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81.
Single-cell multi-omics assays offer unprecedented opportunities to explore epigenetic regulation at cellular level. However, high levels of technical noise and data sparsity frequently lead to a lack of statistical power in correlative analyses, identifying very few, if any, significant associations between different molecular layers. Here we propose SCRaPL, a novel computational tool that increases power by carefully modelling noise in the experimental systems. We show on real and simulated multi-omics single-cell data sets that SCRaPL achieves higher sensitivity and better robustness in identifying correlations, while maintaining a similar level of false positives as standard analyses based on Pearson and Spearman correlation. 相似文献
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Mounted paraffin sections, 2-4μ thick, ˙were stained, dehydrated, allowed to air dry, and given a thin coating of 1 % Plexi-glas solution in chloroform. The chloroform was allowed to evaporate completely in a dry atmosphere. An emulsion whose dried thickness was 100-150μ, was prepared from Ilford G5 type in gel form and glued to the section by means of a 15% solution of shellac in absolute alcohol. The surface of the emulsion was then cleaned with absolute ethyl alcohol, to remove the impermeable shellac layer. The exposure for radiation reaction was made at about 2°C and required, in the conditions of our experiment, about 24 hrs. The emulsions were processed by the “temperature-development method.” With the described procedure, autoradiographs have been obtained of various organs of albino rats, labeled with P32, S35 and other radioisotopes, and very precise localizations of the origin of electron tracks was attempted. This technic has allowed the fixing and staining of the tissues by means of all the reagents commonly employed in histology, without any damage to the emulsion and the obtaining of good adhesion and minimum separation between specimen and emulsion, thus permitting reliable extrapolations of electron tracks. Due to the fact that the emulsion is fully sensitized when placed in contact with the preparation the limits of the exposure times were well defined. The uniform development at all depths of the emulsion achieved by the temperature-development method facilitated the work with fast electron tracks. 相似文献
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Giovanna Carr Paolo Nicoli Marcello Francesco Lingua Beatrice Maffeo Antonio Cartell Paola Circosta Mara Brancaccio Guido Parvis Valentina Gaidano Angelo Guerrasio Giuseppe Saglio Riccardo Taulli Alessandro Morotti 《Journal of cellular and molecular medicine》2020,24(2):1650-1657
The development of drugs able to target BTK, PI3k‐delta and BCL2 has dramatically improved chronic lymphocytic leukaemia (CLL) therapies. However, drug resistance to these therapies has already been reported due to non‐recurrent changes in oncogenic pathways and genes expression signatures. In this study, we investigated the cooperative role of the BCL2 inhibitor venetoclax and the BRD4 inhibitor JQ1. In particular, we found that JQ1 shows additional activity with venetoclax, in CLL cell lines and in ex vivo isolated primary CD19+ lymphocytes, arguing in favour of combination strategies. Lastly, JQ1 is also effective in venetoclax‐resistant CLL cell lines. Together, our findings indicated that the BET inhibitor JQ1 could be a promising therapy in CLL, both as first‐line therapy in combination with venetoclax and as second‐line therapy, after the emergence of venetoclax‐resistant clones. 相似文献
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Gaoqiang Yang Shule Yu Zhenye Kang Yifan Li Guido Bender Bryan S. Pivovar Johney B. Green David A. Cullen Feng‐Yuan Zhang 《Liver Transplantation》2020,10(16)
Low electron/proton conductivities of electrochemical catalysts, especially earth‐abundant nonprecious metal catalysts, severely limit their ability to satisfy the triple‐phase boundary (TPB) theory, resulting in extremely low catalyst utilization and insufficient efficiency in energy devices. Here, an innovative electrode design strategy is proposed to build electron/proton transport nanohighways to ensure that the whole electrode meets the TPB, therefore significantly promoting enhance oxygen evolution reactions and catalyst utilizations. It is discovered that easily accessible/tunable mesoporous Au nanolayers (AuNLs) not only increase the electrode conductivity by more than 4000 times but also enable the proton transport through straight mesopores within the Debye length. The catalyst layer design with AuNLs and ultralow catalyst loading (≈0.1 mg cm?2) augments reaction sites from 1D to 2D, resulting in an 18‐fold improvement in mass activities. Furthermore, using microscale visualization and unique coplanar‐electrode electrolyzers, the relationship between the conductivity and the reaction site is revealed, allowing for the discovery of the conductivity‐determining and Debye‐length‐determining regions for water splitting. These findings and strategies provide a novel electrode design (catalyst layer + functional sublayer + ion exchange membrane) with a sufficient electron/proton transport path for high‐efficiency electrochemical energy conversion devices. 相似文献
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Viere Tobias Amor Ben Berger Nicolas Fanous Ruba Dolfing Arduin Rachel Horta Keller Regula Laurent Alexis Loubet Philippe Strothmann Philip Weyand Steffi Wright Laurie Sonnemann Guido 《The International Journal of Life Cycle Assessment》2021,26(3):511-527
The International Journal of Life Cycle Assessment - Scientific Life Cycle Assessment (LCA) literature provides some examples of LCA teaching in higher education, but not a structured overview of... 相似文献
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Schrijvers Dieuwertje L. Loubet Philippe Sonnemann Guido 《The International Journal of Life Cycle Assessment》2021,26(6):1223-1235
The International Journal of Life Cycle Assessment - How to apply allocation in an life cycle assessment (LCA) is a long-running and controversial debate. Consensus seems to exist on the fact that... 相似文献