2,068 research outputs found

    On soft iterative decoding for ternary recording systems with RLL constraints

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    In this paper, we investigate the soft iterative decoding technique for ternary recoding systems with run-length-limited (RLL) constraints. We employ a simple binary-to-ternary RLL encoder following the LDPC (low density parity check) encoder. In the decoder, the iteratively passing of soft information between the LDPC decoder and a detector is used, where the detector is constructed for a combination of the RLL encoder, PLM (pulse length modulation) precoder and the partial response channel. We provide two different decoding algorithms. For one of the decoding algorithm, we are able to obtain bit-error-rate performance which is inferior to the comparable system without considering the RLL constraint for the high sign-to-noise ratio (SNR) regime and is better for the low-to-moderate SNR regime

    Substrate Specificity and Plasticity of FERM-Containing Protein Tyrosine Phosphatases

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    SummaryEpidermal growth factor receptor (EGFR) pathway substrate 15 (Eps15) is a newly identified substrate for protein tyrosine phosphatase N3 (PTPN3), which belongs to the FERM-containing PTP subfamily comprising five members including PTPN3, N4, N13, N14, and N21. We solved the crystal structures of the PTPN3-Eps15 phosphopeptide complex and found that His812 of PTPN3 and Pro850 of Eps15 are responsible for the specific interaction between them. We defined the critical role of the additional residue Tyr676 of PTPN3, which is replaced by Ile939 in PTPN14, in recognition of tyrosine phosphorylated Eps15. The WPD loop necessary for catalysis is present in all members but not PTPN21. We identified that Glu instead of Asp in the WPE loop contributes to the catalytic incapability of PTPN21 due to an extended distance beyond protonation targeting a phosphotyrosine substrate. Together with in vivo validations, our results provide novel insights into the substrate specificity and plasticity of FERM-containing PTPs

    Elevated BCRP/ABCG2 Expression Confers Acquired Resistance to Gefitinib in Wild-Type EGFR-Expressing Cells

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    The sensitivity of non-small cell lung cancer (NSCLC) patients to EGFR tyrosine kinase inhibitors (TKIs) is strongly associated with activating EGFR mutations. Although not as sensitive as patients harboring these mutations, some patients with wild-type EGFR (wtEGFR) remain responsive to EGFR TKIs, suggesting that the existence of unexplored mechanisms renders most of wtEGFR-expressing cancer cells insensitive.Here, we show that acquired resistance of wtEGFR-expressing cancer cells to an EGFR TKI, gefitinib, is associated with elevated expression of breast cancer resistance protein (BCRP/ABCG2), which in turn leads to gefitinib efflux from cells. In addition, BCRP/ABCG2 expression correlates with poor response to gefitinib in both cancer cell lines and lung cancer patients with wtEGFR. Co-treatment with BCRP/ABCG2 inhibitors enhanced the anti-tumor activity of gefitinib.Thus, BCRP/ABCG2 expression may be a predictor for poor efficacy of gefitinib treatment, and targeting BCRP/ABCG2 may broaden the use of gefitinib in patients with wtEGFR

    東澳嶺崩塌地之地形演育分析

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    梅姬颱風 (2010) 與東北季風之共伴效應於台灣宜蘭縣蘇澳地區帶來了豐沛降雨,高累積雨量造成了台9 線蘇花公路群集性土砂災害,尤其在115.9K 上邊坡更誘發了約210 萬m3 之大規模崩塌土砂災害。本文從現地地質調查、致災機制、水文分析及遙測影像判釋等面向進行討論。由降雨-延時-頻率分析得知近年來誘發重大崩塌事件的雨量皆高於200 年回歸週期,並獲致良好判別致災雨場之I-R 圖降雨臨界線關係(Re+53.5Iave=1,146)。多時期遙測影像判釋指出東澳嶺坡頂之弧型張力裂隙仍有持續溯源發展之趨勢。裸露崩塌地不連續面方位密度分布圖之裂隙位態大致與區域地質構造位態 (N70°W) 相近,顯示本區域崩塌主要仍受地質條件主控。此外,蝕溝溯源侵蝕、剪裂帶分布及凹漥坡型亦為影響研究區崩塌地地貌變遷之重要因子,而前期地震或長延時高強度降雨則為外在促崩因子。Typhoon Megi coupled with the northeastern monsoon induced an extreme rainfall of 939 mm on the Suao area, Yilan County, in eastern Taiwan on October 21st, 2010, causing the Dong-Ao Peak landslide of 2.1 million m3 along the coastal Su-Hua Section of Highway Route 9. This study adopts a geological survey, rainfall data, satellite images, orthophotos, and high-resolution DEM based on airborne laser scanner surveys to quantify the morphological changes before and after landslide events following major rainfall events since 2010. Rainfall frequency analysis indicates the cumulative precipitation triggering landslide events is greater than the 200-year return period. In addition, both the entrainment effect of debris flow and toe erosion on the down-slope is shown to induce regressive sliding failure at the adjacent roadbed. The results suggest that geological factors such as head-cutting erosion and the concave landform shape the landform evolution of the catchment. The occurrence of landslides also depends on antecedent earthquake events and extreme intense rainfalls

    LAMOST Experiment for Galactic Understanding and Exploration (LEGUE) The survey science plan

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    We describe the current plans for a spectroscopic survey of millions of stars in the Milky Way galaxy using the Guo Shou Jing Telescope (GSJT, formerly the Large Area Multi-Object Spectroscopic Telescope - LAMOST). The survey will obtain spectra for 2.5 million stars brighter than r<19r<19 during dark/grey time, and 5 million stars brighter than r<17r<17 or J<16J<16 on nights that are moonlit or have low transparency. The survey will begin in fall of 2012, and will run for at least four years. The telescope design constrains the optimal declination range for observations to 10<δ<5010^\circ<\delta<50^\circ, and site conditions lead to an emphasis on stars in the direction of the Galactic anticenter. The survey is divided into three parts with different target selection strategies: disk, anticenter, and spheroid. The resulting dataset will be used to study the merger history of the Milky Way, the substructure and evolution of the disks, the nature of the first generation of stars through identification of the lowest metallicity stars, and star formation through study of open clusters and the OB associations. Detailed design of the LEGUE survey will be completed after a review of the results of the pilot survey in summer 2012.Comment: 19 pages, 1 figure, accepted for publication in RA

    IKKβ Suppression of TSC1 Links Inflammation and Tumor Angiogenesis via the mTOR Pathway

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    SummaryTNFα has recently emerged as a regulator linking inflammation to cancer pathogenesis, but the detailed cellular and molecular mechanisms underlying this link remain to be elucidated. The tuberous sclerosis 1 (TSC1)/TSC2 tumor suppressor complex serves as a repressor of the mTOR pathway, and disruption of TSC1/TSC2 complex function may contribute to tumorigenesis. Here we show that IKKβ, a major downstream kinase in the TNFα signaling pathway, physically interacts with and phosphorylates TSC1 at Ser487 and Ser511, resulting in suppression of TSC1. The IKKβ-mediated TSC1 suppression activates the mTOR pathway, enhances angiogenesis, and results in tumor development. We further find that expression of activated IKKβ is associated with TSC1 Ser511 phosphorylation and VEGF production in multiple tumor types and correlates with poor clinical outcome of breast cancer patients. Our findings identify a pathway that is critical for inflammation-mediated tumor angiogenesis and may provide a target for clinical intervention in human cancer

    Urinary levels of organophosphate flame retardants metabolites in a young population from Southern Taiwan and potential health effects

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    BackgroundOrganophosphate flame retardants (OPFRs) are widely distributed in the environment and their metabolites are observed in urine, but little is known regarding OPFRs in a broad-spectrum young population from newborns to those aged 18 years.ObjectivesInvestigate urinary levels of OPFRs and OPFR metabolites in Taiwanese infants, young children, schoolchildren, and adolescents within the general population.MethodsDifferent age groups of subjects (n=136) were recruited from southern Taiwan to detect 10 OPFR metabolites in urine samples. Associations between urinary OPFRs and their corresponding metabolites and potential health status were also examined.ResultsThe mean level of urinary Σ10 OPFR in this broad-spectrum young population is 2.25 μg/L (standard deviation (SD) of 1.91 μg/L). Σ10 OPFR metabolites in urine are 3.25 ± 2.84, 3.06 ± 2.21, 1.75 ± 1.10, and 2.32 ± 2.29 μg/L in the age groups comprising of newborns, 1-5 year-olds, 6-10 year-olds, and 11-18 year-olds, respectively, and borderline significant differences were found in the different age groups (p=0.125). The OPFR metabolites of TCEP, BCEP, DPHP, TBEP, DBEP, and BDCPP predominate in urine and comprise more than 90% of the total. TBEP was highly correlated with DBEP in this population (r=0.845, p&lt;0.001). The estimated daily intake (EDI) of Σ5OPFRs (TDCPP, TCEP, TBEP, TNBP, and TPHP) was 2,230, 461, 130, and 184 ng/kg bw/day for newborns, 1-5 yr children, 6-10 yr children, and 11-17 yr adolescents, respectively. The EDI of Σ5OPFRs for newborns was 4.83-17.2 times higher than the other age groups. Urinary OPFR metabolites are significantly correlated with birth length and chest circumference in newborns.ConclusionTo our knowledge, this is the first investigation of urinary OPFR metabolite levels in a broad-spectrum young population. There tended to be higher exposure rates in both newborns and pre-schoolers, though little is known about their exposure levels or factors leading to exposure in the young population. Further studies should clarify the exposure levels and factor relationships
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