Alternative regulation of MYC in lung cancer

Lung cancer is the leading cause of cancer deaths in the United States, accounting for 27% of all cancer induced deaths1. In an attempt to create a effective targeted therapy for the treatment of lung cancer, a strategy used to treat an activated KrasG12D/+;p53 R172H/+ transgenic lung cancer mouse model was to deliver a known tumor suppressive microRNA (miRNA) to stop tumor growth. The tumor suppressive miRNA let-7 was lentivirally delivered in the form of its primary transcript, pri-let-7a-1, and resulted in increased lung size and inflammation compared to lungs exposed to a control lentivirus. It was identified that LIN28Btranscripts were elevated in this transgenic model2 and a truncated MYC protein product, separate from canonical MYC, was overexpressed with activation of the transgenic lung cancer mouse model. LIN28B is a pluripotent factor and post-transcriptional inhibitor of let-7 biogenesis 3–5. Therefore, it was hypothesized that the LIN28B mediated accumulation of pri-let-7a-1 transcripts promoted expression of the truncated MYC protein product, termed T-MYC. Through this work, it was determined that T-MYC expression is not dependent on the LIN28B mediated accumulation of pri-let-7a-1 transcripts and that T-MYC is likely not a variant of canonical MYC

Neutrino Mean Free Path in Neutron Stars

The Landau parameters of nuclear matter and neutron matter are extracted from the Brueckner theory including three-body forces. The dynamical response function to weak neutrino current is calculated in terms of the Landau Parameters in the RPA limit. Then, the neutrino mean free path in neutron stars is calculated for different conditions of density and temperature.Comment: 6 pages, 8 figures, for proceeding of International Symposium on Physics of Unstable Nuclei, Halong Bay(Vietnam) Nov. 2002. Espcrc1.sty is give

Psychological principles of successful aging technologies: A mini-review

Based on resource-oriented conceptions of successful life-span development, we propose three principles for evaluating assistive technology: (a) net resource release; (b) person specificity, and (c) proximal versus distal frames of evaluation. We discuss how these general principles can aid the design and evaluation of assistive technology in adulthood and old age, and propose two technological strategies, one targeting sensorimotor and the other cognitive functioning. The sensorimotor strategy aims at releasing cognitive resources such as attention and working memory by reducing the cognitive demands of sensory or sensorimotor aspects of performance. The cognitive strategy attempts to provide adaptive and individualized cuing structures orienting the individual in time and space by providing prompts that connect properties of the environment to the individual's action goals. We argue that intelligent assistive technology continuously adjusts the balance between `environmental support' and `self-initiated processing' in person-specific and aging-sensitive ways, leading to enhanced allocation of cognitive resources. Furthermore, intelligent assistive technology may foster the generation of formerly latent cognitive resources by activating developmental reserves (plasticity). We conclude that `lifespan technology', if co-constructed by behavioral scientists, engineers, and aging individuals, offers great promise for improving both the transition from middle adulthood to old age and the degree of autonomy in old age in present and future generations. Copyright (C) 2008 S. Karger AG, Basel

Force balance and membrane shedding at the Red Blood Cell surface

During the aging of the red-blood cell, or under conditions of extreme echinocytosis, membrane is shed from the cell plasma membrane in the form of nano-vesicles. We propose that this process is the result of the self-adaptation of the membrane surface area to the elastic stress imposed by the spectrin cytoskeleton, via the local buckling of membrane under increasing cytoskeleton stiffness. This model introduces the concept of force balance as a regulatory process at the cell membrane, and quantitatively reproduces the rate of area loss in aging red-blood cells.Comment: 4 pages, 3 figure

Radial Distribution of Dust Grains Around HR 4796A

We present high-dynamic-range images of circumstellar dust around HR 4796A that were obtained with MIRLIN at the Keck II telescope at lambda = 7.9, 10.3, 12.5 and 24.5 um. We also present a new continuum measurement at 350 um obtained at the Caltech Submillimeter Observatory. Emission is resolved in Keck images at 12.5 and 24.5 um with PSF FWHM's of 0.37" and 0.55", respectively, and confirms the presence of an outer ring centered at 70 AU. Unresolved excess infrared emission is also detected at the stellar position and must originate well within 13 AU of the star. A model of dust emission fit to flux densities at 12.5, 20.8, and 24.5 um indicates dust grains are located 4(+3/-2) AU from the star with effective size, 28+/-6 um, and an associated temperature of 260+/-40 K. We simulate all extant data with a simple model of exozodiacal dust and an outer exo-Kuiper ring. A two-component outer ring is necessary to fit both Keck thermal infrared and HST scattered-light images. Bayesian parameter estimates yield a total cross-sectional area of 0.055 AU^2 for grains roughly 4 AU from the star and an outer-dust disk composed of a narrow large-grain ring embedded within a wider ring of smaller grains. The narrow ring is 14+/-1 AU wide with inner radius 66+/-1 AU and total cross-sectional area 245 AU^2. The outer ring is 80+/-15 AU wide with inner radius 45+/-5 AU and total cross-sectional area 90 AU^2. Dust grains in the narrow ring are about 10 times larger and have lower albedos than those in the wider ring. These properties are consistent with a picture in which radiation pressure dominates the dispersal of an exo-Kuiper belt.Comment: Accepted by Astrophysical Journal (Part1) on September 9, 2004. 13 pages, 10 figures, 2 table

A blinded comparison of fluticasone propionate with budesonide via powder devices in adult patients with moderate-to-severe asthma: a clinical evaluation

In Vitro and in vivo data have demonstrated that there are detectable differences between inhaled corticosteroids commonly used to treat asthma. However, controversy still remains as to whether these differences translate into clinical benefits. This 12-week, international, randomized, doubleblind, parallel-group study was undertaken to compare the efficacy and safety of fluticasone propionate (FP) 800 μg daily, administered as a powder via the Diskhaler®, and budesonide (BUD) 1600 μg daily, administered using the Turbuhaler®, in adult patients with moderate-tosevere asthma. A total of 518 patients participated in the study, 256 of whom received FP and 262 BUD. Assessment of mean morning peak expiratory flow (PEF) over the 12-week treatment period revealed a statistically significant difference in efficacy between FP 800 μg daily and BUD 1600 μg daily in favour of FP (p = 0.003), with an overall improvement of 20.9 l/min with FP compared with 12.4 l/min on BUD. Statistically significant differences in favour of FP were seen over the 12 weeks for mean evening PEF (p = 0.04), diurnal PEF variation (p = 0.03) and percentage predicted PEF (p = 0.003), as well as forced expiratory volume (p = 0.008), forced vital capacity (p = 0.02) and PEF (p = 0.005) measured at clinic visits. The median percentage of symptom-free nights increased over the 12-week study period in both treatment groups, with similar changes seen for the median percentage of days with symptom score < 2, rescue medication use and exacerbations of asthma. The incidence of adverse events was found to be comparable in the two treatment groups. The geometric mean ratios of serum cortisol levels were found to be 1.03 for FP, indicating no mean hypothalamic-pituitary-adrenal axis suppression from baseline, and 0.93 for BUD (p = 0.0002 compared with FP). In summary, FP 800 μg daily showed a greater efficacy/safety ratio in the treatment of moderate-to-severe asthma than BUD 1600 μg daily

History of Plio-Pleistocene Climate in the Northeastern Atlantic, Deep Sea Drilling Project Hole 552A

DSDP Hole 552A, cored with the HPC on Hatton Drift, represents an almost complete and undisturbed sediment section spanning the late Neogene and Quaternary. Lithologic, faunal, isotopic, and paleomagnetic analyses indicate that the section represents the most complete deep sea record of climatic evolution hitherto recovered at high latitudes in the northern hemisphere. A glacial record of remarkable resolution for the late Pliocene and Pleistocene is provided by oxygen and carbon isotope ratios in benthic foraminifers. In the upper part of the section, the whole of the standard oxygen isotope record of the past million years is well preserved. The onset of ice-rafting and glacial-interglacial alternations occurs at about 2.4 m.y. ago