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Letteratura scientifica selezionata sul tema "Base editors"

Autore: Grafiati

Pubblicato: 14 marzo 2023

Ultima modifica: 12 aprile 2025

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Articoli di riviste sul tema "Base editors"

Cao, Di, Manzar Abbas, Fatima, Yunxia Li, Gaoping Zhao, Ghulam Abbas e Xihe Li. "BASE EDITING: A PROMISING TOOL FOR GENETIC MANIPULATION IN MAMMALIAN SOMATIC AND STEM CELL LINES". Pakistan Journal of Science 76, n. 04 (30 dicembre 2024): 553–69. https://doi.org/10.57041/vol76iss04pp553-569.

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The CRISPR system enables precise editing in genomic DNA but relies on intracellular homology-directed recombination (HDR) repair pathways and is extremely inefficient. Base editing technology developed based on the CRISPR/Cas9 system builds three Base editors (BE) by fusing nucleases that have lost cutting activity with different base deaminases: Cytosine base editor (CBE) and Adenine base editor (ABE) and Glycosylase base editors (GBE). These two types of editors can complete the substitution of C > T (G > A) or A > G (T > C) at gene target sites without producing DNA double-strand breaks, and finally achieve accurate base editing. At present, base editing technology has been widely used in gene therapy, animal model construction, precision animal breeding, gene function analysis, and other fields, providing a powerful technical tool for basic and applied research. This paper summarizes the development and optimization process of base editing technology, and its application in livestock and poultry, to provide a reference for researchers in related fields to use base editing systems.

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Bellingrath, Julia-Sophia, Michelle E. McClements, Maria Kaukonen, Manuel Dominik Fischer e Robert E. MacLaren. "In Silico Analysis of Pathogenic CRB1 Single Nucleotide Variants and Their Amenability to Base Editing as a Potential Lead for Therapeutic Intervention". Genes 12, n. 12 (27 novembre 2021): 1908. http://dx.doi.org/10.3390/genes12121908.

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Mutations in the Crumbs homolog 1 (CRB1) gene cause both autosomal recessive retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA). Since three separate CRB1 isoforms are expressed at meaningful levels in the human retina, base editing shows promise as a therapeutic approach. This retrospective analysis aims to summarise the reported pathogenic CRB1 variants and investigate their amenability to treatment with currently available DNA base editors. Pathogenic single nucleotide variants (SNVs) were extracted from the Leiden open-source variation database (LOVD) and ClinVar database and coded by mutational consequence. They were then analyzed for their amenability to currently available DNA base editors and available PAM sites from a selection of different Cas proteins. Of a total of 1115 unique CRB1 variants, 69% were classified as pathogenic SNVs. Of these, 62% were amenable to currently available DNA BEs. Adenine base editors (ABEs) alone have the potential of targeting 34% of pathogenic SNVs; 19% were amenable to a CBE while GBEs could target an additional 9%. Of the pathogenic SNVs targetable with a DNA BE, 87% had a PAM site for a Cas protein. Of the 33 most frequently reported pathogenic SNVs, 70% were targetable with a base editor. The most common pathogenic variant was c.2843G>A, p.Cys948Arg, which is targetable with an ABE. Since 62% of pathogenic CRB1 SNVs are amenable to correction with a base editor and 87% of these mutations had a suitable PAM site, gene editing represents a promising therapeutic avenue for CRB1-associated retinal degenerations.

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Evanoff, Mallory, e Alexis C. Komor. "Base editors: modular tools for the introduction of point mutations in living cells". Emerging Topics in Life Sciences 3, n. 5 (10 settembre 2019): 483–91. http://dx.doi.org/10.1042/etls20190088.

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Abstract (sommario):

Base editors are a new family of programmable genome editing tools that fuse ssDNA (single-stranded DNA) modifying enzymes to catalytically inactive CRISPR-associated (Cas) endonucleases to induce highly efficient single base changes. With dozens of base editors now reported, it is apparent that these tools are highly modular; many combinations of ssDNA modifying enzymes and Cas proteins have resulted in a variety of base editors, each with its own unique properties and potential uses. In this perspective, we describe currently available base editors, highlighting their modular nature and describing the various options available for each component. Furthermore, we briefly discuss applications in synthetic biology and genome engineering where base editors have presented unique advantages over alternative techniques.

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Monsur, Mahmuda Binte, Gaoneng Shao, Yusong Lv, Shakeel Ahmad, Xiangjin Wei, Peisong Hu e Shaoqing Tang. "Base Editing: The Ever Expanding Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Tool Kit for Precise Genome Editing in Plants". Genes 11, n. 4 (24 aprile 2020): 466. http://dx.doi.org/10.3390/genes11040466.

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Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9), a newly developed genome-editing tool, has revolutionized animal and plant genetics by facilitating modification of target genes. This simple, convenient base-editing technology was developed to improve the precision of genome editing. Base editors generate precise point mutations by permanent base conversion at a specific point, with very low levels of insertions and deletions. Different plant base editors have been established by fusing various nucleobase deaminases with Cas9, Cas13, or Cas12a (Cpf1), proteins. Adenine base editors can efficiently convert adenine (A) to guanine (G), whereas cytosine base editors can convert cytosine (C) to thymine (T) in the target region. RNA base editors can induce a base substitution of A to inosine (I) or C to uracil (U). In this review, we describe the precision of base editing systems and their revolutionary applications in plant science; we also discuss the limitations and future perspectives of this approach.

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Kantor, Ariel, Michelle McClements e Robert MacLaren. "CRISPR-Cas9 DNA Base-Editing and Prime-Editing". International Journal of Molecular Sciences 21, n. 17 (28 agosto 2020): 6240. http://dx.doi.org/10.3390/ijms21176240.

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Many genetic diseases and undesirable traits are due to base-pair alterations in genomic DNA. Base-editing, the newest evolution of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas-based technologies, can directly install point-mutations in cellular DNA without inducing a double-strand DNA break (DSB). Two classes of DNA base-editors have been described thus far, cytosine base-editors (CBEs) and adenine base-editors (ABEs). Recently, prime-editing (PE) has further expanded the CRISPR-base-edit toolkit to all twelve possible transition and transversion mutations, as well as small insertion or deletion mutations. Safe and efficient delivery of editing systems to target cells is one of the most paramount and challenging components for the therapeutic success of BEs. Due to its broad tropism, well-studied serotypes, and reduced immunogenicity, adeno-associated vector (AAV) has emerged as the leading platform for viral delivery of genome editing agents, including DNA-base-editors. In this review, we describe the development of various base-editors, assess their technical advantages and limitations, and discuss their therapeutic potential to treat debilitating human diseases.

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Rusk, Nicole. "Better base editors". Nature Methods 15, n. 10 (ottobre 2018): 763. http://dx.doi.org/10.1038/s41592-018-0154-4.

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Tang, Lei. "Base editors beware". Nature Methods 17, n. 1 (gennaio 2020): 21. http://dx.doi.org/10.1038/s41592-019-0705-3.

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Buchumenski, Ilana, Shalom Hillel Roth, Eli Kopel, Efrat Katsman, Ariel Feiglin, Erez Y. Levanon e Eli Eisenberg. "Global quantification exposes abundant low-level off-target activity by base editors". Genome Research 31, n. 12 (19 ottobre 2021): 2354–61. http://dx.doi.org/10.1101/gr.275770.121.

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Abstract (sommario):

Base editors are dedicated engineered deaminases that enable directed conversion of specific bases in the genome or transcriptome in a precise and efficient manner, and hold promise for correcting pathogenic mutations. A major concern limiting application of this powerful approach is the issue of off-target edits. Several recent studies have shown substantial off-target RNA activity induced by base editors and demonstrated that off-target mutations may be suppressed by improved deaminases versions or optimized guide RNAs. Here, we describe a new class of off-target events that are invisible to the established methods for detection of genomic variations and were thus far overlooked. We show that nonspecific, seemingly stochastic, off-target events affect a large number of sites throughout the genome or the transcriptome, and account for the majority of off-target activity. We develop and employ a different, complementary approach that is sensitive to the stochastic off-target activity and use it to quantify the abundant off-target RNA mutations due to current, optimized deaminase editors. We provide a computational tool to quantify global off-target activity, which can be used to optimize future base editors. Engineered base editors enable directed manipulation of the genome or transcriptome at single-base resolution. We believe that implementation of this computational approach would facilitate design of more specific base editors.

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Aparicio-Prat, Estel, Dong Yan, Marco Mariotti, Michael Bassik, Gaelen Hess, Jean-Philippe Fortin, Andrea Weston, Hualin S. Xi e Robert Stanton. "Roadmap for the use of base editors to decipher drug mechanism of action". PLOS ONE 16, n. 9 (21 settembre 2021): e0257537. http://dx.doi.org/10.1371/journal.pone.0257537.

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CRISPR base editors are powerful tools for large-scale mutagenesis studies. This kind of approach can elucidate the mechanism of action of compounds, a key process in drug discovery. Here, we explore the utility of base editors in an early drug discovery context focusing on G-protein coupled receptors. A pooled mutagenesis screening framework was set up based on a modified version of the CRISPR-X base editor system. We determine optimized experimental conditions for mutagenesis where sgRNAs are delivered by cell transfection or viral infection over extended time periods (>14 days), resulting in high mutagenesis produced in a short region located at -4/+8 nucleotides with respect to the sgRNA match. The β2 Adrenergic Receptor (B2AR) was targeted in this way employing a 6xCRE-mCherry reporter system to monitor its response to isoproterenol. The results of our screening indicate that residue 184 of B2AR is crucial for its activation. Based on our experience, we outline the crucial points to consider when designing and performing CRISPR-based pooled mutagenesis screening, including the typical technical hurdles encountered when studying compound pharmacology.

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Li, Chang, Aphrodite Georgakopoulou, Arpit Mishra, Sucheol Gil, R. David Hawkins, Evangelia Yannaki e André Lieber. "In vivo HSPC gene therapy with base editors allows for efficient reactivation of fetal γ-globin in β-YAC mice". Blood Advances 5, n. 4 (23 febbraio 2021): 1122–35. http://dx.doi.org/10.1182/bloodadvances.2020003702.

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Abstract Base editors are capable of installing precise genomic alterations without creating double-strand DNA breaks. In this study, we targeted critical motifs regulating γ-globin reactivation with base editors delivered via HDAd5/35++ vectors. Through optimized design, we successfully produced a panel of cytidine and adenine base editor (ABE) vectors targeting the erythroid BCL11A enhancer or recreating naturally occurring hereditary persistence of fetal hemoglobin (HPFH) mutations in the HBG1/2 promoter. All 5 tested vectors efficiently installed target base conversion and led to γ-globin reactivation in human erythroid progenitor cells. We observed ~23% γ-globin protein production over β-globin, when using an ABE vector (HDAd-ABE-sgHBG-2) specific to the –113A>G HPFH mutation. In a β-YAC mouse model, in vivo hematopoietic progenitor/stem cell (HSPC) transduction with HDAd-ABE-sgHBG-2 followed by in vivo selection resulted in >40% γ-globin+ erythrocytes in the peripheral blood. This result corresponded to 21% γ-globin production over human β-globin. The average –113A>G conversion in total bone marrow cells was 20%. No alterations in hematological parameters, erythropoiesis, and bone marrow cellular composition were observed after treatment. No detectable editing was found at top-scoring, off-target genomic sites. Bone marrow lineage–negative cells from primary mice were capable of reconstituting secondary transplant-recipient mice with stable γ-globin expression. Importantly, the advantage of base editing over CRISPR/Cas9 was reflected by the markedly lower rates of intergenic HBG1/2 deletion and the absence of detectable toxicity in human CD34+ cells. Our observations suggest that HDAd-vectorized base editors represent a promising strategy for precise in vivo genome engineering for the treatment of β-hemoglobinopathies.

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Più fonti

Tesi sul tema "Base editors"

Donati, Francesco. "RNA editing deficient mutants of APOBEC1: from genome editing to cancer". Doctoral thesis, Università di Siena, 2020. http://hdl.handle.net/11365/1096842.

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APOBEC-1 is a cytosine-to-uracil deaminase that exerts its primary physiological role in the editing of the Apolipoprotein B mRNA at C6666. Recent studies outlined the ability of APOBEC1 to edit also DNA, thus linking its mutational property to the its overexpression in cancer. Several reports suggest that APOBEC1 can alter the cellular state by targeting RNA molecules. Our hypothesis portrays APOBEC1 as the trigger for a dual path towards cancer through its DNA- and RNA- targeting abilities, and its activity as central to the onset of tumorigenic features. Aim of my PhD project is to understand whether APOBEC1 oncogenic potential is mainly related to its ability to edit RNA or DNA. To this aim, I assessed the tumorigenic potential of a set of APOBEC1 mutants, selected for a dissociation in their RNA and DNA editing ability: they are DNA editing proficient but unable to edit RNA. I characterized these mutants and I tested them in mice to assess their ability to trigger liver tumors. Even if unable to edit RNA, the APOBEC1 mutants are still able to induce tumor formation. This means that RNA editing does not play a central role in the oncogenic potential of APOBEC1. Moreover, considering the recent developments in genome editing, I have exploited these mutants as base editors -fusions of the DNA targeting Cas9 with a DNA deaminase- that allow the correction of single bases: the most common mutator moiety in cytosine-targeting base editors is based on APOBEC1, but overexpression of the APOBEC1-Cas9 chimera results in a substantial amount of RNA and DNA off-target alterations. Once fused with Cas9, our RNA-editing deficient mutants were able to mutate the target DNA. On the other hand, I demonstrated that their off-target activity on RNA is orders of magnitude lower than that of wild type APOBEC1, at the same levels of the negative controls. Exploitation of these mutants could thus provide tools for safer base editing both in vitro and in vivo.

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Lembo, Gaia. "Substrate targeting and inhibition of editing deaminases". Doctoral thesis, Università di Siena, 2021. http://hdl.handle.net/11365/1144295.

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Identification of small molecules against APOBEC3B The APOBECs are deaminases that act on DNA and RNA to restrict exogenous nucleic acids. Yet, the signature of their mutagenic activity –especially that of APOBEC3A and APOBEC3B- has been observed in the cancer genomes and their ability to increase the genetic heterogeneity of tumours has been linked to the onset of drug resistance in cancer. As such inhibition of their enzymatic activity represents a potential target for anticancer therapies. During my PhD I worked at the identification of APOBEC3B small-molecule inhibitors. To this aim, I used a computational approach to perform a virtual screening on large library of molecules to block APOBEC3B enzymatic activity. I then tested selected molecules from the virtual screening using biochemical assays to quantify their effect on APOBEC3B activity and their capacity to interfere with APOBEC3B binding to DNA. Through this, I was able to identify two small molecules that reduce the activity of this protein, which could provide basis for the development of the first drug for anti-APOBEC activity. Engineering ADAR2 to act on DNA Genome editing technologies have revolutionized our ability to target and modify the genomes of living cells and organisms. The fusion of AID/APOBECs to genome editing tools such as Cas9 allowed the development the first base editor, molecules that can be targeted to mutate specific cytosines. The pool of available Base Editors is in constant expansion as new molecules are developed to target DNA with more specificity and efficiency. As the only adenine-targeting Base Editor is based on TadA- an RNA deaminase-, I focused on the development of a A•T base editor based on the catalytic domain of ADAR2. Adenosine Deaminases Acting on RNA (ADARs), are editing enzymes that catalyse the C6 deamination of adenosine (A) to produce inosine (I) in double-stranded RNA. As human ADAR2 is able to target DNA/RNA hybrids, I first tried -without success- to use chimeras of n/dCas9 and the deaminase domain of ADAR2 to induce mutations in a fluorescent reporter. I then used a bacterial screen to select for mutants of ADAR2 that act on DNA. I selected a mutant that induces a mutator phenotype in bacteria and DNA damage in mammalian cells. I am currently working to engineer this mutant into a Base Editor suitable for biotechnological applications such as gene therapy, antiviral treatment and cancer therapy.

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Fontana, Letizia. "Genome and epigenome editing approaches to treat β-hemoglobinopathies". Electronic Thesis or Diss., Université Paris Cité, 2024. http://www.theses.fr/2024UNIP5230.

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Drépanocytose et bêta-thalassémie sont dues à des mutations affectant la production de la chaîne de globine β. La sévérité clinique est atténuée par des mutations augmentant la quantité d'hémoglobine fœtale (HbF), une condition appelée persistance héréditaire d'HbF à l'âge adulte. La transplantation autologue de cellules souches/progénitrices hématopoïétiques (CSPH) génétiquement corrigées est prometteuse. Une approche CRISPR/Cas9 pour réprimer BCL11A, un répresseur de la globine γ, a été approuvée mais comporte des risques de génotoxicité dues aux cassures double brin (CDB). Nous avons ciblé les sites de liaison (SL) des activateurs transcriptionnels GATA1 et ATF4, présents dans les régions +58-kb et +55-kb, respectivement, des enhancers érythroïdes de BCL11A, avec des éditeurs de base (BEs) pour introduire des mutations ponctuelles précises sans créer de CDBs. Des ARN guides (ARNg) ont été testés dans des cellules souches hématopoïétiques (CSH) de patients drépanocytaires en combinaison avec des BEs, générant différents nucléotides dans les motifs de liaison avec une efficacité d'édition atteignant 90 %, avec peu ou pas d'indels induits par les CDB. La réactivation d'HbF a été observée dans tous les échantillons édités, mesurée par HPLC, mais pas suffisante pour un sauvetage complet du phénotype dans les cellules érythroïdes issues des CSPHs drépanocytaires éditées. Nous avons donc ciblé simultanément les SL de GATA1 et ATF4 pour augmenter les niveaux d'HbF. Les cellules éditées au niveau des enhancers +58 et +55 ont montré une augmentation de l'expression d'HbF par rapport aux cellules recevant des ARNg individuels, dépassant les niveaux atteints avec la stratégie CRISPR/Cas9. Enfin, la réactivation de l'HbF était suffisante pour permettre un sauvetage substantiel du phénotype malade, diminuant le nombre de cellules drépanocytaires à 16,4%. Pour évaluer les effets hors cibles, nous avons utilisé le GUIDE-seq couplé au séquençage ciblé, le séquençage de l'exome entier et le RNA-seq, tandis que les effets indésirables présent dans les sites cibles ont été évalués par séquençage Long read. L'efficacité du BE pour repeupler les CSH a été démontrée en transplantant des CSH éditées dans des souris immunodéficientes, prouvant l'efficacité de l'édition simultanée des éléments transrégulateurs de la globine γ pour la réactivation de l'HbF. Cette preuve de concept permettra le développement préclinique et clinique de CSH modifiées pour le traitement des β-hémoglobinopathies. Cependant, des travaux récents montrent que les BEs peuvent également générer de larges délétions ou indels (Antoniou et al. 2022). Ainsi, une nouvelle stratégie basée sur l'édition de l'épigénome a été développée pour moduler l'expression des gènes sans modifier la séquence d'ADN sous-jacente. Nous avons analysé les marques épigénétiques dans deux régions cis-régulatrices clés, les promoteurs de HBG et les enhancers de BCL11A, dans des cellules érythroïdes dérivées de CSPH. Des marques épigénétiques répressives, telles que la méthylation de l'ADN, ont été détectées au niveau des promoteurs de HBG dans des cellules érythroïdes adultes n'exprimant pas la globine γ. En revanche, la déméthylation de l'ADN et les marques épigénétiques activatrices telles que l'acétylation de la lysine 27 de l'histone 3 (H3K27ac) et la triméthylation de la lysine 4 (H3K4me3) ont été détectées au niveau des promoteurs de HBG dans les cellules érythroïdes exprimant la globine γ. La forte expression de BCL11A dans les cellules érythroïdes adultes est associée à de faibles niveaux de méthylation de l'ADN au niveau des enhancers de BCL11A. L'inactivation des enhancers de BCL11A est associée à une augmentation de la méthylation de l'ADN. Ces données nous ont permis de concevoir des modificateurs de l'épigénome pour manipuler l'architecture épigénétique des promoteurs de HBG et des enhancers de BCL11A afin d'atteindre des niveaux thérapeutiques d'HbF
B-thalassemia and sickle cell disease (SCD) result from mutations that affect the synthesis or structure of adult hemoglobin. Historically, allogeneic hematopoietic stem cell (HSC) transplantation from a compatible donor was the only curative treatment. Transplantation of autologous, genetically modified HSCs offers a promising therapeutic alternative for patients lacking a suitable donor. The clinical severity in b-hemoglobinopathies is mitigated by co-inheritance of hereditary persistence of fetal hemoglobin (HPFH), a benign condition characterized by mutations occurring in the genes encoding the fetal y-globin chains, which lead to increased fetal hemoglobin (HbF, a2y2) expression, which can rescue the b-thalassemic and SCD phenotypes. HbF reactivation can be achieved by down-regulating BCL11A, encoding a key repressor of HbF. A CRISPR/Cas9 strategy targeting the GATA1 binding site (BS) within the +58-kb erythroid-specific enhancer of BCL11A has recently been approved as the first gene-editing therapy for b-thalassemia and SCD. Indeed, the targeting of the BCL11A erythroid-specific enhancer led to an efficient reduction of BCL11A in the erythroid cells, without impacting the differentiation of HSPCs in the other cell lineages. However, site-specific nucleases induce double strand breaks (DSBs), posing significant risks, such apoptosis and generation of large genomic rearrangements. In addition, to obtain an adequate number of corrected cells to transplant, several collections of HSCs are necessary to compensate for the cell loss due to DSB-induced apoptosis. Finally, the clinical study showed variability in the extent of HbF reactivation, still high HbS levels and modest correction of ineffective erythropoiesis. Novel CRISPR/Cas9 derived tools are currently available and can be used to develop therapeutic strategies associated with a low risk of DSB generation and increased HbF expression. In this project, we intend to develop universal, safe and efficacious therapeutic strategies for b-hemoglobinopathies aimed at modifying HSCs using base editors (BEs) and epigenome editors to reactivate HbF expression in their erythroid progeny. BEs are a CRISPR-Cas9-based genome editing technology that allows the introduction of point mutations with little DSB generation. In this work we used this technology to inactivate the GATA1 or the ATF4 transcriptional activator BS in the +58-kb and +55-kb BCL11A erythroid-specific enhancers through the insertion of point mutations. In particular, to reach levels of HbF sufficient to rescue the sickling phenotype, we performed simultaneous targeting of the two BS, achieving similar HbF levels compared to CRISPR/Cas9 nuclease-based approach. Additionally, we showed that BEs generated fewer DSBs and genomic rearrangements compared to the CRISPR/Cas9 nuclease approach. In parallel, we developed a novel epigenome-editing strategy aimed at modulating gene expression without altering the DNA sequence (e.g. without generating DSBs). We designed two approaches to upregulate HbF expression: a first strategy targeting and activating the y-globin promoters and a second approach downregulating BCL11A by targeting its erythroid-specific enhancers. We first identified the epigenetic marks in these trans- and cis-regulatory regions that are associated with active or inactive transcription in adult versus fetal erythroid cells. Then we used epigenome editors to deposit active histone modifications at the y-globin promoters and remove inactive marks such as DNA methylation. In parallel, we decorated the BCL11A enhancers with inactive epigenetic marks. Preliminary results demonstrated y-globin reactivation using both strategies, though the effects diminished over time, indicating the need for further optimization. In conclusion, we proposed two different editing approaches that allow to reduce DSB-associate issues as strategies to treat b-hemoglobinopathies

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McCaskill, George Alexander. "Generating programming environments with integrated text and graphics for VLSI design systems". Thesis, University of Edinburgh, 1987. http://hdl.handle.net/1842/6628.

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The constant improvements in device integration, the development of new technologies and the emergence of new design techniques call for flexible, maintainable and robust software tools. The generic nature of compiler-compiler systems, with their semi-formal specifications, can help in the construction of those tools. This thesis describes the Wright editor generator which is used in the synthesis of language-based graphical editors (LBGEs). An LBGE is a programming environment where the programs being manipulated denote pictures. Editing actions can be specified through both textual and graphical interfaces. Editors generated by the Wright system are specified using the formalism of attribute grammars. The major example editor in this thesis, Stick-Wright, is a design entry system for the construction of VLSI circuits. Stick-Wright is a hierarchical symbolic layout editor which exploits a combination of text and graphics in an interactive environment to provide the circuit designer with a tool for experimenting with circuit topologies. A simpler system, Pict-Wright: a picture drawing system, is also used to illustrate the attribute grammar specification process. This thesis aims to demonstrate the efficacy of formal specification in the generation of software-tools. The generated system Stick-Wright shows that a text/graphic programming environment can form the basis of a powerful VLSI design tool, especially with regard to providing the designer with immediate graphical feedback. Further applications of the LBGE generator approach to system design are given for a range of VLSI design activities.

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Hedman, Per. "Requirement specification Editor : REQUIREMENTS EDITOR BASED ON CONTRACT THEORY". Thesis, KTH, Skolan för informations- och kommunikationsteknik (ICT), 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-177130.

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Vid utveckling av tyngre fordon inför man allt fler avancerade funktione. Mycket av denna funktionalitet handlar om att maskiner automatiskt ska utföra uppgifter för att assistera föraren. Detta leder till att nya risker uppstår. Och till följd av detta har man börjat skapa nya funktionella säkerhetsstandarder. ISO 26262 är en ny funktionell säkerhetsstandard som finns för vanliga personbilar men som ännu inte trätt i kraft för lastbilar. I ISO-26262 standarden ska krav kunna mappas till andra krav samt till systemarkitektur. I nuläget finns det vissa verktyg på marknaden som stödjer användaren när den skriver kravspecifikationer. Men undersökningar av verktyg ledde till att vi kommit fram till att alla hade någon brist. Och ingen hade bra stöd för mappning mellan krav och systemarkitektur. I detta examensarbete har arbetet varit att testa implementera funktionalitet för ett verktyg som assisterar användaren på olika sätt när den skriver kravspecifikationer. Baserat på kontraktteori och konceptet om portar som hjälp för att koppla samman krav med systemarkitektur ska applikationen se till att det finns en formell koppling mellan dessa. För att testa och validera att portar går att använda för att testa intressant funktionalitet har också en applikation utvecklats där mycket funktionalitet implementerats. Resultatet har varit lyckat då vi baserat på kontraktteori lyckats implementera och validera att det är möjligt att använda portar för att skapa koppling mellan krav och systemarkitektur, samt mellan krav och krav. Validering av att det valda lagringsformatet JSON också förser implementeraren med nog starkt stöd för att kunna spara dessa krav så att data i filerna kan brytas ner och lagras i temporära databasen Neo4J och på så sätt skapa ett fungerande kretslopp.
When developing new heavy vehicles today demands for increasingly more advanced features are asked for. A lot of the new functionality is about machines performing tasks automatically to assist the driver when driving. This leads to new risks, and as a result a new functional safety standard has been created. ISO 26262 is a functional safety standard that today exists for ordinary cars, but has not yet became a standard for trucks. According to the ISO 26262-standard requirements can be mapped to other requirements as well as to the system architecture. At present there are several tools on the market that supports the user when writing specifications. However, our research of the tools has led us to conclude that all lacked something. For example neither of the tools had good support for mapping between requirements and system architecture. In this thesis work, functionality for a tool which is supposed to support the user in various ways when writing requirements specifications was to be examined. Based on contract theory and the concept of ports that links requirements together with system architecture, an application can ensure that there is a formal link between the two. To test the suggested functionality a prototype is being developed. The result has been a successful as we based on contract theory could validate that using ports to create links between different requirements as well as between requirements and system architecture works through the implementation of the tool. Validation that the selected storage format JSON also provides the implementer with enough support to save the requirements in a way so that the data files can be decomposed and stored in the Neo4J database.

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Li, Rui. "Operation transformation based concurrency control in group editors". Texas A&M University, 2006. http://hdl.handle.net/1969.1/4151.

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Collaborative editing systems (or group editors) allow a geographically dispersed group of human users to view and modify shared multimedia documents, such as research papers, design diagrams, web pages and source code together over a computer network. In addition to being useful tools, group editors are a classic research vehicle and model of interactive groupware applications, based on which a variety of social and technical issues have been investigated. Consistency maintenance as a fundamental problem in group editors has attracted constant research attention. Operational transformation (OT) is an optimistic consistency maintenance method that supports unconstrained collaboration among human users. Although significant progress has been achieved over the past decade, there is still a large space for improvement on the theoretical part of OT. In this dissertation, we are concerned with three problems: (1) How to evaluate the correctness of OT-based consistency maintenance protocols; (2) How to design and prove correct OT-based protocols; (3) What are the consistency correctness conditions for group editing systems in general. This dissertation addresses the above three problems and makes the following contributions: (1) propose a total order based framework including a new consistency model and the associated design methodology. This framework reduces the complexities of the OT design; (2) improve the total order based framework by introducing a natural order based framework. In contrast, this framework removes the requirement of defining a total order that is not necessary to the OT design; (3) establish a generic consistency model and propose the first set of practical design guidelines in OT based on this model.

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Choudhury, Surajit. "A fragment based program editor /". Thesis, McGill University, 1986. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=65502.

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Han, Kwon Soo. "Surveygen: A web-based survey editor". CSUSB ScholarWorks, 1998. https://scholarworks.lib.csusb.edu/etd-project/1786.

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Amai, Takamitsu. "Development of genome editing technology of mitochondrial DNA in Saccharomyces cerevisiae". Doctoral thesis, Kyoto University, 2021. http://hdl.handle.net/2433/263707.

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Kadlčík, Stanislav. "Webový editor audia". Master's thesis, Vysoké učení technické v Brně. Fakulta informačních technologií, 2013. http://www.nusl.cz/ntk/nusl-413324.

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The Web Based Audio Editor thesis deals with the requirements specification, selection of technologies and with the implementation itself. The thesis uses modern approaches of HTML5 standards and is divided into the client and the server parts. Both the web application and the server are implemented in JavaScript. The Web based audio editor allows basic editing features like cut, shifting, deleting. All this in multiple audio tracks. The application runs in recent versions of the most widely used web browsers.

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Libri sul tema "Base editors"

Bae, Sangsu, e Beomjong Song, a cura di. Base Editors. New York, NY: Springer US, 2023. http://dx.doi.org/10.1007/978-1-0716-2879-9.

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Kirslis, Peter Andre Christopher. The SAGA editor: A language-oriented editor based on an incremental LR(1) parser. Urbana, Ill: Dept. of Computer Science, University of Illinois at Urbana-Champaign, 1986.

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Lisa, Neal, e Szwillus Gerd, a cura di. Structure-based editors and environments. London: Academic Press, 1992.

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Reps, Thomas W. Generating language-based environments. Cambridge, Mass: MIT Press, 2012.

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McDonald, Brendan. A java-based online database table editor. [s.l: The Author], 2001.

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Sims, Darla. Making $$$ at home: Over 1000 editors who want your ideas, know-how & experience. Fairfield, Iowa: Sunstar Pub., 1996.

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Reps, Thomas W. The Synthesizer Generator: A System for Constructing Language-Based Editors. New York, NY: Springer New York, 1989.

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Tim, Teitelbaum, a cura di. The synthesizer generator: A system for constructing language-based editors. New York: Springer-Verlag, 1989.

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Shilling, John. Automated reference librarians for program [l]ibraries and their interaction with language based editors. Urbana, IL (1304 W. Springfield Ave., Urbana 61801): Dept. of Computer Science, University of Illinois at Urbana-Champaign, 1986.

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Jayasuriya, H. Kumar. Big data, big challenges in evidence-based policymaking / H. Kumar Jayasuriya, editor ; Kathryn Ritcheske, contributing editor. St. Paul, MN: West Academic Publishing, 2015.

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Capitoli di libri sul tema "Base editors"

Hwang, Gue-Ho, e Sangsu Bae. "Web-Based Computational Tools for Base Editors". In Methods in Molecular Biology, 13–22. New York, NY: Springer US, 2023. http://dx.doi.org/10.1007/978-1-0716-2879-9_2.

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Eggert, Paul. "1.2.4. Anglophone traditions". In Comparative History of Literatures in European Languages, 141–59. Amsterdam: John Benjamins Publishing Company, 2024. http://dx.doi.org/10.1075/chlel.xxxv.10egg.

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Spurred on by new editions of works of modern literature in which manuscript materials are often extant, editorial theory since the 1980s has been laying the groundwork for the wider introduction of a genetic perspective on the works of Anglophone authors. Resistance to the idea from the 1940s is traced. The editing of writers’ journals during the 1970s–1990s shows a hesitation to follow the brave lead of the Harvard edition of Emerson’s Journals in recording in-text cancellations and additions. Editors’ conceptions of the reader of their editions have evolved since 1950. The advent of the Cornell Wordsworth and Cornell Yeats editions broadened understanding of the editorial-archival function; the method has become accepted as the base-line responsibility of digital editors.

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Song, Beomjong, e Sangsu Bae. "Introduction and Perspectives of DNA Base Editors". In Methods in Molecular Biology, 3–11. New York, NY: Springer US, 2023. http://dx.doi.org/10.1007/978-1-0716-2879-9_1.

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Ng, Esther Feng Ying, e Franz Meitinger. "Genetic Engineering and Screening Using Base Editing and Inducible Gene Knockout". In Methods in Molecular Biology, 167–87. New York, NY: Springer US, 2024. https://doi.org/10.1007/978-1-0716-4224-5_12.

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AbstractGenetic engineering and screening in human cells are powerful techniques for the precise and comprehensive identification and analysis of gene and protein domain functions. Genome-wide knockout screens have been extensively utilized to discover essential genes, tumor suppressors, and genes that regulate responses to various chemicals, including antimitotic and therapeutic drugs. The advent of base editors, which facilitate the targeted mutation of single amino acids, has advanced the identification of critical and functional domains or motifs. In this context, we outline methods for creating efficient base editor and inducible knockout cell lines for targeted gene manipulation and conducting genetic screens to elucidate the roles of genes and their domains within a specific cell biological context.

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Lim, Colin K. W., Angelo J. Miskalis, Pablo Perez-Pinera e Thomas Gaj. "Delivering Base Editors In Vivo by Adeno-Associated Virus Vectors". In Methods in Molecular Biology, 135–58. New York, NY: Springer US, 2023. http://dx.doi.org/10.1007/978-1-0716-2879-9_11.

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See, Ji-Eun, e Yongsub Kim. "Functional Analysis of Variants in BRCA1 Using CRISPR Base Editors". In Methods in Molecular Biology, 73–85. New York, NY: Springer US, 2023. http://dx.doi.org/10.1007/978-1-0716-2879-9_7.

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Kaya, Hilal Betul. "Base Editing and Prime Editing". In A Roadmap for Plant Genome Editing, 17–39. Cham: Springer Nature Switzerland, 2023. http://dx.doi.org/10.1007/978-3-031-46150-7_2.

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AbstractThe development of new adaptations of CRISPR-based genome editing platforms, such as base editing and prime editing, made it possible to broaden the scope and applications of genome editing in plants. First base editing and, more recently, prime editing evade the creation of double-stranded breaks in deoxyribonucleic acid (DNA) and the requirement of donor template of DNA for repair while enhancing editing efficiency and product purity over CRISPR/Cas9. As base-pair changes in genomic DNA determine many significant agronomic traits, crop varieties can be developed by precisely converting specific single bases in plant genomes. While base editing can introduce specific nucleotide changes, such as transition and transversion mutations in the targeted region, prime editing can create precise insertions, deletions, and all 12 types of point mutations using the “search-and-replace” method.This chapter provides the basic principles of base editing and prime editing technologies and their practical applications in plants. The chapter also summarizes the recent breakthroughs in applying base and prime editors in diverse plant species, including their use in improving disease resistance, herbicide resistance, nutritional quality, crop yield, and quality. Finally, this chapter aims to clearly understand base editing and prime editing in plants by outlining potential developments.

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Kim, Daesik. "Profiling Genome-Wide Specificity of dCpf1 Cytidine Base Editors Using Digenome-Seq". In Methods in Molecular Biology, 33–40. New York, NY: Springer US, 2023. http://dx.doi.org/10.1007/978-1-0716-2879-9_4.

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Shyamli, P. Sushree, Sandhya Suranjika, Seema Pradhan e Ajay Parida. "Recent Advances and Application of CRISPR Base Editors for Improvement of Various Traits in Crops". In Genome Editing, 105–31. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-031-08072-2_5.

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Atti di convegni sul tema "Base editors"

Sarhangzadeh, Armin, e Taro Watanabe. "Alignment-Based Decoding Policy for Low-Latency and Anticipation-Free Neural Japanese Input Method Editors". In Findings of the Association for Computational Linguistics ACL 2024, 8043–54. Stroudsburg, PA, USA: Association for Computational Linguistics, 2024. http://dx.doi.org/10.18653/v1/2024.findings-acl.479.

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Zhang, Ningyu, Bozhong Tian, Siyuan Cheng, Xiaozhuan Liang, Yi Hu, Kouying Xue, Yanjie Gou, Xi Chen e Huajun Chen. "InstructEdit: Instruction-Based Knowledge Editing for Large Language Models". In Thirty-Third International Joint Conference on Artificial Intelligence {IJCAI-24}. California: International Joint Conferences on Artificial Intelligence Organization, 2024. http://dx.doi.org/10.24963/ijcai.2024/733.

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Knowledge editing for large language models can offer an efficient solution to alter a model’s behavior without negatively impacting the overall performance. However, the current approaches encounter issues with limited generalizability across tasks, necessitating one distinct editor for each task, significantly hindering the broader applications. To address this, we take the first step to analyze the multi-task generalization issue in knowledge editing. Specifically, we develop an instruction-based editing technique, termed InstructEdit, which facilitates the editor's adaptation to various task performances simultaneously using simple instructions. With only one unified editor for each LLM, we empirically demonstrate that InstructEdit can improve the editor's control, leading to an average 14.86% increase in Reliability in multi-task editing setting. Furthermore, experiments involving holdout unseen task illustrate that InstructEdit consistently surpass previous strong baselines. To further investigate the underlying mechanisms of instruction-based knowledge editing, we analyze the principal components of the editing gradient directions, which unveils that instructions can help control optimization direction with stronger OOD generalization.

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Holtmann, Jörg, Jan-Philipp Steghöfer e Weixing Zhang. "Exploiting Meta-Model Structures in the Generation of Xtext Editors". In 11th International Conference on Model-Based Software and Systems Engineering. SCITEPRESS - Science and Technology Publications, 2023. http://dx.doi.org/10.5220/0011745900003402.

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McNutt, Andrew, e Ravi Chugh. "Projectional Editors for JSON-Based DSLs". In 2023 IEEE Symposium on Visual Languages and Human-Centric Computing (VL/HCC). IEEE, 2023. http://dx.doi.org/10.1109/vl-hcc57772.2023.00015.

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McAleer, Michael. "Ranking the Leading Journals in Finance and Accounting Based on Quantity and Quality Citations". In 1st Electronic Conference of MDPI Editors-in-Chief. Basel, Switzerland: MDPI, 2015. http://dx.doi.org/10.3390/eic2015-b001.

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Kaiser, Katharina, Theresia Gschwandtner e Patrick Martini. "MapFace - An Editor for MetaMap Transfer (MMTx)". In 2008 21st International Symposium on Computer-Based Medical Systems (CBMS). IEEE, 2008. http://dx.doi.org/10.1109/cbms.2008.116.

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Nakano, Marina, Emi Masuda e Masaru Kamada. "A Structure Editor for the English Language". In 2016 19th International Conference on Network-Based Information Systems (NBiS). IEEE, 2016. http://dx.doi.org/10.1109/nbis.2016.38.

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Russo, Andrea, Francesco Mazzeo Rinaldi e Giovanni Giuffrida. "Information balance between newspapers and social networks". In CARMA 2020 - 3rd International Conference on Advanced Research Methods and Analytics. Valencia: Universitat Politècnica de València, 2020. http://dx.doi.org/10.4995/carma2020.2020.11635.

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Competing newspapers, after all, tend to publish the same information in agiven time frame. However, each editor tends to aggregate and present thenews according to certain criteria such as editorial policies, filteringstrategies, readers base, etc. Thus, the proper choice and filtering ofinformation makes one newspaper different from the other and, the propermanagement of such criteria, may deem the success or failure of a newspaper.From the editor’s perspective, the news selection process is a trade-offbetween informativeness and attractiveness, as determined by the readership.Could there be an optimal balance between these two conflicting forces?Moreover, is it possible that cultural and political inputs from social mediamay impact the news selection process?Political news on social networks represent nowadays a valuable informativeasset that gives the possibility to correlate newspaper information with publicrequest expressed on social networks. We believe that it is possible to developa theory to mitigate the newspaper’s cultural identity with the publicinformation needs collected on social media.In our work, we show how to measure the society request for information, andhow this can be conveyed.

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Pik To Cheung. "Manuscripts for the Evidence-Based Medicine Era". In Workshop on Publishing for Biomedical Journal Editors and Reviewers. Kuala Lumpur, Malaysia: Department of Biomedical Imaging, University of Malaya, 2006. http://dx.doi.org/10.2349/biij.2.4.e54-7.

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Matsuo, Tokuro, Dzulqarnain Nasir e Takayuki Fujimoto. "A Textbook Editor Based on a Customware Service". In 2009 International Conference on Network-Based Information Systems (NBIS). IEEE, 2009. http://dx.doi.org/10.1109/nbis.2009.7.

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Rapporti di organizzazioni sul tema "Base editors"

Babenko, Vitalina O., Roman M. Yatsenko, Pavel D. Migunov e Abdel-Badeeh M. Salem. MarkHub Cloud Online Editor as a modern web-based book creation tool. [б. в.], luglio 2020. http://dx.doi.org/10.31812/123456789/3858.

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The main criterion for the competitiveness of a teacher or expert in the field of science is a good ability to present their knowledge to students in an interactive form without spending a lot of time in preparation. The purpose of the study is to analyze modern editors to create educational information content in the modern educational space and to present a modern tool for creating web books based on the latest IT technologies. Modern editors of web material creation have been analyzed, statistics of situations on mastering of knowledge by listeners, using interactive methods of information submission have been investigated. Using the WYSIWYG concept and analyzing modern information tools for presenting graphic material, an effective tool for teaching interactive web material was presented. An adapted version of the MarkHub online editor based on cloud technologies is presented. Using MarkHub cloud-based online editor for the unified development of educational content can significantly increase the author’s productivity in the content creation process. At the same time, the effects of reducing the time spent on formatting the external presentation of the content, making synchronous changes to different versions of the content, tracking the versions of the content, organizing remote teamwork in the network environment are achieved.

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Ballance, Robert A. Design of the Pan Language-Based Editor. Fort Belvoir, VA: Defense Technical Information Center, febbraio 1986. http://dx.doi.org/10.21236/ada173780.

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Bohuslavskyj, Oleh. UKRAINIAN-CANADIAN NEWSPAPER “NEW PATHWAY”: WINNIPEG PERIOD (1941-1977). Ivan Franko National University of Lviv, febbraio 2022. http://dx.doi.org/10.30970/vjo.2022.51.11391.

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The subject of the study is the ideological, financial, economic and socio-social conditions of the publishing house and the editorial board of the magazine “New Pathway” Winnipeg period 1941-1977. The main objectives is to determine the peculiarities of the conditions of publishing a Ukrainian magazine in exile, which provides for the systematization and introduction into scientific circulation of factual material on creative and material activities of the “New Pathway” and socio-political environment that influenced the information and ideological and business policy of the publication. The basis of the research methodology is axiological, cultural, systemic approaches; methods of historicism, analysis, synthesis, generalization were used. The study provides not only a description of the historical path of the publication in this period, but also the reasons for miscalculations and successes, both financial and economic and socio-political, which allowed not only to stay in the information field and market for more than ninety years, technical circumstances of its existence, the political struggle in the new wave of emigration after World War II, changes in demographic and linguistic situation among the Ukrainian diaspora in Canada. The reasons for the situational increase and decrease in the activity of the publication’s subscribers were identified; the mechanisms of expanding the readership, attracting new readers and authors are analyzed; confirmed that the efforts of editors and directors of the publishing house at the initial stage of the Winnipeg period created and strengthened the material and technical base of the publishing house, conducted advertising campaigns and direct work to attract new subscribers and readers; The significance of the study is that for the first time in Ukraine the information about the Winnipeg period of the Ukrainian-Canadian weekly “New Pathway”, its financial and financial problems and creative and editorial successes was analyzed and summarized, thus filling another page in the history of Ukrainian diaspora periodicals.

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Vong, F. Motif-based display editor/manager (MEDM) operators guide. Office of Scientific and Technical Information (OSTI), novembre 1994. http://dx.doi.org/10.2172/204050.

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Blythe, Jim, e Surya Ramachandran. Knowledge Acquisition using an English-Based Method Editor. Fort Belvoir, VA: Defense Technical Information Center, gennaio 1999. http://dx.doi.org/10.21236/ada459377.

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Mohan, Raj, Timothy E. Levin e Cynthia E. Irvine. An Editor for Adaptive XML-Based Policy Management of IPsec. Fort Belvoir, VA: Defense Technical Information Center, dicembre 2003. http://dx.doi.org/10.21236/ada435401.

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McKay, Veronica, e John Daniel. Status of Distance Learning in South Africa: Contemporary Developments and Prospects. Commonwealth of Learning (COL), settembre 2022. http://dx.doi.org/10.56059/11599/4480.

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Files PDF (3.12 MB) Date 2022-09 Authors McKay, Veronica Editor Daniel, John Publisher Commonwealth of Learning (COL) Abstract The report presents a survey of distance learning in South Africa: contemporary developments and prospects. It is based on both archival and field data.

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Li, Jia-Qi, PWH Kwong, YW Sun, WS So e A. Sidarta. A comprehensive appraisal of meta-analyses in exercise-based stroke rehabilitation with trial sequential analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, agosto 2022. http://dx.doi.org/10.37766/inplasy2022.8.0006.

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Review question / Objective: This study aims to use the trial sequential analysis (TSA) method to examine if the published meta-analyses concerning stroke rehabilitation reached the required information size and if the overall effect size is robust as well. Condition being studied: Stroke rehabilitation. Eligibility criteria: Studies were included if they 1) were meta-analyses of random control trials (RCTs) on people with stroke, 2) included meta-analyses results in gait speed (or 6MWT) or bal-ance performance. Studies were excluded if they 1) were conference abstracts, letters to the editor 2) lack the statistical parameters such as mean, standard deviations (SD), and number value in the articles and raw data from the cited studies cannot be found.

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Bdzil, John Bohdan. DSD2D-FLS 2010: Bdzil's 2010 DSD Code Base; Computing tb and Dn with Edits to Reduce the Noise in the Dn Field Near HE Boundaries. Office of Scientific and Technical Information (OSTI), settembre 2016. http://dx.doi.org/10.2172/1327987.

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Prokhorov, Оleksandr V., Vladyslav O. Lisovichenko, Mariia S. Mazorchuk e Olena H. Kuzminska. Developing a 3D quest game for career guidance to estimate students’ digital competences. [б. в.], novembre 2020. http://dx.doi.org/10.31812/123456789/4416.

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This paper reveals the process of creating a career guidance 3D quest game for applicants who aim to apply for IT departments. The game bases on 3D model of computer science and information technologies department in the National Aerospace University “Kharkiv Aviation Institute”. The quest challenges aim to assess the digital competency level of the applicants and first- year students. The paper features leveraged software tools, development stages, implementation challenges, and the gaming application scenario. The game scenario provides for a virtual tour around a department of the 3D university. As far as the game replicates the real-life objects, applicants can see the department's equipment and class-rooms. For the gaming application development team utilized С# and C++, Unity 3D, and Source Engine. For object modeling, we leveraged Hammer Editor, Agisoft PhotoScan Pro, and the photogrammetry technology, that allowed for realistic gameplay. Players are offered various formats of assessment of digital competencies: test task, puzzle, assembling a computer and setting up an IT-specialist workplace. The experiment conducted at the open house day proved the 3D quest game efficiency. The results of digital competence evaluation do not depend on the testing format. The applicants mostly preferred to take a 3D quest, as more up-to-date and attractive engagement.

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