154,468 research outputs found

    Effect of baseline meteorological data selection on hydrological modelling of climate change scenarios

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    This study evaluates how differences in hydrological model parameterisation resulting from the choice of gridded global precipitation data sets and reference evapotranspiration (ETo) equations affects simulated climate change impacts, using the north western Himalayan Beas river catchment as a case study. Six combinations of baseline precipitation data (the Tropical Rainfall Measuring Mission (TRMM) and the Asian Precipitation – Highly Resolved Observational Data Integration Towards Evaluation of Water Resources (APHRODITE)) and Reference Evapotranspiration equations of differing complexity and data requirements (Penman-Monteith, Hargreaves –Samani and Priestley – Taylor) were used in the calibration of the HySim model. Although the six validated hydrological models had similar historical model performance (Nash–Sutcliffe model efficiency coefficient (NSE) from 0.64-0.70), impact response surfaces derived using a scenario neutral approach demonstrated significant deviations in the models’ responses to changes in future annual precipitation and temperature. For example, the change in Q10 varies between -6.5 % to -11.5% in the driest and coolest climate change simulation and +79% to +118% in the wettest and hottest climate change simulation among the six models. The results demonstrate that the baseline meteorological data choices made in model construction significantly condition the magnitude of simulated hydrological impacts of climate change, with important implications for impact study design.NER

    Importin-beta and CRM1 control a RANBP2 spatiotemporal switch essential for mitotic kinetochore function

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    Protein conjugation with small ubiquitin-related modifier (SUMO) is a post-translational modification that modulates protein interactions and localisation. RANBP2 is a large nucleoporin endowed with SUMO E3 ligase and SUMO-stabilising activity, and is implicated in some cancer types. RANBP2 is part of a larger complex, consisting of SUMO-modified RANGAP1, the GTP-hydrolysis activating factor for the GTPase RAN. During mitosis, the RANBP2–SUMO-RANGAP1 complex localises to the mitotic spindle and to kinetochores after microtubule attachment. Here, we address the mechanisms that regulate this localisation and how they affect kinetochore functions. Using proximity ligation assays, we find that nuclear transport receptors importin-β and CRM1 play essential roles in localising the RANBP2–SUMO-RANGAP1 complex away from, or at kinetochores, respectively. Using newly generated inducible cell lines, we show that overexpression of nuclear transport receptors affects the timing of RANBP2 localisation in opposite ways. Concomitantly, kinetochore functions are also affected, including the accumulation of SUMO- conjugated topoisomerase-IIα and stability of kinetochore fibres. These results delineate a novel mechanism through which nuclear transport receptors govern the functional state of kinetochores by regulating the timely deposition of RANBP2

    Immigrant Entrepreneurs in the Massachusetts Biotechnology Industry (2007)

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    Immigrant entrepreneurs are co-founders in 25.7 percent of Massachusetts Biotechnology firms. In 2006, these immigrant-founded biotechnology companies produced over $7.6 billion dollars in sales and employed over 4,000 workers. The foreign-born founders came from across the globe but in larger numbers from Europe, Canada or Asia. Their firms specialize in the most complex, risky, life science-intensive aspects of biotechnology to seek knowledge directly applicable to human health. Biotechnology is a crucial industry for Massachhusetts and the evidence strongly suggests that immigrants have been key contributors to this industry by establishing new businesses as well as bringing intellectual capital and thereby contributing significantly to the overall economic growth of the Commonwealth

    Approximating Word Ranking and Negative Sampling for Word Embedding

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    CBOW (Continuous Bag-Of-Words) is one of the most commonly used techniques to generate word embeddings in various NLP tasks. However, it fails to reach the optimal performance due to uniform involvements of positive words and a simple sampling distribution of negative words. To resolve these issues, we propose OptRank to optimize word ranking and approximate negative sampling for bettering word embedding. Specifically, we first formalize word embedding as a ranking problem. Then, we weigh the positive words by their ranks such that highly ranked words have more importance, and adopt a dynamic sampling strategy to select informative negative words. In addition, an approximation method is designed to efficiently compute word ranks. Empirical experiments show that OptRank consistently outperforms its counterparts on a benchmark dataset with different sampling scales, especially when the sampled subset is small. The code and datasets can be obtained from https://github.com/ouououououou/OptRank

    Thermoconditional modulation of the pleiotropic sensitivity phenotype by the Saccharomyces cerevisiae PRP19 mutant allele pso4-1

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    The conditionally-lethal pso4-1 mutant allele of the spliceosomal-associated PRP19 gene allowed us to study this gene’s influence on pre-mRNA processing, DNA repair and sporulation. Phenotypes related to intron-containing genes were correlated to temperature. Splicing reporter systems and RT–PCR showed splicing efficiency in pso4-1 to be inversely correlated to growth temperature. A single amino acid substitution, replacing leucine with serine, was identified within the N-terminal region of the pso4-1 allele and was shown to affect the interacting properties of Pso4-1p. Amongst 24 interacting clones isolated in a two-hybrid screening, seven could be identified as parts of the RAD2, RLF2 and DBR1 genes. RAD2 encodes an endonuclease indispensable for nucleotide excision repair (NER), RLF2 encodes the major subunit of the chromatin assembly factor I, whose deletion results in sensitivity to UVC radiation, while DBR1 encodes the lariat RNA splicing debranching enzyme, which degrades intron lariat structures during splicing. Characterization of mutagen-sensitive phenotypes of rad2{Delta}, rlf2{Delta} and pso4-1 single and double mutant strains showed enhanced sensitivity for the rad2{Delta} pso4-1 and rlf2{Delta} pso4-1 double mutants, suggesting a functional interference of these proteins in DNA repair processes in Saccharomyces cerevisiae
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