5,416 research outputs found

    Epigenetic inactivation of the miR-34a in hematological malignancies

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    miR-34a is a transcriptional target of p53 and implicated in carcinogenesis. We studied the role of miR-34a methylation in a panel of hematological malignancies including acute leukemia [acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)], chronic leukemia [chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML)], multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). The methylation status of miR-34a promoter was studied in 12 cell lines and 188 diagnostic samples by methylation-specific polymerase chain reaction. miR-34a promoter was unmethylated in normal controls but methylated in 75% lymphoma and 37% myeloma cell lines. Hypomethylating treatment led to re-expression of pri-miR-34a transcript in lymphoma cells with homozygous miR-34a methylation. In primary samples at diagnosis, miR-34a methylation was detected in 4% CLL, 5.5% MM samples and 18.8% of NHL at diagnosis but none of ALL, AML and CML (P = 0.011). In MM patients with paired samples, miR-34a methylation status remained unchanged at progression. Amongst lymphoid malignancies, miR-34a was preferentially methylated in NHL (P = 0.018), in particular natural killer (NK)/T-cell lymphoma. In conclusion, amongst hematological malignancies, miR-34a methylation is preferentially hypermethylated in NHL, in particular NK/T-cell lymphoma, in a tumor-specific manner, therefore the role of miR-34a in lymphomagenesis warrants further study. © The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]

    The pseudokinase CaMKv is required for the activity-dependent maintenance of dendritic spines

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    Inference of person-to-person transmission of COVID-19 reveals hidden super-spreading events during the early outbreak phase

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    Coronavirus disease 2019 (COVID-19) was first identified in late 2019 in Wuhan, Hubei Province, China and spread globally in months, sparking worldwide concern. However, it is unclear whether super-spreading events occurred during the early outbreak phase, as has been observed for other emerging viruses. Here, we analyse 208 publicly available SARS-CoV-2 genome sequences collected during the early outbreak phase. We combine phylogenetic analysis with Bayesian inference under an epidemiological model to trace person-to-person transmission. The dispersion parameter of the offspring distribution in the inferred transmission chain was estimated to be 0.23 (95% CI: 0.13–0.38), indicating there are individuals who directly infected a disproportionately large number of people. Our results showed that super-spreading events played an important role in the early stage of the COVID-19 outbreak

    Mobile measurements of microclimatic variables through the central area of Singapore: An analysis from the pedestrian perspective

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    High-density cities, such as Singapore, are currently facing the urban heat island (UHI) effect, a phenomenon that leads to higher air and surface temperatures within the urban area in comparison to the surroundings and is one of the most critical anthropogenic climate change-related environmental issues for contemporary high-density cities. This study aims to investigate the effect of different urban morphologies such as high-rise and low-rise buildings, green areas, and water bodies on the urban microclimate in Singapore. Mobile measurements taken from a pedestrian perspective were conducted for the first time in the central area of Singapore to explore the severity of the UHI effect through distinctive urban morphologies. The Sky View Factor (SVF) was the metric used to quantify these characteristics. During daytime, the air temperature was higher when SVF increased, except for the water body area. Shading showed to be an important factor to decreasing air temperature in the tropics. Reductions by up to 4.5 ºC were observed due to the buildings shading during daytime, while the cooling effect of vegetation reduced the air temperature by up to 4 ºC during the daytime and 1 ºC at night-time. Thus, this study revealed a strong relationship between the decrease in air temperature and greenery coverage in the city. Therefore, understanding the relationship between urban morphology and microclimate conditions may better drive sustainable urban planning and development in the tropics. Finally, it was demonstrated the importance of using mobile monitoring to retrieve granular data that allows identifying specific environmental issues on a hyperlocal scale, which would not be recognised through other monitoring techniques.This work was partially funded by the Ministerio de Ciencia, Innovación y Universidades de España (RTI2018-093849-B-C31 - MCIU/AEI/FEDER, UE) and by the Ministerio de Ciencia, Innovación y Universidades - Agencia Estatal de Investigación (AEI) (RED2018-102431-T). The authors would like to thank the Catalan Government for the quality accreditation given to their research group (2017 SGR 1537). GREiA is certified agent TECNIO in the category of technology developers from the Government of Catalonia. This work is partially supported by ICREA under the ICREA Academia programme

    Nitrate Anomaly in the Upper Nutricline in the Northern South China Sea - Evidence for Nitrogen Fixation

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    [1] Up to 2 μM of nitrate anomaly, N*, were found in the upper nutricline at the South East Asia Time-series Study (SEATS) site in the northern South China Sea (SCS). These concentrations were among the higher values reported in the Pacific and indicate the significant contribution of the remineralization of nitrogen-rich organic matter formed by nitrogen fixation to the nutrient dynamics of the area. The concentrations were systematically higher, by up to 2.5 μM, in the Fall through the early Spring, during the northeast monsoon, than in the Summer, suggesting that the impact of nitrogen fixation was higher during the former time period. This pattern is in phase with that of the atmospheric deposition of Asian dust to the northern SCS. The coherence is consistent with a coupling between nitrogen fixation and the availability of atmospherically derived iron

    A Relationship: Word Alignment, Phrase Table, and Translation Quality

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    In the last years, researchers conducted several studies to evaluate the machine translation quality based on the relationship between word alignments and phrase table. However, existing methods usually employ ad-hoc heuristics without theoretical support. So far, there is no discussion from the aspect of providing a formula to describe the relationship among word alignments, phrase table, and machine translation performance. In this paper, on one hand, we focus on formulating such a relationship for estimating the size of extracted phrase pairs given one or more word alignment points. On the other hand, a corpus-motivated pruning technique is proposed to prune the default large phrase table. Experiment proves that the deduced formula is feasible, which not only can be used to predict the size of the phrase table, but also can be a valuable reference for investigating the relationship between the translation performance and phrase tables based on different links of word alignment. The corpus-motivated pruning results show that nearly 98% of phrases can be reduced without any significant loss in translation quality
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