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Based on our PAR analysis, the contributions of genetic factors for OA composed by three risk alleles was similar to that of the BMI (31.4% versus 28.4%).
PAR analysis also detected two periods of rapid population growths (from ca. 11,100 and 3900 calibrated years before present (cal yr BP)) and three bottlenecks (around 9180, 7200 and 2200 cal yr BP), likely triggered by climatic change and human impact.
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The output from the Pars analysis was used to construct trees using SplitsTree4 (http://www.splitstree.org) [36].
Cell extracts were centrifuged and stocked at -80°C until u-PAR analysis.
To evaluate the potential of each of the strategies, we will also perform a par protocol analysis, taking into account only those cases that were treated according to protocol.
After discussing the different programs available for each data processing step, we will now describe an exemplary PAR-CLIP analysis pipeline.
To improve the annotation of candidate target genes identified by PAR-CLIP analysis, databases for gene disease correlations or metabolic pathways can be analyzed.
We also observed numerous tRF-5-mRNA chimeras, but very few tRF-1-mRNA chimeras, which is consistent with our PAR-CLIP analysis.
For this reason, we feel that a standalone study is merited to carefully carry out genome-wide PAR-CLIP analysis, and validate and functionally characterize resulting hits (including all possible scenarios such as that some mRNAs may be bound, but not translationally regulated by Aven), rather than just to provide a list of potential Aven mRNA targets in our present study.
SF, JM, MJ performed PAR-CLIP data analysis.
Given that Par-4 sequence analysis revealed potential sites for CK2 phosphorylation that are overall evolutionarily conserved (database http://scansite.mit.edu), we hypothesized that Par-4 could be a target of CK2.
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