62 research outputs found
Inhibition of the p53 E3 Ligase HDM-2 Induces Apoptosis and DNA Damage-Independent p53 Phosphorylation in Mantle Cell Lymphoma
The ubiquitin-proteasome pathway has been validated as a target in non-Hodgkin lymphoma through demonstration of the activity of the proteasome inhibitor bortezomib
A 115-bp MethyLight assay for detection of p16 (CDKN2A) methylation as a diagnostic biomarker in human tissues
<p>Abstract</p> <p>Background</p> <p><it>p16 </it>Methylation is a potential biomarker for prediction of malignant transformation of epithelial dysplasia. A probe-based, quantitative, methylation-specific PCR (MSP) called MethyLight may become an eligible method for detecting this marker clinically. We studied oral mucosa biopsies with epithelial dysplasia from 78 patients enrolled in a published 4-years' followup cohort, in which cancer risk for patients with <it>p16 </it>methylation-positive dysplasia was significantly higher than those without <it>p16 </it>methylation (by 150-bp MSP and bisulfite sequencing; +133 ~ +283, transcription starting site, +1). The <it>p16 </it>methylation status in samples (<it>N </it>= 102) containing sufficient DNA was analyzed by the 70-bp classic (+238 ~ +307) and 115-bp novel (+157 ~ +272) MethyLight assays, respectively.</p> <p>Results</p> <p><it>p16 </it>Methylation was detectable in 75 samples using the classic MethyLight assay. The methylated-<it>p16 </it>positive rate and proportion of methylated-<it>p16 </it>by the MethyLight in MSP-positive samples were higher than those in MSP-negative samples (positive rate: 37/44 vs. 38/58, <it>P</it>=0.035, two-sided; proportion [median]: 0.78 vs. 0.02, <it>P <</it>0.007). Using the published results of MSP as a golden standard, we found sensitivity, specificity, and accuracy for this MethyLight assay to be 70.5%, 84.5%, and 55.0%, respectively. Because amplicon of the classic MethyLight procedure only partially overlapped with the MSP amplicon, we further designed a 115-bp novel MethyLight assay in which the amplicon on the sense-strand fully overlapped with the MSP amplicon on the antisense-strand. Using the 115-bp MethyLight assay, we observed methylated-<it>p16 </it>in 26 of 44 MSP-positive samples and 2 of 58 MSP-negative ones (<it>P </it>= 0.000). These results were confirmed with clone sequencing. Sensitivity, specificity, and accuracy using the 115-bp MethyLight assay were 59.1%, 98.3%, and 57.4%, respectively. Significant differences in the oral cancer rate were observed during the followup between patients (â„60 years) with and without methylated-<it>p16 </it>as detected by the 115-bp MethyLight assay (6/8 vs. 6/22, P = 0.034, two-sided).</p> <p>Conclusions</p> <p>The 115-bp MethyLight assay is a useful and practical assay with very high specificity for the detection of <it>p16 </it>methylation clinically.</p
LSST: from Science Drivers to Reference Design and Anticipated Data Products
(Abridged) We describe here the most ambitious survey currently planned in
the optical, the Large Synoptic Survey Telescope (LSST). A vast array of
science will be enabled by a single wide-deep-fast sky survey, and LSST will
have unique survey capability in the faint time domain. The LSST design is
driven by four main science themes: probing dark energy and dark matter, taking
an inventory of the Solar System, exploring the transient optical sky, and
mapping the Milky Way. LSST will be a wide-field ground-based system sited at
Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m
effective) primary mirror, a 9.6 deg field of view, and a 3.2 Gigapixel
camera. The standard observing sequence will consist of pairs of 15-second
exposures in a given field, with two such visits in each pointing in a given
night. With these repeats, the LSST system is capable of imaging about 10,000
square degrees of sky in a single filter in three nights. The typical 5
point-source depth in a single visit in will be (AB). The
project is in the construction phase and will begin regular survey operations
by 2022. The survey area will be contained within 30,000 deg with
, and will be imaged multiple times in six bands, ,
covering the wavelength range 320--1050 nm. About 90\% of the observing time
will be devoted to a deep-wide-fast survey mode which will uniformly observe a
18,000 deg region about 800 times (summed over all six bands) during the
anticipated 10 years of operations, and yield a coadded map to . The
remaining 10\% of the observing time will be allocated to projects such as a
Very Deep and Fast time domain survey. The goal is to make LSST data products,
including a relational database of about 32 trillion observations of 40 billion
objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures
available from https://www.lsst.org/overvie
Differentiation and adaptation epigenetic networks: Translational research in gastric carcinogenesis
Beyond pandas, the need for a standardized monitoring protocol for large mammals in Chinese nature reserves
Software-defined Vehicular Ad Hoc Networks with Trust Management
With the rising interest of expedient, safe, and high-efficient transportation, vehicular ad hoc networks (VANETs) have turned into a critical technology in smart transportation systems. Because of the high mobility of nodes, VANETs are vulnerable to security attacks. In this paper, we propose a novel framework of software-defined VANETs with trust management. Specifically, we separate the forwarding plane in VANETs from the control plane, which is responsible for the control functionality, such as routing protocols and trust management in VANETs. Using the on-demand distance vector routing (TAODV) protocol as an example, we present a routing protocol named software-defined trust based ad hoc on-demand distance vector routing (SD-TAODV). Simulation results are presented to show the effectiveness of the proposed software-defined VANETs with trust management
Inhibition of the p53 E3 Ligase HDM-2 Induces Apoptosis and DNA DamageâIndependent p53 Phosphorylation in Mantle Cell Lymphoma
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