Time resolved velocity measurements of unsteady systems using spiral imaging

Although biomolecular dynamics has been investigated using NMR for at least 40 years, only in the past 20 years have internal motions been characterized at atomic resolution throughout proteins and nucleic acids. This development was made possible by multidimensional heteronuclear NMR approaches that provide near complete sequential signal assignments of uniformly labeled biomolecules. Recent methodological advances have enabled characterization of internal dynamics on timescales ranging from picoseconds to seconds, both in solution and in the solid state. The size, complexity and functional significance of biomolecules investigated by NMR continue to grow, as do the insights that have been obtained about function. In this article I review a number of recent advances that have made such studies possible, and provide a few examples of where NMR either by itself or in combination with other approaches has paved the way to a better understanding of the complex relationship between dynamics and biomolecular function. Finally, I discuss prospects for further advances in this field.     

Evaluating the goodness of fit of stochastic mortality models

This study sets out a framework to evaluate the goodness of fit of stochastic mortality models and applies it to six different models estimated using English & Welsh male mortality data over ages 64-89 and years 1961-2007. The methodology exploits the structure of each model to obtain various residual series that are predicted to be iid standard normal under the null hypothesis of model adequacy. Goodness of fit can then be assessed using conventional tests of the predictions of iid standard normality. The models considered are: Lee and Carter’s (1992) one-factor model, a version of Renshaw and Haberman’s (2006) extension of the Lee-Carter model to allow for a cohort-effect, the age-period-cohort model, which is a simplified version of the Renshaw-Haberman model, the 2006 Cairns-Blake-Dowd two-factor model and two generalized versions of the latter that allow for a cohort-effect. For the data set considered, there are some notable differences amongst the different models, but none of the models performs well in all tests and no model clearly dominates the others.     

Christoffel symbols and inertia in flat space-time theory

A necessary and sufficient criterion of inertia is presented, for the flat space-time theory of general frames of reference, in terms of the vanishing of some typical components of the affine connection pertaining to curvilinear coordinate systems. The physical identification of inertial forces thus arises in the context of the special theory of relativity.     

Explicit inertial range renormalization theory in a model for turbulent diffusion

The inertial range for a statistical turbulent velocity field consists of those scales that are larger than the dissipation scale but smaller than the integral scale. Here the complete scale-invariant explicit inertial range renormalization theory for all the higher-order statistics of a diffusing passive scalar is developed in a model which, despite its simplicity, involves turbulent diffusion by statistical velocity fields with arbitrarily many scales, infrared divergence, long-range spatial correlations, and rapid fluctuations in time-such velocity fields retain several characteristic features of those in fully developed turbulence. The main tool in the development of this explicit renormalization theory for the model is an exact quantum mechanical analogy which relates higher-order statistics of the diffusing scalar to the properties of solutions of a family ofN- body parabolic quantum problems. The canonical inertial range renormalized statistical fixed point is developed explicitly here as a function of the velocity spectral parameter, which measures the strength of the infrared divergence: for<2, mean-field behavior in the inertial range occurs with Gaussian statistical behavior for the scalar and standard diffusive scaling laws; for>2 a phase transition occurs to a fixed point with anomalous inertial range scaling laws and a non-Gaussian renormalized statistical fixed point. Several explicit connections between the renormalization theory in the model and intermediate asymptotics are developed explicitly as well as links between anomalous turbulent decay and explicit spectral properties of Schrödinger operators. The differences between this inertial range renormalization theory and the earlier theories for large-scale eddy diffusivity developed by Avellaneda and the author in such models are also discussed here.     

Oscillations and concentrations in weak solutions of the incompressible fluid equations

The authors introduce a new concept of measure-valued solution for the 3-D incompressible Euler equations in order to incorporate the complex phenomena present in limits of approximate solutions of these equations. One application of the concepts developed here is the following important result: a sequence of Leray-Hopf weak solutions of the Navier-Stokes equations converges in the high Reynolds number limit to a measure-valued solution of 3-D Euler defined for all positive times. The authors present several explicit examples of solution sequences for 3-D incompressible Euler with uniformly bounded local kinetic energy which exhibit complex phenomena involving both persistence of oscillations and development of concentrations. An extensions of the concept of Young measure is developed to incorporate these complex phenomena in the measure-valued solutions constructed here.Partially supported by N.S.F. GrantPartially supported by N.S.F. Grant 84-0223 and 86-11110     

Nonlinear dynamics of charged particles interacting with combined ac-dc electromagnetic fields

A nonlinear Lorenz model describing interactions between charged particles and combined ac-dc electromagnetic fields is studied for various combinations of frequencies, field strengths and relative angle (θ) between the ac and dc magnetic fields. Strong directional effects on the magnitude and location of resonant particle motion are observed when θ is varied and the regular resonance windows in the aligned field (θ = 0) and linear version of the model studied previously by Durney etaal., break up to form irregular and less well pronounced regions of large and small particle displacements when nonlinearities are taken into account. The length of time takne to achieve resonant behaviour also becomes larger and more variable when nonlinearities are present. The possible relevance of these effects to interactions between electromagnetic fields and biological media is briefly discussed.     

Mining Pareto-optimal modules for delayed product differentiation

This paper presents a framework for finding optimal modules in a delayed product differentiation scenario. Historical product sales data is utilized to estimate demand probability and customer preferences. Then this information is used by a multiple-objective optimization model to form modules. An evolutionary computation approach is applied to solve the optimization model and find the Pareto-optimal solutions. An industrial case study illustrates the ideas presented in the paper. The mean number of assembly operations and expected pre-assembly costs are the two competing objectives that are optimized in the case study. The mean number of assembly operations can be significantly reduced while incurring relatively small increases in the expected pre-assembly cost.     

Microbubble-enhanced hemorrhage control using high intensity focused ultrasound

Our objective was to investigate whether hemorrhage control can be achieved faster when high-intensity focused ultrasound (HIFU) is applied in the presence of ultrasound contrast agents (UCA) as compared to HIFU only application. Incisions (3 cm long and 0.5 cm deep) were produced in the livers of anesthetized rabbits. UCA Optison (0.18 ml/kg) was injected into the mesenteric vein. A HIFU applicator (5.5 MHz, 6800 W/cm² in situ) was scanned at a rate of 1–2 mm/s in one direction over the incision (with multiple passes if needed), until hemostasis was achieved. Hemostasis times were 59 ± 23 s (n = 21) in the presence of Optison and 70 ± 23 s (n = 29) without Optison. The presence of Optison produced on average 37% reduction in hemostasis times normalized to initial bleeding rates (p < 0.05), as well as 60% faster formation of the coagulum seal over the incision (p < 0.05). Gross and histological observations showed similar appearance of HIFU lesions produced in the presence of Optison and HIFU lesions produced without Optison. Our results suggest potential utility of UCA for increasing efficiency of HIFU-induced hemostasis of solid organ injuries.     

Perceptual adaptation by normally hearing listeners to a simulated "hole" in hearing

Simulations of cochlear implants have demonstrated that the deleterious effects of a frequency misalignment between analysis bands and characteristic frequencies at basally shifted simulated electrode locations are significantly reduced with training. However, a distortion of frequency-to-place mapping may also arise due to a region of dysfunctional neurons that creates a "hole" in the tonotopic representation. This study simulated a 10 mm hole in the mid-frequency region. Noise-band processors were created with six output bands (three apical and three basal to the hole). The spectral information that would have been represented in the hole was either dropped or reassigned to bands on either side. Such reassignment preserves information but warps the place code, which may in itself impair performance. Normally hearing subjects received three hours of training in two reassignment conditions. Speech recognition improved considerably with training. Scores were much lower in a baseline (untrained) condition where information from the hole region was dropped. A second group of subjects trained in this dropped condition did show some improvement; however, scores after training were significantly lower than in the reassignment conditions. These results are consistent with the view that speech processors should present the most informative frequency range irrespective of frequency misalignment.