Editing Rules Research Articles

Targeted C•G-to-T•A base editing with TALE-cytosine deaminases in plants

BackgroundTALE-derived DddA-based cytosine base editors (TALE-DdCBEs) can perform efficient base editing of mitochondria and chloroplast genomes. They use transcription activator-like effector (TALE) arrays as programmable DNA-binding domains and a split version of the double-strand DNA cytidine deaminase (DddA) to catalyze C•G-to-T•A editing. This technology has not been optimized for use in plant cells.ResultsTo systematically investigate TALE-DdCBE architectures and editing rules, we established a β-glucuronidase reporter for transient assays in Nicotiana benthamiana. We show that TALE-DdCBEs function with distinct spacer lengths between the DNA-binding sites of their two TALE parts. Compared to canonical DddA, TALE-DdCBEs containing evolved DddA variants (DddA6 or DddA11) showed a significant improvement in editing efficiency in Nicotiana benthamiana and rice. Moreover, TALE-DdCBEs containing DddA11 have broader sequence compatibility for non-TC target editing. We have successfully regenerated rice with C•G-to-T•A conversions in their chloroplast genome, as well as N. benthamiana with C•G-to-T•A editing in the nuclear genome using TALE-DdCBE. We also found that the spontaneous assembly of split DddA halves can cause undesired editing by TALE-DdCBEs in plants.ConclusionsAltogether, our results refined the targeting scope of TALE-DdCBEs and successfully applied them to target the chloroplast and nuclear genomes. Our study expands the base editing toolbox in plants and further defines parameters to optimize TALE-DdCBEs for high-fidelity crop improvement.

Harnessing accurate mitochondrial DNA base editing mediated by DdCBEs in a predictable manner.

Introduction: Mitochondrial diseases caused by mtDNA have no effective cures. Recently developed DddA-derived cytosine base editors (DdCBEs) have potential therapeutic implications in rescuing the mtDNA mutations. However, the performance of DdCBEs relies on designing different targets or improving combinations of split-DddA halves and orientations, lacking knowledge of predicting the results before its application. Methods: A series of DdCBE pairs for wide ranges of aC or tC targets was constructed, and transfected into Neuro-2a cells. The mutation rate of targets was compared to figure out the potential editing rules. Results: It is found that DdCBEs mediated mtDNA editing is predictable: 1) aC targets have a concentrated editing window for mtDNA editing in comparison with tC targets, which at 5'C8-11 (G1333) and 5'C10-13 (G1397) for aC target, while 5'C4-13 (G1333) and 5'C5-14 (G1397) for tC target with 16bp spacer. 2) G1333 mediated C>T conversion at aC targets in DddA-half-specific manner, while G1333 and G1397 mediated C>T conversion are DddA-half-prefer separately for tC and aC targets. 3) The nucleotide adjacent to the 3' end of aC motif affects mtDNA editing. Finally, by the guidance of these rules, a cell model harboring a pathogenic mtDNA mutation was constructed with high efficiency and no bystander effects. Discussion: In summary, this discovery helps us conceive the optimal strategy for accurate mtDNA editing, avoiding time- and effort-consuming optimized screening jobs.

Graded phonological neighborhood effects on lexical retrieval: Evidence from Mandarin Chinese

How phonological neighborhood affects lexical retrieval can shed important light on lexical organization and processing. Yet these effects are unclear, particularly in Mandarin Chinese. This is likely because the working definition of phonological neighbors (i.e., the one-phoneme edit rule) used in Indo-European languages inadequately characterizes the phonological similarity among Mandarin words, which have simpler syllable structures and lexical tones. The current study proposes a graded Mandarin phonological neighborhood and investigates the impacts of near-to-distant Mandarin phonological neighbors on lexical retrieval. In Study 1, we investigated how Mandarin phonological similarity is influenced by the editing of lexical tone, constituent (onset/rime, initial/final) and phoneme. Native Mandarin speakers rated the similarity between the edited monosyllabic words. We found that constituent-edit neighbors were rated as the most dissimilar, followed by phoneme-edit neighbors, while tone-edit neighbors were the most similar. In Study 2, we calculated the constituent-, phoneme- and tone-edit phonological neighborhood densities and frequencies for 4,706 monosyllabic Mandarin words. We then utilized extant datasets to examine how the density and frequency of neighbors at varied distances, as well as of homophonic neighbors, impact response latencies in word naming, visual lexical decision, and picture naming tasks. The results showed that graded phonological neighbors had differential impacts on lexical retrieval efficiency: distant (constituent-edit) neighbors facilitated word retrieval, while near (phoneme-, tone-edit and homophonic) neighbors had inhibitory effects. We discuss these findings within an interactive activation and competition framework and suggest future directions to study the representation and processing of the Mandarin phonological lexicon.

Abu Jalank Al-Halabi's Poetry

The paper studies one of the minor poets of the seventeenth century. He is from Damascus. He is Abu Jalank Ahmed Bin Abi Baker Al-Halabi. The poet is very famous of his excellent description. However, he has not been given his due of study by critics and no one collected his poems. The paper is divided into two parts. The first part is devoted to the poet's life and it examines the thematic and the aesthetic sides of his poetry which is composed in conventional metres and rhyme-schemes, well structured, delicate in expression and smoothly going. The second part is dedicated to collecting, editing and documenting his poetry relying on rare manuscripts, sources and printed works according to rules of sound scientific editing and verification.

Stochastic RNA editing of the Complexin C-terminus within single neurons regulates neurotransmitter release

Neurotransmitter release requires assembly of the SNARE complex fusion machinery, with multiple SNARE-binding proteins regulating when and where synaptic vesicle fusion occurs. The presynaptic protein Complexin (Cpx) controls spontaneous and evoked neurotransmitter release by modulating SNARE complex zippering. Although the central SNARE-binding helix is essential, post-translational modifications to Cpx's C-terminal membrane-binding amphipathic helix regulate its ability to control synaptic vesicle fusion. Here, we demonstrate that RNA editing of the Cpx C-terminus modifies its ability to clamp SNARE-mediated fusion and alters presynaptic output. RNA editing of Cpx across single neurons is stochastic, generating up to eight edit variants that fine tune neurotransmitter release by altering the subcellular localization and clamping properties of the protein. Similar stochastic editing rules for other synaptic genes were observed, indicating editing variability at single adenosines and across multiple mRNAs generates unique synaptic proteomes within the same population of neurons to fine tune presynaptic output.

Parker: Data fusion through consistent repairs using edit rules under partial keys

Data integration is the problem of consolidating information provided by multiple sources. After schema mapping and duplicate detection have been dealt with, the problem consists in fusing disparate data that comes from the sources. In this work, we treat this problem as a data cleaning problem where consistency within and between sources is modelled by respectively edit rules and a partial key. The combination of these constraints leads to the definition of edit rules under a partial key (EPKs). We show that we can adapt the well-known set cover method for edit rules to the setting of EPKs and this yields an efficient algorithm to find minimal-cost repairs. These repairs then provide solutions for the initial data fusion problem. The methodology is implemented in a repair engine called Parker. Empirical results show that Parker is several orders of magnitude faster than state-of-the-art repair tools. At the same time, the quality of the repairs in terms of F1-score ranges from comparable to better compared to these tools.

Exploring Stroke-Level Modifications for Scene Text Editing

Scene text editing (STE) aims to replace text with the desired one while preserving background and styles of the original text. However, due to the complicated background textures and various text styles, existing methods fall short in generating clear and legible edited text images. In this study, we attribute the poor editing performance to two problems: 1) Implicit decoupling structure. Previous methods of editing the whole image have to learn different translation rules of background and text regions simultaneously. 2) Domain gap. Due to the lack of edited real scene text images, the network can only be well trained on synthetic pairs and performs poorly on real-world images. To handle the above problems, we propose a novel network by MOdifying Scene Text image at strokE Level (MOSTEL). Firstly, we generate stroke guidance maps to explicitly indicate regions to be edited. Different from the implicit one by directly modifying all the pixels at image level, such explicit instructions filter out the distractions from background and guide the network to focus on editing rules of text regions. Secondly, we propose a Semi-supervised Hybrid Learning to train the network with both labeled synthetic images and unpaired real scene text images. Thus, the STE model is adapted to real-world datasets distributions. Moreover, two new datasets (Tamper-Syn2k and Tamper-Scene) are proposed to fill the blank of public evaluation datasets. Extensive experiments demonstrate that our MOSTEL outperforms previous methods both qualitatively and quantitatively. Datasets and code will be available at https://github.com/qqqyd/MOSTEL.

How do free-play offers affect gambling behavior?

PurposeThis study aims to understand how free-play credits affect risk-seeking behavior in slot players. Extant results suggest they encourage risk aversion, counter to the primary aim of increasing spend per visit. The results inform operators as to the effectiveness of what has become the primary play incentive for casino marketers within many of the world’s markets.Design/methodology/approachWithin a quasi-experimental grouped design, 365 days of player-level performance data from four different casinos were analyzed to determine whether player losses (casino revenues) and time played differed on visits that included free-play redemptions from those that did not. Hypotheses were tested via paired-samples t-tests and Mann–Whitney U tests.FindingsOn balance, neither player losses nor time played were significantly different on the free-play visits. Neither the house money effect nor the endowment effect was supported. The results were most consistent with the prospect-theory-with-memory editing rule. No findings indicated increased risk-seeking behavior associated with the free-play offers.Practical implicationsCasino operators are afforded insight related to how costly free-play campaigns affect gaming spend and playtime. Both are critical to understanding the impact of free-play on the gambler’s experience.Originality/valueThe 365-day samples extended existing research by analyzing the impact of free-play offers on risk-taking behaviors within the scope of a perpetual/ongoing campaign. Comparisons of observed daily behavior/outcomes were made between separate tiers of like-kind gamblers from each of four different casinos. Quasi-hedonic editing rules were applied to a multistage decision framework.

Efficient multitool/multiplex gene engineering with TALE-BE

TALE base editors are a recent addition to the genome editing toolbox. These molecular tools are fusions of a transcription activator-like effector domain (TALE), split-DddA deaminase halves, and an uracil glycosylase inhibitor (UGI) that have the distinct ability to directly edit double strand DNA, converting a cytosine (C) to a thymine (T). To dissect the editing rules of TALE-BE, we combined the screening of dozens of TALE-BE targeting nuclear genomic loci with a medium/high throughput strategy based on precise knock-in of TALE-BE target site collections into the cell genome. This latter approach allowed us to gain in depth insight of the editing rules in cellulo, while excluding confounding factors such as epigenetic and microenvironmental differences among different genomic loci. Using the knowledge gained, we designed TALE-BE targeting CD52 and achieved very high frequency of gene knock-out (up to 80% of phenotypic CD52 knock out). We further demonstrated that TALE-BE generate only insignificant levels of Indels and byproducts. Finally, we combined two molecular tools, a TALE-BE and a TALEN, for multiplex genome engineering, generating high levels of double gene knock-out (∼75%) without creation of translocations between the two targeted sites.

FortClash: Predicting and Mediating Unintended Behavior in Home Automation

Smart home inhabitants can specify trigger-condition-action rules to control the home's behavior. As the number of rules and their complexity grow, however, so does the probability of issues such as inconsistencies and redundancies. These can lead to unintended behavior, including security vulnerabilities and wasted resources, which harms the inhabitants' trust in the system. Existing approaches to handle unintended behavior typically require inhabitants to define all-encompassing, permanent solutions by modifying the rules. Although this is fitting in certain situations, some unforeseen situations might occur. We argue that the user always must have the last word to avoid unwanted behaviors, without altering the overall behavior. With FortClash, we present an approach to predict many different types of unintended behavior, and contribute four novel mechanisms to mediate them that rely on making one-time exceptions. With FortClash, inhabitants gain a new tool to deal with unintended behavior in the short-term that is compatible with existing long-term approaches such as editing rules.

Dynamic repair of categorical data with edit rules

In this paper, a dynamic setting for data quality improvement is studied. In such a setting, there is a repeated search for data quality rules and a fix of their violations until stability is reached. The constraints considered here are simple constant edit rules and searching is done via association analysis. Repair of violations relies on the set cover method. This paper contributes to the field of data quality in three ways. First, it is shown that with appropriate filtering, association analysis is an appealing tool to discover data quality rules with high precision. Second, when edit rules are limited to logical implications such as association rules, then under reasonable circumstances, time complexity of rule implication reduces from exponential to quadratic. This result is formalized as the strong generator theorem. Third, a detailed analysis of data repair in a dynamic setting is provided and the conditions for termination are shown. Empirical results indicate that if the initial precision of rules is high, then repeated search-and-repair offers a boost in recall with a mitigated drop in precision.

Efficient edit rule implication for nominal and ordinal data

Edit rule implication is an essential subtask when repairing data inconsistencies against a set of edit rules. In this paper, novel techniques to enhance the performance of this subtask are studied. Our work includes several contributions. First, we draw attention to the case of nominal edit rules in particular. We point out that in many cases, starting with a set of edit rules that is as small as possible is important to improve the performance. This could be achieved by folding edit rules together. Besides that, an enhanced nominal edit rule implication algorithm is proposed, exploiting the properties of nominal edit rules. Second, we introduce ordinal edit rules as a generalization of nominal edit rules, used to capture data inconsistencies for data measured on an ordinal scale and we propose an ordinal edit rule implication algorithm. Evaluation of our methods shows promising results for both implication algorithms, with the ordinal algorithm as best performing in general. On average, our techniques improve the state-of-the-art algorithm for edit rule implication with more than 50%.

Changes in the Interpretation of Program Editing Rules in the Broadcasting Act Based on Government Responses

Changes in the Interpretation of Program Editing Rules in the Broadcasting Act Based on Government Responses

An RNA-based theory of natural universal computation

Life is confronted with computation problems in a variety of domains including animal behavior, single-cell behavior, and embryonic development. Yet we currently do not know of a naturally existing biological system that is capable of universal computation, i.e., Turing-equivalent in scope. Generic finite-dimensional dynamical systems (which encompass most models of neural networks, intracellular signaling cascades, and gene regulatory networks) fall short of universal computation, but are assumed to be capable of explaining cognition and development. I present a class of models that bridge two concepts from distant fields: combinatory logic (or, equivalently, lambda calculus) and RNA molecular biology. A set of basic RNA editing rules can make it possible to compute any computable function with identical algorithmic complexity to that of Turing machines. The models do not assume extraordinarily complex molecular machinery or any processes that radically differ from what we already know to occur in cells. Distinct independent enzymes can mediate each of the rules and RNA molecules solve the problem of parenthesis matching through their secondary structure. In the most plausible of these models all of the editing rules can be implemented with merely cleavage and ligation operations at fixed positions relative to predefined motifs. This demonstrates that universal computation is well within the reach of molecular biology. It is therefore reasonable to assume that life has evolved – or possibly began with – a universal computer that yet remains to be discovered. The variety of seemingly unrelated computational problems across many scales can potentially be solved using the same RNA-based computation system. Experimental validation of this theory may immensely impact our understanding of memory, cognition, development, disease, evolution, and the early stages of life.

The arithmetic of outcome editing in financial and social domains

Outcome editing refers to a set of mental rules that people apply when deciding whether to evaluate multiple outcomes jointly or separately, which subsequently affects choice. In a large-scale online survey (n = 2062) we investigate whether individuals use the same outcome editing rules for financial outcomes (e.g., a lottery win) and social outcomes (e.g., a party with friends). We also test the role of numeric ability in explaining outcome editing. Our results show that people’s preferences for combining or separating events depend on whether those events are in the financial or the social domain. Specifically, individuals were more likely to segregate social outcomes than monetary outcomes, except for when all outcomes were negative. Moreover, numeric ability was associated with preferences for outcome editing in the financial domain but not in the social domain. Our findings extend the understanding of the arithmetic operations underlying outcome editing and suggest that people rely more on calculations when making choices involving multiple financial outcomes and more on feelings when making choices involving social outcomes.

Procedural crowd generation for semantically augmented virtual cities

Authoring meaningful crowds to populate a virtual city can be a cumbersome, time-consuming and an error-prone task. In this work, we present a new framework for authoring populated environments in an easier and faster way, by relying on the use of procedural techniques. Our framework consists of the procedural generation of semantically-augmented virtual cities to drive the procedural generation and simulation of crowds. The main novelty lies in the generation of agendas for each individual inhabitant (alone or as part of a family) by using a rule-based grammar that combines city semantics with the autonomous persons’ characteristics. A new population or city can be authored by editing rule files with the flexibility of reusing, combining or extending the rules of previous populations. The results show how logical and consistent sequences of whereabouts can be easily generated for a crowd providing a good starting point to bring virtual cities to life.

Exploring the many tales behind success: understanding translations of the “intrapreneurships” management fashion as editing processes

PurposeThe paper explores a management fashion within the Swedish Public Sector called intrapreneurships. Intrapreneurships became popular during a period of public debate on what forms of organizing are most suitable for the production of welfare. However, while the popularity of the model was short-lived, a few municipalities nevertheless constitute examples of where it was supported for a longer period. The aim of this paper is to investigate how the model became continuously legitimate having lost its appeal elsewhere.Design/methodology/approachThe paper comprises a longitudinal analysis of two municipalities. Field-material was collected through qualitative methods including interviews (35 interviews, 42 interviewees) and document analysis.FindingsThe results draw attention to how management fashions become enduring. The metaphor of translation highlights how different professional actors in a local setting apply editing rules, and how they constitute work acquired for continuous translation of the model in order to make it legitimate, disseminated and supported. The study draws particular attention to the large number of actors involved in the editing process.Originality/valueBesides an extended understanding of management concepts, to explain the anomaly of a long-standing management fashion, the paper illustrates the importance of acknowledging editing as processes and not process. A key notion in why intrapreneurships became legitimate is that professional actors edited the model differently in order to satisfy their desires and needs. This contradicts the more common case study design in translation studies, which seeks a unitary translation process, in a single local setting.

Cinema as a form of composition

Cinema as a form of composition

Abu Jalank Al-Halabi's Poetry

The paper studies one of the minor poets of the seventeenth century. He is from Damascus. He is Abu Jalank Ahmed Bin Abi Baker Al-Halabi. The poet is very famous of his excellent description. However, he has not been given his due of study by critics and no one collected his poems. The paper is divided into two parts. The first part is devoted to the poet's life and it examines the thematic and the aesthetic sides of his poetry which is composed in conventional metres and rhyme-schemes, well structured, delicate in expression and smoothly going. The second part is dedicated to collecting, editing and documenting his poetry relying on rare manuscripts, sources and printed works according to rules of sound scientific editing and verification.

Programas de metas municipais sob olhar do Tribunal de Justiça de São Paulo

A pesquisa se debruçou sobre o entendimento do Tribunal de Justiça do Estado de São Paulo (TJSP) acerca da constitucionalidade de leis municipais instituidoras dos programas (ou “planos) de metas. Para isso, tomou como referência os primeiros estudos sobre a implementação do programa de metas no estado de São Paulo e a análise empírica das decisões judiciais sobre o tema no TJSP entre 2009-2019. A hipótese inicial era a de que as decisões pela inconstitucionalidade representavam uma interferência indevida do TJSP na elaboração de políticas públicas e inviabilizariam a utilização do instrumento a nível municipal. Notou-se, no entanto, que os casos foram trazidos ao Judiciário pelo próprio Executivo, que questionava a legitimidade do Poder Legislativo em editar normas referentes ao exercício de sua atividade administrativa. E que não é claro o impacto das decisões judiciais nos municípios, em que a referência a instrumentos similares se manteve. No âmbito do TJSP, careceu um olhar mais atento às particularidades de cada caso e até mesmo o enfrentamento de previsões similares a do programa de metas presentes no ordenamento jurídico brasileiro.