11,682 research outputs found
Site-specific DNA double-strand breaks greatly increase stable transformation efficiency in Trypanosoma brucei.
No full textGenetic manipulation in African trypanosomes typically relies upon electroporation with chromosomal integration of DNA constructs by homologous recombination. Relatively little is known about chromosomal recombination and repair in these organisms however and low transformation efficiency and position effects can limit forward genetic approaches. In yeast and mammalian cells, site-specific DNA double-strand breaks (DSBs) stimulate targeted integration through homologous recombination-based repair where the exogenous DNA serves as the template. We have explored the effect of DSBs on targeted integration in bloodstream-form Trypanosoma brucei, focusing on the ribosomal RNA-spacer target commonly used to integrate recombinant constructs. DSB-repair within the ribosomal RNA tandem gene-repeats is likely dominated by single-strand annealing allowing approximately 80% of cells to survive the break. In the presence of exogenous DNA, transformation efficiency is increased approximately 250-fold by DSB-induction. In the example presented, more than 1% of cells that survive the procedure were transformed generating 80,000 transformants from a typical experiment
Metadata Representations for Queryable ML Model Zoos
No full textMachine learning (ML) practitioners and organizations are building model zoos of pre-trained models, containing metadata describing properties of the ML models and datasets that are useful for reporting, auditing, reproducibility, and interpretability purposes. The metatada is currently not standardised; its expressivity is limited; and there is no interoperable way to store and query it. Consequently, model search, reuse, comparison, and composition are hindered. In this paper, we advocate for standardized ML model metadata representation and management, proposing a toolkit supported to help practitioners manage and query that metadata.Web Information SystemsHuman-Centred Artificial Intelligenc
A Manifesto of Nodalism
No full textThis paper proposes the notion of Nodalism as a means describing contemporary culture and of understanding my own creative practice in electronic music composition. It draws on theories and ideas from Kirby, Bauman, Bourriaud, Deleuze, Guatarri, and Gochenour, to demonstrate how networks of ideas or connectionist neural models of cognitive behaviour can be used to contextualize, understand and become a creative tool for the creation of contemporary electronic music
Optimizing ML Inference Queries Under Constraints
No full textThe proliferation of pre-trained ML models in public Web-based model zoos facilitates the engineering of ML pipelines to address complex inference queries over datasets and streams of unstructured content. Constructing optimal plan for a query is hard, especially when constraints (e.g. accuracy or execution time) must be taken into consideration, and the complexity of the inference query increases. To address this issue, we propose a method for optimizing ML inference queries that selects the most suitable ML models to use, as well as the order in which those models are executed. We formally define the constraint-based ML inference query optimization problem, formulate it as a Mixed Integer Programming (MIP) problem, and develop an optimizer that maximizes accuracy given constraints. This optimizer is capable of navigating a large search space to identify optimal query plans on various model zoos.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Web Information SystemsHuman-Centred Artificial Intelligenc
DNA strand-nicking principles of Mucuna birdwoodiana
No full textDuring our research program to find DNA strand-scission agents from higher plants, the MeOH extracts of the stems of Mucuna birdwoodiana Tutcher. (Leguminosae) exhibited the most potent activity with an IC50 value of 4.9 μg/ml. Thus, detailed laboratory investigation was performed, and led to the isolation of known compounds, (±)-catechin (1) and (-)-epicatechin (2) as active principles. Compounds 1 and 2 showed significant activity of DNA strand-scission with IC50 values of 10.8 and 7.5 μg/ml, respectively (positive control, bleomycin: IC50 3.3 μg/ml)
Structure of the Helicase Domain of DNA Polymerase Theta Reveals a Possible Role in the Microhomology-Mediated End-Joining Pathway
No full textDNA polymerase theta (Polθ) has been identified as a crucial alternative non-homologous end-joining factor in mammalian cells. Polθ is upregulated in a range of cancer cell types defective in homologous recombination, and knockdown has been shown to inhibit cell survival in a subset of these, making it an attractive target for cancer treatment. We present crystal structures of the helicase domain of human Polθ in the presence and absence of bound nucleotides, and a characterization of its DNA-binding and DNA-stimulated ATPase activities. Comparisons with related helicases from the Hel308 family identify several unique features. Polθ exists as a tetramer both in the crystals and in solution. We propose a model for DNA binding to the Polθ helicase domain in the context of the Polθ tetramer, which suggests a role for the helicase domain in strand annealing of DNA templates for subsequent processing by the polymerase domain
Evaluation of the national roll-out of parenting programmes across England : the parenting early intervention programme (PEIP)
No full textBackground:
Evidence based parenting programmes can improve parenting skills and the behaviour of children exhibiting, or at risk of developing, antisocial behaviour. In order to develop a public policy for delivering these programmes it is necessary not only to demonstrate their efficacy through rigorous trials but also to determine that they can be rolled out on a large scale. The aim of the present study was to evaluate the UK government funded national implementation of its Parenting Early Intervention Programme, a national roll-out of parenting programmes for parents of children 8–13 years in all 152 local authorities (LAs) across England. Building upon our study of the Pathfinder (2006–08) implemented in 18 LAs. To the best of our knowledge this is the first comparative study of a national roll-out of parenting programmes and the first study of parents of children 8–13 years.
Methods:
The UK government funded English LAs to implement one or more of five evidence based programmes (later increased to eight): Triple P, Incredible Years, Strengthening Families Strengthening Communities, Families and Schools Together (FAST), and the Strengthening Families Programme (10–14). Parents completed measures of parenting style (laxness and over-reactivity), and mental well-being, and also child behaviour at three time points: pre- and post-course and again one year later.
Results:
6143 parents from 43 LAs were included in the study of whom 3325 provided post-test data and 1035 parents provided data at one-year follow up. There were significant improvements for each programme, with effect sizes (Cohen’s d) for the combined sample of 0.72 parenting laxness, 0.85 parenting over-reactivity, 0.79 parent mental well-being, and 0.45 for child conduct problems. These improvements were largely maintained one year later. All four programmes for which we had sufficient data for comparison were effective. There were generally larger effects on both parent and child measures for Triple P, but not all between programme comparisons were significant. Results for the targeted group of parents of children 8–13 years were very similar.
Conclusions:
Evidence-based parenting programmes can be rolled out effectively in community settings on a national scale. This study also demonstrates the impact of research on shaping government policy
Building a generalisable ML pipeline at ING
No full textAdvances in data science have caused an increase in the use of Artificial Intelligence (AI), specifically Machine Learning (ML), throughout various fields. Not only in research but in the industry as well, has ML been receiving increasing amounts of interest. Many companies rely on ML models to increase the efficiency of existing processes or offer new services and products. The industry, however, is facing several additional challenges compared to the academic context. One of those challenges is applying the Development Operations (DevOps) model to an ML application, also referred to as MLOps. This thesis sets out to find the specific challenges that practitioners encounter while operationalising ML models. To do so, we perform a single-case case study on an ML pipeline built by the Trade & Communication Surveillance team at the ING bank. This case study consists of conducting a set of interviews and performing a manual code inspection of the pipeline. The team faces challenges ranging from having insufficient time for operationalising each ML project individually to operating in the highlyregulated fintech context. Their pipeline is able to deploy a single ML model but it does not generalise well to other projects. We present the first version of an application that mitigates these challenges. The application is able to deploy ML models to the development environment at ING and can be operated by data scientists to reduce the effort of operationalising an ML model. Computer Science | Software Technolog
'Project smells' - Experiences in Analysing the Software Quality of ML Projects with mllint
No full textMachine Learning (ML) projects incur novel challenges in their development and productionisation over traditional software applications, though established principles and best practices in ensuring the project's software quality still apply. While using static analysis to catch code smells has been shown to improve software quality attributes, it is only a small piece of the software quality puzzle, especially in the case of ML projects given their additional challenges and lower degree of Software Engineering (SE) experience in the data scientists that develop them. We introduce the novel concept of project smells which consider deficits in project management as a more holistic perspective on software quality in ML projects. An open-source static analysis tool mllint was also implemented to help detect and mitigate these. Our research evaluates this novel concept of project smells in the industrial context of ING, a global bank and large software- and data-intensive organisation. We also investigate the perceived importance of these project smells for proof-of-concept versus production-ready ML projects, as well as the perceived obstructions and benefits to using static analysis tools such as mllint. Our findings indicate a need for context-aware static analysis tools, that fit the needs of the project at its current stage of development, while requiring minimal configuration effort from the user. Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Software EngineeringSoftware Technolog
Audiomobiles, Sculptures and Conundrums
No full textRoberto Gerhard was a pioneer of electronic music in England creating a number of substantial concert, theatre and radio works from as early as 1954. Gerhard’s electronic music is one of the richest repositories for understanding the development of the composer’s late compositional technique. Apart from the Symphony no.3, ‘Collages’, none of Gerhard’s electronic music is published. This paper will discuss aspects of Gerhard’s electronic music, focusing on Audiomobiles (1958-59) and Sculptures (1963)
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