Phosphatase and tensin homolog (PTEN), which negatively regulates tumorigenic phosphatidylinositol (3,4,5)-trisphosphate (PIP3) signaling, is a commonly mutated tumor suppressor. The majority of ...cancer-associated PTEN mutations block its essential PIP3 phosphatase activity. However, there is a group of clinically identified PTEN mutations that maintain enzymatic activity, and it is unknown how these mutations contribute to tumor pathogenesis. Here, we show that these enzymatically competent PTEN mutants fail to translocate to the plasma membrane where PTEN converts PIP3 to PI(4,5)P2. Artificial membrane tethering of the PTEN mutants effectively restores tumor suppressor activity and represses excess PIP3 signaling in cells. Thus, our findings reveal a novel mechanism of tumorigenic PTEN deficiency.
The magnetic and crystallographic microstructures in Fe2.5Zn0.5O4 (FZO) wires fabricated using nano-imprint lithography, pulsed laser deposition and a molybdenum lift-off mask technique were studied ...by transmission electron microscopy (TEM). A process using a focused ion beam completely separated the FZO wires from the insulating MgO substrate, and accordingly allowed in-depth TEM studies of the domain structures. Observations using energy-filtered TEM demonstrated good crystallinity of the FZO wires. Both Lorentz microscopy and electron holography studies revealed unexpectedly small magnetic domains (∼100nm or smaller) due to a significant interaction with antiphase boundaries. The role of antiphase boundaries on the functionalities observed in the constrained wires (e.g., nonlinear I–V characteristics and large magnetoresistance) is discussed on the basis of these microscopic observations.
The Cosmic-Ray Energetics And Mass balloon-borne experiment has been launched twice in Antarctica, first in December 2004 and again in December 2005. It circumnavigated the South Pole three times ...during the first flight, which set a flight duration record of 42 days. A cumulative duration of 70 days within 13 months was achieved when the second flight completed 28 days during two circumnavigations of the Pole on 13 January 2006. Both the science instrument and support systems functioned extremely well, and a total 117
GB of data including 67 million science events were collected during these two flights. Preliminary analysis indicates that the data extend well above 100
TeV and follow reasonable power laws. The payload recovered from the first flight has been refurbished for the third flight in 2007, whereas the payload from the second flight is being refurbished to be ready for the fourth flight in 2008. Each flight will extend the reach of precise cosmic-ray composition measurements to energies not previously possible.
The goals of the Mix Campaign are to determine how mix affects performance, locate the "mix cliff", locate the source of the mix, and develop mitigation methods that allow performance to be ...increased. We have used several different drive pulse shapes and capsule designs in the Mix Campaign, to understand sensitivity to drive peak power, level of coast, rise time to peak power, adiabat, and dopant level in the capsule. Ablator material mixing into the hot spot has been shown conclusively with x-ray spectroscopy. The observed neutron yield drops steeply when the hot spot mix mass becomes too large. The mix appears to be driven by ablation- front Rayleigh-Taylor instabilities. A high foot, higher adiabat drive has a more stable ablation front and has allowed the mix mass in the hot spot to be reduced significantly. Two recent high foot shots achieved neutron yields > 1015 and measured neutron yield over clean 1D simulation (YOC) > 50%, which was one of the central goals of the Mix Campaign.
A detailed study of edge-localized mode (ELM) dynamics in the KSTAR tokamak is performed using a two-dimensional (2D) electron cyclotron emission imaging (ECEI) diagnostic system. Highly coherent ...mode structures rotating in the poloidal view plane are routinely observed in the inter-ELM pedestal region where the optical thickness for ECE rapidly changes and the interpretation of emission intensity is complicated. To have confidence on the measurements, the observed images are compared with synthetic images of the ELM structure deduced from three-field BOUT++ simulations. The synthetic process considers instrumental effects of the ECEI diagnostic, intrinsic broadening of the ECE and background noise. The synthetic 2D images highly resemble the observed structure, providing confidence that the ELM dynamics can be visualized by ECEI.
We report searches for B0 → invisible and B0 → invisible + γ decays, where the energy of the photon is required to be larger than 0.5 GeV. These results are obtained from a 711 fb−1 data sample that ...contains 772 × 106 BB pairs and was collected near the Υ(4S) resonance with the Belle detector at the KEKB e+e− collider. We observe no significant signal for either decay and set upper limits on their branching fractions at 90% confidence level of B(B0 → invisible ) < 7.8 × 10−5 and B(B0 → invisible + γ ) < 1.6 × 10−5.
The extension of both median and maximum lifespan and the suppression of age-related diseases in laboratory animals by reduced food intake, i.e., calorie restriction (CR) are regarded as hallmarks of ...CR's anti-aging action. The diverse efficacy of CR to counteract aging effects and its experimental reproducibility has made it the gold standard of many aging intervention studies of recent years. Although CR originally was used as a tool to perturb the aging process of laboratory animals as to uncover clues of underlying mechanisms of aging processes, current CR research interests have shifted to the retardation of aging-related functional decline and the prevention of age-related diseases. Advances in CR research on non-human primates and recent endeavors using human subjects offer a promising outlook for CR's beneficial effects in healthy human aging.
In this review, several major issues related to CR's anti-aging mechanisms are discussed by highlighting the importance of modulating deleterious chronic inflammation at molecular levels and the impact of epigenetic chromatin and histone modifications by CR at the ultimate control sites of gene expression. The recent research on rapamycin as a CR mimetic is summarized and a brief description of intermittent feeding patterns is reviewed in comparison to the CR effect.
► Several major issues related to CR’s anti-aging mechanisms are discussed. ► The impacts of epigenetic regulation of CR’s anti-aging mechanisms are discussed. ► The recent research on rapamycin as a CR mimetic is summarized. ► Brief description and effects of intermittent feeding patterns are reviewed.
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