, was administered as single oral daily doses from days 8 to 34 inclusive. 3 The plasma protein binding of phenytoin was determined immediately before oral phenytoin administration on days 1 and 29. Pharmacokinetic parameters were estimated from the serum phenytoin concentration-time curves derived on days 4 and 32 following the phenytoin infusions. The differences between the pre- and post-treatment mean percentage of unbound plasma phenytoin and mean pharmacokinetic parameters were compared between treatment groups. 4 Tenidap sodium 120 mg day-1, at steady state, increased the percentage of unbound phenytoin in plasma by approximately 25%, but did not significantly affect AUC(0,48h) or Cmax. 5 Since tenidap increases the percentage of unbound phenytoin in plasma, when monitoring phenytoin plasma concentrations free concentrations of phenytoin should be considered. 6 Tenidap was well tolerated throughout the study. PMID:7547092

Computational aspects of pseudospectral Laguerre approximations

NASA Technical Reports Server (NTRS)

Funaro, Daniele

1989-01-01

Pseudospectral approximations in unbounded domains by Laguerre polynomials lead to ill-conditioned algorithms. Introduced are a scaling function and appropriate numerical procedures in order to limit these unpleasant phenomena.

Nanopolyaniline as immobilization template for signal enhancement of surface plasmon resonance biosensor - A preliminary study

NASA Astrophysics Data System (ADS)

Kamarun, Dzaraini; Abdul Azem, Nor Hazirah Kamel; Sarijo, Siti Halimah; Mohd, Ahmad Faiza; Abdullah @ Mohd Noor, Mashita

2012-07-01

A technique for the enhancement of Surface Plasmon Resonance (SPR) signal for sensing biomolecular interactions is described. Polyaniline (PANI) of particle size in the range of 1 to 15 nm was synthesized and used as the template for the immobilization of protein molecules. Biomolecular interactions of unbound and PANI-bound proteins with antibody molecules were SPR-monitored using a model system comprising of Bovine Serum Albumin (BSA) and anti BSA. A 7-fold increased in the signal was recorded from interactions of the PANI-bound BSA with anti BSA compared to the interactions of its unbound counterpart. This preliminary observation provides new avenue in immunosensor technology for improving the detection sensitivity of SPR biosensor; and thereby increasing the lower detection limit of biomolecules.

Sensors closeness test based on an improved [0, 1] bounded Mahalanobis distance Δ{sup 2}

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

Masnan, Maz Jamilah, E-mail: mazjamilah@unimap.edu.my; Mahat, Nor Idayu, E-mail: noridayu@uum.edu.my; Shakaff, Ali Yeon Md, E-mail: aliyeon@unimap.edu.my

2015-12-11

Mahalanobis distance Δ{sup 2} values are commonly in the range of 0 to +∞ where higher values represent greater distance between class means or points. The increase in Mahalanobis distance is unbounded as the distance multiply. To certain extend, the unbounded distance values pose difficulties in the evaluation and decision for instance in the sensors closeness test. This paper proposes an approach to [0, 1] bounded Mahalanobis distance Δ{sup 2} that enable researcher to easily perform sensors closeness test. The experimental data of four different types of rice based on three different electronic nose sensors namely InSniff, PEN3, and Cyranose320more » were analyzed and sensor closeness test seems successfully performed within the [0, 1] bound.« less

Localized states in an unbounded neural field equation with smooth firing rate function: a multi-parameter analysis.

PubMed

Faye, Grégory; Rankin, James; Chossat, Pascal

2013-05-01

The existence of spatially localized solutions in neural networks is an important topic in neuroscience as these solutions are considered to characterize working (short-term) memory. We work with an unbounded neural network represented by the neural field equation with smooth firing rate function and a wizard hat spatial connectivity. Noting that stationary solutions of our neural field equation are equivalent to homoclinic orbits in a related fourth order ordinary differential equation, we apply normal form theory for a reversible Hopf bifurcation to prove the existence of localized solutions; further, we present results concerning their stability. Numerical continuation is used to compute branches of localized solution that exhibit snaking-type behaviour. We describe in terms of three parameters the exact regions for which localized solutions persist.

Classical and quantum dynamics in an inverse square potential

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

Guillaumín-España, Elisa, E-mail: ege@correo.azc.uam.mx; Núñez-Yépez, H. N., E-mail: nyhn@xanum.uam.mx; Salas-Brito, A. L., E-mail: asb@correo.azc.uam.mx

2014-10-15

The classical motion of a particle in a 3D inverse square potential with negative energy, E, is shown to be geodesic, i.e., equivalent to the particle's free motion on a non-compact phase space manifold irrespective of the sign of the coupling constant. We thus establish that all its classical orbits with E < 0 are unbounded. To analyse the corresponding quantum problem, the Schrödinger equation is solved in momentum space. No discrete energy levels exist in the unrenormalized case and the system shows a complete “fall-to-the-center” with an energy spectrum unbounded by below. Such behavior corresponds to the non-existence ofmore » bound classical orbits. The symmetry of the problem is SO(3) × SO(2, 1) corroborating previously obtained results.« less

Stabilisation of discrete-time polynomial fuzzy systems via a polynomial lyapunov approach

NASA Astrophysics Data System (ADS)

Nasiri, Alireza; Nguang, Sing Kiong; Swain, Akshya; Almakhles, Dhafer

2018-02-01

This paper deals with the problem of designing a controller for a class of discrete-time nonlinear systems which is represented by discrete-time polynomial fuzzy model. Most of the existing control design methods for discrete-time fuzzy polynomial systems cannot guarantee their Lyapunov function to be a radially unbounded polynomial function, hence the global stability cannot be assured. The proposed control design in this paper guarantees a radially unbounded polynomial Lyapunov functions which ensures global stability. In the proposed design, state feedback structure is considered and non-convexity problem is solved by incorporating an integrator into the controller. Sufficient conditions of stability are derived in terms of polynomial matrix inequalities which are solved via SOSTOOLS in MATLAB. A numerical example is presented to illustrate the effectiveness of the proposed controller.

Analytical close-to-source investigation for an isotropic point source in an unbounded, anisotropically scattering medium

NASA Astrophysics Data System (ADS)

Rinzema, Kees; ten Bosch, Jaap J.; Ferwerda, Hedzer A.; Hoenders, Bernhard J.

1995-01-01

The diffusion approximation, which is often used to describe the propagation of light in biological tissues, is only good at a sufficient distance from sources and boundaries. Light- tissue interaction is however most intense in the region close to the source. It would therefore be interesting to study this region more closely. Although scattering in biological tissues is predominantly forward peaked, explicit solutions to the transport equation have only been obtained in the case of isotropic scattering. Particularly, for the case of an isotropic point source in an unbounded, isotropically scattering medium the solution is well known. We show that this problem can also be solved analytically if the scattering is no longer isotropic, while everything else remains the same.

The range and valence of a real Smirnov function

NASA Astrophysics Data System (ADS)

Ferguson, Timothy; Ross, William T.

2018-02-01

We give a complete description of the possible ranges of real Smirnov functions (quotients of two bounded analytic functions on the open unit disk where the denominator is outer and such that the radial boundary values are real almost everywhere on the unit circle). Our techniques use the theory of unbounded symmetric Toeplitz operators, some general theory of unbounded symmetric operators, classical Hardy spaces, and an application of the uniformization theorem. In addition, we completely characterize the possible valences for these real Smirnov functions when the valence is finite. To do so we construct Riemann surfaces we call disk trees by welding together copies of the unit disk and its complement in the Riemann sphere. We also make use of certain trees we call valence trees that mirror the structure of disk trees.

Irreversible particle motion in surfactant-laden interfaces due to pressure-dependent surface viscosity

NASA Astrophysics Data System (ADS)

Manikantan, Harishankar; Squires, Todd M.

2017-09-01

The surface shear viscosity of an insoluble surfactant monolayer often depends strongly on its surface pressure. Here, we show that a particle moving within a bounded monolayer breaks the kinematic reversibility of low-Reynolds-number flows. The Lorentz reciprocal theorem allows such irreversibilities to be computed without solving the full nonlinear equations, giving the leading-order contribution of surface pressure-dependent surface viscosity. In particular, we show that a disc translating or rotating near an interfacial boundary experiences a force in the direction perpendicular to that boundary. In unbounded monolayers, coupled modes of motion can also lead to non-intuitive trajectories, which we illustrate using an interfacial analogue of the Magnus effect. This perturbative approach can be extended to more complex geometries, and to two-dimensional suspensions more generally.

Influence of Sampling on the Determination of Warfarin and Warfarin Alcohols in Oral Fluid

PubMed Central

Lomonaco, Tommaso; Ghimenti, Silvia; Piga, Isabella; Biagini, Denise; Onor, Massimo; Fuoco, Roger; Di Francesco, Fabio

2014-01-01

Background and Objective The determination of warfarin, RS/SR- and RR/SS-warfarin alcohols in oral fluid may offer additional information to the INR assay. This study aimed to establish an optimized sampling technique providing the best correlation between the oral fluid and the unbound plasma concentrations of these compounds. Materials and Methods Samples of non-stimulated and stimulated oral fluid, and blood were collected from 14 patients undergoing warfarin therapy. After acidification, analytes were extracted with a dichloromethane/hexane mixture and determined by HPLC with fluorescence detection. Plasma samples were also ultrafiltered for the determination of the unbound fraction. The chromatographic separation was carried out in isocratic conditions with a phosphate buffer/methanol mobile phase on a C-18 reversed-phase column. The absence of interfering compounds was verified by HPLC-ESI-Q-TOF. Results Stimulation generally increased the oral fluid pH to values close to blood pH in about 6 minutes. The concentration of warfarin and RS/SR-warfarin alcohols in oral fluid followed the same trend, whereas the concentration of RR/SS-warfarin alcohols was not affected. Six minute stimulation with chewing gum followed by collection with a polyester swab was the best sampling procedure, with a good repeatability (RSD <10%) and relatively low inter-subject variability (RSD  = 30%) of the oral fluid to plasma ratio. This procedure provided strong correlations between the measured oral fluid and unbound plasma concentration of warfarin (r  =  0.92, p <0.001) and RS/SR-warfarin alcohols (r  =  0.84, p <0.001), as well as between stimulated oral fluid and total plasma concentration of warfarin (r  =  0.78, p <0.001) and RS/SR-warfarin alcohols (r  =  0.81, p <0.001). Conclusion The very good correlation between oral fluid and unbound plasma concentration of warfarin and RS/SR-warfarin alcohols suggests that oral fluid analysis could provide clinically useful information for the monitoring of anticoagulant therapy, complementary to the INR assay. PMID:25478864

ARE ULTRA-LONG GAMMA-RAY BURSTS CAUSED BY BLUE SUPERGIANT COLLAPSARS, NEWBORN MAGNETARS, OR WHITE DWARF TIDAL DISRUPTION EVENTS?

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

Ioka, Kunihito; Hotokezaka, Kenta; Piran, Tsvi, E-mail: kunihito.ioka@yukawa.kyoto-u.ac.jp

Ultra-long gamma-ray bursts (ulGRBs) are a new population of GRBs with extreme durations of ∼10{sup 4} s. Leading candidates for their origin are blue supergiant collapsars, magnetars, and white dwarf tidal disruption events (WD-TDEs) caused by massive black holes (BHs). Recent observations of supernova-like (SN-like) bumps associated with ulGRBs challenged both the WD-TDE and the blue supergiant models because of the detection of SNe and the absence of hydrogen lines, respectively. We propose that WD-TDEs can accommodate the observed SN-like bumps if the fallback WD matter releases energy into the unbound WD ejecta. The observed ejecta energy, luminosity, and velocitymore » are explained by the gravitational energy, Eddington luminosity, and escape velocity of the formed accretion disk, respectively. We also show that the observed X-rays can ionize the ejecta, eliminating lines. The SN-like light curves (SN 2011kl) for the ulGRB 111209A are consistent with all three models, although a magnetar model is unnatural because the spin-down time required to power the SN-like bump is a hundred times longer than the GRB. Our results imply that TDEs are a possible energy source for SN-like events in general and for ulGRBs in particular.« less

Nonlinear dynamics of an elliptic vortex embedded in an oscillatory shear flow.

PubMed

Ryzhov, Eugene A

2017-11-01

The nonlinear dynamics of an elliptic vortex subjected to a time-periodic linear external shear flow is studied numerically. Making use of the ideas from the theory of nonlinear resonance overlaps, the study focuses on the appearance of chaotic regimes in the ellipse dynamics. When the superimposed flow is stationary, two general types of the steady-state phase portrait are considered: one that features a homoclinic separatrix delineating bounded and unbounded phase trajectories and one without a separatrix (all the phase trajectories are bounded in a periodic domain). When the external flow is time-periodic, the ensuing nonlinear dynamics differs significantly in both cases. For the case with a separatrix and two distinct types of phase trajectories: bounded and unbounded, the effect of the most influential nonlinear resonance with the winding number of 1:1 is analyzed in detail. Namely, the process of occupying the central stability region associated with the steady-state elliptic critical point by the stability region associated with the nonlinear resonance of 1:1 as the perturbation frequency gradually varies is investigated. A stark increase in the persistence of the central regular dynamics region against perturbation when the resonance of 1:1 associated stability region occupies the region associated with the steady-state elliptic critical point is observed. An analogous persistence of the regular motion occurs for higher perturbation frequencies when the corresponding stability islands reach the central stability region associated with the steady-state elliptic point. An analysis for the case with the resonance of 1:2 is presented. For the second case with only bounded phase trajectories and, therefore, no separatrix, the appearance of much bigger stability islands associated with nonlinear resonances compared with the case with a separatrix is reported.

An Alternative Origin for Hypervelocity Stars

NASA Astrophysics Data System (ADS)

Abadi, Mario G.; Navarro, Julio F.; Steinmetz, Matthias

2009-02-01

Halo stars with unusually high radial velocity (hypervelocity stars, or HVS) are thought to be stars unbound to the Milky Way that originate from the gravitational interaction of stellar systems with the supermassive black hole at the Galactic center. We examine the latest HVS compilation and find peculiarities that are unexpected in this black hole ejection scenario. For example, a large fraction of HVS cluster around the constellation of Leo and share a common travel time of ~100-200 Myr. Furthermore, their velocities are not really extreme if, as suggested by recent galaxy formation models, the Milky Way is embedded within a 2.5 × 1012 h -1 M sun dark halo with virial velocity of ~220 km s-1. In this case, the escape velocity at ~50 kpc would be ~600 km s-1, and very few HVS would be truly unbound. We use numerical simulations to show that disrupting dwarf galaxies may contribute halo stars with velocities up to and sometimes exceeding the nominal escape speed of the system. These stars are arranged in a thinly collimated outgoing "tidal tail" stripped from the dwarf during its latest pericentric passage. We speculate that some HVS may, therefore, be tidal debris from a dwarf recently disrupted near the center of the Galaxy. In this interpretation, the angular clustering of HVS results because, from our perspective, the tail is seen nearly "end on," whereas the common travel time simply reflects the fact that these stars were stripped simultaneously from the dwarf during a single pericentric passage. This proposal is eminently falsifiable, since it makes a number of predictions which are distinct from the black hole ejection mechanism and which should be testable with improved HVS datasets.

Mass gathering medicine: event factors predicting patient presentation rates.

PubMed

Locoh-Donou, Samuel; Yan, Guofen; Berry, Thomas; O'Connor, Robert; Sochor, Mark; Charlton, Nathan; Brady, William

2016-08-01

This study was conducted to identify the event characteristics of mass gatherings that predict patient presentation rates held in a southeastern US university community. We conducted a retrospective review of all event-based emergency medical services (EMS) records from mass gathering patient presentations over an approximate 23 month period, from October 24, 2009 to August 27, 2011. All patrons seen by EMS were included. Event characteristics included: crowd size, venue percentage filled seating, venue location (inside/outside), venue boundaries (bounded/unbounded), presence of free water (i.e., without cost), presence of alcohol, average heat index, presence of climate control (i.e., air conditioning), and event category (football, concerts, public exhibitions, non-football athletic events). We identified 79 mass gathering events, for a total of 670 patient presentations. The cumulative patron attendance was 917,307 persons. The patient presentation rate (PPR) for each event was calculated as the number of patient presentations per 10,000 patrons in attendance. Overdispersed Poisson regression was used to relate this rate to the event characteristics while controlling for crowd size. In univariate analyses, increased rates of patient presentations were strongly associated with outside venues [rate ratio (RR) = 3.002, p < 0.001], unbounded venues (RR = 2.839, p = 0.001), absence of free water (RR = 1.708, p = 0.036), absence of climate control (RR = 3.028, p < 0.001), and a higher heat index (RR = 1.211 per 10-unit heat index increase, p = 0.003). The presence of alcohol was not significantly associated with the PPR. Football events had the highest PPR, followed sequentially by public exhibitions, concerts, and non-football athletic events. In multivariate models, the strong predictors from the univariate analyses retained their predictive significance for the PPR, together with heat index and percent seating. In the setting of mass event medical care, we note that several factors are strongly associated with an increased patient census, including outside (external) or unbounded venues, the absence of fee water (i.e., without cost), no climate control, percent (occupied) seating, and increasing heat index. Although the presence of alcohol is noted to increase patient needs, it does not do so significantly. Regarding event type, collegiate football games have the highest patient census among the range of other events studied. These findings should be considered during the process of EMS resource planning for mass gatherings.

Search for unbound nuclides and beam/fragment optics with the MoNA/LISA segmented target at NSCL

NASA Astrophysics Data System (ADS)

Gueye, Paul; Frank, Nathan; Thoennessen, Michael; Redpath, Thomas; MoNA Collaboration

2017-09-01

A multi-layered Si/Be segmented target consisting of three 700 mg/cm2 thick Be9 slabs and four 140 microns Si detectors was used by the MoNA Collaboration at the National Superconducting Cyclotron Laboratory of Michigan State University to study the O26 lifetime. This target provides unprecedented information on the incident beams and fragments (energy loss and position), thus allowing for better determination of the incident and outgoing energies and momenta of the detected particles compare to previous experiments conducted at this facility. With the availability of a newly developed Geant4 Monte Carlo simulation of the full N2 vault, we will present and discuss the performances of this target. Search for unbound nuclides and beam/fragment optics with the MoNA/LISA segmented target at NSCL.

Propagation of arbitrary initial wave packets in a quantum parametric oscillator: Instability zones for higher order moments

NASA Astrophysics Data System (ADS)

Biswas, Subhadip; Chattopadhyay, Rohitashwa; Bhattacharjee, Jayanta K.

2018-05-01

We consider the dynamics of a particle in a parametric oscillator with a view to exploring any quantum feature of the initial wave packet that shows divergent (in time) behaviour for parameter values where the classical motion dynamics of the mean position is bounded. We use Ehrenfest's theorem to explore the dynamics of nth order moment which reduces exactly to a linear non autonomous differential equation of order n + 1. It is found that while the width and skewness of the packet is unbounded exactly in the zones where the classical motion is unbounded, the kurtosis of an initially non-gaussian wave packet can become infinitely large in certain additional zones. This implies that the shape of the wave packet can change drastically with time in these zones.

On the possibility of using polycrystalline material in the development of structure-based generic assays

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

Allaire, Marc, E-mail: allaire@bnl.gov; Moiseeva, Natalia; Botez, Cristian E.

The correlation coefficients calculated between raw powder diffraction profiles can be used to identify ligand-bound/unbound states of lysozyme. The discovery of ligands that bind specifically to a targeted protein benefits from the development of generic assays for high-throughput screening of a library of chemicals. Protein powder diffraction (PPD) has been proposed as a potential method for use as a structure-based assay for high-throughput screening applications. Building on this effort, powder samples of bound/unbound states of soluble hen-egg white lysozyme precipitated with sodium chloride were compared. The correlation coefficients calculated between the raw diffraction profiles were consistent with the known bindingmore » properties of the ligands and suggested that the PPD approach can be used even prior to a full description using stereochemically restrained Rietveld refinement.« less

Parabolic transformation cloaks for unbounded and bounded cloaking of matter waves

NASA Astrophysics Data System (ADS)

Chang, Yu-Hsuan; Lin, De-Hone

2014-01-01

Parabolic quantum cloaks with unbounded and bounded invisible regions are presented with the method of transformation design. The mass parameters of particles for perfect cloaking are shown to be constant along the parabolic coordinate axes of the cloaking shells. The invisibility performance of the cloaks is inspected from the viewpoints of waves and probability currents. The latter shows the controllable characteristic of a probability current by a quantum cloak. It also provides us with a simpler and more efficient way of exhibiting the performance of a quantum cloak without the solutions of the transformed wave equation. Through quantitative analysis of streamline structures in the cloaking shell, one defines the efficiency of the presented quantum cloak in the situation of oblique incidence. The cloaking models presented here give us more choices for testing and applying quantum cloaking.

Effects of type 1 and type 2 diabetes on the pharmacokinetics of tramadol enantiomers in patients with neuropathic pain phenotyped as cytochrome P450 2D6 extensive metabolizers.

PubMed

de Moraes, Natália Valadares; Lauretti, Gabriela Rocha; Lanchote, Vera Lucia

2014-09-01

The aim of this study was to evaluate the influence of poorly controlled type 1 (T1DM) and type 2 diabetes mellitus (T2DM) on the pharmacokinetics and metabolism of tramadol enantiomers in patients with neuropathic pain. Nondiabetic patients (control group, n = 12), patients with T1DM (n = 9) or T2DM (n = 9), all with neuropathic pain and phenotyped as cytochrome P450 2D6 extensive metabolizers, received a single oral dose of 100 mg racemic tramadol. Serial blood samples were collected over a 24-h period. Patients with T1DM showed reduced Cmax of both tramadol enantiomers. The plasma concentrations of the active (+)-M1 were significantly reduced in T1DM (area under the curve plasma concentration versus time (AUC∞ ): 313.1 ng·h/ml) when compared with nondiabetic patients (AUC∞ : 1246.6 ng·h/ml). The fraction unbound of (+)-M1 was increased in patients with T1DM. Patients with T1DM and T2DM showed reduced AUC and increased fraction unbound of (-)-M1. The reduced total plasma concentrations of the active (+)-M1 in patients with T1DM may not be of clinical relevance because they are counterbalanced by the increased fraction unbound. © 2014 Royal Pharmaceutical Society.

Determination of Cefalothin and Cefazolin in Human Plasma, Urine and Peritoneal Dialysate by UHPLC-MS/MS: application to a pilot pharmacokinetic study in humans.

PubMed

Parker, Suzanne L; Guerra Valero, Yarmarly C; Roberts, Darren M; Lipman, Jeffrey; Roberts, Jason A; Wallis, Steven C

2016-06-01

An ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the analysis of cefazolin and cefalothin in human plasma (total and unbound), urine and peritoneal dialysate has been developed and validated. Total plasma concentrations are measured following protein precipitation and are suitable for the concentration range of 1-500 µg/mL. Unbound concentrations are measured from ultra-filtered plasma acquired using Centrifree(®) devices and are suitable for the concentration range of 0.1-500 µg/mL for cefazolin and 1-500 µg/mL for cefalothin. The urine method is suitable for a concentration range of 0.1-20 mg/mL for cefazolin and 0.2-20 mg/mL for cefalothin. Peritoneal dialysate concentrations are measured using direct injection, and are suitable for the concentration range of 0.2-100 µg/mL for both cefazolin and cefalothin. The cefazolin and cefalothin plasma (total and unbound), urine and peritoneal dialysate results are reported for recovery, inter-assay precision and accuracy, and the lower limit of quantification, linearity, stability and matrix effects, with all results meeting acceptance criteria. The method was used successfully in a pilot pharmacokinetic study with patients with peritoneal dialysis-associated peritonitis, receiving either intraperitoneal cefazolin or cefalothin. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Measuring in vitro biotransformation rates of super hydrophobic chemicals in rat liver s9 fractions using thin-film sorbent-phase dosing.

PubMed

Lee, Yung-Shan; Otton, S Victoria; Campbell, David A; Moore, Margo M; Kennedy, Chris J; Gobas, Frank A P C

2012-01-03

Methods for rapid and cost-effective assessment of the biotransformation potential of very hydrophobic and potentially bioaccumulative chemicals in mammals are urgently needed for the ongoing global evaluation of the environmental behavior of commercial chemicals. We developed and tested a novel solvent-free, thin-film sorbent-phase in vitro dosing system to measure the in vitro biotransformation rates of very hydrophobic chemicals in male Sprague-Dawley rat liver S9 homogenates and compared the rates to those measured by conventional solvent-delivery dosing. The thin-film sorbent-phase dosing system using ethylene vinyl acetate coated vials was developed to eliminate the incomplete dissolution of very hydrophobic substances in largely aqueous liver homogenates, to determine biotransformation rates at low substrate concentrations, to measure the unbound fraction of substrate in solution, and to simplify chemical analysis by avoiding the difficult extraction of test chemicals from complex biological matrices. Biotransformation rates using sorbent-phase dosing were 2-fold greater than those measured using solvent-delivery dosing. Unbound concentrations of very hydrophobic test chemicals were found to decline with increasing S9 and protein concentrations, causing measured biotransformation rates to be independent of S9 or protein concentrations. The results emphasize the importance of specifying both protein content and unbound substrate fraction in the measurement and reporting of in vitro biotransformation rates of very hydrophobic substances, which can be achieved in a thin-film sorbent-phase dosing system.

Bounded and unbounded boundaries - Untangling mechanisms for estuarine-marine ecological connectivity: Scales of m to 10,000 km - A review

NASA Astrophysics Data System (ADS)

Wolanski, Eric

2017-11-01

Recent advances in our understanding of the self-recruitment and connectivity of estuarine and coastal fauna and flora were made possible by an integration of physical oceanographic observations and modelling with results from studies of the behaviour of the seeds, eggs, larvae, propagules, juveniles and polyps, of population dynamics, microchemical tagging using natural and artificial markers, genetics and direct observations of trajectories. The species studied in those case studies were jellyfish in marine lakes, corals in acidified bays, seagrass, mangrove propagules, mussels and oysters, prawns, some estuarine fish larvae, the copepod Calanus finmarchius in the North Sea, sea turtles in the Coral Sea, and the ornate spiny lobster Panulirus ornatus in the Southeast Asia archipelago. The spatial scales for self-recruitment and connectivity vary with the species from a few m to 10,000 km, and the temporal scales vary from one to three generations. These studies suggest that, with increasing physical openness of a given site for a given species, self-recruiting increasingly relies on the behaviour of the species. Estuarine and coastal systems thus are simultaneously bounded and unbounded depending on the sites and the species considered and, although often ignored, the integration of oceanographic and behavioural understanding is increasingly required. This paper has shown the importance of understanding the hydrological and ecological dynamics with unbounded boundaries in creating the connectivity between parts of the aquatic continuum from the river catchment to the open seas.

Limits on Achievable Dimensional and Photon Efficiencies with Intensity-Modulation and Photon-Counting Due to Non-Ideal Photon-Counter Behavior

NASA Technical Reports Server (NTRS)

Moision, Bruce; Erkmen, Baris I.; Farr, William; Dolinar, Samuel J.; Birnbaum, Kevin M.

2012-01-01

An ideal intensity-modulated photon-counting channel can achieve unbounded photon information efficiencies (PIEs). However, a number of limitations of a physical system limit the practically achievable PIE. In this paper, we discuss several of these limitations and illustrate their impact on the channel. We show that, for the Poisson channel, noise does not strictly bound PIE, although there is an effective limit, as the dimensional information efficiency goes as e[overline] e PIE beyond a threshold PIE. Since the Holevo limit is bounded in the presence of noise, this illustrates that the Poisson approximation is invalid at large PIE for any number of noise modes. We show that a finite transmitter extinction ratio bounds the achievable PIE to a maximum that is logarithmic in the extinction ratio. We show how detector jitter limits the ability to mitigate noise in the PPM signaling framework. We illustrate a method to model detector blocking when the number of detectors is large, and illustrate mitigation of blocking with spatial spreading and altering. Finally, we illustrate the design of a high photon efficiency system using state-of-the-art photo-detectors and taking all these effects into account.

Ekman-Hartmann layer in a magnetohydrodynamic Taylor-Couette flow

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

Szklarski, Jacek; Ruediger, Guenther

2007-12-15

We study magnetic effects induced by rigidly rotating plates enclosing a cylindrical magnetohydrodynamic (MHD) Taylor-Couette flow at the finite aspect ratio H/D=10. The fluid confined between the cylinders is assumed to be liquid metal characterized by small magnetic Prandtl number, the cylinders are perfectly conducting, an axial magnetic field is imposed with Hartmann number Ha{approx_equal}10, and the rotation rates correspond to Reynolds numbers of order 10{sup 2}-10{sup 3}. We show that the end plates introduce, besides the well-known Ekman circulation, similar magnetic effects which arise for infinite, rotating plates, horizontally unbounded by any walls. In particular, there exists the Hartmannmore » current, which penetrates the fluid, turns in the radial direction, and together with the applied magnetic field gives rise to a force. Consequently, the flow can be compared with a Taylor-Dean flow driven by an azimuthal pressure gradient. We analyze the stability of such flows and show that the currents induced by the plates can give rise to instability for the considered parameters. When designing a MHD Taylor-Couette experiment, special care must be taken concerning the vertical magnetic boundaries so that they do not significantly alter the rotational profile.« less

Boundary integral method for interfacial potential flows in unbounded axi-symmetric domains

NASA Astrophysics Data System (ADS)

Tjan, Kuan-Khoon

The numerical simulation of the deformation of a liquid free surface subjected to an impulse (acoustically generated or otherwise) in an axisymmetric semi-infinite domain is considered. Using an inviscid boundary integral formulation, the free surface is evolved under the influence of inertial, interfacial and gravitational forces. Within a range of Atwood ratio, Weber number and Froude number, the evolution eventually led to the ejection of droplets. This research is part of a study of the lung damage caused by ultrasonic imaging. It has been observed in animal experiments that a focused ultrasonic beam can cause lung hemorrhage. A possible explanation is that the hemorrhage is caused by the ejected droplets penetrating gas filled cavities which occurs in the pleural surface of the lungs. It was found that the relationship between Weber number and the size and the velocity of the emitted drop is such that there exists a critical Weber number which maximizes the energy and momentum of the drop. While the objective is to explore alternative damage mechanisms due to ultrasound, the work is not restricted as such. Indeed, the work is concerned with surface tension driven singularities at fluid interface in general. Within this study, different regimes are found and the conditions which define them are summarized with a phase diagram.

An Evaluation of App-Based and Paper-Based Number Lines for Teaching Number Comparison

ERIC Educational Resources Information Center

Weng, Pei-Lin; Bouck, Emily C.

2016-01-01

Number comparison is a fundamental skill required for academic and functional mathematics (e.g., time, money, purchasing) for students with disabilities. The most commonly used method to teach number comparison is number lines. Although historically paper number lines are used, app-based number lines may offer greater flexibility. This study…

General Relativity and Energy

ERIC Educational Resources Information Center

Jackson, A. T.

1973-01-01

Reviews theoretical and experimental fundamentals of Einstein's theory of general relativity. Indicates that recent development of the theory of the continually expanding universe may lead to revision of the space-time continuum of the finite and unbounded universe. (CC)

Behavior of plastic sand confinement grids

DOT National Transportation Integrated Search

1986-01-01

The concept of improving the load carrying ability of unbound aggregates, particularly sand, by lateral confinement has been investigated for some time. Extensive full-scale testing of the trafficability of confined beach sand pavement layers has bee...

Dynamical analysis of an n‑H‑T cosmological quintessence real gas model with a general equation of state

NASA Astrophysics Data System (ADS)

Ivanov, Rossen I.; Prodanov, Emil M.

2018-01-01

The cosmological dynamics of a quintessence model based on real gas with general equation of state is presented within the framework of a three-dimensional dynamical system describing the time evolution of the number density, the Hubble parameter and the temperature. Two global first integrals are found and examples for gas with virial expansion and van der Waals gas are presented. The van der Waals system is completely integrable. In addition to the unbounded trajectories, stemming from the presence of the conserved quantities, stable periodic solutions (closed orbits) also exist under certain conditions and these represent models of a cyclic Universe. The cyclic solutions exhibit regions characterized by inflation and deflation, while the open trajectories are characterized by inflation in a “fly-by” near an unstable critical point.

Real-time assays with molecular beacons and other fluorescent nucleic acid hybridization probes.

PubMed

Marras, Salvatore A E; Tyagi, Sanjay; Kramer, Fred Russell

2006-01-01

A number of formats for nucleic acid hybridization have been developed to identify DNA and RNA sequences that are involved in cellular processes and that aid in the diagnosis of genetic and infectious diseases. The introduction of hybridization probes with interactive fluorophore pairs has enabled the development of homogeneous hybridization assays for the direct identification of nucleic acids. A change in the fluorescence of these probes indicates the presence of a target nucleic acid, and there is no need to separate unbound probes from hybridized probes. The advantages of homogeneous hybridization assays are their speed and simplicity. In addition, homogeneous assays can be combined with nucleic acid amplification, enabling the detection of rare target nucleic acids. These assays can be followed in real time, providing quantitative determination of target nucleic acids over a broad range of concentrations.

Quantum-correlated two-photon transitions to excitons in semiconductor quantum wells.

PubMed

Salazar, L J; Guzmán, D A; Rodríguez, F J; Quiroga, L

2012-02-13

The dependence of the excitonic two-photon absorption on the quantum correlations (entanglement) of exciting biphotons by a semiconductor quantum well is studied. We show that entangled photon absorption can display very unusual features depending on space-time-polarization biphoton parameters and absorber density of states for both bound exciton states as well as for unbound electron-hole pairs. We report on the connection between biphoton entanglement, as quantified by the Schmidt number, and absorption by a semiconductor quantum well. Comparison between frequency-anti-correlated, unentangled and frequency-correlated biphoton absorption is addressed. We found that exciton oscillator strengths are highly increased when photons arrive almost simultaneously in an entangled state. Two-photon-absorption becomes a highly sensitive probe of photon quantum correlations when narrow semiconductor quantum wells are used as two-photon absorbers.

The stability of colorectal cancer mathematical models

NASA Astrophysics Data System (ADS)

Khairudin, Nur Izzati; Abdullah, Farah Aini

2013-04-01

Colorectal cancer is one of the most common types of cancer. To better understand about the kinetics of cancer growth, mathematical models are used to provide insight into the progression of this natural process which enables physicians and oncologists to determine optimal radiation and chemotherapy schedules and develop a prognosis, both of which are indispensable for treating cancer. This thesis investigates the stability of colorectal cancer mathematical models. We found that continuous saturating feedback is the best available model of colorectal cancer growth. We also performed stability analysis. The result shows that cancer progress in sequence of genetic mutations or epigenetic which lead to a very large number of cells population until become unbounded. The cell population growth initiate and its saturating feedback is overcome when mutation changes causing the net per-capita growth rate of stem or transit cells exceed critical threshold.

Coexistence of stable stationary behavior and partial synchrony in an all-to-all coupled spiking neural network

NASA Astrophysics Data System (ADS)

de Smet, Filip; Aeyels, Dirk

2010-12-01

We consider the stationary and the partially synchronous regimes in an all-to-all coupled neural network consisting of an infinite number of leaky integrate-and-fire neurons. Using analytical tools as well as simulation results, we show that two threshold values for the coupling strength may be distinguished. Below the lower threshold, no synchronization is possible; above the upper threshold, the stationary regime is unstable and partial synchrony prevails. In between there is a range of values for the coupling strength where both regimes may be observed. The assumption of an infinite number of neurons is crucial: simulations with a finite number of neurons indicate that above the lower threshold partial synchrony always prevails—but with a transient time that may be unbounded with increasing system size. For values of the coupling strength in a neighborhood of the lower threshold, the finite model repeatedly builds up toward synchronous behavior, followed by a sudden breakdown, after which the synchronization is slowly built up again. The “transient” time needed to build up synchronization again increases with increasing system size, and in the limit of an infinite number of neurons we retrieve stationary behavior. Similarly, within some range for the coupling strength in this neighborhood, a stable synchronous solution may exist for an infinite number of neurons.

SU-F-T-678: Clotrimazole Sensitizes MCF-7 Breast Cancer Cell Line to Radiation

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

Garcia, L; Tambasco, M

2016-06-15

Purpose: To study the effects of Clotrimazole (CLT) on radiosensitivity of MCF-7 Cells in correlation to detachment of Hexokinase II from the Voltage Dependent Anion Channel on the outer membrane of the mitochondria. Apoptotic fractions were also analyzed in relation to the detachment of Hexokinase. Methods: This study focused on the mammary adenocarcinoma cell line, MCF-7. Colony forming assays were used to analyze radiosensitization by CLT. Flow cytometry methods were used to analyze apoptotic vs necrotic fractions after treatment with CLT. Spectrophotometery was used to analyze the mitochondrial bound and soluble fraction of Hexokinase by means of relative enzymatic activity.more » Results: Our preliminary data have shown that CLT sensitizes MCF-7 cells to radiation in a dose and incubation time dependent manner up. We have also demonstrated that there are two radiosensitizing periods in MCF-7 cells with the first corresponding to the cycle arrest after 24 hours observed in other cell lines. The second radiosensitizing period occurs with incubation in CLT after irradiation which reaches maximum effect around 24 hours of incubation time. Preliminary data from our Hexokinase detachment assay show a factor of two increase in the ratio of unbound to bound Hexokinase when comparing incubation for 24 hours in media containing 0 and 20 µM CLT. Conclusion: This study and others indicate CLT as a possible radiosensitizing agent in cancer therapies. While CLT itself shows toxicity to the liver in high doses, this study further demonstrates that disruption of the Warburg Effect and unbinding of mitochondrial bound Hexokinase as a possible pathway for cancer treatment.« less

Limits to TYMS and TP53 genes as predictive determinants for fluoropyrimidine sensitivity and further evidence for an RNA-based toxicity as a major influence

PubMed Central

Brody, Jonathan R.; Hucl, Tomas; Costantino, Christina L.; Eshleman, James; Gallmeier, Eike; Zhu, Heng; Heijden, Michael S. van der; Winter, Jordan M; Wikiewicz, Agnieszka K.; Yeo, Charles J.; Kern, Scott E.

2010-01-01

The major determinants of 5-flurouracil response would appear, based on accumulated literature, to be thymidylate synthase (TYMS, TS) expression levels, TS gene modifications, and TP53 status. We tested 5-fluorouracil sensitivity in yeast and human cancer cell models in which TS or TP53 alleles and expression were varied. Polymorphic TS tandem repeat status, TS expression levels reported, TS intragenic mutations, and TP53 status in outbred and experimental cancer cell lines did not predict 5-FU sensitivity or resistance. Novel observations included a dose-resistant persistence of unbound TS protein in many cancers and, upon 5-FU treatment of the colon cancer cell line, HCT116, evidence of allelic switching favoring transcripts of the mutant TS allele. The reported alleles having an intragenic mutation could not be causally associated with major degrees of 5-FU sensitivity. In yeast, TS protein was altered upon treatment with fluoro-deoxyuridine monophosphate, but 5-FU toxicity appeared largely to be RNA-based, being rescued by uridine rather than by thymidine. Cancer cell lines were also rescued from 5-FU toxicity with uridine rather than thymidine. Additionally, a TS (CDC21) knockout yeast strain, obviating any potential role for TS protein as a target, was hypersensitive to 5-FU. When denatured proteins from cancer cells treated with radio-labeled 5-FU were, labeled species with alternative molecular weights other than TS were visualized, providing further evidence for alternative 5-FU protein targets. These data emphasize that TS and TP53 status do not consistently explain the variance in responses of fluoropyrimidine-treated cancer cells, in part due to RNA-based toxicity. PMID:19155291

The Mental Number Line in Dyscalculia: Impaired Number Sense or Access From Symbolic Numbers?

PubMed

Lafay, Anne; St-Pierre, Marie-Catherine; Macoir, Joël

Numbers may be manipulated and represented mentally over a compressible number line oriented from left to right. According to numerous studies, one of the primary reasons for dyscalculia is related to improper understanding of the mental number line. Children with dyscalculia usually show difficulty when they have to place Arabic numbers on a physical number line. However, it remains unclear whether they have a deficit with the mental number line per se or a deficit with accessing it from nonsymbolic and/or symbolic numbers. Quebec French-speaking 8- to 9-year-old children with (24) and without (37) dyscalculia were assessed with transcoding tasks ( number-to-position and position-to-number) designed to assess the acuity of the mental number line with Arabic and spoken numbers as well as with analogic numerosities. Results showed that children with dyscalculia produced a larger percentage absolute error than children without mathematics difficulties in every task except the number-to-position transcoding task with analogic numerosities. Hence, these results suggested that children with dyscalculia do not have a general deficit of the mental number line but rather a deficit with accessing it from symbolic numbers.

Improving accuracy of unbound resilient modulus testing

DOT National Transportation Integrated Search

1997-07-01

The P46 Laboratory Startup and Quality Control Procedure was developed to ensure the accuracy and reliability of the resilient modulus data produced while testing soil and aggregate materials using closed-loop servo-hydraulic systems. It was develope...

Prometheus unbound: A study of the Dallas/Fort Worth Regional Airport. [Socio-economic considerations

NASA Technical Reports Server (NTRS)

Starling, J. D.; Brown, J.; Dominus, M. I.

1975-01-01

The history of the controversies in the development of the Dallas/Fort Worth Regional Airport is detailed. Present technological and organizational management problems are outlined. Maps and illustrations are included.

50 CFR 679.61 - Formation and operation of fishery cooperatives.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ECONOMIC ZONE OFF ALASKA American Fisheries Act and Aleutian Island Directed Pollock Fishery Management... duplication on unbound single-sided 8.5- by-11-inch paper, or in an alternative format approved in advance by...

Standardizing lightweight deflectometer modulus measurements for compaction quality assurance

DOT National Transportation Integrated Search

2017-09-01

To evaluate the compaction of unbound geomaterials under unsaturated conditions and replace the conventional methods with a practical modulus-based specification using LWD, this study examined three different LWDs, the Zorn ZFG 3000 LWD, Dynatest 303...

Low-cost rural surface alternatives : literature review and recommendations.

DOT National Transportation Integrated Search

2013-12-01

Freezing and thawing action induces damage to unbound gravel roads in Iowa resulting in maintenance costs for secondary road departments. Some approaches currently used by County Engineers to deal with this problem include temporarily spreading rock ...

Operator algebra as an application of logarithmic representation of infinitesimal generators

NASA Astrophysics Data System (ADS)

Iwata, Yoritaka

2018-02-01

The operator algebra is introduced based on the framework of logarithmic representation of infinitesimal generators. In conclusion a set of generally-unbounded infinitesimal generators is characterized as a module over the Banach algebra.

Constraining gluon distributions in nuclei using dijets in proton-proton and proton-lead collisions at $$\\sqrt{s_{_\\mathrm{NN}}} =$$ 5.02 TeV

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

Sirunyan, Albert M; et al.

2018-05-12

The pseudorapidity distributions of dijets as a function of their average transverse momentum (more » $$p_\\mathrm{T}^\\text{ave}$$) are measured in proton-lead (pPb) and proton-proton (pp) collisions. The data samples were collected by the CMS experiment at the CERN LHC, at a nucleon-nucleon center-of-mass energy of 5.02 TeV. A significant modification of the pPb spectra with respect to the pp spectra is observed in all $$p_\\mathrm{T}^\\text{ave}$$ intervals investigated. The ratios of the pPb and pp distributions are compared to next-to-leading order perturbative quantum chromodynamics calculations with unbound nucleon and nuclear parton distribution functions (PDFs). These results give the first evidence that the gluon PDF at large Bjorken $x$ in lead ions is strongly suppressed with respect to the PDF in unbound nucleons.« less

The control gain region for synchronization in non-diffusively coupled complex networks

NASA Astrophysics Data System (ADS)

Gequn, Liu; Wenhui, Li; Huijie, Yang; Knowles, Gareth

2014-07-01

The control gain region for synchronization of non-diffusively coupled networks was studied with respect to three conditions: synchronization, synchronization in finite time, and synchronization in the minimum time. Based on cancellation control methodology and master stability function formalism, we found that a complete feasible control gain region may be bounded, unbounded, empty or a union of several bounded and unbounded regions, with a similar shape to the synchronized region. An interesting possibility emerged that a network could be synchronized by both negative and positive feedback control simultaneously. By bridging synchronizability and synchronizing response speeds with a settling time index, we have developed timed synchronized region (TSR) as a substitute for the classical synchronized region to study finite time synchronization. As for the last condition, a graphical method was developed to estimate control gain with the minimum synchronization time (CGMST). Each condition has examples provided for illustration and verification.

In vivo excitation of nanoparticles using luminescent bacteria

PubMed Central

Dragavon, Joe; Blazquez, Samantha; Rekiki, Abdessalem; Samson, Chelsea; Theodorou, Ioanna; Rogers, Kelly L.; Tournebize, Régis; Shorte, Spencer L.

2012-01-01

The lux operon derived from Photorhabdus luminescens incorporated into bacterial genomes, elicits the production of biological chemiluminescence typically centered on 490 nm. The light-producing bacteria are widely used for in vivo bioluminescence imaging. However, in living samples, a common difficulty is the presence of blue-green absorbers such as hemoglobin. Here we report a characterization of fluorescence by unbound excitation from luminescence, a phenomenon that exploits radiating luminescence to excite nearby fluorophores by epifluorescence. We show that photons from bioluminescent bacteria radiate over mesoscopic distances and induce a red-shifted fluorescent emission from appropriate fluorophores in a manner distinct from bioluminescence resonance energy transfer. Our results characterizing fluorescence by unbound excitation from luminescence, both in vitro and in vivo, demonstrate how the resulting blue-to-red wavelength shift is both necessary and sufficient to yield contrast enhancement revealing mesoscopic proximity of luminescent and fluorescent probes in the context of living biological tissues. PMID:22615349

The quantum holonomy-diffeomorphism algebra and quantum gravity

NASA Astrophysics Data System (ADS)

Aastrup, Johannes; Grimstrup, Jesper Møller

2016-03-01

We introduce the quantum holonomy-diffeomorphism ∗-algebra, which is generated by holonomy-diffeomorphisms on a three-dimensional manifold and translations on a space of SU(2)-connections. We show that this algebra encodes the canonical commutation relations of canonical quantum gravity formulated in terms of Ashtekar variables. Furthermore, we show that semiclassical states exist on the holonomy-diffeomorphism part of the algebra but that these states cannot be extended to the full algebra. Via a Dirac-type operator we derive a certain class of unbounded operators that act in the GNS construction of the semiclassical states. These unbounded operators are the type of operators, which we have previously shown to entail the spatial three-dimensional Dirac operator and Dirac-Hamiltonian in a semiclassical limit. Finally, we show that the structure of the Hamilton constraint emerges from a Yang-Mills-type operator over the space of SU(2)-connections.

Metronidazole and hydroxymetronidazole central nervous system distribution: 2. cerebrospinal fluid concentration measurements in patients with external ventricular drain.

PubMed

Frasca, Denis; Dahyot-Fizelier, Claire; Adier, Christophe; Mimoz, Olivier; Debaene, Bertrand; Couet, William; Marchand, Sandrine

2014-01-01

This study explored metronidazole and hydroxymetronidazole distribution in the cerebrospinal fluid (CSF) of brain-injured patients. Four brain-injured patients with external ventricular drain received 500 mg of metronidazole over 0.5 h every 8 h. CSF and blood samples were collected at steady state over 8 h, and the metronidazole and hydroxymetronidazole concentrations were assayed by high-pressure liquid chromatograph. A noncompartmental analysis was performed. Metronidazole is distributed extensively within CSF, with a mean CSF to unbound plasma AUC0-τ ratio of 86% ± 16%. However, the concentration profiles in CSF were mostly flat compared to the plasma profiles. Hydroxymetronidazole concentrations were much lower than those of metronidazole both in plasma and in CSF, with a corresponding CSF/unbound plasma AUC0-τ ratio of 79% ± 16%. We describe here for the first time in detail the pharmacokinetics of metronidazole and hydroxymetronidazole in CSF.

Modeling and Managing Risk in Billing Infrastructures

NASA Astrophysics Data System (ADS)

Baiardi, Fabrizio; Telmon, Claudio; Sgandurra, Daniele

This paper discusses risk modeling and risk management in information and communications technology (ICT) systems for which the attack impact distribution is heavy tailed (e.g., power law distribution) and the average risk is unbounded. Systems with these properties include billing infrastructures used to charge customers for services they access. Attacks against billing infrastructures can be classified as peripheral attacks and backbone attacks. The goal of a peripheral attack is to tamper with user bills; a backbone attack seeks to seize control of the billing infrastructure. The probability distribution of the overall impact of an attack on a billing infrastructure also has a heavy-tailed curve. This implies that the probability of a massive impact cannot be ignored and that the average impact may be unbounded - thus, even the most expensive countermeasures would be cost effective. Consequently, the only strategy for managing risk is to increase the resilience of the infrastructure by employing redundant components.

Superior memory efficiency of quantum devices for the simulation of continuous-time stochastic processes

NASA Astrophysics Data System (ADS)

Elliott, Thomas J.; Gu, Mile

2018-03-01

Continuous-time stochastic processes pervade everyday experience, and the simulation of models of these processes is of great utility. Classical models of systems operating in continuous-time must typically track an unbounded amount of information about past behaviour, even for relatively simple models, enforcing limits on precision due to the finite memory of the machine. However, quantum machines can require less information about the past than even their optimal classical counterparts to simulate the future of discrete-time processes, and we demonstrate that this advantage extends to the continuous-time regime. Moreover, we show that this reduction in the memory requirement can be unboundedly large, allowing for arbitrary precision even with a finite quantum memory. We provide a systematic method for finding superior quantum constructions, and a protocol for analogue simulation of continuous-time renewal processes with a quantum machine.

A computational tool to predict the evolutionarily conserved protein-protein interaction hot-spot residues from the structure of the unbound protein.

PubMed

Agrawal, Neeraj J; Helk, Bernhard; Trout, Bernhardt L

2014-01-21

Identifying hot-spot residues - residues that are critical to protein-protein binding - can help to elucidate a protein's function and assist in designing therapeutic molecules to target those residues. We present a novel computational tool, termed spatial-interaction-map (SIM), to predict the hot-spot residues of an evolutionarily conserved protein-protein interaction from the structure of an unbound protein alone. SIM can predict the protein hot-spot residues with an accuracy of 36-57%. Thus, the SIM tool can be used to predict the yet unknown hot-spot residues for many proteins for which the structure of the protein-protein complexes are not available, thereby providing a clue to their functions and an opportunity to design therapeutic molecules to target these proteins. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Predicted space motions for hypervelocity and runaway stars: proper motions and radial velocities for the Gaia Era

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

Kenyon, Scott J.; Brown, Warren R.; Geller, Margaret J.

We predict the distinctive three-dimensional space motions of hypervelocity stars (HVSs) and runaway stars moving in a realistic Galactic potential. For nearby stars with distances less than 10 kpc, unbound stars are rare; proper motions alone rarely isolate bound HVSs and runaways from indigenous halo stars. At large distances of 20-100 kpc, unbound HVSs are much more common than runaways; radial velocities easily distinguish both from indigenous halo stars. Comparisons of the predictions with existing observations are encouraging. Although the models fail to match observations of solar-type HVS candidates from SEGUE, they agree well with data for B-type HVS andmore » runaways from other surveys. Complete samples of g ≲ 20 stars with Gaia should provide clear tests of formation models for HVSs and runaways and will enable accurate probes of the shape of the Galactic potential.« less

Stellar dynamics. The fastest unbound star in our Galaxy ejected by a thermonuclear supernova.

PubMed

Geier, S; Fürst, F; Ziegerer, E; Kupfer, T; Heber, U; Irrgang, A; Wang, B; Liu, Z; Han, Z; Sesar, B; Levitan, D; Kotak, R; Magnier, E; Smith, K; Burgett, W S; Chambers, K; Flewelling, H; Kaiser, N; Wainscoat, R; Waters, C

2015-03-06

Hypervelocity stars (HVSs) travel with velocities so high that they exceed the escape velocity of the Galaxy. Several acceleration mechanisms have been discussed. Only one HVS (US 708, HVS 2) is a compact helium star. Here we present a spectroscopic and kinematic analysis of US 708. Traveling with a velocity of ~1200 kilometers per second, it is the fastest unbound star in our Galaxy. In reconstructing its trajectory, the Galactic center becomes very unlikely as an origin, which is hardly consistent with the most favored ejection mechanism for the other HVSs. Furthermore, we detected that US 708 is a fast rotator. According to our binary evolution model, it was spun-up by tidal interaction in a close binary and is likely to be the ejected donor remnant of a thermonuclear supernova. Copyright © 2015, American Association for the Advancement of Science.

Method and apparatus for shape and end position determination using an optical fiber

NASA Technical Reports Server (NTRS)

Moore, Jason P. (Inventor)

2010-01-01

A method of determining the shape of an unbound optical fiber includes collecting strain data along a length of the fiber, calculating curvature and bending direction data of the fiber using the strain data, curve-fitting the curvature and bending direction data to derive curvature and bending direction functions, calculating a torsion function using the bending direction function, and determining the 3D shape from the curvature, bending direction, and torsion functions. An apparatus for determining the 3D shape of the fiber includes a fiber optic cable unbound with respect to a protective sleeve, strain sensors positioned along the cable, and a controller in communication with the sensors. The controller has an algorithm for determining a 3D shape and end position of the fiber by calculating a set of curvature and bending direction data, deriving curvature, bending, and torsion functions, and solving Frenet-Serret equations using these functions.

Coordinating Numeric and Linear Units: Elementary Students' Strategies for Locating Whole Numbers on the Number Line

ERIC Educational Resources Information Center

Saxe, Geoffrey B.; Shaughnessy, Meghan M.; Gearhart, Maryl; Haldar, Lina Chopra

2013-01-01

Two investigations of fifth graders' strategies for locating whole numbers on number lines revealed patterns in students' coordination of numeric and linear units. In Study 1, we investigated the effects of context on students' placements of three numbers on an open number line. For one group ("n"?=?24), the line was presented in a…

Mental Number Line, Number Line Estimation, and Mathematical Achievement: Their Interrelations in Grades 5 and 6

ERIC Educational Resources Information Center

Schneider, Michael; Grabner, Roland H.; Paetsch, Jennifer

2009-01-01

As indicated by the distance effect and the spatial-numerical association of response codes (SNARC) effect, natural numbers are mentally represented on a number line. Purportedly, this number line underlies children's number sense, which supports the acquisition of more advanced mathematical competencies. In 3 studies with a total of 429 fifth and…

Children's Early Mental Number Line: Logarithmic or Decomposed Linear?

ERIC Educational Resources Information Center

Moeller, Korbinean; Pixner, Silvia; Kaufmann, Liane; Nuerk, Hans-Christoph

2009-01-01

Recently, the nature of children's mental number line has received much investigation. In the number line task, children are required to mark a presented number on a physical number line with fixed endpoints. Typically, it was observed that the estimations of younger/inexperienced children were accounted for best by a logarithmic function, whereas…

A single scan skeletonization algorithm: application to medical imaging of trabecular bone

NASA Astrophysics Data System (ADS)

Arlicot, Aurore; Amouriq, Yves; Evenou, Pierre; Normand, Nicolas; Guédon, Jean-Pierre

2010-03-01

Shape description is an important step in image analysis. The skeleton is used as a simple, compact representation of a shape. A skeleton represents the line centered in the shape and must be homotopic and one point wide. Current skeletonization algorithms compute the skeleton over several image scans, using either thinning algorithms or distance transforms. The principle of thinning is to delete points as one goes along, preserving the topology of the shape. On the other hand, the maxima of the local distance transform identifies the skeleton and is an equivalent way to calculate the medial axis. However, with this method, the skeleton obtained is disconnected so it is required to connect all the points of the medial axis to produce the skeleton. In this study we introduce a translated distance transform and adapt an existing distance driven homotopic algorithm to perform skeletonization with a single scan and thus allow the processing of unbounded images. This method is applied, in our study, on micro scanner images of trabecular bones. We wish to characterize the bone micro architecture in order to quantify bone integrity.

Windowed Green function method for the Helmholtz equation in the presence of multiply layered media

NASA Astrophysics Data System (ADS)

Bruno, O. P.; Pérez-Arancibia, C.

2017-06-01

This paper presents a new methodology for the solution of problems of two- and three-dimensional acoustic scattering (and, in particular, two-dimensional electromagnetic scattering) by obstacles and defects in the presence of an arbitrary number of penetrable layers. Relying on the use of certain slow-rise windowing functions, the proposed windowed Green function approach efficiently evaluates oscillatory integrals over unbounded domains, with high accuracy, without recourse to the highly expensive Sommerfeld integrals that have typically been used to account for the effect of underlying planar multilayer structures. The proposed methodology, whose theoretical basis was presented in the recent contribution (Bruno et al. 2016 SIAM J. Appl. Math. 76, 1871-1898. (doi:10.1137/15M1033782)), is fast, accurate, flexible and easy to implement. Our numerical experiments demonstrate that the numerical errors resulting from the proposed approach decrease faster than any negative power of the window size. In a number of examples considered in this paper, the proposed method is up to thousands of times faster, for a given accuracy, than corresponding methods based on the use of Sommerfeld integrals.

Windowed Green function method for the Helmholtz equation in the presence of multiply layered media.

PubMed

Bruno, O P; Pérez-Arancibia, C

2017-06-01

This paper presents a new methodology for the solution of problems of two- and three-dimensional acoustic scattering (and, in particular, two-dimensional electromagnetic scattering) by obstacles and defects in the presence of an arbitrary number of penetrable layers. Relying on the use of certain slow-rise windowing functions, the proposed windowed Green function approach efficiently evaluates oscillatory integrals over unbounded domains, with high accuracy, without recourse to the highly expensive Sommerfeld integrals that have typically been used to account for the effect of underlying planar multilayer structures. The proposed methodology, whose theoretical basis was presented in the recent contribution (Bruno et al. 2016 SIAM J. Appl. Math. 76 , 1871-1898. (doi:10.1137/15M1033782)), is fast, accurate, flexible and easy to implement. Our numerical experiments demonstrate that the numerical errors resulting from the proposed approach decrease faster than any negative power of the window size. In a number of examples considered in this paper, the proposed method is up to thousands of times faster, for a given accuracy, than corresponding methods based on the use of Sommerfeld integrals.

Dynamics of flexible fibers transported in confined viscous flows

NASA Astrophysics Data System (ADS)

Cappello, Jean; Duprat, Camille; Du Roure, Olivia; Nagel, Mathias; Gallaire, François; Lindner, Anke

2017-11-01

The dynamics of elongated objects has been extensively studied in unbounded media as for example the sedimentation of fibers at low Reynolds numbers. It has recently been shown that these transport dynamics are strongly modified by bounding walls. Here we focus on the dynamics of flexible fibers confined by the top and bottom walls of a microchannel and transported in pressure-driven flows. We combine well-controlled microfluidic experiments and simulations using modified Brinkmann equations. We control shape, orientation, and mechanical properties of our fibers using micro-fabrication techniques and in-situ characterization methods. These elastic fibers can be deformed by viscous and pressure forces leading to very rich transport dynamics coupling lateral drift with shape evolution. We show that the bending of a perpendicular fiber is proportional to an elasto-viscous number and we fully characterize the influence of the confinement on the deformation of the fiber. Experiments on parallel flexible fibers reveal the existence of a buckling threshold. The European Research Council is acknowledged for funding the work through a consolidator Grant (ERC PaDyFlow 682367).

An evaluation of the CYP2D6 and CYP3A4 inhibition potential of metoprolol metabolites and their contribution to drug-drug and drug-herb interaction by LC-ESI/MS/MS.

PubMed

Borkar, Roshan M; Bhandi, Murali Mohan; Dubey, Ajay P; Ganga Reddy, V; Komirishetty, Prashanth; Nandekar, Prajwal P; Sangamwar, Abhay T; Kamal, Ahmed; Banerjee, Sanjay K; Srinivas, R

2016-10-01

The aim of the present study was to evaluate the contribution of metabolites to drug-drug interaction and drug-herb interaction using the inhibition of CYP2D6 and CYP3A4 by metoprolol (MET) and its metabolites. The peak concentrations of unbound plasma concentration of MET, α-hydroxy metoprolol (HM), O-desmethyl metoprolol (ODM) and N-desisopropyl metoprolol (DIM) were 90.37 ± 2.69, 33.32 ± 1.92, 16.93 ± 1.70 and 7.96 ± 0.94 ng/mL, respectively. The metabolites identified, HM and ODM, had a ratio of metabolic area under the concentration-time curve (AUC) to parent AUC of ≥0.25 when either total or unbound concentration of metabolite was considered. In vitro CYP2D6 and CYP3A4 inhibition by MET, HM and ODM study revealed that MET, HM and ODM were not inhibitors of CYP3A4-catalyzed midazolam metabolism and CYP2D6-catalyzed dextromethorphan metabolism. However, DIM only met the criteria of >10% of the total drug related material and <25% of the parent using unbound concentrations. If CYP inhibition testing is solely based on metabolite exposure, DIM metabolite would probably not be considered. However, the present study has demonstrated that DIM contributes significantly to in vitro drug-drug interaction. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Strength and Persistence of Energy-Based Vessel Seals Rely on Tissue Water and Glycosaminoglycan Content.

PubMed

Kramer, Eric A; Cezo, James D; Fankell, Douglas P; Taylor, Kenneth D; Rentschler, Mark E; Ferguson, Virginia L

2016-11-01

Vessel ligation using energy-based surgical devices is steadily replacing conventional closure methods during minimally invasive and open procedures. In exploring the molecular nature of thermally-induced tissue bonds, novel applications for surgical resection and repair may be revealed. This work presents an analysis of the influence of unbound water and hydrophilic glycosaminoglycans on the formation and resilience of vascular seals via: (a) changes in pre-fusion tissue hydration, (b) the enzymatic digestion of glycosaminoglycans (GAGs) prior to fusion and (c) the rehydration of vascular seals following fusion. An 11% increase in pre-fusion unbound water led to an 84% rise in vascular seal strength. The digestion of GAGs prior to fusion led to increases of up to 82% in seal strength, while the rehydration of native and GAG-digested vascular seals decreased strengths by 41 and 44%, respectively. The effects of increased unbound water content prior to fusion combined with the effects of seal rehydration after fusion suggest that the heat-induced displacement of tissue water is a major contributor to tissue adhesion during energy-based vessel sealing. The effects of pre-fusion GAG-digestion on seal integrity indicate that GAGs are inhibitory to the bond formation process during thermal ligation. GAG digestion may allow for increased water transport and protein interaction during the fusion process, leading to the formation of stronger bonds. These findings provide insight into the physiochemical nature of the fusion bond, its potential for optimization in vascular closure and its application to novel strategies for vascular resection and repair.

Effect of alpha(1)-acid glycoprotein on the pharmacokinetics of tamsulosin in rats treated with turpentine oil.

PubMed

Matsushima, H; Watanabe, T; Higuchi, S

2000-04-01

The pharmacokinetics of tamsulosin (TAM) was investigated using male Sprague-Dawley rats in which plasma alpha(1)-acid glycoprotein (alpha(1)-AGP) levels were elevated by the subcutaneous injection of 0.2 mL/kg of turpentine oil. alpha(1)-AGP levels increased about eight times after turpentine oil treatment, causing a threefold decrease in plasma unbound fraction (f(u)) of TAM. When 0.3 mg/kg of TAM was dosed intravenously, total and nonrenal clearances (CL(tot) and CL(nr)) in turpentine-treated rats were 47% and 44% lower than those in nontreated controls, respectively. The area under the concentration-time curve of plasma unbound TAM (AUC(inf,u)) was lower than that in the control. When 1 mg/kg of TAM was dosed orally, oral clearance (CL(oral)) in alpha1-AGP-induced rats was 65% lower than in the control. The AUC(inf,u) and unbound oral clearance (CL(oral,u)) were nearly equal in both groups. Moreover, a positive correlation was observed between fu and CL(oral) of TAM (r(2) = 0.603, P < 0.01), whereas no correlation was observed between f(u) and CL(oral,u). The absolute bioavailability (BA) increased from 19.2% to 46.9% by induction of alpha(1)-AGP. These results suggest that decreased f(u) caused by the elevation of plasma alpha(1)-AGP level affects the pharmacokinetics of TAM, but does not affect the CL(oral,u,) which represents the hepatic metabolism of TAM. Copyright 2000 Wiley-Liss, Inc.

Tacrolimus placental transfer at delivery and neonatal exposure through breast milk.

PubMed

Zheng, Songmao; Easterling, Thomas R; Hays, Karen; Umans, Jason G; Miodovnik, Menachem; Clark, Shannon; Calamia, Justina C; Thummel, Kenneth E; Shen, Danny D; Davis, Connie L; Hebert, Mary F

2013-12-01

The current investigation aims to provide new insights into fetal exposure to tacrolimus in utero by evaluating maternal and umbilical cord blood (venous and arterial), plasma and unbound concentrations at delivery. This study also presents a case report of tacrolimus excretion via breast milk. Maternal and umbilical cord (venous and arterial) samples were obtained at delivery from eight solid organ allograft recipients to measure tacrolimus and metabolite bound and unbound concentrations in blood and plasma. Tacrolimus pharmacokinetics in breast milk were assessed in one subject. Mean (±SD) tacrolimus concentrations at the time of delivery in umbilical cord venous blood (6.6 ± 1.8 ng ml(-1)) were 71 ± 18% (range 45-99%) of maternal concentrations (9.0 ± 3.4 ng ml(-1)). The mean umbilical cord venous plasma (0.09 ± 0.04 ng ml(-1)) and unbound drug concentrations (0.003 ± 0.001 ng ml(-1)) were approximately one fifth of the respective maternal concentrations. Arterial umbilical cord blood concentrations of tacrolimus were 100 ± 12% of umbilical venous concentrations. In addition, infant exposure to tacrolimus through the breast milk was less than 0.3% of the mother's weight-adjusted dose. Differences between maternal and umbilical cord tacrolimus concentrations may be explained in part by placental P-gp function, greater red blood cell partitioning and higher haematocrit levels in venous cord blood. The neonatal drug exposure to tacrolimus via breast milk is very low and likely does not represent a health risk to the breastfeeding infant. © 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.

Quantified Gamow shell model interaction for p s d -shell nuclei

NASA Astrophysics Data System (ADS)

Jaganathen, Y.; Betan, R. M. Id; Michel, N.; Nazarewicz, W.; Płoszajczak, M.

2017-11-01

Background: The structure of weakly bound and unbound nuclei close to particle drip lines is one of the major science drivers of nuclear physics. A comprehensive understanding of these systems goes beyond the traditional configuration interaction approach formulated in the Hilbert space of localized states (nuclear shell model) and requires an open quantum system description. The complex-energy Gamow shell model (GSM) provides such a framework as it is capable of describing resonant and nonresonant many-body states on equal footing. Purpose: To make reliable predictions, quality input is needed that allows for the full uncertainty quantification of theoretical results. In this study, we carry out the optimization of an effective GSM (one-body and two-body) interaction in the p s d f -shell-model space. The resulting interaction is expected to describe nuclei with 5 ≤A ≲12 at the p -s d -shell interface. Method: The one-body potential of the 4He core is modeled by a Woods-Saxon + spin-orbit + Coulomb potential, and the finite-range nucleon-nucleon interaction between the valence nucleons consists of central, spin-orbit, tensor, and Coulomb terms. The GSM is used to compute key fit observables. The χ2 optimization is performed using the Gauss-Newton algorithm augmented by the singular value decomposition technique. The resulting covariance matrix enables quantification of statistical errors within the linear regression approach. Results: The optimized one-body potential reproduces nucleon-4He scattering phase shifts up to an excitation energy of 20 MeV. The two-body interaction built on top of the optimized one-body field is adjusted to the bound and unbound ground-state binding energies and selected excited states of the helium, lithium, and beryllium isotopes up to A =9 . A very good agreement with experimental results was obtained for binding energies. First applications of the optimized interaction include predictions for two-nucleon correlation densities and excitation spectra of light nuclei with quantified uncertainties. Conclusion: The new interaction will enable comprehensive and fully quantified studies of structure and reactions aspects of nuclei from the p s d region of the nuclear chart.

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

Jaganathen, Y.; Betan, R. M. Id; Michel, N.

Background: The structure of weakly bound and unbound nuclei close to particle drip lines is one of the major science drivers of nuclear physics. A comprehensive understanding of these systems goes beyond the traditional configuration interaction approach formulated in the Hilbert space of localized states (nuclear shell model) and requires an open quantum system description. The complex-energy Gamow shell model (GSM) provides such a framework as it is capable of describing resonant and nonresonant many-body states on equal footing. Purpose: To make reliable predictions, quality input is needed that allows for the full uncertainty quantification of theoretical results. In thismore » study, we carry out the optimization of an effective GSM (one-body and two-body) interaction in the psdf-shell-model space. The resulting interaction is expected to describe nuclei with 5 ≤ A ≲ 12 at the p-sd-shell interface. Method: The one-body potential of the 4He core is modeled by a Woods-Saxon + spin-orbit + Coulomb potential, and the finite-range nucleon-nucleon interaction between the valence nucleons consists of central, spin-orbit, tensor, and Coulomb terms. The GSM is used to compute key fit observables. The χ 2 optimization is performed using the Gauss-Newton algorithm augmented by the singular value decomposition technique. The resulting covariance matrix enables quantification of statistical errors within the linear regression approach. Results: The optimized one-body potential reproduces nucleon- 4He scattering phase shifts up to an excitation energy of 20 MeV. The two-body interaction built on top of the optimized one-body field is adjusted to the bound and unbound ground-state binding energies and selected excited states of the helium, lithium, and beryllium isotopes up to A = 9 . A very good agreement with experimental results was obtained for binding energies. First applications of the optimized interaction include predictions for two-nucleon correlation densities and excitation spectra of light nuclei with quantified uncertainties. In conclusion: The new interaction will enable comprehensive and fully quantified studies of structure and reactions aspects of nuclei from the psd region of the nuclear chart.« less

Quantified Gamow shell model interaction for p s d -shell nuclei

DOE PAGES

Jaganathen, Y.; Betan, R. M. Id; Michel, N.; ...

2017-11-20

Background: The structure of weakly bound and unbound nuclei close to particle drip lines is one of the major science drivers of nuclear physics. A comprehensive understanding of these systems goes beyond the traditional configuration interaction approach formulated in the Hilbert space of localized states (nuclear shell model) and requires an open quantum system description. The complex-energy Gamow shell model (GSM) provides such a framework as it is capable of describing resonant and nonresonant many-body states on equal footing. Purpose: To make reliable predictions, quality input is needed that allows for the full uncertainty quantification of theoretical results. In thismore » study, we carry out the optimization of an effective GSM (one-body and two-body) interaction in the psdf-shell-model space. The resulting interaction is expected to describe nuclei with 5 ≤ A ≲ 12 at the p-sd-shell interface. Method: The one-body potential of the 4He core is modeled by a Woods-Saxon + spin-orbit + Coulomb potential, and the finite-range nucleon-nucleon interaction between the valence nucleons consists of central, spin-orbit, tensor, and Coulomb terms. The GSM is used to compute key fit observables. The χ 2 optimization is performed using the Gauss-Newton algorithm augmented by the singular value decomposition technique. The resulting covariance matrix enables quantification of statistical errors within the linear regression approach. Results: The optimized one-body potential reproduces nucleon- 4He scattering phase shifts up to an excitation energy of 20 MeV. The two-body interaction built on top of the optimized one-body field is adjusted to the bound and unbound ground-state binding energies and selected excited states of the helium, lithium, and beryllium isotopes up to A = 9 . A very good agreement with experimental results was obtained for binding energies. First applications of the optimized interaction include predictions for two-nucleon correlation densities and excitation spectra of light nuclei with quantified uncertainties. In conclusion: The new interaction will enable comprehensive and fully quantified studies of structure and reactions aspects of nuclei from the psd region of the nuclear chart.« less

Effect of drainage in unbound aggregate bases on flexible pavement performance.

DOT National Transportation Integrated Search

2008-05-01

It has been well demonstrated that a positive subsurface drainage is beneficial in enhancing pavement performance and thus extending pavement service life. Typical permeable base materials include asphalt/cement-treated, open-graded aggregates and un...

Backcalculation of unbound granular layer moduli.

DOT National Transportation Integrated Search

2011-03-01

The state of Michigan is geographically located within the wet-freeze zone identified by the : American Association of States and Highway Transportation Officials (AASHTO). The frost : depth in the State ranges from 2.5 feet near the Ohio and Indiana...

Accelerated characterization of full-scale flexible pavements using a vibroseis.

DOT National Transportation Integrated Search

2010-03-01

Geosynthetic basal reinforcement has been used in flexible pavements and unbound roads to limit the occurrence of rutting, fatigue, and environmental-related cracking, and to permit reduction in base course thickness. However, the lack of a represent...

Tumor-specific detection of an optically targeted antibody combined with a quencher-conjugated neutravidin "quencher-chaser": a dual "quench and chase" strategy to improve target to nontarget ratios for molecular imaging of cancer.

PubMed

Ogawa, Mikako; Kosaka, Nobuyuki; Choyke, Peter L; Kobayashi, Hisataka

2009-01-01

In vivo molecular cancer imaging with monoclonal antibodies has great potential not only for cancer detection, but also for cancer characterization. However, the prolonged retention of intravenously injected antibody in the blood causes low target tumor-to-background ratio (TBR). Avidin has been used as a "chase" to clear the unbound, circulating biotinylated antibody and decrease the background signal. Here, we utilize a combined approach of a fluorescence resonance energy transfer (FRET) quenched antibody with an "avidin chase" to increase TBR. Trastuzumab, a humanized monoclonal antibody against human epidermal growth factor receptor type 2 (HER2), was biotinylated and conjugated with the near-infrared (NIR) fluorophore Alexa680 to synthesize Tra-Alexa680-biotin. Next, the FRET quencher, QSY-21, was conjugated to avidin, neutravidin (nAv), or streptavidin (sAv), thus creating Av-QSY21, nAv-QSY21, or sAv-QSY21 as "chasers". The fluorescence was quenched in vitro by binding Tra-Alexa680-biotin to Av-QSY21, nAv-QSY21, or sAv-QSY21. To evaluate if the injection of quencher-conjugated avidin derivatives can improve target TBR by using a dual "quench and chase" strategy, both target (3T3/HER2+) and nontarget (Balb3T3/ZsGreen) tumor-bearing mice were employed. The "FRET quench" effect induced by all the QSY21 avidin-based conjugates reduced but did not totally eliminate background signal from the blood pool. The addition of nAv-QSY21 administration increased target TBR mainly because of the "chase" effect where unbound conjugated antibody was preferentially cleared to the liver. The relatively slow clearance of unbound nAv-QSY21 leads to further reductions in background signal by leaking out of the vascular space and binding to unbound antibodies in the extravascular space of tumors, resulting in decreased nontarget tumor-to-background ratios but increased target TBR due to the "FRET quench" effect, because target-bound antibodies were internalized and could not bind to nAv-QSY21. In conclusion, the proposed "quench-and-chase" system combines two strategies, fluorescent quenching and avidin chasing, to improve target TBR and reduce nontarget TBR, which should result in both improved tumor sensitivity and improved specificity.

Greener Protection for Steel Bridges : Testing Nano-Enhanced Corrosion-Resistant Coatings

DOT National Transportation Integrated Search

2013-06-03

Permanent deformation within the unbound granular is a predominant feature that results in the degradation and loss of serviceability to the pavement structure as the passage of traffic wheel loads accumulate. Proper characterization of the multi-lay...

Characterization of unbound materials (soils/aggregates) for mechanistic-empirical pavement design guide.

DOT National Transportation Integrated Search

2009-02-01

The resilient modulus (MR) input parameters in the Mechanistic-Empirical Pavement Design Guide (MEPDG) program have a significant effect on the projected pavement performance. The MEPDG program uses three different levels of inputs depending on the d...

Polygon patterns on Europa

NASA Technical Reports Server (NTRS)

Smalley, I. J.

1981-01-01

The formation of polygon patterns in the development of crack networks in cooling basalt flows and similar contracting systems, and under natural conditions in an essentially unbounded basalt flow, are analyzed, and the characteristics of hexagonal and pentagonal patterns in isotropic stress fields are discussed.

3 CFR 8435 - Proclamation 8435 of October 7, 2009. Leif Erikson Day, 2009

Code of Federal Regulations, 2010 CFR

2010-01-01

... determined not to turn back, in order to learn what lay beyond the setting sun. This same spirit lived within... their pioneering spirit continues to embody our Nation’s unbounded enthusiasm for discovery and learning...

Out of bounds additive manufacturing

DOE PAGES

Holshouser, Chris; Newell, Clint; Palas, Sid; ...

2013-03-01

Lockheed Martin and Oak Ridge National Laboratory are working on an additive manufacturing system capable of manufacturing components measured not in terms of inches or feet, but multiple yards in all dimensions with the potential to manufacture parts that are completely unbounded in size.

Accelerated Characterization of Full-Scale Reinforced Flexible Pavement Models Using Vibroseis

DOT National Transportation Integrated Search

2010-03-01

Geosynthetic basal reinforcement has been used in flexible pavements and unbound roads to limit the occurrence of rutting, fatigue, and environmental-related cracking, and to permit reduction in base course thickness. However, the lack of a represent...

The Mental Number Line in Dyscalculia: Impaired Number Sense or Access from Symbolic Numbers?

ERIC Educational Resources Information Center

Lafay, Anne; St-Pierre, Marie-Catherine; Macoir, Joël

2017-01-01

Numbers may be manipulated and represented mentally over a compressible number line oriented from left to right. According to numerous studies, one of the primary reasons for dyscalculia is related to improper understanding of the mental number line. Children with dyscalculia usually show difficulty when they have to place Arabic numbers on a…

Exciton absorption of entangled photons in semiconductor quantum wells

NASA Astrophysics Data System (ADS)

Rodriguez, Ferney; Guzman, David; Salazar, Luis; Quiroga, Luis; Condensed Matter Physics Group Team

2013-03-01

The dependence of the excitonic two-photon absorption on the quantum correlations (entanglement) of exciting biphotons by a semiconductor quantum well is studied. We show that entangled photon absorption can display very unusual features depending on space-time-polarization biphoton parameters and absorber density of states for both bound exciton states as well as for unbound electron-hole pairs. We report on the connection between biphoton entanglement, as quantified by the Schmidt number, and absorption by a semiconductor quantum well. Comparison between frequency-anti-correlated, unentangled and frequency-correlated biphoton absorption is addressed. We found that exciton oscillator strengths are highly increased when photons arrive almost simultaneously in an entangled state. Two-photon-absorption becomes a highly sensitive probe of photon quantum correlations when narrow semiconductor quantum wells are used as two-photon absorbers. Research funds from Facultad de Ciencias, Universidad de los Andes

Constraints on baryonic dark matter in the Galactic halo and Local Group

NASA Technical Reports Server (NTRS)

Richstone, Douglas; Gould, Andrew; Guhathakurta, Puragra; Flynn, Chris

1992-01-01

A four-color method and deep CCD data are used to search for very faint metal-poor stars in the direction of the south Galactic pole. The results make it possible to limit the contribution of ordinary old, metal-poor stars to the dynamical halo of the Galaxy or to the Local Group. The ratio of the mass of the halo to its ordinary starlight must be more than about 2000, unless the halo is very small. For the Local Group, this ratio is greater than about 400. If this local dark matter is baryonic, the process of compact-object formation must produce very few 'impurities' in the form of stars similar to those found in globular clusters. The expected number of unbound stars with MV not greater than 6 within 100 pc of the sun is less than 1 based on the present 90-percent upper limit to the Local Group starlight.

Periodic differential equations with self-adjoint monodromy operator

NASA Astrophysics Data System (ADS)

Yudovich, V. I.

2001-04-01

A linear differential equation \\dot u=A(t)u with p-periodic (generally speaking, unbounded) operator coefficient in a Euclidean or a Hilbert space \\mathbb H is considered. It is proved under natural constraints that the monodromy operator U_p is self-adjoint and strictly positive if A^*(-t)=A(t) for all t\\in\\mathbb R.It is shown that Hamiltonian systems in the class under consideration are usually unstable and, if they are stable, then the operator U_p reduces to the identity and all solutions are p-periodic.For higher frequencies averaged equations are derived. Remarkably, high-frequency modulation may double the number of critical values.General results are applied to rotational flows with cylindrical components of the velocity a_r=a_z=0, a_\\theta=\\lambda c(t)r^\\beta, \\beta<-1, c(t) is an even p-periodic function, and also to several problems of free gravitational convection of fluids in periodic fields.

Coupling Functions Enable Secure Communications

NASA Astrophysics Data System (ADS)

Stankovski, Tomislav; McClintock, Peter V. E.; Stefanovska, Aneta

2014-01-01

Secure encryption is an essential feature of modern communications, but rapid progress in illicit decryption brings a continuing need for new schemes that are harder and harder to break. Inspired by the time-varying nature of the cardiorespiratory interaction, here we introduce a new class of secure communications that is highly resistant to conventional attacks. Unlike all earlier encryption procedures, this cipher makes use of the coupling functions between interacting dynamical systems. It results in an unbounded number of encryption key possibilities, allows the transmission or reception of more than one signal simultaneously, and is robust against external noise. Thus, the information signals are encrypted as the time variations of linearly independent coupling functions. Using predetermined forms of coupling function, we apply Bayesian inference on the receiver side to detect and separate the information signals while simultaneously eliminating the effect of external noise. The scheme is highly modular and is readily extendable to support different communications applications within the same general framework.

Trailing edge flow conditions as a factor in airfoil design

NASA Technical Reports Server (NTRS)

Ormsbee, A. I.; Maughmer, M. D.

1984-01-01

Some new developments relevant to the design of single-element airfoils using potential flow methods are presented. In particular, the role played by the non-dimensional trailing edge velocity in design is considered and the relationship between the specified value and the resulting airfoil geometry is explored. In addition, the ramifications of the unbounded trailing edge pressure gradients generally present in the potential flow solution of the flow over an airfoil are examined, and the conditions necessary to obtain a class of airfoils having finite trailing edge pressure gradients developed. The incorporation of these conditions into the inverse method of Eppler is presented and the modified scheme employed to generate a number of airfoils for consideration. The detailed viscous analysis of airfoils having finite trailing edge pressure gradients demonstrates a reduction in the strong inviscid-viscid interactions generally present near the trailing edge of an airfoil.

Toward inflation models compatible with the no-boundary proposal

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

Hwang, Dong-il; Yeom, Dong-han, E-mail: dongil.j.hwang@gmail.com, E-mail: innocent.yeom@gmail.com

2014-06-01

In this paper, we investigate various inflation models in the context of the no-boundary proposal. We propose that a good inflation model should satisfy three conditions: observational constraints, plausible initial conditions, and naturalness of the model. For various inflation models, we assign the probability to each initial condition using the no-boundary proposal and define a quantitative standard, typicality, to check whether the model satisfies the observational constraints with probable initial conditions. There are three possible ways to satisfy the typicality criterion: there was pre-inflation near the high energy scale, the potential is finely tuned or the inflationary field space ismore » unbounded, or there are sufficient number of fields that contribute to inflation. The no-boundary proposal rejects some of naive inflation models, explains some of traditional doubts on inflation, and possibly, can have observational consequences.« less

Strong Neutron Pairing in core+4 n Nuclei

NASA Astrophysics Data System (ADS)

Revel, A.; Marqués, F. M.; Sorlin, O.; Aumann, T.; Caesar, C.; Holl, M.; Panin, V.; Vandebrouck, M.; Wamers, F.; Alvarez-Pol, H.; Atar, L.; Avdeichikov, V.; Beceiro-Novo, S.; Bemmerer, D.; Benlliure, J.; Bertulani, C. A.; Boillos, J. M.; Boretzky, K.; Borge, M. J. G.; Caamaño, M.; Casarejos, E.; Catford, W. N.; Cederkäll, J.; Chartier, M.; Chulkov, L.; Cortina-Gil, D.; Cravo, E.; Crespo, R.; Datta Pramanik, U.; Díaz Fernández, P.; Dillmann, I.; Elekes, Z.; Enders, J.; Ershova, O.; Estradé, A.; Farinon, F.; Fraile, L. M.; Freer, M.; Galaviz, D.; Geissel, H.; Gernhäuser, R.; Golubev, P.; Göbel, K.; Hagdahl, J.; Heftrich, T.; Heil, M.; Heine, M.; Heinz, A.; Henriques, A.; Ignatov, A.; Johansson, H. T.; Jonson, B.; Kahlbow, J.; Kalantar-Nayestanaki, N.; Kanungo, R.; Kelic-Heil, A.; Knyazev, A.; Kröll, T.; Kurz, N.; Labiche, M.; Langer, C.; Le Bleis, T.; Lemmon, R.; Lindberg, S.; Machado, J.; Marganiec, J.; Movsesyan, A.; Nacher, E.; Najafi, M.; Nilsson, T.; Nociforo, C.; Paschalis, S.; Perea, A.; Petri, M.; Pietri, S.; Plag, R.; Reifarth, R.; Ribeiro, G.; Rigollet, C.; Röder, M.; Rossi, D.; Savran, D.; Scheit, H.; Simon, H.; Syndikus, I.; Taylor, J. T.; Tengblad, O.; Thies, R.; Togano, Y.; Velho, P.; Volkov, V.; Wagner, A.; Weick, H.; Wheldon, C.; Wilson, G.; Winfield, J. S.; Woods, P.; Yakorev, D.; Zhukov, M.; Zilges, A.; Zuber, K.; R³B Collaboration

2018-04-01

The emission of neutron pairs from the neutron-rich N =12 isotones 18C and 20O has been studied by high-energy nucleon knockout from 19N and 21O secondary beams, populating unbound states of the two isotones up to 15 MeV above their two-neutron emission thresholds. The analysis of triple fragment-n -n correlations shows that the decay 19N (-1 p ) 18C* → 16C +n +n is clearly dominated by direct pair emission. The two-neutron correlation strength, the largest ever observed, suggests the predominance of a 14C core surrounded by four valence neutrons arranged in strongly correlated pairs. On the other hand, a significant competition of a sequential branch is found in the decay 21O (-1 n )20O*→18O +n +n , attributed to its formation through the knockout of a deeply bound neutron that breaks the 16O core and reduces the number of pairs.

Medical Lasers At The Crossroads: Directions For The Next Five Years

NASA Astrophysics Data System (ADS)

Brauer, Fritz A.

1988-09-01

Of course, much can be attributed to our relative youth - the sheer number and scope of the opportunities have distorted focus and strained resources. However, I believe that we have reached a point - a crossroads - where the topography is more clearly defined and where some discernible trends point to the direction this industry will take over the next five years. These will be important years - investors, especially, expect signs of maturity to replace unbounded youthful optimism. How many of us can look back on the business plans we wrote five years ago and not feel chastened (or depressed). Our excuse is that we got everything right except the timing. Well, the "timing" is the next five years! So my talk today will center upon my personal view of these next five years. I wish to emphasize the personal aspect of my discussion: this is my prescription for future happiness.

A GPU accelerated and error-controlled solver for the unbounded Poisson equation in three dimensions

NASA Astrophysics Data System (ADS)

Exl, Lukas

2017-12-01

An efficient solver for the three dimensional free-space Poisson equation is presented. The underlying numerical method is based on finite Fourier series approximation. While the error of all involved approximations can be fully controlled, the overall computation error is driven by the convergence of the finite Fourier series of the density. For smooth and fast-decaying densities the proposed method will be spectrally accurate. The method scales with O(N log N) operations, where N is the total number of discretization points in the Cartesian grid. The majority of the computational costs come from fast Fourier transforms (FFT), which makes it ideal for GPU computation. Several numerical computations on CPU and GPU validate the method and show efficiency and convergence behavior. Tests are performed using the Vienna Scientific Cluster 3 (VSC3). A free MATLAB implementation for CPU and GPU is provided to the interested community.

The Number Line Is a Critical Spatial-Numerical Representation: Evidence from a Fraction Intervention

ERIC Educational Resources Information Center

Hamdan, Noora; Gunderson, Elizabeth A.

2017-01-01

Children's ability to place fractions on a number line strongly correlates with math achievement. But does the number line play a causal role in fraction learning or does it simply index more advanced fraction knowledge? The number line may be a particularly effective representation for fraction learning because its properties align with the…

Local infiltration analgesia in knee and hip arthroplasty efficacy and safety.

PubMed

Affas, Fatin

2016-10-01

This is a secondary publication of a PhD thesis. Local infiltration analgesia (LIA) is a new multimodal wound infiltration method for treating postoperative pain after knee and hip arthroplasty. This method is based on systematic infiltration of a mixture of ropivacaine, a long acting local anaesthetic, ketorolac, a cyclooxygenase inhibitor (NSAID), and adrenalin around all structures subject to surgical trauma in knee and hip arthroplasty. Paper I: to assess whether pain relief after LIA in total knee arthroplasty (TKA) is as effective as femoral block. Paper II: to assess whether the plasma concentration of ropivacaine and ketorolac after LIA in TKA reaches levels linked to toxicity. Paper III: to assess whether the plasma concentration of unbound ropivacaine after LIA in THA reaches levels linked to toxicity and if it is higher in THA as compared to TKA. Paper IV: to assess whether the plasma concentration of ketorolac after LIA in THA reaches levels linked to toxicity, and whether administration of ketorolac in LIA is safer as compared to the intramuscular route. Two patient cohorts of 40 patients scheduled for elective total knee arthroplasty (TKA) and 15 patients scheduled for total hip arthroplasty (THA) contributed to this work. In a randomized trial the efficacy of LIA in TKA with regard to pain at rest and upon movement was compared to femoral block. Both methods result in a high quality pain relief and similar morphine consumption during the 24h monitoring period. In the same patient cohort the maximal total plasma concentration of ropivacaine was below the established toxic threshold for most patients. All patients in the THA cohort were subjected to the routine LIA protocol. In these patients both the total and unbound plasma concentration of ropivacaine was determined. The concentration was below the established toxic threshold. As ropivacaine binds to α-1 acid glycoprotein (AAG) we assessed the possibility that increased AAG may decrease the unbound concentration of ropivacaine. A 40% increase in AAG was detected during the first 24h after surgery, however the fraction of unbound ropivacaine remained the same. There was a trend towards increased C max of ropivacaine with increasing age and decreasing creatinine clearance but the statistical power was too low to draw any conclusion. Administration of 30mg ketorolac according to the LIA protocol both in TKA and THA resulted in a similar C max as previously reported after 10mg intramuscular ketorolac. Neither age, nor body weight or BMI, nor creatinine clearance, correlates to maximal ketorolac plasma concentration or total exposure to ketorolac (AUC). LIA provides good postoperative analgesia which is similar to femoral block after total knee arthroplasty. The plasma concentration of ropivacaine seems to be below toxic levels in most TKA patients. The unbound plasma concentration of ropivacaine in THA seems to be below the toxic level. The use of ketorolac in LIA may not be safer than other routes of administration, and similar restrictions should be applied in patients at risk of developing side effects. Copyright © 2016. Published by Elsevier B.V.

Influence of surface tension on the instabilities and bifurcations of a particle in a drop under shear

NASA Astrophysics Data System (ADS)

Gallaire, Francois; Zhu, Lailai

2016-11-01

While the deformation regimes under flow of anuclear cells, like red blood cells, have been widely analyzed, the dynamics of nuclear cells are less explored. The objective of this work is to investigate the interplay between the stiff nucleus, modeled here as a rigid spherical particle and the surrounding deformable cell membrane, modeled for simplicity as an immiscible droplet, subjected to an external unbounded plane shear flow. A three-dimensional boundary integral implementation is developed to describe the interface-structure interaction characterized by two dimensionless numbers: the capillary number Ca , defined as the ratio of shear to capillary forces and and the particle-droplet size ratio. For large Ca , i.e. very deformable droplets, the particle has a stable equilibrium position at the center of the droplet. However, for smaller Ca , both the plane symmetry and the time invariance are broken and the particle migrates to a closed orbit located off the symmetry plane, reaching a limit cycle. For even smaller capillary numbers, the time invariance is restored and the particle reaches a steady equilibrium position off the symmetry plane. This series of bifurcations is analyzed and possible physical mechanisms from which they originate are discussed. Financial support by ERC Grant SimCoMiCs 280117 is gratefully acknowledged.

Scattering of plane evanescent waves by cylindrical shells and wave vector coupling conditions for exciting flexural waves

NASA Astrophysics Data System (ADS)

Marston, Philip L.

2002-05-01

The coupling of sound to buried targets can be associated with acoustic evanescent waves when the sea bottom is smooth. To understand the excitation of flexural waves on buried shells by acoustic evanescent waves, the partial wave series for the scattering is found for cylindrical shells at normal incidence in an unbounded medium. The formulation uses the simplifications of thin-shell dynamics. In the case of ordinary waves incident on a shell, a ray formulation is available to describe the coupling to subsonic flexural waves [P. L. Marston and N. H. Sun, J. Acoust. Soc. Am. 97, 777-783 (1995)]. When the incident wave is evanescent, the distance between propagating plane wavefronts is smaller than the ordinary acoustical wavelength at the same frequency and the coupling condition for the excitation of flexural waves on shells or plates is modified. Instead of matching the flexural wave number with the propagating part of the acoustic wave number only at the coincidence frequency, a second low-frequency wave number matching condition is found for highly evanescent waves. Numerical evaluation of the modified partial-wave-series appropriate for an evanescent wave is used to investigate the low-frequency coupling of evanescent waves with flexural wave resonances of shells.

Continuum Level Density in Complex Scaling Method

NASA Astrophysics Data System (ADS)

Suzuki, R.; Myo, T.; Katō, K.

2005-11-01

A new calculational method of continuum level density (CLD) at unbound energies is studied in the complex scaling method (CSM). It is shown that the CLD can be calculated by employing the discretization of continuum states in the CSM without any smoothing technique.

Computed parameters : moisture content for unbound materials at seasonal monitoring program sites

DOT National Transportation Integrated Search

2000-01-01

Moisture content plays a significant role in the performance of pavements. Variation in the amount of moisture in the subgrade can change the volume of swelling soil, which may result in detrimental deformation of the pavement structure. An increase ...

Financial impact of fines in the unbound pavement layers.

DOT National Transportation Integrated Search

2014-10-01

This study continued the research effort on evaluating the resilient behavior of D-1 base course materials when there is limited water : access during freezing. D-1 material from the Northern region of Alaska was used, and a closed system was adopted...

Use of Subcutaneous and Intraperitoneal Administration Methods to Facilitate Cassette Dosing in Microdialysis Studies in Rats.

PubMed

Durk, Matthew R; Deshmukh, Gauri; Valle, Nicole; Ding, Xiao; Liederer, Bianca M; Liu, Xingrong

2018-07-01

Microdialysis is a powerful technique allowing for real-time measurement of unbound drug concentrations in brain interstitial fluid in conscious animals. Use of microdialysis in drug discovery is limited by high resource requirement and low throughput, but this may be improved by cassette dosing. Administering multiple compounds intravenously of diverse physiochemical properties, it is often very challenging and time consuming to identify a vehicle that can dissolve all of the compounds. To overcome this limitation, the present study explores the possibility of administering a cassette dose of nine diverse compounds (carbamazepine, citalopram, desmethylclozapine, diphenhydramine, gabapentin, metoclopramide, naltrexone, quinidine, and risperidone) in suspension, rather than in solution, by intraperitoneal and subcutaneous routes, and determining if this is a viable option for assessing blood-brain barrier penetration in microdialysis studies. Repeated hourly subcutaneous dosing during the 6-hour microdialysis study allowed for the best attainment of distributional equilibrium between brain and plasma, resulting in less than a 2-fold difference in the unbound brain to unbound plasma concentration ratio for the cassette dosing method versus discrete dosing. Both subcutaneous and intraperitoneal repeated dosing can provide a more practical substitute for intravenous dosing in determining brain penetration of a cassette of diverse compounds in brain microdialysis studies. The results from the present study demonstrate that dosing compounds in suspension represents a practical approach to eliminating the technical challenge and labor-intensive step of preparation of solutions of a mixture of compounds and will enable the use of the cassette brain microdialysis method in a central nervous system drug discovery setting. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Modeling of Abrasion and Crushing of Unbound Granular Materials During Compaction

NASA Astrophysics Data System (ADS)

Ocampo, Manuel S.; Caicedo, Bernardo

2009-06-01

Unbound compacted granular materials are commonly used in engineering structures as layers in road pavements, railroad beds, highway embankments, and foundations. These structures are generally subjected to dynamic loading by construction operations, traffic and wheel loads. These repeated or cyclic loads cause abrasion and crushing of the granular materials. Abrasion changes a particle's shape, and crushing divides the particle into a mixture of many small particles of varying sizes. Particle breakage is important because the mechanical and hydraulic properties of these materials depend upon their grain size distribution. Therefore, it is important to evaluate the evolution of the grain size distribution of these materials. In this paper an analytical model for unbound granular materials is proposed in order to evaluate particle crushing of gravels and soils subjected to cyclic loads. The model is based on a Markov chain which describes the development of grading changes in the material as a function of stress levels. In the model proposed, each particle size is a state in the system, and the evolution of the material is the movement of particles from one state to another in n steps. Each step is a load cycle, and movement between states is possible with a transition probability. The crushing of particles depends on the mechanical properties of each grain and the packing density of the granular material. The transition probability was calculated using both the survival probability defined by Weibull and the compressible packing model developed by De Larrard. Material mechanical properties are considered using the Weibull probability theory. The size and shape of the grains, as well as the method of processing the packing density are considered using De Larrard's model. Results of the proposed analytical model show a good agreement with the experimental tests carried out using the gyratory compaction test.

An Investigation into the Prediction of in Vivo Clearance for a Range of Flavin-containing Monooxygenase Substrates.

PubMed

Jones, Barry C; Srivastava, Abhishek; Colclough, Nicola; Wilson, Joanne; Reddy, Venkatesh Pilla; Amberntsson, Sara; Li, Danxi

2017-10-01

Flavin-containing monooxygenases (FMO) are metabolic enzymes mediating the oxygenation of nucleophilic atoms such as nitrogen, sulfur, phosphorus, and selenium. These enzymes share similar properties to the cytochrome P450 system but can be differentiated through heat inactivation and selective substrate inhibition by methimazole. This study investigated 10 compounds with varying degrees of FMO involvement to determine the nature of the correlation between human in vitro and in vivo unbound intrinsic clearance. To confirm and quantify the extent of FMO involvement six of the compounds were investigated in human liver microsomal (HLM) in vitro assays using heat inactivation and methimazole substrate inhibition. Under these conditions FMO contribution varied from 21% (imipramine) to 96% (itopride). Human hepatocyte and HLM intrinsic clearance (CL int ) data were scaled using standard methods to determine the predicted unbound intrinsic clearance (predicted CL int u ) for each compound. This was compared with observed unbound intrinsic clearance (observed CL int u ) values back calculated from human pharmacokinetic studies. A good correlation was observed between the predicted and observed CL int u using hepatocytes ( R 2 = 0.69), with 8 of the 10 compounds investigated within or close to a factor of 2. For HLM the in vitro-in vivo correlation was maintained ( R 2 = 0.84) but the accuracy was reduced with only 3 out of 10 compounds falling within, or close to, twofold. This study demonstrates that human hepatocytes and HLM can be used with standard scaling approaches to predict the human in vivo clearance for FMO substrates. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Protein binding and its potential for eliciting minimal systemic side effects with a novel inhaled corticosteroid, ciclesonide.

PubMed

Rohatagi, Shashank; Luo, Yongyi; Shen, Liduo; Guo, Zuyu; Schemm, Christina; Huang, Yongqing; Chen, Kelly; David, Michael; Nave, Ruediger; King, S Peter

2005-01-01

Freely circulating, protein unbound, active inhaled corticosteroid (ICS) can cause systemic adverse effects. Desisobutyryl-ciclesonide (des-CIC) is the active metabolite of ciclesonide, an effective, novel ICS for persistent asthma. This study examines the free fraction of ciclesonide and des-CIC and determines whether the presence of other agents or disease states affects protein binding. Protein binding of des-CIC (0.5, 5.0, 25, 100, and 500 ng/mL) was determined, using both equilibrium dialysis and ultrafiltration, in plasma from humans (healthy and either renally or hepatically impaired) and several animal species and in the presence of either salicylates or warfarin. Dialyzed samples were analyzed by liquid chromatography with tandem mass spectroscopy to determine both free and bound concentrations of des-CIC. After ultrafiltration, spiked plasma plus H-des-CIC was separated into free and bound fractions by centrifugation and quantified by scintillation counting. Additionally, in another study, protein binding of ciclesonide was determined by equilibrium dialysis. For equilibrium dialysis, the mean percentages of des-CIC (0.5-500 ng/mL) plasma protein binding across species were high, approximately 99%, and no apparent saturation of protein binding was observed. Results were similar for ultrafiltration analysis. Protein binding of des-CIC did not change in the presence of warfarin or salicylates or in the plasma of renally or hepatically impaired patients. The protein binding of ciclesonide was 99.4% in human serum. The very low fraction of unbound des-CIC in the systemic circulation suggests minimal systemic exposure of unbound des-CIC, thus suggesting a low potential for systemic adverse effects after administration of inhaled ciclesonide.

Oviduct binding and elevated environmental ph induce protein tyrosine phosphorylation in stallion spermatozoa.

PubMed

Leemans, Bart; Gadella, Bart M; Sostaric, Edita; Nelis, Hilde; Stout, Tom A E; Hoogewijs, Maarten; Van Soom, Ann

2014-07-01

Sperm-oviduct binding is an essential step in the capacitation process preparing the sperm for fertilization in several mammalian species. In many species, capacitation can be induced in vitro by exposing spermatozoa to bicarbonate, Ca(2+), and albumin; however, these conditions are insufficient in the horse. We hypothesized that binding to the oviduct epithelium is an essential requirement for the induction of capacitation in stallion spermatozoa. Sperm-oviduct binding was established by coincubating equine oviduct explants for 2 h with stallion spermatozoa (2 × 10(6) spermatozoa/ml), during which it transpired that the highest density (per mm(2)) of oviduct-bound spermatozoa was achieved under noncapacitating conditions. In subsequent experiments, sperm-oviduct incubations were performed for 6 h under noncapacitating versus capacitating conditions. The oviduct-bound spermatozoa showed a time-dependent protein tyrosine phosphorylation response, which was not observed in unbound spermatozoa or spermatozoa incubated in oviduct explant conditioned medium. Both oviduct-bound and unbound sperm remained motile with intact plasma membrane and acrosome. Since protein tyrosine phosphorylation can be induced in equine spermatozoa by media with high pH, the intracellular pH (pHi) of oviduct explant cells and bound spermatozoa was monitored fluorometrically after staining with BCECF-AM dye. The epithelial secretory cells contained large, alkaline vesicles. Moreover, oviduct-bound spermatozoa showed a gradual increase in pHi, presumably due to an alkaline local microenvironment created by the secretory epithelial cells, given that unbound spermatozoa did not show pHi changes. Thus, sperm-oviduct interaction appears to facilitate equine sperm capacitation by creating an alkaline local environment that triggers intracellular protein tyrosine phosphorylation in bound sperm. © 2014 by the Society for the Study of Reproduction, Inc.

Vinorelbine Delivery and Efficacy in the MDA-MB-231BR Preclinical Model of Brain Metastases of Breast Cancer.

PubMed

Samala, Ramakrishna; Thorsheim, Helen R; Goda, Satyanarayana; Taskar, Kunal; Gril, Brunilde; Steeg, Patricia S; Smith, Quentin R

2016-12-01

To evaluate vinorelbine drug exposure and activity in brain metastases of the human MDA-MB-231BR breast cancer model using integrated imaging and analysis. Brain and systemic metastases were created by administration of cancer cells in female NuNu mice. After metastases developed, animals were administered vinorelbine at the maximal tolerated dose (12 mg/kg), and were evaluated thereafter for total and unbound drug pharmacokinetics, biomarker TUNEL staining, and barrier permeability to Texas red. Median brain metastasis drug exposure was 4-fold greater than normal brain, yet only ~8% of non-barrier systemic metastases, which suggests restricted brain exposure. Unbound vinorelbine tissue/plasma partition coefficient, K p,uu , equaled ~1.0 in systemic metastases, but 0.03-0.22 in brain metastases, documenting restricted equilibration. In select sub-regions of highest drug-uptake brain metastases, K p,uu approached 1.0, indicating complete focal barrier breakdown. Most vinorelbine-treated brain metastases exhibited little or no positive early apoptosis TUNEL staining in vivo. The in vivo unbound vinorelbine IC 50 for TUNEL-positive staining (56 nM) was 4-fold higher than that measured in vitro (14 nM). Consistent with this finding, P-glycoprotein expression was observed to be substantially upregulated in brain metastasis cells in vivo. Vinorelbine exposure at maximum tolerated dose was less than one-tenth that in systemic metastases in >70% of brain metastases, and was associated with negligible biomarker effect. In small subregions of the highest uptake brain metastases, compromise of blood-tumor barrier appeared complete. The results suggest that restricted delivery accounts for 80% of the compromise in drug efficacy for vinorelbine against this model.

Effects of atmospheric relative humidity on Stratum Corneum structure at the molecular level: ex vivo Raman spectroscopy analysis.

PubMed

Vyumvuhore, Raoul; Tfayli, Ali; Duplan, Hélène; Delalleau, Alexandre; Manfait, Michel; Baillet-Guffroy, Arlette

2013-07-21

Skin hydration plays an important role in the optimal physical properties and physiological functions of the skin. Despite the advancements in the last decade, dry skin remains the most common characteristic of human skin disorders. Thus, it is important to understand the effect of hydration on Stratum Corneum (SC) components. In this respect, our interest consists in correlating the variations of unbound and bound water content in the SC with structural and organizational changes in lipids and proteins using a non-invasive technique: Raman spectroscopy. Raman spectra were acquired on human SC at different relative humidity (RH) levels (4-75%). The content of different types of water, bound and free, was measured using the second derivative and curve fitting of the Raman bands in the range of 3100-3700 cm(-1). Changes in lipidic order were evaluated using νC-C and νC-H. To analyze the effect of RH on the protein structure, we examined in the Amide I region, the Fermi doublet of tyrosine, and the νasymCH3 vibration. The contributions of totally bound water were found not to vary with humidity, while partially bound water varied with three different rates. Unbound water increased greatly when all sites for bound water were saturated. Lipid organization as well as protein deployment was found to be optimal at intermediate RH values (around 60%), which correspond to the maximum of SC water binding capacity. This analysis highlights the relationship between bound water, the SC barrier state and the protein structure and elucidates the optimal conditions. Moreover, our results showed that increased content of unbound water in the SC induces disorder in the structures of lipids and proteins.

From Continuous Improvement to Organisational Learning: Developmental Theory.

ERIC Educational Resources Information Center

Murray, Peter; Chapman, Ross

2003-01-01

Explores continuous improvement methods, which underlie total quality management, finding barriers to implementation in practice that are related to a one-dimensional approach. Suggests a multiple, unbounded learning cycle, a holistic approach that includes adaptive learning, learning styles, generative learning, and capability development.…

Study of LTPP laboratory resilient modulus test data and response characteristics.

DOT National Transportation Integrated Search

2002-10-01

The resilient modulus of every unbound structural layer of the Long Term Pavement Performance (LTPP) Specific Pavement and : General Pavement Studies Test Sections is being measured in the laboratory using LTPP test protocol P46. A total of 2,014 : r...

Strategic planning unbound.

PubMed

Hiam, A

1993-01-01

The strategic planner's role has not kept up with the demands of today's complex business environment. But catching up is the planner's responsibility. Become participative, missionary, and aggressively iconoclastic, and you can be a catalyst of positive change. Stay rooted in the past, and you're just an impediment.

Interactive Algorithms for Unsupervised Machine Learning

DTIC Science & Technology

2015-06-01

committee members, Nina Balcan, Sanjoy Dasgupta, and John Langford. Nina’s unbounded energy and her passion for machine learning are qualities that I...52 3.3.2 Simulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 3.3.3 Real World Experiments...80 4.4.1 Simulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 4.4.2 Real World

Evaluation of the Enhanced Integrated Climatic Model for modulus-based construction specification for Oklahoma pavements.

DOT National Transportation Integrated Search

2013-07-01

The study provides estimation of site specific variation in environmental factors that can be : used in predicting seasonal and long-term variations in moduli of unbound materials. Using : these site specific estimates, the EICM climatic input files ...

Review of non-nuclear density gauges as possible replacements for ITD's nuclear density gauges.

DOT National Transportation Integrated Search

2015-01-01

This report examines the possibility of replacing nuclear density gauges (NDGs) with non-nuclear density gauges (NNDGs) to : measure density of hot mix asphalt (HMA) and unbound pavement layers in the field. The research team evaluated the : effectiv...

γ-ray decay from neutron-bound and unbound states in 95Mo and a novel technique for spin determination

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

Wiedeking, M.; Krticka, M.; Bernstein, L. A.

2016-02-01

The emission of γ rays from neutron-bound and neutron-unbound states in 95Mo, populated in the 94Mo(d,p) reaction, has been investigated. Charged particles and γ radiation were detected with arrays of annular silicon and Clover-type high-purity Germanium detectors, respectively. Utilizing p-γ and p-γ-γ coincidences, the 95Mo level scheme was greatly enhanced with 102 new transitions and 43 new states. It agrees well with shell model calculations for excitation energies below ≈2 MeV. From p-γ coincidence data, a new method for the determination of spins of discrete levels is proposed. The method exploits the suppression of high-angular momentum neutron emission from levelsmore » with high spins populated in the (d,p) reaction above the neutron separation energy. As a result, spins for almost all 95Mo levels below 2 MeV (and for a few levels above) have been determined with this method.« less

Coexistence and local μ-stability of multiple equilibrium points for memristive neural networks with nonmonotonic piecewise linear activation functions and unbounded time-varying delays.

PubMed

Nie, Xiaobing; Zheng, Wei Xing; Cao, Jinde

2016-12-01

In this paper, the coexistence and dynamical behaviors of multiple equilibrium points are discussed for a class of memristive neural networks (MNNs) with unbounded time-varying delays and nonmonotonic piecewise linear activation functions. By means of the fixed point theorem, nonsmooth analysis theory and rigorous mathematical analysis, it is proven that under some conditions, such n-neuron MNNs can have 5 n equilibrium points located in ℜ n , and 3 n of them are locally μ-stable. As a direct application, some criteria are also obtained on the multiple exponential stability, multiple power stability, multiple log-stability and multiple log-log-stability. All these results reveal that the addressed neural networks with activation functions introduced in this paper can generate greater storage capacity than the ones with Mexican-hat-type activation function. Numerical simulations are presented to substantiate the theoretical results. Copyright © 2016 Elsevier Ltd. All rights reserved.

Importance of Relating Efficacy Measures to Unbound Drug Concentrations for Anti-Infective Agents

PubMed Central

Gonzalez, Daniel; Schmidt, Stephan

2013-01-01

SUMMARY For the optimization of dosing regimens of anti-infective agents, it is imperative to have a good understanding of pharmacokinetics (PK) and pharmacodynamics (PD). Whenever possible, drug efficacy needs to be related to unbound concentrations at the site of action. For anti-infective drugs, the infection site is typically located outside plasma, and a drug must diffuse through capillary membranes to reach its target. Disease- and drug-related factors can contribute to differential tissue distribution. As a result, the assumption that the plasma concentration of drugs represents a suitable surrogate of tissue concentrations may lead to erroneous conclusions. Quantifying drug exposure in tissues represents an opportunity to relate the pharmacologically active concentrations to an observed pharmacodynamic parameter, such as the MIC. Selection of an appropriate specimen to sample and the advantages and limitations of the available sampling techniques require careful consideration. Ultimately, the goal will be to assess the appropriateness of a drug and dosing regimen for a specific pathogen and infection. PMID:23554417

Newborn Jaundice Technologies: Unbound Bilirubin and Bilirubin Binding Capacity In Neonates

PubMed Central

Amin, Sanjiv B.; Lamola, Angelo A.

2011-01-01

Neonatal jaundice (hyperbilirubinemia), extremely common in neonates, can be associated with neurotoxicity. A safe level of bilirubin has not been defined in either premature or term infants. Emerging evidence suggest that the level of unbound (or “free”) bilirubin has a better sensitivity and specificity than total serum bilirubin for bilirubin-induced neurotoxicity. Although recent studies suggest the usefulness of free bilirubin measurements in managing high-risk neonates including premature infants, there currently exists no widely available method to assay the serum free bilirubin concentration. To keep pace with the growing demand, in addition to reevaluation of old methods, several promising new methods are being developed for sensitive, accurate, and rapid measurement of free bilirubin and bilirubin binding capacity. These innovative methods need to be validated before adopting for clinical use. We provide an overview of some promising methods for free bilirubin and binding capacity measurements with the goal to enhance research in this area of active interest and apparent need. PMID:21641486

Using the fast fourier transform in binding free energy calculations.

PubMed

Nguyen, Trung Hai; Zhou, Huan-Xiang; Minh, David D L

2018-04-30

According to implicit ligand theory, the standard binding free energy is an exponential average of the binding potential of mean force (BPMF), an exponential average of the interaction energy between the unbound ligand ensemble and a rigid receptor. Here, we use the fast Fourier transform (FFT) to efficiently evaluate BPMFs by calculating interaction energies when rigid ligand configurations from the unbound ensemble are discretely translated across rigid receptor conformations. Results for standard binding free energies between T4 lysozyme and 141 small organic molecules are in good agreement with previous alchemical calculations based on (1) a flexible complex ( R≈0.9 for 24 systems) and (2) flexible ligand with multiple rigid receptor configurations ( R≈0.8 for 141 systems). While the FFT is routinely used for molecular docking, to our knowledge this is the first time that the algorithm has been used for rigorous binding free energy calculations. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Multi-dimensional stable fundamental solitons and excitations in PT-symmetric harmonic-Gaussian potentials with unbounded gain-and-loss distributions

NASA Astrophysics Data System (ADS)

Chen, Yong; Yan, Zhenya

2018-04-01

We demonstrate the parity-time- (PT-) symmetric harmonic-Gaussian potential with unbounded gain-and-loss distribution can support entirely-real linear spectra, stable spatial and spatio-temporal solitons in an inhomogeneous nonlinear medium (e.g., cubic nonlinear Schrödinger equation with the self-focusing and defocusing cases). Exact analytical solitons are derived in both one-dimensional (1D) and higher-dimensional (e.g., 2D, 3D) geometries such that they are verified to be stable in the given parameters regions. Particularly, several families of numerical fundamental solitons (especially the 1D double-peaked solitons, 2D vortex solitons, and 3D double bullets) can be found to be stable around the propagation parameters for exact solitons. Other significant properties of solitons are also explored including the interactions of solitons, stable soliton excitations, and transverse power flows. The results may excite the corresponding theoretical analysis and experiment designs.

Directional radiation pattern in structural-acoustic coupled system

NASA Astrophysics Data System (ADS)

Seo, Hee-Seon; Kim, Yang-Hann

2005-07-01

In this paper we demonstrate the possibility of designing a radiator using structural-acoustic interaction by predicting the pressure distribution and radiation pattern of a structural-acoustic coupling system that is composed by a wall and two spaces. If a wall separates spaces, then the wall's role in transporting the acoustic characteristics of the spaces is important. The spaces can be categorized as bounded finite space and unbounded infinite space. The wall considered in this study composes two plates and an opening, and the wall separates one space that is highly reverberant and the other that is unbounded without any reflection. This rather hypothetical circumstance is selected to study the general coupling problem between the finite and infinite acoustic domains. We developed an equation that predicts the energy distribution and energy flow in the two spaces separated by a wall, and its computational examples are presented. Three typical radiation patterns that include steered, focused, and omnidirected are presented. A designed radiation pattern is also presented by using the optimal design algorithm.

Global dynamics of a delay differential equation with spatial non-locality in an unbounded domain

NASA Astrophysics Data System (ADS)

Yi, Taishan; Zou, Xingfu

In this paper, we study the global dynamics of a class of differential equations with temporal delay and spatial non-locality in an unbounded domain. Adopting the compact open topology, we describe the delicate asymptotic properties of the nonlocal delayed effect and establish some a priori estimate for nontrivial solutions which enables us to show the permanence of the equation. Combining these results with a dynamical systems approach, we determine the global dynamics of the equation under appropriate conditions. Applying the main results to the model with Ricker's birth function and Mackey-Glass's hematopoiesis function, we obtain threshold results for the global dynamics of these two models. We explain why our results on the global attractivity of the positive equilibrium in C∖{0} under the compact open topology becomes invalid in C∖{0} with respect to the usual supremum norm, and we identify a subset of C∖{0} in which the positive equilibrium remains attractive with respect to the supremum norm.

High-order boundary integral equation solution of high frequency wave scattering from obstacles in an unbounded linearly stratified medium

NASA Astrophysics Data System (ADS)

Barnett, Alex H.; Nelson, Bradley J.; Mahoney, J. Matthew

2015-09-01

We apply boundary integral equations for the first time to the two-dimensional scattering of time-harmonic waves from a smooth obstacle embedded in a continuously-graded unbounded medium. In the case we solve, the square of the wavenumber (refractive index) varies linearly in one coordinate, i.e. (Δ + E +x2) u (x1 ,x2) = 0 where E is a constant; this models quantum particles of fixed energy in a uniform gravitational field, and has broader applications to stratified media in acoustics, optics and seismology. We evaluate the fundamental solution efficiently with exponential accuracy via numerical saddle-point integration, using the truncated trapezoid rule with typically 102 nodes, with an effort that is independent of the frequency parameter E. By combining with a high-order Nyström quadrature, we are able to solve the scattering from obstacles 50 wavelengths across to 11 digits of accuracy in under a minute on a desktop or laptop.

Metronidazole and Hydroxymetronidazole Central Nervous System Distribution: 2. Cerebrospinal Fluid Concentration Measurements in Patients with External Ventricular Drain

PubMed Central

Frasca, Denis; Dahyot-Fizelier, Claire; Adier, Christophe; Mimoz, Olivier; Debaene, Bertrand; Couet, William

2014-01-01

This study explored metronidazole and hydroxymetronidazole distribution in the cerebrospinal fluid (CSF) of brain-injured patients. Four brain-injured patients with external ventricular drain received 500 mg of metronidazole over 0.5 h every 8 h. CSF and blood samples were collected at steady state over 8 h, and the metronidazole and hydroxymetronidazole concentrations were assayed by high-pressure liquid chromatograph. A noncompartmental analysis was performed. Metronidazole is distributed extensively within CSF, with a mean CSF to unbound plasma AUC0–τ ratio of 86% ± 16%. However, the concentration profiles in CSF were mostly flat compared to the plasma profiles. Hydroxymetronidazole concentrations were much lower than those of metronidazole both in plasma and in CSF, with a corresponding CSF/unbound plasma AUC0–τ ratio of 79% ± 16%. We describe here for the first time in detail the pharmacokinetics of metronidazole and hydroxymetronidazole in CSF. PMID:24277050

Quantum Steering Inequality with Tolerance for Measurement-Setting Errors: Experimentally Feasible Signature of Unbounded Violation

NASA Astrophysics Data System (ADS)

Rutkowski, Adam; Buraczewski, Adam; Horodecki, Paweł; Stobińska, Magdalena

2017-01-01

Quantum steering is a relatively simple test for proving that the values of quantum-mechanical measurement outcomes come into being only in the act of measurement. By exploiting quantum correlations, Alice can influence—steer—Bob's physical system in a way that is impossible in classical mechanics, as shown by the violation of steering inequalities. Demonstrating this and similar quantum effects for systems of increasing size, approaching even the classical limit, is a long-standing challenging problem. Here, we prove an experimentally feasible unbounded violation of a steering inequality. We derive its universal form where tolerance for measurement-setting errors is explicitly built in by means of the Deutsch-Maassen-Uffink entropic uncertainty relation. Then, generalizing the mutual unbiasedness, we apply the inequality to the multisinglet and multiparticle bipartite Bell state. However, the method is general and opens the possibility of employing multiparticle bipartite steering for randomness certification and development of quantum technologies, e.g., random access codes.

Large-scale single-chirality separation of single-wall carbon nanotubes by simple gel chromatography

PubMed Central

Liu, Huaping; Nishide, Daisuke; Tanaka, Takeshi; Kataura, Hiromichi

2011-01-01

Monostructured single-wall carbon nanotubes (SWCNTs) are important in both scientific research and electronic and biomedical applications; however, the bulk separation of SWCNTs into populations of single-chirality nanotubes remains challenging. Here we report a simple and effective method for the large-scale chirality separation of SWCNTs using a single-surfactant multicolumn gel chromatography method utilizing one surfactant and a series of vertically connected gel columns. This method is based on the structure-dependent interaction strength of SWCNTs with an allyl dextran-based gel. Overloading an SWCNT dispersion on the top column results in the adsorption sites of the column becoming fully occupied by the nanotubes that exhibit the strongest interaction with the gel. The unbound nanotubes flow through to the next column, and the nanotubes with the second strongest interaction with the gel are adsorbed in this stage. In this manner, 13 different (n, m) species were separated. Metallic SWCNTs were finally collected as unbound nanotubes because they exhibited the lowest interaction with the gel. PMID:21556063

Probing protein flexibility reveals a mechanism for selective promiscuity

PubMed Central

Pabon, Nicolas A; Camacho, Carlos J

2017-01-01

Many eukaryotic regulatory proteins adopt distinct bound and unbound conformations, and use this structural flexibility to bind specifically to multiple partners. However, we lack an understanding of how an interface can select some ligands, but not others. Here, we present a molecular dynamics approach to identify and quantitatively evaluate the interactions responsible for this selective promiscuity. We apply this approach to the anticancer target PD-1 and its ligands PD-L1 and PD-L2. We discover that while unbound PD-1 exhibits a hard-to-drug hydrophilic interface, conserved specific triggers encoded in the cognate ligands activate a promiscuous binding pathway that reveals a flexible hydrophobic binding cavity. Specificity is then established by additional contacts that stabilize the PD-1 cavity into distinct bound-like modes. Collectively, our studies provide insight into the structural basis and evolution of multiple binding partners, and also suggest a biophysical approach to exploit innate binding pathways to drug seemingly undruggable targets. DOI: http://dx.doi.org/10.7554/eLife.22889.001 PMID:28432789

A Step Beyond BRET: Fluorescence by Unbound Excitation from Luminescence (FUEL)

PubMed Central

Dragavon, Joseph; Sinow, Carolyn; Holland, Alexandra D.; Rekiki, Abdessalem; Theodorou, Ioanna; Samson, Chelsea; Blazquez, Samantha; Rogers, Kelly L.; Tournebize, Régis; Shorte, Spencer L.

2014-01-01

Fluorescence by Unbound Excitation from Luminescence (FUEL) is a radiative excitation-emission process that produces increased signal and contrast enhancement in vitro and in vivo. FUEL shares many of the same underlying principles as Bioluminescence Resonance Energy Transfer (BRET), yet greatly differs in the acceptable working distances between the luminescent source and the fluorescent entity. While BRET is effectively limited to a maximum of 2 times the Förster radius, commonly less than 14 nm, FUEL can occur at distances up to µm or even cm in the absence of an optical absorber. Here we expand upon the foundation and applicability of FUEL by reviewing the relevant principles behind the phenomenon and demonstrate its compatibility with a wide variety of fluorophores and fluorescent nanoparticles. Further, the utility of antibody-targeted FUEL is explored. The examples shown here provide evidence that FUEL can be utilized for applications where BRET is not possible, filling the spatial void that exists between BRET and traditional whole animal imaging. PMID:24894759

Triiodothyronine and thyroxine in urine. II. Renal handling, and effect of urinary protein.

PubMed

Burke, C W; Shakespear, R A

1976-03-01

Mean urinary clearances of T3 were 164 ml/min in normal subjects, 177 in pregnancy, 221 in thyrotoxicosis, 174 in hypothyroidism, and 194 in 3 persons with undetectable T4 but normal T3 levels. T4 clearances were 38 ml/min in normal subjects, 48 in thyrotoxicosis, and 138 in hypothyroidism. Low creatinine clearance was associated with low clearances of T4 and T3. The data suggest urinary excretion of T3 by glomerular filtration of serum unbound T3 with added tubular excretion; and T4 excretion by glomerular filtration of unbound T4 and tubular reabsorption. However, 3-9% of urinary T3 and 5-12% of urinary T4 were bound to urinary proteins, and increased protein excretion caused markedly increased T4 excretion. In addition, 52% of urinary T3 and 68% of urinary T4 were bound to other substances of approximate mol wt 500-2,000, which may influence tubular handling of T3 or T4.

Preparation of milk protein-vitamin A complexes and their evaluation for vitamin A binding ability.

PubMed

Gupta, Chitra; Arora, Sumit; Syama, M A; Sharma, Apurva

2017-12-15

The recent trends for consumption of low fat and fat free foods have led to an increase in deficiencies of vitamin A. Vitamin A is susceptible to light and heat and thus require stabilization in aqueous medium. Stability can be improved by binding of vitamin A to milk protein. In the present research work, succinylated milk proteins were also prepared. 3.2 mol of succinic anhydride/mole of lysine content gave maximum degree of succinylation for both sodium caseinate and milk protein concentrate. Native, reassembled and succinylated milk proteins were used for the preparation of milk protein-Vitamin A (Vit A) complexes. These complexes were further evaluated for unbound vitamin A, ability of milk protein to bind vitamin A and solubility of protein and vitamin A as affected by complexation. Estimation of unbound vitamin A in milk protein-Vit A complexes was carried out using ammonium sulphate for precipitation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Zooming in and out from the Mental Number Line: Evidence for a Number Range Effect

ERIC Educational Resources Information Center

Pinhas, Michal; Pothos, Emmanuel M.; Tzelgov, Joseph

2013-01-01

The representation of numbers is commonly viewed as an ordered continuum of magnitudes, referred to as the "mental number line." Previous work has repeatedly shown that number representations evoked by a given task can be easily altered, yielding an ongoing discussion about the basic properties of the mental number line and how malleable…

The Relationship between the Shape of the Mental Number Line and Familiarity with Numbers in 5- to 9-Year Old Children: Evidence for a Segmented Linear Model

ERIC Educational Resources Information Center

Ebersbach, Mirjam; Luwel, Koen; Frick, Andrea; Onghena, Patrick; Verschaffel, Lieven

2008-01-01

This experiment aimed to expand previous findings on the development of mental number representation. We tested the hypothesis that children's familiarity with numbers is directly reflected by the shape of their mental number line. This mental number line was expected to be linear as long as numbers lay within the range of numbers children were…

Canine status epilepticus treated with fosphenytoin: A proof of principle study.

PubMed

Patterson, Edward E; Leppik, Ilo E; Coles, Lisa D; Podell, Michael; Vite, Charles H; Bush, William; Cloyd, James C

2015-06-01

There are a limited number of marketed intravenous antiepileptic drugs (AEDs) available to treat status epilepticus (SE). All were first developed for chronic therapy of epilepsy, not specifically for SE. Epilepsy and canine SE (CSE) occur naturally in dogs, with prevalence, presentation, and percentage of refractory cases similar to human epilepsy. The objective of this study was to determine if CSE treated with fosphenytoin (FOS) results in a similar responder rate as for people. A randomized clinical trial was performed for dogs with CSE. Dogs who presented during a seizure or who had additional seizures after enrolling received intravenous (i.v.) benzodiazepine (BZD) followed immediately by intravenous infusion of 15 mg/kg phenytoin equivalent (PE) of fosphenytoin (FOS) or saline placebo (PBO). If seizures continued, additional AEDs were administered per the standard of care for veterinary patients. Total and unbound plasma phenytoin (PHT) concentrations were measured. Consent was obtained for 50 dogs with CSE. Thirty-one had additional motor seizures and were randomized to the study intervention (22 FOS and 9 PBO). There was a statistically significant difference in the 12 h responder rate, with 63% in the FOS group versus 22% in the placebo group (p = 0.043) having no further seizures. The unbound PHT concentrations at 30 and 60 min were within the therapeutic concentrations for people (1-2 μg/ml) with the exception of one dog. There was mild vomiting in 36% of the FOS group (7/22) within 20 min of FOS administration and none of the placebo group (0/9) (p = 0.064). This proof of concept study provides the first evidence that FOS is tolerated and effective in canine SE at PHT concentrations clinically relevant for human SE. Furthermore, naturally occurring CSE can be utilized as a translational platform for future studies of novel SE compounds. © 2015 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

Probing structure-induced optical behavior in a new class of self-activated luminescent 0D/1D CaWO₄ metal oxide – CdSe nanocrystal composite heterostructures

DOE PAGES

Han, Jinkyu; McBean, Coray; Wang, Lei; ...

2015-01-30

In this report, we synthesize and characterize the structural and optical properties of novel heterostructures composed of (i) semiconducting nanocrystalline CdSe quantum dot (QDs) coupled with (ii) both one and zero-dimensional (1D and 0D) motifs of self-activated luminescence CaWO₄ metal oxides. Specifically, ~4 nm CdSe QDs have been anchored onto (i) high-aspect ratio 1D nanowires, measuring ~230 nm in diameter and ~3 μm in length, as well as onto (ii) crystalline 0D nanoparticles (possessing an average diameter of ~ 80 nm) of CaWO₄ through the mediation of 3-mercaptopropionic acid (MPA) as a connecting linker. Composite formation was confirmed by complementarymore » electron microscopy and spectroscopy (i.e. IR and Raman) data. In terms of luminescent properties, our results show that our 1D and 0D heterostructures evince photoluminescence (PL) quenching and shortened PL lifetimes of CaWO₄ as compared with unbound CaWO₄. We propose that a photo-induced electron transfer process occurs from CaWO₄ to CdSe QDs, a scenario which has been confirmed by NEXAFS measurements and which highlights a decrease in the number of unoccupied orbitals in the conduction bands of CdSe QDs. By contrast, the PL signature and lifetimes of MPA-capped CdSe QDs within these heterostructures do not exhibit noticeable changes as compared with unbound MPA-capped CdSe QDs. The striking difference in optical behavior between CaWO₄ nanostructures and CdSe QDs within our heterostructures can be correlated with the relative positions of their conduction and valence energy band levels. In addition, the PL quenching behaviors for CaWO₄ within the heterostructure configuration were examined by systematically varying (i) the quantities and coverage densities of CdSe QDs as well as (ii) the intrinsic morphology (and by extension, the inherent crystallite size) of CaWO₄ itself.« less

An artificial neural network to discover hypervelocity stars: candidates in Gaia DR1/TGAS

NASA Astrophysics Data System (ADS)

Marchetti, T.; Rossi, E. M.; Kordopatis, G.; Brown, A. G. A.; Rimoldi, A.; Starkenburg, E.; Youakim, K.; Ashley, R.

2017-09-01

The paucity of hypervelocity stars (HVSs) known to date has severely hampered their potential to investigate the stellar population of the Galactic Centre and the Galactic potential. The first Gaia data release (DR1, 2016 September 14) gives an opportunity to increase the current sample. The challenge is the disparity between the expected number of HVSs and that of bound background stars. We have applied a novel data mining algorithm based on machine learning techniques, an artificial neural network, to the Tycho-Gaia astrometric solution catalogue. With no pre-selection of data, we could exclude immediately ˜99 per cent of the stars in the catalogue and find 80 candidates with more than 90 per cent predicted probability to be HVSs, based only on their position, proper motions and parallax. We have cross-checked our findings with other spectroscopic surveys, determining radial velocities for 30 and spectroscopic distances for five candidates. In addition, follow-up observations have been carried out at the Isaac Newton Telescope for 22 stars, for which we obtained radial velocities and distance estimates. We discover 14 stars with a total velocity in the Galactic rest frame >400 km s-1, and five of these have a probability of >50 per cent of being unbound from the Milky Way. Tracing back their orbits in different Galactic potential models, we find one possible unbound HVS with v ˜ 520 km s-1, five bound HVSs and, notably, five runaway stars with median velocity between 400 and 780 km s-1. At the moment, uncertainties in the distance estimates and ages are too large to confirm the nature of our candidates by narrowing down their ejection location, and we wait for future Gaia releases to validate the quality of our sample. This test successfully demonstrates the feasibility of our new data-mining routine.

Heat capacity of the neutron star inner crust within an extended nuclear statistical equilibrium model

NASA Astrophysics Data System (ADS)

Burrello, S.; Gulminelli, F.; Aymard, F.; Colonna, M.; Raduta, Ad. R.

2015-11-01

Background: Superfluidity in the crust is a key ingredient for the cooling properties of proto-neutron stars. Present theoretical calculations employ the quasiparticle mean-field Hartree-Fock-Bogoliubov theory with temperature-dependent occupation numbers for the quasiparticle states. Purpose: Finite temperature stellar matter is characterized by a whole distribution of different nuclear species. We want to assess the importance of this distribution on the calculation of heat capacity in the inner crust. Method: Following a recent work, the Wigner-Seitz cell is mapped into a model with cluster degrees of freedom. The finite temperature distribution is then given by a statistical collection of Wigner-Seitz cells. We additionally introduce pairing correlations in the local density BCS approximation both in the homogeneous unbound neutron component, and in the interface region between clusters and neutrons. Results: The heat capacity is calculated in the different baryonic density conditions corresponding to the inner crust, and in a temperature range varying from 100 KeV to 2 MeV. We show that accounting for the cluster distribution has a small effect at intermediate densities, but it considerably affects the heat capacity both close to the outer crust and close to the core. We additionally show that it is very important to consider the temperature evolution of the proton fraction for a quantitatively reliable estimation of the heat capacity. Conclusions: We present the first modelization of stellar matter containing at the same time a statistical distribution of clusters at finite temperature, and pairing correlations in the unbound neutron component. The effect of the nuclear distribution on the superfluid properties can be easily added in future calculations of the neutron star cooling curves. A strong influence of resonance population on the heat capacity at high temperature is observed, which deserves to be further studied within more microscopic calculations.

Stiffening of flexible SUMO1 protein upon peptide-binding: Analysis with anisotropic network model.

PubMed

Sarkar, Ranja

2018-01-01

SUMO (small ubiquitin-like modifier) proteins interact with a large number of target proteins via a key regulatory event called sumoylation that encompasses activation, conjugation and ligation of SUMO proteins through specific E1, E2, and E3-type enzymes respectively. Single-molecule atomic force microscopic (AFM) experiments performed to unravel bound SUMO1 along its NC termini direction reveal that E3-ligases (in the form of small peptides) increase mechanical stability (along the axis) of the flexible protein upon binding. The experimental results are expected to correlate with the intrinsic flexibility of bound SUMO1 protein in the native state i.e., the bound conformation of SUMO1 without the binding peptide. The native protein flexibility/stiffness can be measured as a spring constant by normal mode analysis. In the present study, protein normal modes are computed from the protein structural data (as input from protein databank) via a simple anisotropic network model (ANM). ANM is computationally inexpensive and hence, can be explored to investigate and compare the native conformational dynamics of unbound and bound (without the binding partner) structures, if the corresponding structural data (NMR/X-ray) are available. The paper illustrates that SUMO1 stiffens (native flexibility decreases) along the NC termini (end-to-end) direction of the protein upon binding to small peptides; however, the degree of stiffening is peptide sequence-specific. The theoretical results are demonstrated for NMR structures of unbound SUMO1 and that bound to two peptides having short amino acid motifs and of similar size, one being an M-IR2 peptide derived from RanBP2 protein and the other one derived from PIASX protein. The peptide derived from PIASX stiffens SUMO1 remarkably which is evident from an atomic-level normal mode analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

Survivability Extensions for Dynamic Ultralog Environments

DTIC Science & Technology

2004-12-07

8217 on line number 2018 doDo: Wrong number of tokens for ’Do’ on line number 2049 doDo: Wrong number of tokens for ’Do’ on line number 2069 doDo...discuss survivability as defined in the " bible of computational complexity", namely, the book "Computers and Intractability, a Guide to the Theory of

Changing Mental Representations Using Related Physical Models: The Effects of Analyzing Number Lines on Learner Internal Scale of Numerical Magnitude

ERIC Educational Resources Information Center

Bengtson, Barbara J.

2013-01-01

Understanding the linear relationship of numbers is essential for doing practical and abstract mathematics throughout education and everyday life. There is evidence that number line activities increase learners' number sense, improving the linearity of mental number line representations (Siegler & Ramani, 2009). Mental representations of…

In Silico Prediction of Toxicokinetic Parameters for Environmentally Relevant Chemicals for Risk-Based Prioritization

EPA Science Inventory

Toxicokinetic (TK) models can address an important component of chemical risk assessments by helping bridge the gap between chemical exposure and measured toxicity endpoints. The metabolic clearance rate (CLint) and fraction of a chemical unbound by plasma proteins (Fub) are crit...

Identifying Fractions on a Number Line

ERIC Educational Resources Information Center

Wong, Monica

2013-01-01

Fractions are generally introduced to students using the part--whole model. Yet the number line is another important representation which can be used to build fraction concepts (Australian Curriculum Assessment and Reporting Authority [ACARA], 2012). Number lines are recognised as key in students' number development not only of fractions, but…

Designer stabilizer for preparation of pristine graphene/polysiloxane films and networks

NASA Astrophysics Data System (ADS)

Parviz, Dorsa; Yu, Ziniu; Hedden, Ronald C.; Green, Micah J.

2014-09-01

A conductive polymer film containing pristine graphene was prepared by designing a polysiloxane-based stabilizer for graphene. The stabilizer was prepared by grafting 1-ethynylpyrene to the backbone of a poly(dimethylsiloxane)-co-(methylhydrosiloxane) (PDMS-PHMS) random copolymer by Pt-catalyzed hydrosilylation with a SiH-ethynyl ratio of 1.0 : 1.3. The resulting copolymer was able to stabilize pristine graphene in chloroform solution via π-π interactions between the pyrene groups and graphene sheets. TEM and SEM images show a homogeneous distribution of the graphene in cast films deposited from chloroform. The conductivity of a graphene/PDMS film prepared from copolymer with a 1.7 vol.% graphene loading was measured as 220 S m-1 after the removal of unbound polymer by a simple separation technique. With a SiH-ethynyl ratio of 1.7 : 1.0, the copolymer self-crosslinked at 110 °C in the presence of adventitious moisture, providing a straightforward route to incorporate graphene into silicone elastomers. The crosslinking process (with and without added graphene) was characterized by FT-IR spectroscopy and by swelling and extraction of the obtained networks. Again, unbound polymer removal increases the conductivity of the composite.A conductive polymer film containing pristine graphene was prepared by designing a polysiloxane-based stabilizer for graphene. The stabilizer was prepared by grafting 1-ethynylpyrene to the backbone of a poly(dimethylsiloxane)-co-(methylhydrosiloxane) (PDMS-PHMS) random copolymer by Pt-catalyzed hydrosilylation with a SiH-ethynyl ratio of 1.0 : 1.3. The resulting copolymer was able to stabilize pristine graphene in chloroform solution via π-π interactions between the pyrene groups and graphene sheets. TEM and SEM images show a homogeneous distribution of the graphene in cast films deposited from chloroform. The conductivity of a graphene/PDMS film prepared from copolymer with a 1.7 vol.% graphene loading was measured as 220 S m-1 after the removal of unbound polymer by a simple separation technique. With a SiH-ethynyl ratio of 1.7 : 1.0, the copolymer self-crosslinked at 110 °C in the presence of adventitious moisture, providing a straightforward route to incorporate graphene into silicone elastomers. The crosslinking process (with and without added graphene) was characterized by FT-IR spectroscopy and by swelling and extraction of the obtained networks. Again, unbound polymer removal increases the conductivity of the composite. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr01431f

Orbital fitting of imaged planetary companions with high eccentricities and unbound orbits. Their application to Fomalhaut b and PZ Telecopii B

NASA Astrophysics Data System (ADS)

Beust, H.; Bonnefoy, M.; Maire, A.-L.; Ehrenreich, D.; Lagrange, A.-M.; Chauvin, G.

2016-03-01

Context. Regular follow-up of imaged companions to main-sequence stars often allows a projected orbital motion to be detected. Markov chain Monte Carlo (MCMC) has become very popular recent years for fitting and constraining their orbits. Some of these imaged companions appear to move on very eccentric, possibly unbound orbits. This is, in particular, the case for the exoplanet Fomalhaut b and the brown dwarf companion PZ Tel B on which we focus here. Aims: For these orbits, standard MCMC codes that assume only bound orbits may be inappropriate. Our goal is to develop a new MCMC implementation that is able to handle both bound and unbound orbits in a continuous manner, and to apply this to the cases of Fomalhaut b and PZ Tel B. Methods: We present here this code, based on the use of universal Keplerian variables and Stumpff functions. We present two versions of this code, the second one using a different set of angular variables that were designed to avoid degeneracies arising when the projected orbital motion is quasi-radial, as is the case for PZ Tel B. We also present additional observations of PZ Tel B. Results: The code is applied to Fomalhaut b and PZ Tel B. We confirm previous results in relation to, but we show that on the sole basis of the astrometric data, open orbital solutions are also possible. The eccentricity distribution nevertheless still peaks around ~0.9 in the bound regime. We present a first successful orbital fit of PZ Tel B, which shows in particular that, while both bound and unbound orbital solutions are equally possible, the eccentricity distribution presents a sharp peak very close to e = 1, meaning a quasi-parabolic orbit. Conclusions: It has recently been suggested that the presence of unseen inner companions to imaged ones may lead orbital fitting algorithms to artificially give very high eccentricities. We show that this caveat is unlikely to apply to Fomalhaut b. Concerning PZ Tel B, we derive a possible solution, which involves an inner ~12 MJup companion, that would mimic a e = 1 orbit, despite a real eccentricity of around 0.7, but a dynamical analysis reveals that this type of system would not be stable. We thus conclude that our orbital fit is robust. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere, Chile (Program ID: 085.C-0867(B) and 085.C-0277(B)).

Tumor Specific Detection of an Optically Targeted Antibody Combined with a Quencher-conjugated Neutravidin “Quencher-Chaser”: A Dual “Quench and Chase” Strategy to Improve Target to Non-target Ratios for Molecular Imaging of Cancer

PubMed Central

Ogawa, Mikako; Kosaka, Nobuyuki; Choyke, Peter L; Kobayashi, Hisataka

2009-01-01

In vivo molecular cancer imaging with monoclonal antibodies has great potential not only for cancer detection but also for cancer characterization. However, the prolonged retention of intravenously injected antibody in the blood causes low target tumor-to-background ratio (TBR). Avidin has been used as a “chase” to clear the unbound, circulating biotinylated antibody and decrease the background signal. Here, we utilize a combined approach of a Fluorescence Resonance Energy Transfer (FRET) quenched antibody with an “avidin chase” to increase TBR. Trastuzumab, a humanized monoclonal antibody against human epidermal growth factor receptor type 2 (HER2), was biotinylated and conjugated with the near-infrared (NIR) fluorophore Alexa680 to synthesize Tra-Alexa680-biotin. Next, the FRET quencher, QSY-21, was conjugated to avidin, neutravidin (nAv) or streptavidin (sAv), thus creating Av-QSY21, nAv-QSY21 or sAv-QSY21 as “chasers”. The fluorescence was quenched in vitro by binding Tra-Alexa680-biotin to Av-QSY21, nAv-QSY21 or sAv-QSY21. To evaluate if the injection of quencher-conjugated avidin-derivatives can improve target TBR by using a dual “quench and chase” strategy, both target (3T3/HER2+) and non-target (Balb3T3/ZsGreen) tumor bearing mice were employed. The “FRET quench” effect induced by all the QSY21 avidin-based conjugates reduced but did not totally eliminate background signal from the blood pool. The addition of nAv-QSY21 administration increased target TBR mainly due to the “chase” effect where unbound conjugated antibody was preferentially cleared to the liver. The relatively slow clearance of unbound nAv-QSY21 leads to further reductions in background signal by leaking out of the vascular space and binding to unbound antibodies in the extravascular space of tumors resulting in decreased non-target tumor-to-background ratios but increased target TBR due to the “FRET quench” effect because target-bound antibodies were internalized and could not bind to nAv-QSY21. In conclusion, the proposed “quench-and-chase” system combines two strategies, fluorescent quenching and avidin chasing to improve target TBR and reduce non target TBR which should result in both improved tumor sensitivity and specificity. PMID:19072537

Shape Complementarity of Protein-Protein Complexes at Multiple Resolutions

PubMed Central

Zhang, Qing; Sanner, Michel; Olson, Arthur J.

2010-01-01

Biological complexes typically exhibit intermolecular interfaces of high shape complementarity. Many computational docking approaches use this surface complementarity as a guide in the search for predicting the structures of protein-protein complexes. Proteins often undergo conformational changes in order to create a highly complementary interface when associating. These conformational changes are a major cause of failure for automated docking procedures when predicting binding modes between proteins using their unbound conformations. Low resolution surfaces in which high frequency geometric details are omitted have been used to address this problem. These smoothed, or blurred, surfaces are expected to minimize the differences between free and bound structures, especially those that are due to side chain conformations or small backbone deviations. In spite of the fact that this approach has been used in many docking protocols, there has yet to be a systematic study of the effects of such surface smoothing on the shape complementarity of the resulting interfaces. Here we investigate this question by computing shape complementarity of a set of 66 protein-protein complexes represented by multi-resolution blurred surfaces. Complexed and unbound structures are available for these protein-protein complexes. They are a subset of complexes from a non-redundant docking benchmark selected for rigidity (i.e. the proteins undergo limited conformational changes between their bound and unbound states). In this work we construct the surfaces by isocontouring a density map obtained by accumulating the densities of Gaussian functions placed at all atom centers of the molecule. The smoothness or resolution is specified by a Gaussian fall-off coefficient, termed “blobbyness”. Shape complementarity is quantified using a histogram of the shortest distances between two proteins' surface mesh vertices for both the crystallographic complexes and the complexes built using the protein structures in their unbound conformation. The histograms calculated for the bound complex structures demonstrate that medium resolution smoothing (blobbyness=−0.9) can reproduce about 88% of the shape complementarity of atomic resolution surfaces. Complexes formed from the free component structures show a partial loss of shape complementarity (more overlaps and gaps) with the atomic resolution surfaces. For surfaces smoothed to low resolution (blobbyness=−0.3), we find more consistency of shape complementarity between the complexed and free cases. To further reduce bad contacts without significantly impacting the good contacts we introduce another blurred surface, in which the Gaussian densities of flexible atoms are reduced. From these results we discuss the use of shape complementarity in protein-protein docking. PMID:18837463

Effect of solid boundaries on a motile microorganism in a viscoelastic fluid

NASA Astrophysics Data System (ADS)

Karimi, Alireza; Li, Gaojin; Ardekani, Arezoo

2014-11-01

Microorganisms swimming in viscoelastic fluids are ubiquitous in nature; this includes biofilms grown on surfaces, Helicobacter pylori colonizing in the mucus layer covering the stomach and spermatozoa swimming through cervical mucus inside the mammalian female reproductive tract. Previous studies have focused on the locomotion of microorganisms in an unbounded viscoelastic fluid. However in many situations, microorganisms interact with solid boundaries and their hydrodynamic interaction is poorly understood. In this work, we numerically study the effect of solid boundaries on the swimming behavior of an archetypal low-Reynolds number swimmer, called ``squirmer,'' in a viscoelastic fluid. A Giesekus constitutive equation is used to model both viscoelasticity and shear-thinning behavior of the background fluid. We found that the time a neutral squirmer spends in the close proximity of the wall increases with polymer relaxation time and reaches a maximum at Weissenberg number of unity. A pusher is found to be trapped near the wall in a viscoelastic fluid, but the puller is less affected. This publication was made possible, in part, with support from NSF (Grant No. CBET-1150348-CAREER) and Indiana Clinical and Translational Sciences Institute Collaboration in Biomedical/Translational Research (Grant No. TR000006) from NIH.

The Dynamics of Power laws: Fitness and Aging in Preferential Attachment Trees

NASA Astrophysics Data System (ADS)

Garavaglia, Alessandro; van der Hofstad, Remco; Woeginger, Gerhard

2017-09-01

Continuous-time branching processes describe the evolution of a population whose individuals generate a random number of children according to a birth process. Such branching processes can be used to understand preferential attachment models in which the birth rates are linear functions. We are motivated by citation networks, where power-law citation counts are observed as well as aging in the citation patterns. To model this, we introduce fitness and age-dependence in these birth processes. The multiplicative fitness moderates the rate at which children are born, while the aging is integrable, so that individuals receives a finite number of children in their lifetime. We show the existence of a limiting degree distribution for such processes. In the preferential attachment case, where fitness and aging are absent, this limiting degree distribution is known to have power-law tails. We show that the limiting degree distribution has exponential tails for bounded fitnesses in the presence of integrable aging, while the power-law tail is restored when integrable aging is combined with fitness with unbounded support with at most exponential tails. In the absence of integrable aging, such processes are explosive.

[Dynamics of diazotrophic bacteria number in the root zone of wheat Vrn lines isogenic by genes].

PubMed

Samoĭlov, A M; Zhmurko, V V

2012-01-01

The number of diazotrophic bacteria and nitrogenase activity in the root zone of isogenic monogene-dominant Vrn lines were measured in the field experiments throughout their vegetation from tillering to heading. The total number of diazotrophic bacteria and nitrogenase activity in the root zone of these lines during this period were increased irrespective of their genotypes. The above indices of the winter cultivar (Vrn loci bottom recessive) were lower than those of the spring lines--Vrn-A1, Vrn-B1 and Vrn-D1. Plants of Vrn-B1 line have the lowest indices among the spring lines with the exception of some indices. This line plants flowered later than those of Vrn-A1 and Vrn-D1 lines. We hypothesized the differences between plants of these lines as to nitrogen fixation activity and the number of diazotrophic bacteria are mediately determined by Vrn loci through their effects on metabolism intensity and assimilate reflux in the form of root exudates, therefore the total number of diazotrophic bacteria and nitrogenase activity increases.

Current singularities at quasi-separatrix layers and three-dimensional magnetic nulls

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

Craig, I. J. D.; Effenberger, Frederic, E-mail: feffen@waikato.ac.nz

2014-11-10

The open problem of how singular current structures form in line-tied, three-dimensional magnetic fields is addressed. A Lagrangian magneto-frictional relaxation method is employed to model the field evolution toward the final near-singular state. Our starting point is an exact force-free solution of the governing magnetohydrodynamic equations that is sufficiently general to allow for topological features like magnetic nulls to be inside or outside the computational domain, depending on a simple set of parameters. Quasi-separatrix layers (QSLs) are present in these structures and, together with the magnetic nulls, they significantly influence the accumulation of current. It is shown that perturbations affectingmore » the lateral boundaries of the configuration lead not only to collapse around the magnetic null but also to significant QSL currents. Our results show that once a magnetic null is present, the developing currents are always attracted to that specific location and show a much stronger scaling with resolution than the currents that form along the QSL. In particular, the null-point scalings can be consistent with models of 'fast' reconnection. The QSL currents also appear to be unbounded but give rise to weaker singularities, independent of the perturbation amplitude.« less

The body unbound: vestibular-motor hallucinations and out-of-body experiences.

PubMed

Cheyne, J Allan; Girard, Todd A

2009-02-01

Among the varied hallucinations associated with sleep paralysis (SP), out-of-body experiences (OBEs) and vestibular-motor (V-M) sensations represent a distinct factor. Recent studies of direct stimulation of vestibular cortex report a virtually identical set of bodily-self hallucinations. Both programs of research agree on numerous details of OBEs and V-M experiences and suggest similar hypotheses concerning their association. In the present study, self-report data from two on-line surveys of SP-related experiences were employed to assess hypotheses concerning the causal structure of relations among V-M experiences and OBEs during SP episodes. The results complement neurophysiological evidence and are consistent with the hypothesis that OBEs represent a breakdown in the normal binding of bodily-self sensations and suggest that out-of-body feelings (OBFs) are consequences of anomalous V-M experiences and precursors to a particular form of autoscopic experience, out-of-body autoscopy (OBA). An additional finding was that vestibular and motor experiences make relatively independent contributions to OBE variance. Although OBEs are superficially consistent with universal dualistic and supernatural intuitions about the nature of the soul and its relation to the body, recent research increasingly offers plausible alternative naturalistic explanations of the relevant phenomenology.

Compact solid-state CMOS single-photon detector array for in vivo NIR fluorescence lifetime oncology measurements.

PubMed

Homulle, H A R; Powolny, F; Stegehuis, P L; Dijkstra, J; Li, D-U; Homicsko, K; Rimoldi, D; Muehlethaler, K; Prior, J O; Sinisi, R; Dubikovskaya, E; Charbon, E; Bruschini, C

2016-05-01

In near infrared fluorescence-guided surgical oncology, it is challenging to distinguish healthy from cancerous tissue. One promising research avenue consists in the analysis of the exogenous fluorophores' lifetime, which are however in the (sub-)nanosecond range. We have integrated a single-photon pixel array, based on standard CMOS SPADs (single-photon avalanche diodes), in a compact, time-gated measurement system, named FluoCam. In vivo measurements were carried out with indocyanine green (ICG)-modified derivatives targeting the αvβ 3 integrin, initially on a genetically engineered mouse model of melanoma injected with ICG conjugated with tetrameric cyclic pentapeptide (ICG-E[c(RGD f K)4]), then on mice carrying tumour xenografts of U87-MG (a human primary glioblastoma cell line) injected with monomeric ICG-c(RGD f K). Measurements on tumor, muscle and tail locations allowed us to demonstrate the feasibility of in vivo lifetime measurements with the FluoCam, to determine the characteristic lifetimes (around 500 ps) and subtle lifetime differences between bound and unbound ICG-modified fluorophores (10% level), as well as to estimate the available photon fluxes under realistic conditions.

Studies of the field-of-view resolution tradeoff in virtual-reality systems

NASA Technical Reports Server (NTRS)

Piantanida, Thomas P.; Boman, Duane; Larimer, James; Gille, Jennifer; Reed, Charles

1992-01-01

Most virtual-reality systems use LCD-based displays that achieve a large field-of-view at the expense of resolution. A typical display will consist of approximately 86,000 pixels uniformly distributed over an 80-degree by 60-degree image. Thus, each pixel subtends about 13 minutes of arc at the retina; about the same as the resolvable features of the 20/200 line of a Snellen Eye Chart. The low resolution of LCD-based systems limits task performance in some applications. We have examined target-detection performance in a low-resolution virtual world. Our synthesized three-dimensional virtual worlds consisted of target objects that could be positioned at a fixed distance from the viewer, but at random azimuth and constrained elevation. A virtual world could be bounded by chromatic walls or by wire-frame, or it could be unbounded. Viewers scanned these worlds and indicated by appropriate gestures when they had detected the target object. By manipulating the viewer's field size and the chromatic and luminance contrast of annuli surrounding the field-of-view, we were able to assess the effect of field size on the detection of virtual objects in low-resolution synthetic worlds.

Novel method for in vitro depletion of T cells by monoclonal antibody-targeted photosensitization.

PubMed

Berki, T; Németh, P

1998-02-01

An immunotargeting method (called photo-immunotargeting) has been developed for selective in vitro cell destruction. The procedure combines the photosensitizing (toxic) effect of light-induced dye-molecules, e.g., hematoporphyrin (HP) and the selective binding ability of monoclonal antibodies (mAb) to cell surface molecules. The photosensitizer HP molecules were covalently attached to monoclonal antibodies (a-Thy-1) recognizing an antigen on the surface of T lymphocytes, and used for T cell destruction. To increase the selectivity of the conventional targeting methods, a physical activation step (local light irradiation) as a second degree of specificity was employed. The HP in conjugated form was sufficient to induce T cell (thymocytes, EL-4 cell line) death after irradiation at 400 nm, at tenfold lower concentration compared to the photosensitizing effect of unbound HP. The selective killing of T lymphocytes (bearing the Thy-1 antigen) in a mixed cell population was demonstrated after a treatment with the phototoxic conjugate and light irradiation. This method can be useful for selective destruction of one population (target cell) in an in vitro heterogeneous cell mixture, e.g., in bone marrow transplants for T cell depletion to avoid graft vs. host reaction.

Longitudinal development of number line estimation and mathematics performance in primary school children.

PubMed

Friso-van den Bos, Ilona; Kroesbergen, Evelyn H; Van Luit, Johannes E H; Xenidou-Dervou, Iro; Jonkman, Lisa M; Van der Schoot, Menno; Van Lieshout, Ernest C D M

2015-06-01

Children's ability to relate number to a continuous quantity abstraction visualized as a number line is widely accepted to be predictive of mathematics achievement. However, a debate has emerged with respect to how children's placements are distributed on this number line across development. In the current study, different models were applied to children's longitudinal number placement data to get more insight into the development of number line representations in kindergarten and early primary school years. In addition, longitudinal developmental relations between number line placements and mathematical achievement, measured with a national test of mathematics, were investigated using cross-lagged panel modeling. A group of 442 children participated in a 3-year longitudinal study (ages 5-8 years) in which they completed a number-to-position task every 6 months. Individual number line placements were fitted to various models, of which a one-anchor power model provided the best fit for many of the placements at a younger age (5 or 6 years) and a two-anchor power model provided better fit for many of the children at an older age (7 or 8 years). The number of children who made linear placements also grew with age. Cross-lagged panel analyses indicated that the best fit was provided with a model in which number line acuity and mathematics performance were mutually predictive of each other rather than models in which one ability predicted the other in a non-reciprocal way. This indicates that number line acuity should not be seen as a predictor of math but that both skills influence each other during the developmental process. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Left to Right: Representational Biases for Numbers and the Effect of Visuomotor Adaptation

ERIC Educational Resources Information Center

Loftus, Andrea M.; Nicholls, Michael E. R.; Mattingley, Jason B.; Bradshaw, John L.

2008-01-01

Adaptation to right-shifting prisms improves left neglect for mental number line bisection. This study examined whether adaptation affects the mental number line in normal participants. Thirty-six participants completed a mental number line task before and after adaptation to either: left-shifting prisms, right-shifting prisms or control…

Fort Play Children Recreate Recess

ERIC Educational Resources Information Center

Powell, Mark

2007-01-01

Recess beckons well before it actually arrives. Its allure can be heard in children's lunchtime conversations as they discuss imaginary roles, plans, alliances and teams, with an obvious appetite for play and its unbounded possibility. For some children, recess provides the most important reasons to come to school. In team sports, games of chase…

Non-Lipschitzian dynamics for neural net modelling

NASA Technical Reports Server (NTRS)

Zak, Michail

1989-01-01

Failure of the Lipschitz condition in unstable equilibrium points of dynamical systems leads to a multiple-choice response to an initial deterministic input. The evolution of such systems is characterized by a special type of unpredictability measured by unbounded Liapunov exponents. Possible relation of these systems to future neural networks is discussed.

Parallel Processable Cryptographic Methods with Unbounded Practical Security.

ERIC Educational Resources Information Center

Rothstein, Jerome

Addressing the problem of protecting confidential information and data stored in computer databases from access by unauthorized parties, this paper details coding schemes which present such astronomical work factors to potential code breakers that security breaches are hopeless in any practical sense. Two procedures which can be used to encode for…

University Unbound! Higher Education in the Age of "Free"

ERIC Educational Resources Information Center

Harney, John O.

2012-01-01

Innovators and entrepreneurs are using technologies to make freely available the things for which universities charge significant money. MOOCs (massive open online courses), free online courses, lecture podcasts, low-cost off-the-shelf general education courses, online tutorials, digital collections of open learning resources, open badges--all are…

Bifurcations and complete chaos for the diamagnetic Kepler problem

NASA Astrophysics Data System (ADS)

Hansen, Kai T.

1995-03-01

We describe the structure of bifurcations in the unbounded classical diamagnetic Kepler problem. We conjecture that this system does not have any stable orbits and that the nonwandering set is described by a complete trinary symbolic dynamics for scaled energies larger than ɛc=0.328 782. . ..

MnROAD cells 16-23 (phase II) : forensic investigation into recycled unbound base and asphalt surface materials.

DOT National Transportation Integrated Search

2017-06-01

This report presents the findings from an eight-year performance evaluation of eight cells (Cells 16-23) built at the Minnesota Road Research Facility (MnROAD) in 2008. The constructed cells were used for two performance evaluation studies of: 1) unb...

Some Fundamental Issues of Mathematical Simulation in Biology

NASA Astrophysics Data System (ADS)

Razzhevaikin, V. N.

2018-02-01

Some directions of simulation in biology leading to original formulations of mathematical problems are overviewed. Two of them are discussed in detail: the correct solvability of first-order linear equations with unbounded coefficients and the construction of a reaction-diffusion equation with nonlinear diffusion for a model of genetic wave propagation.

In Silico Prediction of Toxicokinetic Parameters for Environmentally Relevant Chemicals with Application to Risk-Based Prioritization

EPA Science Inventory

Toxicokinetic (TK) models can help bridge the gap between chemical exposure and measured toxicity endpoints, thereby addressing an important component of chemical risk assessments. The fraction of a chemical unbound by plasma proteins (Fub) and metabolic clearance rate (CLint) ar...

Toxicity challenges in environmental chemicals: Prediction of human plasma protein binding through quantitative structure-activity relationship (QSAR) models

EPA Science Inventory

The present study explores the merit of utilizing available pharmaceutical data to construct a quantitative structure-activity relationship (QSAR) for prediction of the fraction of a chemical unbound to plasma protein (Fub) in environmentally relevant compounds. Independent model...

A simple derivation and analysis of a helical cone beam tomographic algorithm for long object imaging via a novel definition of region of interest

NASA Astrophysics Data System (ADS)

Hu, Jicun; Tam, Kwok; Johnson, Roger H.

2004-01-01

We derive and analyse a simple algorithm first proposed by Kudo et al (2001 Proc. 2001 Meeting on Fully 3D Image Reconstruction in Radiology and Nuclear Medicine (Pacific Grove, CA) pp 7-10) for long object imaging from truncated helical cone beam data via a novel definition of region of interest (ROI). Our approach is based on the theory of short object imaging by Kudo et al (1998 Phys. Med. Biol. 43 2885-909). One of the key findings in their work is that filtering of the truncated projection can be divided into two parts: one, finite in the axial direction, results from ramp filtering the data within the Tam window. The other, infinite in the z direction, results from unbounded filtering of ray sums over PI lines only. We show that for an ROI defined by PI lines emanating from the initial and final source positions on a helical segment, the boundary data which would otherwise contaminate the reconstruction of the ROI can be completely excluded. This novel definition of the ROI leads to a simple algorithm for long object imaging. The overscan of the algorithm is analytically calculated and it is the same as that of the zero boundary method. The reconstructed ROI can be divided into two regions: one is minimally contaminated by the portion outside the ROI, while the other is reconstructed free of contamination. We validate the algorithm with a 3D Shepp-Logan phantom and a disc phantom.

Brentuximab vedotin exerts profound antiproliferative and pro-apoptotic efficacy in CD30-positive as well as cocultured CD30-negative germ cell tumour cell lines.

PubMed

Schönberger, Stefan; van Beekum, Cornelius; Götz, Barbara; Nettersheim, Daniel; Schorle, Hubert; Schneider, Dominik T; Casati, Anna; Craveiro, Rogerio B; Calaminus, Gabriele; Dilloo, Dagmar

2018-01-01

Prognosis in patients suffering from high-risk, refractory and relapsed germ cell tumours (GCT) often comprising of CD30-positive embryonal carcinoma (EC) components remains poor. Thus, novel treatment strategies are warranted. The antibody-drug conjugate (ADC) brentuximab vedotin delivers the potent antimitotic drug monomethyl auristatin E (MMAE) to CD30-expressing tumour cells. After CD30 binding, internalization and intracellular linker cleavage cytotoxic MMAE can efflux and eradicate neighbouring CD30-negative cells. To analyse cytotoxicity and a potential bystander effect of brentuximab vedotin in GCT, we established an in vitro coculture model mimicking GCT of heterogeneous CD30 positivity and measured cell viability, proliferation and apoptosis after exposure to brentuximab vedotin and unbound MMAE by MTS- and flow cytometry-based CFSE/Hoechst assay. CD30 expression being assessed by quantitative RT-PCR and immunohistochemistry was apparent in all EC cell lines with different intensity. Brentuximab vedotin abrogates cell viability of CD30-positive GCT27 EC line exerting marked time-dependent antiproliferative and pro-apoptotic activity. CD30-negative JAR cultured alone barely responds to brentuximab vedotin, while in coculture with GCT27 brentuximab vedotin induces clear dose-dependent cytotoxicity. Cellular proliferation and cell death are significantly enhanced in CD30-negative JAR cocultured with CD30-positive GCT27 compared to JAR cultured alone in proof of substantial bystander activity of brentuximab vedotin in CD30-negative GCT. We present first evidence that in an in vitro model mimicking GCT of heterogeneous histology, brentuximab vedotin exerts potent antiproliferative and pro-apoptotic activity against both CD30-positive as well as CD30-negative GCT subsets. Our results strongly support translational efforts to evaluate clinical efficacy of brentuximab vedotin in high-risk GCT of heterogeneous CD30 positivity. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

New insights into time series analysis. II - Non-correlated observations

NASA Astrophysics Data System (ADS)

Ferreira Lopes, C. E.; Cross, N. J. G.

2017-08-01

Context. Statistical parameters are used to draw conclusions in a vast number of fields such as finance, weather, industrial, and science. These parameters are also used to identify variability patterns on photometric data to select non-stochastic variations that are indicative of astrophysical effects. New, more efficient, selection methods are mandatory to analyze the huge amount of astronomical data. Aims: We seek to improve the current methods used to select non-stochastic variations on non-correlated data. Methods: We used standard and new data-mining parameters to analyze non-correlated data to find the best way to discriminate between stochastic and non-stochastic variations. A new approach that includes a modified Strateva function was performed to select non-stochastic variations. Monte Carlo simulations and public time-domain data were used to estimate its accuracy and performance. Results: We introduce 16 modified statistical parameters covering different features of statistical distribution such as average, dispersion, and shape parameters. Many dispersion and shape parameters are unbound parameters, I.e. equations that do not require the calculation of average. Unbound parameters are computed with single loop and hence decreasing running time. Moreover, the majority of these parameters have lower errors than previous parameters, which is mainly observed for distributions with few measurements. A set of non-correlated variability indices, sample size corrections, and a new noise model along with tests of different apertures and cut-offs on the data (BAS approach) are introduced. The number of mis-selections are reduced by about 520% using a single waveband and 1200% combining all wavebands. On the other hand, the even-mean also improves the correlated indices introduced in Paper I. The mis-selection rate is reduced by about 18% if the even-mean is used instead of the mean to compute the correlated indices in the WFCAM database. Even-statistics allows us to improve the effectiveness of both correlated and non-correlated indices. Conclusions: The selection of non-stochastic variations is improved by non-correlated indices. The even-averages provide a better estimation of mean and median for almost all statistical distributions analyzed. The correlated variability indices, which are proposed in the first paper of this series, are also improved if the even-mean is used. The even-parameters will also be useful for classifying light curves in the last step of this project. We consider that the first step of this project, where we set new techniques and methods that provide a huge improvement on the efficiency of selection of variable stars, is now complete. Many of these techniques may be useful for a large number of fields. Next, we will commence a new step of this project regarding the analysis of period search methods.

Antitumoral, antihypertensive, antimicrobial, and antioxidant effects of an octanuclear copper(II)-telmisartan complex with an hydrophobic nanometer hole.

PubMed

Islas, María S; Martínez Medina, Juan J; López Tévez, Libertad L; Rojo, Teófilo; Lezama, Luis; Griera Merino, Mercedes; Calleros, Laura; Cortes, María A; Rodriguez Puyol, Manuel; Echeverría, Gustavo A; Piro, Oscar E; Ferrer, Evelina G; Williams, Patricia A M

2014-06-02

A new Cu(II) complex with the antihypertensive drug telmisartan, [Cu8Tlm16]·24H2O (CuTlm), was synthesized and characterized by elemental analysis and electronic, FTIR, Raman and electron paramagnetic resonance spectroscopy. The crystal structure (at 120 K) was solved by X-ray diffraction methods. The octanuclear complex is a hydrate of but otherwise isostructural to the previously reported [Cu8Tlm16] complex. [Cu8Tlm16]·24H2O crystallizes in the tetragonal P4/ncc space group with a = b = 47.335(1), c = 30.894(3) Å, Z = 4 molecules per unit cell giving a macrocyclic ring with a double helical structure. The Cu(II) ions are in a distorted bipyramidal environment with a somewhat twisted square basis, cis-coordinated at their core N2O2 basis to two carboxylate oxygen and two terminal benzimidazole nitrogen atoms. Cu8Tlm16 has a toroidal-like shape with a hydrophobic nanometer hole, and their crystal packing defines nanochannels that extend along the crystal c-axis. Several biological activities of the complex and the parent ligand were examined in vitro. The antioxidant measurements indicate that the complex behaves as a superoxide dismutase mimic with improved superoxide scavenger power as compared with native sartan. The capacity of telmisartan and its copper complex to expand human mesangial cells (previously contracted by angiotensin II treatment) is similar to each other. The antihypertensive effect of the compounds is attributed to the strongest binding affinity to angiotensin II type 1 receptor and not to the antioxidant effects. The cytotoxic activity of the complex and that of its components was determined against lung cancer cell line A549 and three prostate cancer cell lines (LNCaP, PC-3, and DU 145). The complex displays some inhibitory effect on the A549 line and a high viability decrease on the LNCaP (androgen-sensitive) line. From flow cytometric analysis, an apoptotic mechanism was established for the latter cell line. Telmisartan and CuTlm show antibacterial and antifungal activities in various strains, and CuTlm displays improved activity against the Staphylococcus aureus strain as compared with unbounded copper(II).

Fractions, Number Lines, Third Graders

ERIC Educational Resources Information Center

Cramer, Kathleen; Ahrendt, Sue; Monson, Debra; Wyberg, Terry; Colum, Karen

2017-01-01

The Common Core State Standards for Mathematics (CCSSM) (CCSSI 2010) outlines ambitious goals for fraction learning, starting in third grade, that include the use of the number line model. Understanding and constructing fractions on a number line are particularly complex tasks. The current work of the authors centers on ways to successfully…

Going to College Online? A PEST Analysis of MOOCs

ERIC Educational Resources Information Center

Lin, Hong

2014-01-01

Massively open? College unbound? What are the roots of Massive Open Online Courses (MOOCs), and how much of a trend is it? What promises and anxieties do MOOCs bring to higher education, academic leaders, and faculty? 2013 has witnessed one of the most rapid and enthusiastic adoptions of educational innovation in history, generating numerous…

Phystosterols and their derivatives: structural diversity, distribution, metabolism, analysis, and health promoting uses

USDA-ARS?s Scientific Manuscript database

Phytosterols (plant sterols) occur in the cells of all plants. They are important structural components that stabilize the biological membranes of plants. Sterols can occur in the “free” unbound form or they can be covalently bound via an ester or glycosidic bond. Since our previous 2002 review o...

Concurrence control for transactions with priorities

NASA Technical Reports Server (NTRS)

Marzullo, Keith

1989-01-01

Priority inversion occurs when a process is delayed by the actions of another process with less priority. With atomic transactions, the concurrency control mechanism can cause delays, and without taking priorities into account can be a source of priority inversion. Three traditional concurrency control algorithms are extended so that they are free from unbounded priority inversion.

Fueling the Engine: Smarter, Better Ways to Fund Education Innovators

ERIC Educational Resources Information Center

Hess, Frederick M.

2010-01-01

In "Education Unbound: The Promise and Practice of Greenfield Schooling," this author argued for new education service-delivery organizations that, free from the constricting norms and rules of traditional providers, focused single-mindedly on executing their model. The challenge for reformers is to recognize that enabling such providers is not…

Vlasov-Maxwell and Vlasov-Poisson equations as models of a one-dimensional electron plasma

NASA Technical Reports Server (NTRS)

Klimas, A. J.; Cooper, J.

1983-01-01

The Vlasov-Maxwell and Vlasov-Poisson systems of equations for a one-dimensional electron plasma are defined and discussed. A method for transforming a solution of one system which is periodic over a bounded or unbounded spatial interval to a similar solution of the other is constructed.

Limits on Planets Orbiting Massive Stars from Radio Pulsar Timing

NASA Technical Reports Server (NTRS)

Thorsett, S. E.; Dewey, R. J.

1993-01-01

When a massive star collapses to a neutron star, rapidly losing over half its mass in a symmetric supernova explosiosn, any planets orbiting the star will be unbound. However, to explain the observed space velocity and binary fraction of radio pulsars, an asymmetric kick must be given to the neutron star of birth.

Hypertextual Ultrastructures: Movement and Containment in Texts and Hypertexts

ERIC Educational Resources Information Center

Coste, Rosemarie L.

2009-01-01

The surface-level experience of hypertextuality as formless and unbounded, blurring boundaries among texts and between readers and writers, is created by a deep structure which is not normally presented to readers and which, like the ultrastructure of living cells, defines and controls texts' nature and functions. Most readers, restricted to…

Effects of lignin-metal complexation on enzymatic hydrolysis of cellulose

Treesearch

H. Liu; Junyong Zhu; S.Y. Fu

2010-01-01

This study investigated the inhibition of enzymatic hydrolysis by unbound lignin (soluble and insoluble) with or without the addition of metal compounds. Sulfonated, Organosolv, and Kraft lignin were added in aqueous enzyme-cellulose systems at different concentrations before hydrolysis. The measured substrate enzymatic digestibility (SED) of cellulose was decreased by...

Detection and quantification of unbound phytochelatin 2 in plant extracts of Brassica napus grown with different levels of mercury.

PubMed

Iglesia-Turiño, Santiago; Febrero, Anna; Jauregui, Olga; Caldelas, Cristina; Araus, Jose Luis; Bort, Jordi

2006-10-01

The mercury (Hg) accumulation mechanism was studied in rape (Brassica napus) plants grown under a Hg concentration gradient (0 microm-1,000 microm). Hg mainly accumulated in roots. Therefore, the presence of phytochelatins (PCs) was studied in the roots of the plants. The high stability of the PC-Hg multicomplexes (mPC-nHg) seems to be the main reason for the lack of previous Hg-PC characterization studies. We propose a modification of the method to detect and quantify unbound PC of Hg in plant extracts via high-performance liquid chromatography coupled to electrospray tandem mass spectrometry and inductively coupled plasma mass spectrometry in parallel. We separated the PC from the Hg by adding the chelating agent sodium 2,3-dimercaptopropanesulfonate monohydrate. We only detected the presence of PC after the addition of the chelating agent. Some multicomplexes mPC-nHg could be formed but, due to their large sizes, could not be detected. In this study, only PC(2) was observed in plant samples. Hg accumulation was correlated with PC(2) concentration (r(2) = 0.98).

Numerical solution of the general coupled nonlinear Schrödinger equations on unbounded domains.

PubMed

Li, Hongwei; Guo, Yue

2017-12-01

The numerical solution of the general coupled nonlinear Schrödinger equations on unbounded domains is considered by applying the artificial boundary method in this paper. In order to design the local absorbing boundary conditions for the coupled nonlinear Schrödinger equations, we generalize the unified approach previously proposed [J. Zhang et al., Phys. Rev. E 78, 026709 (2008)PLEEE81539-375510.1103/PhysRevE.78.026709]. Based on the methodology underlying the unified approach, the original problem is split into two parts, linear and nonlinear terms, and we then achieve a one-way operator to approximate the linear term to make the wave out-going, and finally we combine the one-way operator with the nonlinear term to derive the local absorbing boundary conditions. Then we reduce the original problem into an initial boundary value problem on the bounded domain, which can be solved by the finite difference method. The stability of the reduced problem is also analyzed by introducing some auxiliary variables. Ample numerical examples are presented to verify the accuracy and effectiveness of our proposed method.

Location-Unbound Color-Shape Binding Representations in Visual Working Memory.

PubMed

Saiki, Jun

2016-02-01

The mechanism by which nonspatial features, such as color and shape, are bound in visual working memory, and the role of those features' location in their binding, remains unknown. In the current study, I modified a redundancy-gain paradigm to investigate these issues. A set of features was presented in a two-object memory display, followed by a single object probe. Participants judged whether the probe contained any features of the memory display, regardless of its location. Response time distributions revealed feature coactivation only when both features of a single object in the memory display appeared together in the probe, regardless of the response time benefit from the probe and memory objects sharing the same location. This finding suggests that a shared location is necessary in the formation of bound representations but unnecessary in their maintenance. Electroencephalography data showed that amplitude modulations reflecting location-unbound feature coactivation were different from those reflecting the location-sharing benefit, consistent with the behavioral finding that feature-location binding is unnecessary in the maintenance of color-shape binding. © The Author(s) 2015.

Dynamical analysis of bounded and unbounded orbits in a generalized Hénon-Heiles system

NASA Astrophysics Data System (ADS)

Dubeibe, F. L.; Riaño-Doncel, A.; Zotos, Euaggelos E.

2018-04-01

The Hénon-Heiles potential was first proposed as a simplified version of the gravitational potential experimented by a star in the presence of a galactic center. Currently, this system is considered a paradigm in dynamical systems because despite its simplicity exhibits a very complex dynamical behavior. In the present paper, we perform a series expansion up to the fifth-order of a potential with axial and reflection symmetries, which after some transformations, leads to a generalized Hénon-Heiles potential. Such new system is analyzed qualitatively in both regimes of bounded and unbounded motion via the Poincaré sections method and plotting the exit basins. On the other hand, the quantitative analysis is performed through the Lyapunov exponents and the basin entropy, respectively. We find that in both regimes the chaoticity of the system decreases as long as the test particle energy gets far from the critical energy. Additionally, we may conclude that despite the inclusion of higher order terms in the series expansion, the new system shows wider zones of regularity (islands) than the ones present in the Hénon-Heiles system.

Evaluation of Unbound Engineered Nanoparticles from a Worker Exposure and Environmental Release Perspective

NASA Astrophysics Data System (ADS)

Bunker, K.; Casuccio, G.; Lersch, T.; Ogle, R.; Wahl, L.

2009-12-01

Nanotechnology and the use of unbound engineered nanoparticles (UNP) is a rapidly developing area of materials science. UNP are defined as engineered nanoparticles that are not contained within a matrix that would prevent the nanoparticles from being mobile and a potential source of exposure. At this time there are no regulatory environmental release limits or worker exposure limits for UNP. The Lawrence Berkeley National Laboratory (LBNL) has initiated a study to evaluate worker exposure and potential environmental release of UNP related to various research activities at LBNL. The study is being performed to help identify and manage potential health and safety hazards as well as environmental impacts related to UNP. A key component of the study is the characterization of starting (source) UNP materials to assist in the determination of worker exposure and environmental release. Analysis of the starting materials is being used to establish source signatures. The source signatures will then be used in the evaluation of worker exposure and environmental release. This presentation will provide an overview of the LBNL study with a focus on the methodologies being used to analyze the samples.

Critical screening in the one- and two-electron Yukawa atoms

NASA Astrophysics Data System (ADS)

Montgomery, H. E.; Sen, K. D.; Katriel, Jacob

2018-02-01

The one- and two-electron Yukawa atoms, also referred to as the Debye-Hückel or screened Coulomb atoms, have been topics of considerable interest both for intrinsic reasons and because of their relevance to terrestrial and astrophysical plasmas. At sufficiently high screening the one-electron Yukawa atom ceases to be bound. Some calculations appeared to suggest that as the screening increases in the ground state of the two-electron Yukawa atom (in which both the one-particle attraction and the interparticle repulsion are screened) the two electrons are detached simultaneously, at the same screening constant at which the one-electron atom becomes unbound. Our results rule this scenario out, offering an alternative that is not less interesting. In particular, it is found that for Z <1 a mild amount of screening actually increases the binding energy of the second electron. At the nuclear charge Zc≈0.911028 ... , at which the bare Coulomb two-electron atom becomes unbound, and even over a range of lower nuclear charges, an appropriate amount of screening gives rise to a bound two-electron system.

Random Walk Particle Tracking For Multiphase Heat Transfer

NASA Astrophysics Data System (ADS)

Lattanzi, Aaron; Yin, Xiaolong; Hrenya, Christine

2017-11-01

As computing capabilities have advanced, direct numerical simulation (DNS) has become a highly effective tool for quantitatively predicting the heat transfer within multiphase flows. Here we utilize a hybrid DNS framework that couples the lattice Boltzmann method (LBM) to the random walk particle tracking (RWPT) algorithm. The main challenge of such a hybrid is that discontinuous fields pose a significant challenge to the RWPT framework and special attention must be given to the handling of interfaces. We derive a method for addressing discontinuities in the diffusivity field, arising at the interface between two phases. Analytical means are utilized to develop an interfacial tracer balance and modify the RWPT algorithm. By expanding the modulus of the stochastic (diffusive) step and only allowing a subset of the tracers within the high diffusivity medium to undergo a diffusive step, the correct equilibrium state can be restored (globally homogeneous tracer distribution). The new RWPT algorithm is implemented within the SUSP3D code and verified against a variety of systems: effective diffusivity of a static gas-solids mixture, hot sphere in unbounded diffusion, cooling sphere in unbounded diffusion, and uniform flow past a hot sphere.

Unbound motion on a Schwarzschild background: Practical approaches to frequency domain computations

NASA Astrophysics Data System (ADS)

Hopper, Seth

2018-03-01

Gravitational perturbations due to a point particle moving on a static black hole background are naturally described in Regge-Wheeler gauge. The first-order field equations reduce to a single master wave equation for each radiative mode. The master function satisfying this wave equation is a linear combination of the metric perturbation amplitudes with a source term arising from the stress-energy tensor of the point particle. The original master functions were found by Regge and Wheeler (odd parity) and Zerilli (even parity). Subsequent work by Moncrief and then Cunningham, Price and Moncrief introduced new master variables which allow time domain reconstruction of the metric perturbation amplitudes. Here, I explore the relationship between these different functions and develop a general procedure for deriving new higher-order master functions from ones already known. The benefit of higher-order functions is that their source terms always converge faster at large distance than their lower-order counterparts. This makes for a dramatic improvement in both the speed and accuracy of frequency domain codes when analyzing unbound motion.

Novel concept of washing for microfluidic paper-based analytical devices based on capillary force of paper substrates.

PubMed

Mohammadi, Saeed; Busa, Lori Shayne Alamo; Maeki, Masatoshi; Mohamadi, Reza M; Ishida, Akihiko; Tani, Hirofumi; Tokeshi, Manabu

2016-11-01

A novel washing technique for microfluidic paper-based analytical devices (μPADs) that is based on the spontaneous capillary action of paper and eliminates unbound antigen and antibody in a sandwich immunoassay is reported. Liquids can flow through a porous medium (such as paper) in the absence of external pressure as a result of capillary action. Uniform results were achieved when washing a paper substrate in a PDMS holder which was integrated with a cartridge absorber acting as a porous medium. Our study demonstrated that applying this washing technique would allow μPADs to become the least expensive microfluidic device platform with high reproducibility and sensitivity. In a model μPAD assay that utilized this novel washing technique, C-reactive protein (CRP) was detected with a limit of detection (LOD) of 5 μg mL -1 . Graphical Abstract A novel washing technique for microfluidic paper-based analytical devices (μPADs) that is based on the spontaneous capillary action of paper and eliminates unbound antigen and antibody in a sandwich immunoassay is reported.

Kinematically Optimal Robust Control of Redundant Manipulators

NASA Astrophysics Data System (ADS)

Galicki, M.

2017-12-01

This work deals with the problem of the robust optimal task space trajectory tracking subject to finite-time convergence. Kinematic and dynamic equations of a redundant manipulator are assumed to be uncertain. Moreover, globally unbounded disturbances are allowed to act on the manipulator when tracking the trajectory by the endeffector. Furthermore, the movement is to be accomplished in such a way as to minimize both the manipulator torques and their oscillations thus eliminating the potential robot vibrations. Based on suitably defined task space non-singular terminal sliding vector variable and the Lyapunov stability theory, we derive a class of chattering-free robust kinematically optimal controllers, based on the estimation of transpose Jacobian, which seem to be effective in counteracting both uncertain kinematics and dynamics, unbounded disturbances and (possible) kinematic and/or algorithmic singularities met on the robot trajectory. The numerical simulations carried out for a redundant manipulator of a SCARA type consisting of the three revolute kinematic pairs and operating in a two-dimensional task space, illustrate performance of the proposed controllers as well as comparisons with other well known control schemes.

Robust Task Space Trajectory Tracking Control of Robotic Manipulators

NASA Astrophysics Data System (ADS)

Galicki, M.

2016-08-01

This work deals with the problem of the accurate task space trajectory tracking subject to finite-time convergence. Kinematic and dynamic equations of a redundant manipulator are assumed to be uncertain. Moreover, globally unbounded disturbances are allowed to act on the manipulator when tracking the trajectory by the end-effector. Furthermore, the movement is to be accomplished in such a way as to reduce both the manipulator torques and their oscillations thus eliminating the potential robot vibrations. Based on suitably defined task space non-singular terminal sliding vector variable and the Lyapunov stability theory, we propose a class of chattering-free robust controllers, based on the estimation of transpose Jacobian, which seem to be effective in counteracting both uncertain kinematics and dynamics, unbounded disturbances and (possible) kinematic and/or algorithmic singularities met on the robot trajectory. The numerical simulations carried out for a redundant manipulator of a SCARA type consisting of the three revolute kinematic pairs and operating in a two-dimensional task space, illustrate performance of the proposed controllers as well as comparisons with other well known control schemes.

Quantum tagging for tags containing secret classical data

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

Kent, Adrian

Various authors have considered schemes for quantum tagging, that is, authenticating the classical location of a classical tagging device by sending and receiving quantum signals from suitably located distant sites, in an environment controlled by an adversary whose quantum information processing and transmitting power is potentially unbounded. All of the schemes proposed elsewhere in the literature assume that the adversary is able to inspect the interior of the tagging device. All of these schemes have been shown to be breakable if the adversary has unbounded predistributed entanglement. We consider here the case in which the tagging device contains a finitemore » key string shared with distant sites but kept secret from the adversary, and show this allows the location of the tagging device to be authenticated securely and indefinitely. Our protocol relies on quantum key distribution between the tagging device and at least one distant site, and demonstrates a new practical application of quantum key distribution. It also illustrates that the attainable security in position-based cryptography can depend crucially on apparently subtle details in the security scenario considered.« less

Blind Deconvolution for Distributed Parameter Systems with Unbounded Input and Output and Determining Blood Alcohol Concentration from Transdermal Biosensor Data.

PubMed

Rosen, I G; Luczak, Susan E; Weiss, Jordan

2014-03-15

We develop a blind deconvolution scheme for input-output systems described by distributed parameter systems with boundary input and output. An abstract functional analytic theory based on results for the linear quadratic control of infinite dimensional systems with unbounded input and output operators is presented. The blind deconvolution problem is then reformulated as a series of constrained linear and nonlinear optimization problems involving infinite dimensional dynamical systems. A finite dimensional approximation and convergence theory is developed. The theory is applied to the problem of estimating blood or breath alcohol concentration (respectively, BAC or BrAC) from biosensor-measured transdermal alcohol concentration (TAC) in the field. A distributed parameter model with boundary input and output is proposed for the transdermal transport of ethanol from the blood through the skin to the sensor. The problem of estimating BAC or BrAC from the TAC data is formulated as a blind deconvolution problem. A scheme to identify distinct drinking episodes in TAC data based on a Hodrick Prescott filter is discussed. Numerical results involving actual patient data are presented.

Phenytoin kinetics during pregnancy and the puerperium.

PubMed

Knott, C; Williams, C P; Reynolds, F

1986-10-01

During pregnancy changes in maternal physiology and plasma composition may alter drug binding and dose requirements. We have measured plasma unbound and total phenytoin, and saliva concentrations at intervals in 11 pregnant epileptics. Plasma albumin concentrations were also measured in pregnant and non-pregnant women. Saliva phenytoin correlated closely with the plasma unbound concentrations (r = 0.98). The saliva:plasma (S:P) ratio, reflecting the free fraction, was variable during pregnancy but tended to increase to maximal values at delivery and return to non-pregnant values within 2-8 weeks thereafter. Plasma albumin concentrations correlated poorly with phenytoin binding. Binding in umbilical cord plasma appeared higher than that in maternal plasma and total fetal concentrations correlated closely with maternal plasma concentrations at delivery. No ill effects of phenytoin were detected in the newborn infant. During the third trimester phenytoin dose increments were necessary to maintain therapeutic concentrations. After delivery maternal saliva phenytoin concentrations rose, and dose reductions were necessary to avoid clinical symptoms of toxicity. It is therefore appropriate to monitor saliva phenytoin concentrations regularly both during pregnancy and the puerperium.

A Colorful Walk, But Is It on the Mental Number Line? Reply to Cohen Kadosh, Tzelgov, and Henik

ERIC Educational Resources Information Center

Verguts, Tom; Opstal, Filip Van

2008-01-01

Cohen Kadosh, Tzelgov, and Henik [Cohen Kadosh, R., Tzelgov, J., & Henik, A. (2008). A synesthetic walk on the number line: The size effect. "Cognition", 106, 548-557] present a new paradigm to probe properties of the mental number line. They describe two experiments which they argue to be inconsistent with the exact small number model proposed by…

Number Sense on the Number Line

ERIC Educational Resources Information Center

Woods, Dawn Marie; Ketterlin Geller, Leanne; Basaraba, Deni

2018-01-01

A strong foundation in early number concepts is critical for students' future success in mathematics. Research suggests that visual representations, like a number line, support students' development of number sense by helping them create a mental representation of the order and magnitude of numbers. In addition, explicitly sequencing instruction…

Strong Neutron Pairing in core+4n Nuclei.

PubMed

Revel, A; Marqués, F M; Sorlin, O; Aumann, T; Caesar, C; Holl, M; Panin, V; Vandebrouck, M; Wamers, F; Alvarez-Pol, H; Atar, L; Avdeichikov, V; Beceiro-Novo, S; Bemmerer, D; Benlliure, J; Bertulani, C A; Boillos, J M; Boretzky, K; Borge, M J G; Caamaño, M; Casarejos, E; Catford, W N; Cederkäll, J; Chartier, M; Chulkov, L; Cortina-Gil, D; Cravo, E; Crespo, R; Datta Pramanik, U; Díaz Fernández, P; Dillmann, I; Elekes, Z; Enders, J; Ershova, O; Estradé, A; Farinon, F; Fraile, L M; Freer, M; Galaviz, D; Geissel, H; Gernhäuser, R; Golubev, P; Göbel, K; Hagdahl, J; Heftrich, T; Heil, M; Heine, M; Heinz, A; Henriques, A; Ignatov, A; Johansson, H T; Jonson, B; Kahlbow, J; Kalantar-Nayestanaki, N; Kanungo, R; Kelic-Heil, A; Knyazev, A; Kröll, T; Kurz, N; Labiche, M; Langer, C; Le Bleis, T; Lemmon, R; Lindberg, S; Machado, J; Marganiec, J; Movsesyan, A; Nacher, E; Najafi, M; Nilsson, T; Nociforo, C; Paschalis, S; Perea, A; Petri, M; Pietri, S; Plag, R; Reifarth, R; Ribeiro, G; Rigollet, C; Röder, M; Rossi, D; Savran, D; Scheit, H; Simon, H; Syndikus, I; Taylor, J T; Tengblad, O; Thies, R; Togano, Y; Velho, P; Volkov, V; Wagner, A; Weick, H; Wheldon, C; Wilson, G; Winfield, J S; Woods, P; Yakorev, D; Zhukov, M; Zilges, A; Zuber, K

2018-04-13

The emission of neutron pairs from the neutron-rich N=12 isotones ^{18}C and ^{20}O has been studied by high-energy nucleon knockout from ^{19}N and ^{21}O secondary beams, populating unbound states of the two isotones up to 15 MeV above their two-neutron emission thresholds. The analysis of triple fragment-n-n correlations shows that the decay ^{19}N(-1p)^{18}C^{*}→^{16}C+n+n is clearly dominated by direct pair emission. The two-neutron correlation strength, the largest ever observed, suggests the predominance of a ^{14}C core surrounded by four valence neutrons arranged in strongly correlated pairs. On the other hand, a significant competition of a sequential branch is found in the decay ^{21}O(-1n)^{20}O^{*}→^{18}O+n+n, attributed to its formation through the knockout of a deeply bound neutron that breaks the ^{16}O core and reduces the number of pairs.

Gold nanoparticles as a factor of influence on doxorubicin-bovine serum albumin complex

NASA Astrophysics Data System (ADS)

Goncharenko, N. A.; Pavlenko, O. L.; Dmytrenko, O. P.; Kulish, M. P.; Lopatynskyi, A. M.; Chegel, V. I.

2018-04-01

The interaction between doxorubicin (Dox) and bovine serum albumin (BSA) complex with gold nanoparticles (AuNPs) was investigated by optical spectroscopy. The optical absorption of Dox and BSA solutions was studied. The formation of Dox-BSA complexes with a binding constant K = 7.56 × 106 M-2 and the number of binding sites n = 2 was found out. With pH 6.9, the concentration of complexes is an order of magnitude lower than the concentration of unbound antibiotic molecules. Optical absorption in solutions of Dox-BSA conjugates in the presence of AuNPs undergoes a significant rearrangement, which manifests the changes in the magnitude of the hydrophobic interaction of BSA with Dox, changes in the conformational state of antibiotic, and, as a consequence, a plasmon-induced change in the mechanism of complex formation. The aggregation of the Dox-AuNPs conjugate depends on the presence and concentration of BSA and in the case of formation of the Dox-BSA complex is minimal.

Reply & Supply: Efficient crowdsourcing when workers do more than answer questions

PubMed Central

McAndrew, Thomas C.; Guseva, Elizaveta A.

2017-01-01

Crowdsourcing works by distributing many small tasks to large numbers of workers, yet the true potential of crowdsourcing lies in workers doing more than performing simple tasks—they can apply their experience and creativity to provide new and unexpected information to the crowdsourcer. One such case is when workers not only answer a crowdsourcer’s questions but also contribute new questions for subsequent crowd analysis, leading to a growing set of questions. This growth creates an inherent bias for early questions since a question introduced earlier by a worker can be answered by more subsequent workers than a question introduced later. Here we study how to perform efficient crowdsourcing with such growing question sets. By modeling question sets as networks of interrelated questions, we introduce algorithms to help curtail the growth bias by efficiently distributing workers between exploring new questions and addressing current questions. Experiments and simulations demonstrate that these algorithms can efficiently explore an unbounded set of questions without losing confidence in crowd answers. PMID:28806413

Solving Fractional Programming Problems based on Swarm Intelligence

NASA Astrophysics Data System (ADS)

Raouf, Osama Abdel; Hezam, Ibrahim M.

2014-04-01

This paper presents a new approach to solve Fractional Programming Problems (FPPs) based on two different Swarm Intelligence (SI) algorithms. The two algorithms are: Particle Swarm Optimization, and Firefly Algorithm. The two algorithms are tested using several FPP benchmark examples and two selected industrial applications. The test aims to prove the capability of the SI algorithms to solve any type of FPPs. The solution results employing the SI algorithms are compared with a number of exact and metaheuristic solution methods used for handling FPPs. Swarm Intelligence can be denoted as an effective technique for solving linear or nonlinear, non-differentiable fractional objective functions. Problems with an optimal solution at a finite point and an unbounded constraint set, can be solved using the proposed approach. Numerical examples are given to show the feasibility, effectiveness, and robustness of the proposed algorithm. The results obtained using the two SI algorithms revealed the superiority of the proposed technique among others in computational time. A better accuracy was remarkably observed in the solution results of the industrial application problems.

On the computation of molecular surface correlations for protein docking using fourier techniques.

PubMed

Sakk, Eric

2007-08-01

The computation of surface correlations using a variety of molecular models has been applied to the unbound protein docking problem. Because of the computational complexity involved in examining all possible molecular orientations, the fast Fourier transform (FFT) (a fast numerical implementation of the discrete Fourier transform (DFT)) is generally applied to minimize the number of calculations. This approach is rooted in the convolution theorem which allows one to inverse transform the product of two DFTs in order to perform the correlation calculation. However, such a DFT calculation results in a cyclic or "circular" correlation which, in general, does not lead to the same result as the linear correlation desired for the docking problem. In this work, we provide computational bounds for constructing molecular models used in the molecular surface correlation problem. The derived bounds are then shown to be consistent with various intuitive guidelines previously reported in the protein docking literature. Finally, these bounds are applied to different molecular models in order to investigate their effect on the correlation calculation.

The effect of suspended particles on Jean's criterion for gravitational instability

NASA Technical Reports Server (NTRS)

Wollkind, David J.; Yates, Kemble R.

1990-01-01

The effect that the proper inclusion of suspended particles has on Jeans' criterion for the self-gravitational instability of an unbounded nonrotating adiabatic gas cloud is examined by formulating the appropriate model system, introducing particular physically plausible equations of state and constitutive relations, performing a linear stability analysis of a uniformly expanding exact solution to these governing equations, and exploiting the fact that there exists a natural small material parameter for this problem given by N sub 1/n sub 1, the ratio of the initial number density for the particles to that for the gas. The main result of this investigation is the derivation of an altered criterion which can substantially reduce Jeans' original critical wavelength for instability. It is then shown that the existing discrepancy between Jeans' theoretical prediction using and actual observational data relevant to the Andromeda nebula M31 can be accounted for by this new criterion of assuming suspended particles of a reasonable grain size and distribution to be present.

Hypervelocity star candidates in Gaia DR1/TGAS

NASA Astrophysics Data System (ADS)

Marchetti, T.; Rossi, E. M.; Kordopatis, G.; Brown, A. G. A.; Rimoldi, A.; Starkenburg, E.; Youakim, K.; Ashley, R.

2018-04-01

Hypervelocity stars (HVSs) are characterized by a total velocity in excess of the Galactic escape speed, and with trajectories consistent with coming from the Galactic Centre. We apply a novel data mining routine, an artificial neural network, to discover HVSs in the TGAS subset of the first data release of the Gaia satellite, using only the astrometry of the stars. We find 80 stars with a predicted probability >90% of being HVSs, and we retrieved radial velocities for 47 of those. We discover 14 objects with a total velocity in the Galactic rest frame >400 km s-1, and 5 of these have a probability >50% of being unbound from the Milky Way. Tracing back orbits in different Galactic potentials, we discover 1 HVS candidate, 5 bound HVS candidates, and 5 runaway star candidates with remarkably high velocities, between 400 and 780 km s-1. We wait for future Gaia releases to confirm the goodness of our sample and to increase the number of HVS candidates.

Point-of-care rare cell cancer diagnostics.

PubMed

Issadore, David

2015-01-01

The sparse cells that are shed from tumors into peripheral circulation are an increasingly promising resource for noninvasive monitoring of cancer progression, early diagnosis of disease, and serve as a tool for improving our understanding of cancer metastasis. However, the extremely sparse concentration of circulating tumor cells (CTCs) in blood (~1-100 CTC in 7.5 mL of blood) as well as their heterogeneous biomarker expression has limited their detection using conventional laboratory techniques. To overcome these challenges, we have developed a microfluidic chip-based micro-Hall detector (μHD), which can directly measure single, immunomagnetically tagged cells in whole blood. The μHD can detect individual cells even in the presence of vast numbers of blood cells and unbound reactants, and does not require any washing or purification steps. Furthermore, this cost-effective, single-cell analytical technique is well suited for miniaturization into a mobile platform for low-cost point-of-care use. In this chapter, we describe the methodology used to design, fabricate, and apply these chips to cancer diagnostics.

Energy Landscape and Transition State of Protein-Protein Association

NASA Astrophysics Data System (ADS)

Alsallaq, Ramzi; Zhou, Huan-Xiang

2006-11-01

Formation of a stereospecific protein complex is favored by specific interactions between two proteins but disfavored by the loss of translational and rotational freedom. Echoing the protein folding process, we have previously proposed a transition state for protein-protein association. Here we clarify the specification of the transition state by working with two toy models for protein association. The models demonstrate that a sharp transition between the bound state with numerous short-range interactions but restricted translation and rotational freedom and the unbound state with at most a small number of interactions but expanded configurational freedom. This transition sets the outer boundary of the bound state as well as the transition state for association. The energy landscape is funnel-like, with the deep well of the bound state surrounded by a broad shallow basin. This formalism of protein-protein association is applied to four protein-protein complexes, and is found to give accurate predictions for the effects of charge mutations and ionic strength on the association rates.

Replica Exchange Improves Sampling in Low-Resolution Docking Stage of RosettaDock

PubMed Central

Zhang, Zhe; Lange, Oliver F.

2013-01-01

Many protein-protein docking protocols are based on a shotgun approach, in which thousands of independent random-start trajectories minimize the rigid-body degrees of freedom. Another strategy is enumerative sampling as used in ZDOCK. Here, we introduce an alternative strategy, ReplicaDock, using a small number of long trajectories of temperature replica exchange. We compare replica exchange sampling as low-resolution stage of RosettaDock with RosettaDock's original shotgun sampling as well as with ZDOCK. A benchmark of 30 complexes starting from structures of the unbound binding partners shows improved performance for ReplicaDock and ZDOCK when compared to shotgun sampling at equal or less computational expense. ReplicaDock and ZDOCK consistently reach lower energies and generate significantly more near-native conformations than shotgun sampling. Accordingly, they both improve typical metrics of prediction quality of complex structures after refinement. Additionally, the refined ReplicaDock ensembles reach significantly lower interface energies and many previously hidden features of the docking energy landscape become visible when ReplicaDock is applied. PMID:24009670

Comparative total and unbound pharmacokinetics of cefazolin administered by bolus versus continuous infusion in patients undergoing major surgery: a randomized controlled trial.

PubMed

Naik, B I; Roger, C; Ikeda, K; Todorovic, M S; Wallis, S C; Lipman, J; Roberts, J A

2017-06-01

Perioperative administration of cefazolin reduces the incidence of perioperative infections. Intraoperative re-dosing of cefazolin is commonly given between 2 and 5 h after the initial dose. This study was undertaken to determine whether intraoperative continuous infusions of cefazolin achieve better probability of target attainment (PTA) and fractional target attainment (FTA) than intermittent dosing. Patients undergoing major surgery received cefazolin 2 g before surgical incision. They were subsequently randomized to receive either an intermittent bolus (2 g every 4 h) or continuous infusion (500 mg h -1 ) of cefazolin until skin closure. Blood samples were analysed for total and unbound cefazolin concentrations using a validated chromatographic method. Population pharmacokinetic modelling was performed using Pmetrics ® software. Calculations of PTA and FTA were performed for common pathogens. Ten patients were enrolled in each arm. A two-compartment linear model best described the time course of the total plasma cefazolin concentrations. The covariates that improved the model were body weight and creatinine clearance. Protein binding varied with time [mean (range) 69 (44-80)%] with a fixed 21% unbound value of cefazolin used for the simulations (120 min post-initial dosing). Mean ( sd ) central volume of distribution was 5.73 (2.42) litres, and total cefazolin clearance was 4.72 (1.1) litres h -1 . Continuous infusions of cefazolin consistently achieved better drug exposures and FTA for different weight and creatinine clearances, particularly for less susceptible pathogens. Our study demonstrates that intraoperative continuous infusions of cefazolin increase the achievement of target plasma concentrations, even with lower infusion doses. Renal function and body weight are important when considering the need for alternative dosing regimens. NCT02058979. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Assessment of CAPRI predictions in rounds 3-5 shows progress in docking procedures.

PubMed

Méndez, Raúl; Leplae, Raphaël; Lensink, Marc F; Wodak, Shoshana J

2005-08-01

The current status of docking procedures for predicting protein-protein interactions starting from their three-dimensional (3D) structure is reassessed by evaluating blind predictions, performed during 2003-2004 as part of Rounds 3-5 of the community-wide experiment on Critical Assessment of PRedicted Interactions (CAPRI). Ten newly determined structures of protein-protein complexes were used as targets for these rounds. They comprised 2 enzyme-inhibitor complexes, 2 antigen-antibody complexes, 2 complexes involved in cellular signaling, 2 homo-oligomers, and a complex between 2 components of the bacterial cellulosome. For most targets, the predictors were given the experimental structures of 1 unbound and 1 bound component, with the latter in a random orientation. For some, the structure of the free component was derived from that of a related protein, requiring the use of homology modeling. In some of the targets, significant differences in conformation were displayed between the bound and unbound components, representing a major challenge for the docking procedures. For 1 target, predictions could not go to completion. In total, 1866 predictions submitted by 30 groups were evaluated. Over one-third of these groups applied completely novel docking algorithms and scoring functions, with several of them specifically addressing the challenge of dealing with side-chain and backbone flexibility. The quality of the predicted interactions was evaluated by comparison to the experimental structures of the targets, made available for the evaluation, using the well-agreed-upon criteria used previously. Twenty-four groups, which for the first time included an automatic Web server, produced predictions ranking from acceptable to highly accurate for all targets, including those where the structures of the bound and unbound forms differed substantially. These results and a brief survey of the methods used by participants of CAPRI Rounds 3-5 suggest that genuine progress in the performance of docking methods is being achieved, with CAPRI acting as the catalyst.

1D momentum-conserving systems: the conundrum of anomalous versus normal heat transport

NASA Astrophysics Data System (ADS)

Li, Yunyun; Liu, Sha; Li, Nianbei; Hänggi, Peter; Li, Baowen

2015-04-01

Transport and the spread of heat in Hamiltonian one dimensional momentum conserving nonlinear systems is commonly thought to proceed anomalously. Notable exceptions, however, do exist of which the coupled rotator model is a prominent case. Therefore, the quest arises to identify the origin of manifest anomalous energy and momentum transport in those low dimensional systems. We develop the theory for both, the statistical densities for momentum- and energy-spread and particularly its momentum-/heat-diffusion behavior, as well as its corresponding momentum/heat transport features. We demonstrate that the second temporal derivative of the mean squared deviation of the momentum spread is proportional to the equilibrium correlation of the total momentum flux. Subtracting the part which corresponds to a ballistic momentum spread relates (via this integrated, subleading momentum flux correlation) to an effective viscosity, or equivalently, to the underlying momentum diffusivity. We next put forward the intriguing hypothesis: normal spread of this so adjusted excess momentum density causes normal energy spread and alike normal heat transport (Fourier Law). Its corollary being that an anomalous, superdiffusive broadening of this adjusted excess momentum density in turn implies an anomalous energy spread and correspondingly anomalous, superdiffusive heat transport. This hypothesis is successfully corroborated within extensive molecular dynamics simulations over large extended time scales. Our numerical validation of the hypothesis involves four distinct archetype classes of nonlinear pair-interaction potentials: (i) a globally bounded pair interaction (the noted coupled rotator model), (ii) unbounded interactions acting at large distances (the coupled rotator model amended with harmonic pair interactions), (iii) the case of a hard point gas with unbounded square-well interactions and (iv) a pair interaction potential being unbounded at short distances while displaying an asymptotic free part (Lennard-Jones model). We compare our findings with recent predictions obtained from nonlinear fluctuating hydrodynamics theory.

Molecular simulations and Markov state modeling reveal the structural diversity and dynamics of a theophylline-binding RNA aptamer in its unbound state

PubMed Central

Warfield, Becka M.

2017-01-01

RNA aptamers are oligonucleotides that bind with high specificity and affinity to target ligands. In the absence of bound ligand, secondary structures of RNA aptamers are generally stable, but single-stranded and loop regions, including ligand binding sites, lack defined structures and exist as ensembles of conformations. For example, the well-characterized theophylline-binding aptamer forms a highly stable binding site when bound to theophylline, but the binding site is unstable and disordered when theophylline is absent. Experimental methods have not revealed at atomic resolution the conformations that the theophylline aptamer explores in its unbound state. Consequently, in the present study we applied 21 microseconds of molecular dynamics simulations to structurally characterize the ensemble of conformations that the aptamer adopts in the absence of theophylline. Moreover, we apply Markov state modeling to predict the kinetics of transitions between unbound conformational states. Our simulation results agree with experimental observations that the theophylline binding site is found in many distinct binding-incompetent states and show that these states lack a binding pocket that can accommodate theophylline. The binding-incompetent states interconvert with binding-competent states through structural rearrangement of the binding site on the nanosecond to microsecond timescale. Moreover, we have simulated the complete theophylline binding pathway. Our binding simulations supplement prior experimental observations of slow theophylline binding kinetics by showing that the binding site must undergo a large conformational rearrangement after the aptamer and theophylline form an initial complex, most notably, a major rearrangement of the C27 base from a buried to solvent-exposed orientation. Theophylline appears to bind by a combination of conformational selection and induced fit mechanisms. Finally, our modeling indicates that when Mg2+ ions are present the population of binding-competent aptamer states increases more than twofold. This population change, rather than direct interactions between Mg2+ and theophylline, accounts for altered theophylline binding kinetics. PMID:28437473

Feasibility of Using Unbound Mixed Recycled Aggregates from CDW over Expansive Clay Subgrade in Unpaved Rural Roads

PubMed Central

Del Rey, Isaac; Ayuso, Jesús; Galvín, Adela P.; Jiménez, José R.; Barbudo, Auxi

2016-01-01

Social awareness aims to increase practical skills, such as sustainable development, which seeks to increase the use of different types of waste in construction activities. Although insufficient attention is sometimes given to these actions, it is essential to spread information regarding new studies in the field of waste recycling, which encourages and promotes waste use. Reusing and recycling construction waste in the creation of buildings and infrastructure are fundamental strategies to achieving sustainability in the construction and engineering sectors. In this context, the concept of waste would no longer exist, as waste would become a material resource. Therefore, this study analyses the behaviours of two unbound mixed recycled aggregates (MRA) in the structural layers of an unpaved rural road with low traffic (category T43). The sections were built on inappropriate soil (A-7-6) with a high degree of free swelling. The experimental road consisted of three sections: the first was made with natural aggregates (NA) that were used as a control, the second was composed of MRA in the subbase and NA in the base, and the third section was completely composed of MRA. The materials were characterised in the laboratory. The behaviours of the structural layers in the experimental road were determined by controlling compaction (“in situ” density and moisture) and measuring the deflections and load capacity (deflectometer) during the 18 months after construction. The results show that the sections made with recycled aggregates meet the technical specifications required by General Technical Specifications for Road and Bridge Works (PG-3). Therefore, the water-soluble sulphate content and Los Angeles abrasion coefficient limits can be increased for recycled aggregates without compromising the quality of this type of road with low traffic. To the best of our knowledge, this is the first study regarding the use of unbound MRA made from construction and demolition waste (CDW) in the construction of an unpaved rural road with low traffic on an expansive clay subgrade. PMID:28774053

Protein-protein docking using region-based 3D Zernike descriptors

PubMed Central

2009-01-01

Background Protein-protein interactions are a pivotal component of many biological processes and mediate a variety of functions. Knowing the tertiary structure of a protein complex is therefore essential for understanding the interaction mechanism. However, experimental techniques to solve the structure of the complex are often found to be difficult. To this end, computational protein-protein docking approaches can provide a useful alternative to address this issue. Prediction of docking conformations relies on methods that effectively capture shape features of the participating proteins while giving due consideration to conformational changes that may occur. Results We present a novel protein docking algorithm based on the use of 3D Zernike descriptors as regional features of molecular shape. The key motivation of using these descriptors is their invariance to transformation, in addition to a compact representation of local surface shape characteristics. Docking decoys are generated using geometric hashing, which are then ranked by a scoring function that incorporates a buried surface area and a novel geometric complementarity term based on normals associated with the 3D Zernike shape description. Our docking algorithm was tested on both bound and unbound cases in the ZDOCK benchmark 2.0 dataset. In 74% of the bound docking predictions, our method was able to find a near-native solution (interface C-αRMSD ≤ 2.5 Å) within the top 1000 ranks. For unbound docking, among the 60 complexes for which our algorithm returned at least one hit, 60% of the cases were ranked within the top 2000. Comparison with existing shape-based docking algorithms shows that our method has a better performance than the others in unbound docking while remaining competitive for bound docking cases. Conclusion We show for the first time that the 3D Zernike descriptors are adept in capturing shape complementarity at the protein-protein interface and useful for protein docking prediction. Rigorous benchmark studies show that our docking approach has a superior performance compared to existing methods. PMID:20003235

Protein-protein docking using region-based 3D Zernike descriptors.

PubMed

Venkatraman, Vishwesh; Yang, Yifeng D; Sael, Lee; Kihara, Daisuke

2009-12-09

Protein-protein interactions are a pivotal component of many biological processes and mediate a variety of functions. Knowing the tertiary structure of a protein complex is therefore essential for understanding the interaction mechanism. However, experimental techniques to solve the structure of the complex are often found to be difficult. To this end, computational protein-protein docking approaches can provide a useful alternative to address this issue. Prediction of docking conformations relies on methods that effectively capture shape features of the participating proteins while giving due consideration to conformational changes that may occur. We present a novel protein docking algorithm based on the use of 3D Zernike descriptors as regional features of molecular shape. The key motivation of using these descriptors is their invariance to transformation, in addition to a compact representation of local surface shape characteristics. Docking decoys are generated using geometric hashing, which are then ranked by a scoring function that incorporates a buried surface area and a novel geometric complementarity term based on normals associated with the 3D Zernike shape description. Our docking algorithm was tested on both bound and unbound cases in the ZDOCK benchmark 2.0 dataset. In 74% of the bound docking predictions, our method was able to find a near-native solution (interface C-alphaRMSD < or = 2.5 A) within the top 1000 ranks. For unbound docking, among the 60 complexes for which our algorithm returned at least one hit, 60% of the cases were ranked within the top 2000. Comparison with existing shape-based docking algorithms shows that our method has a better performance than the others in unbound docking while remaining competitive for bound docking cases. We show for the first time that the 3D Zernike descriptors are adept in capturing shape complementarity at the protein-protein interface and useful for protein docking prediction. Rigorous benchmark studies show that our docking approach has a superior performance compared to existing methods.

No large population of unbound or wide-orbit Jupiter-mass planets.

PubMed

Mróz, Przemek; Udalski, Andrzej; Skowron, Jan; Poleski, Radosław; Kozłowski, Szymon; Szymański, Michał K; Soszyński, Igor; Wyrzykowski, Łukasz; Pietrukowicz, Paweł; Ulaczyk, Krzysztof; Skowron, Dorota; Pawlak, Michał

2017-08-10

Planet formation theories predict that some planets may be ejected from their parent systems as result of dynamical interactions and other processes. Unbound planets can also be formed through gravitational collapse, in a way similar to that in which stars form. A handful of free-floating planetary-mass objects have been discovered by infrared surveys of young stellar clusters and star-forming regions as well as wide-field surveys, but these studies are incomplete for objects below five Jupiter masses. Gravitational microlensing is the only method capable of exploring the entire population of free-floating planets down to Mars-mass objects, because the microlensing signal does not depend on the brightness of the lensing object. A characteristic timescale of microlensing events depends on the mass of the lens: the less massive the lens, the shorter the microlensing event. A previous analysis of 474 microlensing events found an excess of ten very short events (1-2 days)-more than known stellar populations would suggest-indicating the existence of a large population of unbound or wide-orbit Jupiter-mass planets (reported to be almost twice as common as main-sequence stars). These results, however, do not match predictions of planet-formation theories and surveys of young clusters. Here we analyse a sample of microlensing events six times larger than that of ref. 11 discovered during the years 2010-15. Although our survey has very high sensitivity (detection efficiency) to short-timescale (1-2 days) microlensing events, we found no excess of events with timescales in this range, with a 95 per cent upper limit on the frequency of Jupiter-mass free-floating or wide-orbit planets of 0.25 planets per main-sequence star. We detected a few possible ultrashort-timescale events (with timescales of less than half a day), which may indicate the existence of Earth-mass and super-Earth-mass free-floating planets, as predicted by planet-formation theories.

Locating Fractions on a Number Line

ERIC Educational Resources Information Center

Wong, Monica

2013-01-01

Understanding fractions remains problematic for many students. The use of the number line aids in this understanding, but requires students to recognise that a fraction represents the distance from zero to a dot or arrow marked on a number line which is a linear scale. This article continues the discussion from "Identifying Fractions on a…

Life on the Number Line: Routes to Understanding Fraction Magnitude for Students With Difficulties Learning Mathematics.

PubMed

Gersten, Russell; Schumacher, Robin F; Jordan, Nancy C

Magnitude understanding is critical for students to develop a deep understanding of fractions and more advanced mathematics curriculum. The research reports in this special issue underscore magnitude understanding for fractions and emphasize number lines as both an assessment and an instructional tool. In this commentary, we discuss how number lines broaden the concept of fractions for students who are tied to the more general part-whole representations of area models. We also discuss how number lines, compared to other representations, are a superior and more mathematically correct way to explain fraction concepts.

Distinct Representations of Magnitude and Spatial Position within Parietal Cortex during Number-Space Mapping.

PubMed

Kanayet, Frank J; Mattarella-Micke, Andrew; Kohler, Peter J; Norcia, Anthony M; McCandliss, Bruce D; McClelland, James L

2018-02-01

Mapping numbers onto space is foundational to mathematical cognition. These cognitive operations are often conceptualized in the context of a "mental number line" and involve multiple brain regions in or near the intraparietal sulcus (IPS) that have been implicated both in numeral and spatial cognition. Here we examine possible differentiation of function within these brain areas in relating numbers to spatial positions. By isolating the planning phase of a number line task and introducing spatiotopic mapping tools from fMRI into mental number line task research, we are able to focus our analysis on the neural activity of areas in anterior IPS (aIPS) previously associated with number processing and on spatiotopically organized areas in and around posterior IPS (pIPS), while participants prepare to place a number on a number line. Our results support the view that the nonpositional magnitude of a numerical symbol is coded in aIPS, whereas the position of a number in space is coded in posterior areas of IPS. By focusing on the planning phase, we are able to isolate activation related to the cognitive, rather than the sensory-motor, aspects of the task. Also, to allow the separation of spatial position from magnitude, we tested both a standard positive number line (0 to 100) and a zero-centered mixed number line (-100 to 100). We found evidence of a functional dissociation between aIPS and pIPS: Activity in aIPS was associated with a landmark distance effect not modulated by spatial position, whereas activity in pIPS revealed a contralateral preference effect.

"Battleship Numberline": A Digital Game for Improving Estimation Accuracy on Fraction Number Lines

ERIC Educational Resources Information Center

Lomas, Derek; Ching, Dixie; Stampfer, Eliane; Sandoval, Melanie; Koedinger, Ken

2011-01-01

Given the strong relationship between number line estimation accuracy and math achievement, might a computer-based number line game help improve math achievement? In one study by Rittle-Johnson, Siegler and Alibali (2001), a simple digital game called "Catch the Monster" provided practice in estimating the location of decimals on a…

A comparative genomic hybridization approach to study gene copy number variations among Chinese hamster cell lines.

PubMed

Vishwanathan, Nandita; Bandyopadhyay, Arpan; Fu, Hsu-Yuan; Johnson, Kathryn C; Springer, Nathan M; Hu, Wei-Shou

2017-08-01

Chinese Hamster Ovary (CHO) cells are aneuploid in nature. The genome of recombinant protein producing CHO cell lines continuously undergoes changes in its structure and organization. We analyzed nine cell lines, including parental cell lines, using a comparative genomic hybridization (CGH) array focused on gene-containing regions. The comparison of CGH with copy-number estimates from sequencing data showed good correlation. Hierarchical clustering of the gene copy number variation data from CGH data revealed the lineage relationships between the cell lines. On analyzing the clones of a clonal population, some regions with altered genomic copy number status were identified indicating genomic changes during passaging. A CGH array is thus an effective tool in quantifying genomic alterations in industrial cell lines and can provide insights into the changes in the genomic structure during cell line derivation and long term culture. Biotechnol. Bioeng. 2017;114: 1903-1908. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.