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PubMed2005

Inversion recovery measurements in the presence of radiation damping and implications for evaluating contrast agents in magnetic resonance.

Relaxation measurements performed at high magnetic field in magnetic resonance (MR) may be adversely affected by the influence of radiation damping in concentrated samples such as water. We consider how the measured value of T1 is affected by this phenomenon for a gadolinium-doped water sample and for an undoped water sample and consider the implications for evaluating contrast agents. A simple method involving the application of a pulsed field gradient to de-phase residual transverse components of the magnetization is shown to be an effective method for suppressing this effect. Given the central role that measurement of the T1 of water plays in the assessment of contrast agents as well as a host of other MR applications, care should always be employed when measuring and interpreting T1 measurements at high magnetic fields.

Brain↗

PubMed2006

Elastic and damping forces generated by confined arrays of dynamic microtubules.

In addition to serving as structural elements and as tracks for motor proteins, microtubules use chemical energy derived from the hydrolysis of GTP to generate forces when growing and shrinking. These forces are used to push or pull on organelles such as chromosomes and the mitotic spindle. If an array of microtubules grows out from a nucleation site and is confined by the periphery of the cell, pushing and pulling forces can give rise to interesting collective phenomena. In this paper, I show that pushing forces center the array provided that the microtubules are dynamic in the sense that they switch from pushing to shrinking after reaching the periphery. Microtubule dynamics of free ends is neither necessary nor sufficient for centering. Buckling can augment the centering force. For small displacements and velocities, the array can be modeled very simply as a damped spring. The dynamic stiffness of the array is orders of magnitude smaller than its static stiffness, and the relaxation time is on the order of the time that it takes for a microtubule to grow from the center to the periphery. Replacement of a dynamic polymer array with an equivalent mechanical circuit provides a bridge between molecular and cellular mechanics.

Biomechanical Phenomena↗

PubMed2003

Mitochondrial DNA depletion can be prevented by dGMP and dAMP supplementation in a resting culture of deoxyguanosine kinase-deficient fibroblasts.

Deoxyguanosine kinase is a constitutively expressed, mitochondrial enzyme of the deoxyribonucleoside salvage pathway. Deficiency of deoxyguanosine kinase causes early-onset, hepatocerebral mitochondrial DNA (mtDNA) depletion syndrome. To clarify the molecular mechanism of the disease, a skin fibroblast culture was studied from a patient carrying a homozygous nonsense mutation in the gene for deoxyguanosine kinase. In situ examination of DNA synthesis demonstrated that, although mtDNA synthesis is cell cycle independent in control fibroblasts, mtDNA synthesis occurs mainly during the S-phase in deoxyguanosine kinase-deficient cells. Consistent with this observation, it was found that the mtDNA content of exponentially growing, deoxyguanosine kinase-deficient cells is only mildly affected. When cycling is inhibited by serum-deprivation and cells are in a resting state, however, the mtDNA content drops considerably in deoxyguanosine kinase-deficient cells, yet remains stable in control fibroblasts. The decline in mtDNA content in resting, deoxyguanosine kinase-deficient cells can be prevented by dGMP and dAMP supplementation, providing conclusive evidence that substrate limitation triggers mtDNA depletion in deoxyguanosine kinase-deficient cells.

Cell Cycle↗

PubMed1997

Indoor air quality and health: validity and determinants of reported home dampness and moulds.

BACKGROUND: Questionnaire-based surveys from several countries have consistently detected adverse health associated with home dampness and mould growth. METHODS: To test the validity of questions commonly used to indicate the presence of indoor mould, questionnaires were administered in 403 homes where dust samples were taken for viable fungi and air samples for ergosterol. RESULTS: Geometric mean concentrations of the total viable fungi were 255 (SE 116) x 10(3) CFU/g when mouldy odours were reported and 155 (SE 55) when odours were not reported (P = 0.01). Similarly, reported water damage was associated with a 50% increase (P = 0.06). Geometric mean concentrations of the predominantly indoor-source fungi, Aspergillus plus Penicillium, were twice as high when mould or mildew was reported than when not mentioned (P = 0.01). The presence of reported mould or water damage was unrelated to the presence of detectable levels of ergosterol. There was evidence for reporting bias: in the presence of low concentrations of viable fungi in dust, respondents reporting allergies were more likely to report visible mould growth (odds ratio [OR] = 1.8, 95% confidence interval [CI]: 0.9-3.5, P = 0.10. In the presence of elevated concentrations of dust fungi, respondents who smoked were less likely to report visible mould growth, (OR = 0.4, 95% CI: 0.2-0.7, P = 0.005). CONCLUSIONS: Reported mould, water damage, and mouldy odours were associated with elevated levels of indoor fungi. However, inaccuracy was high and there was evidence of a systematic reporting bias. Future research should concentrate on developing accurate objective measures of exposure to fungi, and then use this information to develop valid questionnaires. Currently, objective measures not questionnaires, are recommended to clarify the health effects of indoor fungi.

Adult↗

PubMed1995

On the mechanism of preferential incorporation of dAMP at abasic sites in translesional DNA synthesis. Role of proofreading activity of DNA polymerase and thermodynamic characterization of model template-primers containing an abasic site.

DNA polymerase preferentially incorporate dAMP opposite abasic sites (A-rule). The mechanism of the A-rule can be studied by analyzing three dissected stages of the reaction including (i) initial nucleotide insertion, (ii) proofreading excision of the inserted nucleotide and (iii) extension of the nascent primer terminus. To assess the role of the stage (ii) in the A-rule, kinetic parameters of the proofreading excision of primer terminus nucleotides opposite abasic sites were determined using E.coli DNA polymerase I Klenow fragment. The relative efficiency of the excision (Vmax/Km) revealed that removal of A was the least favored of the four nucleotides, but the differences in the efficiencies between excision of A and the other nucleotides was less than 2-fold. In addition, in an attempt to reconcile kinetic data associated with the stage (i) or (ii), the differences in free energy changes (delta delta G degrees) for the formation of model template-primer termini containing XN pairs (X = abasic site, N = A, G, C or T) were determined by temperature dependent UV-melting measurements. The order of delta delta G degrees was XG > XA = XC > or = XT, with delta delta G degrees being 0.5 kcal/mol for the most stable XG and the least stable XT. Based on these data, the role of the stage (ii) and energetic aspects of the A-rule are discussed.

Base Sequence↗

PubMed1989

Cardiac injury with damped sine and trapezoidal defibrillator waveforms.

To assess defibrillator-induced cardiac damage, 49 anaesthetized greyhounds received either no shocks (control group) or five shocks from a defibrillator delivering one of five waveforms (Lown, Edmark, Belfast damped sine waveforms: 5 and 20 ms trapezoidal waveforms). At 3 days the hearts of the 36 surviving dogs were examined for macroscopic damage. The Belfast and Edmark waveforms caused significantly more damage (mean 21.1 +/- SEM 2.9 g and 16.0 +/- 3.7 g) respectively than the Lown waveform (3.5 +/- 1.3 g) P less than 0.01. The 20 ms trapezoid caused significantly more damage (8.1 +/- 3.1 g) than the 5 ms pulse (0.7 +/- 1.3 g) P less than 0.05). The ventricular ectopic counts per minute were not significantly different in the three sine wave and 20 ms trapezoidal groups at 24 and 48 h (P greater than 0.05), but at 2 and 72 h were significantly greater in the Belfast and Edmark groups than in the Lown group (2 h, Belfast P less than 0.01, Edmark P less than 0.05: 72 h P less than 0.05). At 15 min there was more right chest ST-segment elevation in the Belfast than in the Lown, Edmark and 20 ms trapezoid groups (P less than 0.01), while left chest ST elevation was greater in the Belfast and Edmark than in the Lown (P less than 0.05) and 20 ms trapezoid groups (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2000

Chromosomal insertion of phenazine-1-carboxylic acid biosynthetic pathway enhances efficacy of damping-off disease control by Pseudomonas fluorescens.

A disarmed Tn5 vector (pUT::Ptac-phzABCDEFG) was used to introduce a single copy of the genes responsible for phenazine-1-carboxylic acid (PCA) biosynthesis into the chromosome of a plant-growth-promoting rhizobacterium Pseudomonas fluorescens. The PCA gene cluster was modified for expression under a constitutive Ptac promoter and lacked the phzIR regulators. PCA-producing variants significantly improved the ability of the wild-type P. fluorescens to reduce damping-off disease of pea seedlings caused by Pythium ultimum, even under conditions of heavy soil infestation. Under conditions of oxygen limitation that are typical of the rhizosphere, PCA production per cell in vitro was greater than that recorded in fast-growing, nutrient-rich cultures. Similarly, when the in vitro nutrient supply was limited, P fluorescens::phz variants that produced the most PCA effectively competed against P. ultimum by suppressing mycelial development. Soil-based bioassays confirmed that the level of PCA biosynthesis correlated directly with the efficacy of biological control and the persistence of inocula in soil microcosms. They also showed that soil pretreatment with bacteria provides a suitable method for plant protection by reducing infection, effectively decontaminating the soil. These data demonstrate that the insertion of a single chromosomal copy of the genes for a novel antifungal compound, PCA, enhances the ecological fitness of a natural isolate already adapted to the rhizosphere and capable of suppressing fungal disease.

DNA Transposable Elements↗

PubMed2007

Eosinophilic granulocytes and damage-associated molecular pattern molecules (DAMPs): role in the inflammatory response within tumors.

The development of a tumor over many years typically leads to reciprocal alternations in the host and the tumor, enabling tumor growth paradoxically in the setting of substantial necrosis and inflammation. When evaluating a tumor, it is important to assess 3 elements: (1) the quantity and quality of tumor-associated leukocytes, (2) their state of activation, and (3) tumor microenvironment. Peripheral blood eosinophilia and tumor-associated tissue eosinophilia are frequently associated with some tumor types and also found after immunotherapy with IL-2, IL-4, granulocyte-macrophage colony-stimulating factor, and antibody to CTLA-4. Within several tumor types including gastrointestinal tumors, tumor-associated tissue eosinophilia is associated with a significantly better prognosis. The converse is true in other tumor types such as differentiated oral squamous cell carcinoma. On the basis of the emergent data, tumor-associated eosinophils have at least 2 dominant nonoverlapping activities: (1) destructive effector functions potentially limiting tumor growth as well as causing recruitment and activation of other leukocytes, (2) immunoregulative and remodeling activities which suppress immune response and promote tumor proliferation. The mechanism by which eosinophils in particular are recruited into tumor tissue is largely unknown. Candidates for causing eosinophil chemotaxis into tumor tissue are the released damage-associated molecular pattern molecules (DAMPs) including the nuclear protein high mobility group box 1. High mobility group box 1 is released upon necrotic cell death and secreted by many cells, particularly during periods of nutrient, hypoxic, or oxidant stress. This overview on eosinophil biology in the context of cancer and necrosis, introduces intriguing and novel strategies targeting eosinophils to enable more effective biologic therapy for cancer patients.

Eosinophils↗

PubMed1999

Bifurcations and chaos in a parametrically damped two-well Duffing oscillator subjected to symmetric periodic pulses.

We study a parametrically damped two-well Duffing oscillator, subjected to a periodic string of symmetric pulses. The order-chaos threshold when altering solely the width of the pulses is investigated theoretically through Melnikov analysis. We show analytically and numerically that most of the results appear independent of the particular wave form of the pulses provided that the transmitted impulse is the same. By using this property, the stability boundaries of the stationary solutions are determined to first approximation by means of an elliptic harmonic balance method. Finally, the bifurcation behavior at the stability boundaries is determined numerically.

Journal Article↗

PubMed1999

Breathers and multibreathers in a periodically driven damped discrete nonlinear Schrödinger equation.

We study an integrable discretization of the nonlinear Schrödinger equation (NLS) under the effects of damping and periodic driving, from the point of view of spatially localized solutions oscillating in time with the driver's frequency. We locate the equilibrium states of the discretized (DNLS) system in the plane of its dissipation gamma and forcing amplitude H parameters and use a shooting algorithm to construct the desired solutions psi(n)(t)=phi(n) exp(it) as homoclinic orbits of a four-dimensional symplectic map in the complex phi(n),phi(n+1) space, for -infinity<n<infinity. We derive, in the gamma=0 case, closed form expressions for two fundamental such solutions having a single hump in n, psi(n)+, and psi(n)-, and determine analytically their threshold of existence in the (gamma,H) plane using Mel'nikov's theory. Then, we demonstrate numerically that above this threshold a remarkable variety of multihump structures appear, whose complexity in terms of their spatial extrema grows with increasing H. All these solutions are numerically found to be unstable in time, except for psi(n)-, which is seen to be stable over a certain region in the (gamma,H) plane. In the continuum limit our results are in close agreement with recent studies on the NLS equation. From a more general perspective, we view these DNLS multihump solutions as homoclinic orbits of a higher-dimensional map thereby providing a possible mechanism for explaining the occurrence of similar structures called discrete (multi-) breathers found in a wide variety of one-dimensional nonlinear lattices.

Journal Article↗

PubMed1999

Intrinsic localized modes and chaos in damped driven rotator lattices.

It is shown that intrinsic localized rotational modes (ILRMs) in parametrically driven damped lattices of coupled classical dipole rotators can become chaotic without losing their localized character. Insight into this behavior is obtained by means of a nonlinear stability analysis. Moreover, we discuss a robust scheme for exploiting a spatially extended chaotic state to generate stationary randomly spaced arrays of driven ILRMs, and show that the associated absorption exhibits unusual signatures.

Journal Article↗

PubMed2000

Damped stochastic system driven by colored noise: analytical solution by a path integral approach

We consider the nonlinear non-Markovian stochastic process associated with the damped nonlinear dynamical system driven by Ornstein-Uhlenbeck noise. An approximate Fokker-Planck-type equation governing the above stochastic process is derived using the path-integral approach. The stationary probability density function (SPDF) of the above process is then computed using the matrix continued fraction method. The SPDF compares favorably with the corresponding digital simulation results obtained by us.

Journal Article↗

PubMed2000

Asymptotic evolution of nonlinear landau damping

The long-time evolution of nonlinear Landau damping in collisionless plasmas is analyzed by solving the Vlasov-Poisson system numerically. The value of the parameter marking the transition between Landau's and O'Neil's regimes is determined and compared with analytical results. The long-time evolution of a finite-amplitude electric field with wavelength lambda equal to the length of the simulation box L is given by a superposition of two counterpropagating "averaged" Bernstein-Greene-Kruskal (BGK) waves. When L>lambda and longer wavelength modes can be excited, the BGK waves correspond to an intermediate regime that is eventually modified by the excitation of the sideband instability. Ions dynamics is found not to affect these behaviors significantly.

Journal Article↗

PubMed2000

Causal implications of viscous damping in compressible fluid flows

Classically, a compressible, isothermal, viscous fluid is regarded as a mathematical continuum and its motion is governed by the linearized continuity, Navier-Stokes, and state equations. Unfortunately, solutions of this system are of a diffusive nature and hence do not satisfy causality. However, in the case of a half-space of fluid set to motion by a harmonically vibrating plate the classical equation of motion can, under suitable conditions, be approximated by the damped wave equation. Since this equation is hyperbolic, the resulting solutions satisfy causal requirements. In this work the Laplace transform and other analytical and numerical tools are used to investigate this apparent contradiction. To this end the exact solutions, as well as their special and limiting cases, are found and compared for the two models. The effects of the physical parameters on the solutions and associated quantities are also studied. It is shown that propagating wave fronts are only possible under the hyperbolic model and that the concept of phase speed has different meanings in the two formulations. In addition, discontinuities and shock waves are noted and a physical system is modeled under both formulations. Overall, it is shown that the hyperbolic form gives a more realistic description of the physical problem than does the classical theory. Lastly, a simple mechanical analog is given and connections to viscoelastic fluids are noted. In particular, the research presented here supports the notion that linear compressible, isothermal, viscous fluids can, at least in terms of causality, be better characterized as a type of viscoelastic fluid.

Journal Article↗

PubMed2001

Driven kinks in discrete chains: phonon damping.

Phonon radiation is shown numerically to damp the motion of a relativistically driven straight phi(4) soliton, even in the extremely weak discreteness limit. At higher discreteness, the soliton mobility is characterized by a discontinuous dependence on the driving force; jumps are related to phonon and breather-radiation thresholds. Moreover, the speed of a frictionless soliton cannot be lowered below a certain threshold value, or else it might get trapped between two adjacent chain sites.

Journal Article↗

PubMed2001

Radiation damping in real time.

We study the nonequilibrium dynamics of a charge interacting with its own radiation, which originates the radiation damping. The real-time equation of motion for the charge and the associated Langevin equation is found in classical limit. The equation of motion for the charge allows one to obtain the frequency-dependent coefficient of friction. In the lowest order we find that although the coefficient of static friction vanishes, there is dynamical dissipation represented by a non-Markovian dissipative kernel.

Journal Article↗

PubMed2001

Pattern formation and localization in the forced-damped Fermi-Pasta-Ulam lattice.

We study spatial pattern formation and energy localization in the dynamics of an anharmonic chain with quadratic and quartic intersite potential, subject to an optical, sinusoidally oscillating field and a weak damping. The zone-boundary mode is stable and locked to the driving field below a critical forcing that we determine analytically using an approximate model, which describes mode interactions. Above such a forcing, a standing modulated wave forms for driving frequencies below the band edge, while a "multibreather" state develops at higher frequencies. Of the former, we give an explicit approximate analytical expression, which compares well with numerical data. At higher forcing, space-time chaotic patterns are observed.

Journal Article↗

PubMed2001

Solution of Kramers' problem for a moderately to heavily damped elastic string.

We obtain the nucleation rate of critical droplets for an elastic string moving in a double-well potential and subject to noise and damping forces. We obtain this rate for a class of potentials that includes both the asymmetric straight phi(4) and the straight phi(6) potentials. The frequencies of small oscillations about the critical droplet are obtained from a Heun equation. We solve the Fokker-Planck equation for the phase-space probability density by projecting onto the eigenfunction basis. We present a comparison with simulations for the case of the asymmetric straight phi(4) potential.

Journal Article↗