Argon protects against hypoxic-ischemic brain injury in neonatal rats through activation of Nuclear factor (erythroid-derived 2)-like 2

Perinatal hypoxic ischaemic encephalopathy (HIE) has a high mortality rate with neuropsychological impairment. This study investigated the neuroprotective effects of argon against neonatal hypoxic-ischaemic brain injury. In vitro cortical neuronal cell cultures derived from rat foetuses were subjected to an oxygen and glucose deprivation (OGD) challenge for 90 minutes and then exposed to 70% argon or nitrogen with 5% carbon dioxide and balanced with oxygen for 2 hours. In vivo, seven-day-old rats were subjected to unilateral common carotid artery ligation followed by hypoxic (8% oxygen balanced with nitrogen) insult for 90 minutes. They were exposed to 70% argon or nitrogen balanced with oxygen for 2 hours. In vitro, argon treatment of cortical neuronal cultures resulted in a significant increase of p-mTOR and Nuclear factor (erythroid-derived 2)-like 2(Nrf2) and protection against OGD challenge. Inhibition of m-TOR through Rapamycin or Nrf2 through siRNA abolished argon-mediated cyto-protection. In vivo, argon exposure significantly enhanced Nrf2 and its down-stream effector NAD(P)H Dehydrogenase, Quinone 1(NQO1) and superoxide dismutase 1(SOD1). Oxidative stress, neuroinflammation and neuronal cell death were significantly decreased and brain infarction was markedly reduced. Blocking PI-3K through wortmannin or ERK1/2 through U0126 attenuated argon-mediated neuroprotection. These data provide a new molecular mechanism for the potential application of Argon as a neuroprotectant in HIE

Two scenarios for avalanche dynamics in inclined granular layers

We report experimental measurements of avalanche behavior of thin granular layers on an inclined plane for low volume flow rate. The dynamical properties of avalanches were quantitatively and qualitatively different for smooth glass beads compared to irregular granular materials such as sand. Two scenarios for granular avalanches on an incline are identified and a theoretical explanation for these different scenarios is developed based on a depth-averaged approach that takes into account the differing rheologies of the granular materials.Comment: 4 pages, 4 figures, accepted to Phys. Rev. Let

Vaginal cancer in patient presenting with advanced pelvic organ prolapse: case report and literature review

Background: Vaginal cancer presenting concurrently with stage 4 uterovaginal prolapse is a rare occurrence, representing less than 1% of all gynecologic malignancies. Case: We review the case of an 82-year-old woman who presented for care of prolapse. Examination demonstrated complete uterovaginal prolapse and a vaginal ulcer, later confirmed to be vaginal cancer. Conclusion: The management of these complicated patients is limited by a lack of data available to guide treatment. This case and the literature review highlight the need for a multi-disciplinary approach to treatment and a high level of clinical suspicion for diagnosis of these very challenging cases

Calibration of the LIGO displacement actuators via laser frequency modulation

We present a frequency modulation technique for calibration of the displacement actuators of the LIGO 4-km-long interferometric gravitational-wave detectors. With the interferometer locked in a single-arm configuration, we modulate the frequency of the laser light, creating an effective length variation that we calibrate by measuring the amplitude of the frequency modulation. By simultaneously driving the voice coil actuators that control the length of the arm cavity, we calibrate the voice coil actuation coefficient with an estimated 1-sigma uncertainty of less than one percent. This technique enables a force-free, single-step actuator calibration using a displacement fiducial that is fundamentally different from those employed in other calibration methods.Comment: 10 pages, 5 figures, submitted to Classical and Quantum Gravit

Flavor changing interactions mediated by scalars at the weak scale

The quark and lepton mass matrices possess approximate flavor symmetries. Several results follow if the interactions of new scalars possess these approximate symmetries. Present experimental bounds allow these exotic scalars to have a weak scale mass. The Glashow-Weinberg criterion is rendered unnecessary. Finally, rare leptonic B meson decays provide powerful probes of these scalars, especially if they are leptoquarks.Comment: 13 pages, report LBL-3234

Mechanistic mathematical model of polarity in yeast

The establishment of cell polarity involves positive-feedback mechanisms that concentrate polarity regulators, including the conserved GTPase Cdc42p, at the “front” of the polarized cell. Previous studies in yeast suggested the presence of two parallel positive-feedback loops, one operating as a diffusion-based system, and the other involving actin-directed trafficking of Cdc42p on vesicles. F-actin (and hence directed vesicle traffic) speeds fluorescence recovery of Cdc42p after photobleaching, suggesting that vesicle traffic of Cdc42p contributes to polarization. We present a mathematical modeling framework that combines previously developed mechanistic reaction-diffusion and vesicle-trafficking models. Surprisingly, the combined model recapitulated the observed effect of vesicle traffic on Cdc42p dynamics even when the vesicles did not carry significant amounts of Cdc42p. Vesicle traffic reduced the concentration of Cdc42p at the front, so that fluorescence recovery mediated by Cdc42p flux from the cytoplasm took less time to replenish the bleached pool. Simulations in which Cdc42p was concentrated into vesicles or depleted from vesicles yielded almost identical predictions, because Cdc42p flux from the cytoplasm was dominant. These findings indicate that vesicle-mediated delivery of Cdc42p is not required to explain the observed Cdc42p dynamics, and raise the question of whether such Cdc42p traffic actually contributes to polarity establishment

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Contains reports on three research projects.Lincoln Laboratory (Purchase Order DDL B-00368)United States ArmyUnited States NavyUnited States Air Force (Contract AF19(604)-7400)National Institutes of Health (Grant MH-04737-02)National Science Foundation (Grant G-16526

Subdiffusive axial transport of granular materials in a long drum mixer

Granular mixtures rapidly segregate radially by size when tumbled in a partially filled horizontal drum. The smaller component moves toward the axis of rotation and forms a buried core, which then splits into axial bands. Models have generally assumed that the axial segregation is opposed by diffusion. Using narrow pulses of the smaller component as initial conditions, we have characterized axial transport in the core. We find that the axial advance of the segregated core is well described by a self-similar concentration profile whose width scales as $t^\alpha$, with $\alpha \sim 0.3 < 1/2$. Thus, the process is subdiffusive rather than diffusive as previously assumed. We find that $\alpha$ is nearly independent of the grain type and drum rotation rate within the smoothly streaming regime. We compare our results to two one-dimensional PDE models which contain self-similarity and subdiffusion; a linear fractional diffusion model and the nonlinear porous medium equation.Comment: 4 pages, 4 figures, 1 table. Submitted to Phys Rev Lett. For more info, see http://www.physics.utoronto.ca/nonlinear