EasyPrime high strength bonding agent for porcelain paving.

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Simply add the powdered primer to cold, clean water (one 5Kg sachet to 2 litres of water) and mix with a powered mixing paddle for three to five minutes to form a smooth, lump-free slurry. Genome-editing technologies have revolutionized genetic studies ranging from those involving traditional interventions to precise manipulations of DNA sequences, offering both simplicity and robust outcomes [ 1]. Among different genome-editing technologies, the clustered regularly interspaced short palindromic repeats (CRISPR)–based systems [ 2, 3, 4] are the most widely used ones. Different CRISPR-based systems have their own strengths and weaknesses. Standard CRISPR-Cas9 approaches tend to introduce imprecise edits with indels varying in size from a single nucleotide to hundreds of nucleotides through nonhomologous end joining (NHEJ) [ 4]. In contrast, base editors can generate transition point mutations with high efficiency and accuracy without introducing double-strand breaks [ 5, 6, 7]. However, base editors are not suitable for generating other types of point mutations or for insertions and deletions. Zhou X, Edmonson MN, Wilkinson MR, Patel A, Wu G, Liu Y, et al. Exploring genomic alteration in pediatric cancer using ProteinPaint. Nat. Genet. 2016;48(1):4–6. https://doi.org/10.1038/ng.3466.

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Y.L. and Y.C. designed the project. Y.L and J.C. processed and analyzed data. S.T. provided conceptual advice and technical expertise. All authors discussed the results and assisted in the preparation of the manuscript. The author(s) read and approved the final manuscript. Corresponding authors See https://easy-prime.readthedocs.io/en/latest/content/Installation.html for step-by-step installation screenshots. Usage Yang L, Yang B, Chen J. One prime for all editing. Cell. 2019;179(7):1448–50. https://doi.org/10.1016/j.cell.2019.11.030. Petri K, Zhang W, Ma J, Schmidts A, Lee H, Horng JE, et al. CRISPR prime editing with ribonucleoprotein complexes in zebrafish and primary human cells. Nat. Biotechnol. 2021. https://doi.org/10.1038/s41587-021-00901-y. Anzalone AV, Koblan LW, Liu DR. Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors. Nat. Biotechnol. 2020;38:824–44.Li Yichao Chen Jingjing, Tsai Shengdar, Cheng Yong. Easy-Prime: a machine learning–based prime editor design tool. Datasets. Gene Expression Omnibus. 2021 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE175955. Lin Q, Zong Y, Xue C, Wang S, Jin S, Zhu Z, et al. Prime genome editing in rice and wheat. Nat. Biotechnol. 2020;38(5):582–5. https://doi.org/10.1038/s41587-020-0455-x. Anzalone AV, Randolph PB, Davis JR, Sousa AA, Koblan LW, Levy JM, et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature. 2019;576(7785):149–57. https://doi.org/10.1038/s41586-019-1711-4. GWAS data were accessed on 5-3-2020 and comprised 185,725 disease/trait associations [ 25]. Associations that do not have SNP ID were removed. We mapped the SNP ID to dbSNP 152 in hg19. If multiple alternative alleles existed, we expanded the variant to multiple rows. In total, 152,351 GWAS variants were input to Easy-Prime. Editing efficiency of designed pegRNA and ngRNA sets

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We developed Easy-Prime, a knowledge-based, one-step solution, to search and optimize the design of PEs automatically. Compared with other approaches, Easy-Prime weighs and combines the contributions of different features to predict editing efficiency and prioritize candidate sequences. In addition to features known to be associated with PE efficiency, Easy-Prime enables us to explore hidden features such as RNA folding and, thus, provides new insights into the mechanism of prime editing. Kevin Pang was the primary editor of this article and managed its editorial process and peer review in collaboration with the rest of the editorial team. Review history And that’s not all: if you opt for the eDreams Prime Plus subscription plan you will be able to share your discounts with up to 9 people, even when you’re not travelling with them.Only just started using Scott’s but as a landscaper I appreciate good service & indeed materials when I see it. Floor Levellers & Preparation We offer a range of single & two-part flexible, reinforced and deep fill floor levellers, bulking concrete, primers and vapour suppressants for preparation of your subfloor prior to tiling or laying floor coverings. The third PE data used for an independent test for Easy-Prime was collected from Hsu et al. [ 12]. Feature extraction X means the input to machine learning models. Here, rawX basically means the file before machine learning featurization. Specifically, rawX contains 11 + 1 columns. The first 5 columns are from the input vcf file: sample_ID, chr, pos, ref, alt, where sample_ID ends with _candidate_xxx, this indicates the N-th combination. The next 6 columns are genomic coordinates: type, seq, chr, start, end, strand, where the type could be sgRNA, PBS, RTT, or ngRNA. Since for one PE design, it has to have these 4 components, which means that for one unique sample_ID, it has 4 rows specifying the sequences for each of them. The 12-th column, which is optional, is the predicted efficiency; in other words, the Y for machine learning.

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Siegner SM, Karasu ME, Schröder MS, Kontarakis Z, Corn JE. PnB Designer: a web application to design prime and base editor guide RNAs for animals and plants. BMC Bioinformatics. 2021;22(1):101. https://doi.org/10.1186/s12859-021-04034-6. Marzec M, Brąszewska-Zalewska A, Hensel G. Prime editing: a new way for genome editing. Trends Cell Biol. 2020;30(4):257–9. https://doi.org/10.1016/j.tcb.2020.01.004. The first PE data source was collected from the DeepPE paper [ 17], including 46,614 samples that are generated by high-throughput integration system. This PE data was divided into training and testing sets by the authors and we used the same data splits when building and evaluating the PE2 model.Liu Y, Li X, He S, Huang S, Li C, Chen Y, et al. Efficient generation of mouse models with the prime editing system. Cell Discov. 2020;6(1):27. https://doi.org/10.1038/s41421-020-0165-z.