1,305 research outputs found
A Simple Method for Computing Singular or Nearly Singular Integrals on Closed Surfaces
We present a simple, accurate method for computing singular or nearly
singular integrals on a smooth, closed surface, such as layer potentials for
harmonic functions evaluated at points on or near the surface. The integral is
computed with a regularized kernel and corrections are added for regularization
and discretization, which are found from analysis near the singular point. The
surface integrals are computed from a new quadrature rule using surface points
which project onto grid points in coordinate planes. The method does not
require coordinate charts on the surface or special treatment of the
singularity other than the corrections. The accuracy is about , where
is the spacing in the background grid, uniformly with respect to the point
of evaluation, on or near the surface. Improved accuracy is obtained for points
on the surface. The treecode of Duan and Krasny for Ewald summation is used to
perform sums. Numerical examples are presented with a variety of surfaces.Comment: to appear in Commun. Comput. Phy
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Time-of-flight resolved light field fluctuations reveal deep human tissue physiology.
Red blood cells (RBCs) transport oxygen to tissues and remove carbon dioxide. Diffuse optical flowmetry (DOF) assesses deep tissue RBC dynamics by measuring coherent fluctuations of multiply scattered near-infrared light intensity. While classical DOF measurements empirically correlate with blood flow, they remain far-removed from light scattering physics and difficult to interpret in layered media. To advance DOF measurements closer to the physics, here we introduce an interferometric technique, surmounting challenges of bulk motion to apply it in awake humans. We reveal two measurement dimensions: optical phase, and time-of-flight (TOF), the latter with 22 picosecond resolution. With this multidimensional data, we directly confirm the unordered, or Brownian, nature of optically probed RBC dynamics typically assumed in classical DOF. We illustrate how incorrect absorption assumptions, anisotropic RBC scattering, and layered tissues may confound classical DOF. By comparison, our direct method enables accurate and comprehensive assessment of blood flow dynamics in humans
A fully resolved active musculo-mechanical model for esophageal transport
Esophageal transport is a physiological process that mechanically transports
an ingested food bolus from the pharynx to the stomach via the esophagus, a
multi-layered muscular tube. This process involves interactions between the
bolus, the esophagus, and the neurally coordinated activation of the esophageal
muscles. In this work, we use an immersed boundary (IB) approach to simulate
peristaltic transport in the esophagus. The bolus is treated as a viscous fluid
that is actively transported by the muscular esophagus, which is modeled as an
actively contracting, fiber-reinforced tube. A simplified version of our model
is verified by comparison to an analytic solution to the tube dilation problem.
Three different complex models of the multi-layered esophagus, which differ in
their activation patterns and the layouts of the mucosal layers, are then
extensively tested. To our knowledge, these simulations are the first of their
kind to incorporate the bolus, the multi-layered esophagus tube, and muscle
activation into an integrated model. Consistent with experimental observations,
our simulations capture the pressure peak generated by the muscle activation
pulse that travels along the bolus tail. These fully resolved simulations
provide new insights into roles of the mucosal layers during bolus transport.
In addition, the information on pressure and the kinematics of the esophageal
wall due to the coordination of muscle activation is provided, which may help
relate clinical data from manometry and ultrasound images to the underlying
esophageal motor function
P53 inhibition exacerbates late-stage anthracycline cardiotoxicity
AIMS:
Doxorubicin (DOX) is an effective anti-cancer therapeutic, but is associated with both acute and late-stage cardiotoxicity. Children are particularly sensitive to DOX-induced heart failure. Here, the impact of p53 inhibition on acute vs. late-stage DOX cardiotoxicity was examined in a juvenile model.
METHODS AND RESULTS:
Two-week-old MHC-CB7 mice (which express dominant-interfering p53 in cardiomyocytes) and their non-transgenic (NON-TXG) littermates received weekly DOX injections for 5 weeks (25 mg/kg cumulative dose). One week after the last DOX treatment (acute stage), MHC-CB7 mice exhibited improved cardiac function and lower levels of cardiomyocyte apoptosis when compared with the NON-TXG mice. Surprisingly, by 13 weeks following the last DOX treatment (late stage), MHC-CB7 exhibited a progressive decrease in cardiac function and higher rates of cardiomyocyte apoptosis when compared with NON-TXG mice. p53 inhibition blocked transient DOX-induced STAT3 activation in MHC-CB7 mice, which was associated with enhanced induction of the DNA repair proteins Ku70 and Ku80. Mice with cardiomyocyte-restricted deletion of STAT3 exhibited worse cardiac function, higher levels of cardiomyocyte apoptosis, and a greater induction of Ku70 and Ku80 in response to DOX treatment during the acute stage when compared with control animals.
CONCLUSION:
These data support a model wherein a p53-dependent cardioprotective pathway, mediated via STAT3 activation, mitigates DOX-induced myocardial stress during drug delivery. Furthermore, these data suggest an explanation as to how p53 inhibition can result in cardioprotection during drug treatment and, paradoxically, enhanced cardiotoxicity long after the cessation of drug treatment
Surveillance of Smokeless Tobacco Products Sold in Massachusetts (1997-2010)
Background: Moist snuff and snus are smokeless tobacco products that are marketed toward smokers for use at times smoking is prohibited. Little information is available about the nicotine content and design features of these products, particularly snus.
Methods: Data on free nicotine levels and design features (pH, total nicotine content, tobacco leaf cut and flavor) of smokeless tobacco products were obtained from manufactures’ annual reports to Massachusetts Department of Public Health between 1997 and 2010. Descriptive statistics were provided overall, and by manufacturer and product type.
Results: Mean level of free nicotine in moist snuff remained relatively constant within the range of 3 to 5 mg/g between 1997 and 2010, although this varies by manufacturer, brand, and design characteristics. Mean free nicotine was higher in snus than in moist snuff and increased over time. Average free nicotine content of Swedish Match snus increased sharply since 2003 and reached \u3e6 mg/g in 2010 while that of American brands of snus decreased from 2.9 mg/g in 2001 to 1.7 mg/g in 2010. Swedish Match snus had significantly higher pH than American brands of snus and moist snuff, and experienced a sharp increase from 7.3 in 2003 to 8.3 in 2010. Wide variations in nicotine and pH levels were present among manufacturers. Free nicotine level was associated with pH level of both snus and moist snuff products, and with tobacco leaf-cut for moist snuff. The number of sub-brands of both snus and moist snuff products increased during the study period.
Conclusion: There was notable increasing trend in free nicotine concentration in Swedish Match snus that are marketed to US consumers. The increase in number sub-brands suggests greater marketing efforts by the manufacturers in recent years. Continued surveillance of smokeless tobacco products in MA is an important component of the State’s control effort
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