75 research outputs found

    Limited Macrophage Positional Dynamics in Progressing or Regressing Murine Atherosclerotic PlaquesBrief Report

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    Objective Macrophages play important roles in the pathogenesis of atherosclerosis, but their dynamics within plaques remain obscure. We aimed to quantify macrophage positional dynamics within progressing and regressing atherosclerotic plaques. Approach and Results In a stable intravital preparation, large asymmetrical foamy macrophages in the intima of carotid artery plaques were sessile, but smaller rounded cells nearer plaque margins, possibly newly recruited monocytes, mobilized laterally along plaque borders. Thus, to test macrophage dynamics in plaques over a longer period of time in progressing and regressing disease, we quantified displacement of nondegradable phagocytic particles within macrophages for up to 6 weeks. In progressing plaques, macrophage-associated particles appeared to mobilize to deeper layers in plaque, whereas in regressing plaques, the label was persistently located near the lumen. By measuring the distance of the particles from the floor of the plaque, we discovered that particles remained at the same distance from the floor regardless of plaque progression or regression. The apparent deeper penetration of labeled cells in progressing conditions could be attributed to monocyte recruitment that generated new superficial layers of macrophages over the labeled phagocytes. Conclusion: s Although there may be individual exceptions, as a population, newly differentiated macrophages fail to penetrate significantly deeper than the limited depth they reside on initial entry, regardless of plaque progression, or regression. These limited dynamics may prevent macrophages from escaping areas with unfavorable conditions (such as hypoxia) and pose a challenge for newly recruited macrophages to clear debris through efferocytosis deep within plaque

    Manual therapy directed at the knee or lumbopelvic region does not influence quadriceps spinal reflex excitability

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    Manual therapies, directed to the knee and lumbopelvic region, have demonstrated the ability to improve neuromuscular quadriceps function in individuals with knee pathology. It remains unknown if manual therapies may alter impaired spinal reflex excitability, thus identifying a potential mechanism in which manual therapy may improve neuromuscular function following knee injury

    A Genome Wide Survey of SNP Variation Reveals the Genetic Structure of Sheep Breeds

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    The genetic structure of sheep reflects their domestication and subsequent formation into discrete breeds. Understanding genetic structure is essential for achieving genetic improvement through genome-wide association studies, genomic selection and the dissection of quantitative traits. After identifying the first genome-wide set of SNP for sheep, we report on levels of genetic variability both within and between a diverse sample of ovine populations. Then, using cluster analysis and the partitioning of genetic variation, we demonstrate sheep are characterised by weak phylogeographic structure, overlapping genetic similarity and generally low differentiation which is consistent with their short evolutionary history. The degree of population substructure was, however, sufficient to cluster individuals based on geographic origin and known breed history. Specifically, African and Asian populations clustered separately from breeds of European origin sampled from Australia, New Zealand, Europe and North America. Furthermore, we demonstrate the presence of stratification within some, but not all, ovine breeds. The results emphasize that careful documentation of genetic structure will be an essential prerequisite when mapping the genetic basis of complex traits. Furthermore, the identification of a subset of SNP able to assign individuals into broad groupings demonstrates even a small panel of markers may be suitable for applications such as traceability

    Emergence and equilibration of jets in beta-plane turbulence: applications of Stochastic Structural Stability Theory

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    Stochastic Structural Stability Theory (S3T) provides analytical methods for understanding the emergence and equilibration of jets from the turbulence in planetary atmospheres based on the dynamics of the statistical mean state of the turbulence closed at second order. Predictions for formation and equilibration of turbulent jets made using S3T are critically compared with results of simulations made using the associated quasi-linear and nonlinear models. S3T predicts the observed bifurcation behavior associated with the emergence of jets, their equilibration and their breakdown as a function of parameters. Quantitative differences in bifurcation parameter values between predictions of S3T and results of nonlinear simulations are traced to modification of the eddy spectrum which results from two processes: nonlinear eddy-eddy interactions and formation of discrete non-zonal structures. Remarkably, these non-zonal structures, which substantially modify the turbulence spectrum, are found to arise from S3T instability. Formation as linear instabilities and equilibration at finite amplitude of multiple equilibria for identical parameter values in the form of jets with distinct meridional wavenumbers is verified as is the existence at equilibrium of finite amplitude non-zonal structures in the form of nonlinearly modified Rossby waves. When zonal jets and nonlinearly modified Rossby waves coexist at finite amplitude the jet structure is generally found to dominate even if it is linearly less unstable. The physical reality of the manifold of S3T jets and non-zonal structures is underscored by the existence in nonlinear simulations of jet structure at subcritical S3T parameter values which are identified with stable S3T jet modes excited by turbulent fluctuations.Comment: 18 pages, 18 figures, submitted to the Journal of the Atmospheric Science

    Employee stock options: much more valuable than you thought

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    Previous papers have argued that trading restrictions can result in a typical employee stock option having a subjective value (certainty equivalent value) that is substantially less than its Black-Scholes value. However, these analyses ignore the manager's ability to (at least partially) control the risk level within the firm. In this paper, we show how managerial control can lead to such options having much larger certainty equivalent values for employees who can exercise control. We also show that the potential for early exercise is substantially less valuable with managerial control. The certainty equivalent value for a European option with managerial control can easily exceed the Black-Scholes value for a comparable option without control. However, it is questionable whether Black-Scholes is an appropriate benchmark for an option where the underlying process exhibits controlled volatility. We show how to obtain a risk-neutral valuation for such an option. That risk-neutral value can be substantially greater or less than the Black- Scholes value. Furthermore, the option's certainty equivalent value can also be greater or less than its risk-neutral value

    Managerial Responses to Incentives: Control of Firm Risk, Derivative Pricing Implications, and Outside Wealth Management

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    We model a firm’s value process controlled by a manager maximizing expected utility from restricted shares and employee stock options. The manager also dynamically controls allocation of his outside wealth. We explore interactions between those controls as he partially hedges his exposure to firm risk. Conditioning on his optimal behavior, control of firm risk increases the expected time to exercise for his employee stock options. It also reduces the percentage gap between his certainty equivalent and the firm’s fair value for his compensation, but that gap remains substantial. Managerial control also causes traded options to exhibit an implied volatility smile
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