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Records with

  • Person's Name = Thomas Knudsen,
  • Person's Role = Any.
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Records 1 to 25 of 361

An AOP-based Ontology for Spina Bifida Caused by Disturbance in Retinoic Acid Signaling
(PRESENTATION) [Presented : Mar 14, 2019]
The retinoic acid (RA) pathway serves as a prototype for adverse outcome pathway (AOP) elucidation for developmental defects. The biology of the RA pathway was used for the construction of an ontology for neural tube closure defects. The ontology describes an AOP network incorpor...
CHEMICAL PRIORITIZATION FOR DEVELOPMENTAL TOXICITY USING LITERATURE MINING-BASED WEIGHTING OF TOXCAST ASSAYS
(PRESENTATION) [Presented : Jun 28, 2011]
Defining a predictive model of developmental toxicity from in vitro and high-throughput screening (HTS) assays can be limited by the availability of developmental defects data. ToxRefDB (www.epa.gov/ncct/todrefdb) was built from animal studies on data-rich environmental chemicals...
Identification of vascular disruptor compounds by analysis in zebrafish embryos and mouse embryonic endothelial cells
(JOURNAL) [Published : Jun 01, 2017]
The large number of diverse chemicals in production or in the environment has motivated medium to high throughput in vitro or small animal approaches to efficiently profile chemical-biological interactions and to utilize this information to assess risks of chemical exposures on h...
In vitro data and in silico models for computational toxicology (Teratology Society ILSI HESI workshop)
(PRESENTATION) [Presented : Jun 28, 2017]
The challenge of assessing the potential developmental health risks for the tens of thousands of environmental chemicals is beyond the capacity for resource-intensive animal protocols. Large data streams coming from high-throughput (HTS) and high-content (HCS) profiling of biolog...
20181114 - In Silico Dynamic Models for Developmental Toxicity (FutureTox)
(PRESENTATION) [Presented : Nov 16, 2018]
Computer modeling and simulation of complex dynamical systems can provide a virtual framework for translating biomolecular lesions into critical phenomena underlying developmental processes and toxicities. In silico cell agent-based models (ABMs) may be executed to simulate how b...
20190908 - Towards a Mechanistic Approach in Toxicology: Retinoic Acid Balance Disturbance Leading to Neural Tube Closure Defects - EuroTox 2019
(PRESENTATION) [Presented : Sep 11, 2019]
Retinoid signaling plays an important role in vertebrate embryo-fetal development and its disruption is teratogenic. The retinoic acid (RA) pathway controls retinoid homeostasis and regulates embryonic cell fate via nuclear receptor (RAR, RXR) activation. The RA pathway thus serv...
20190917 - Status and Prospect of the Virtual Embryo Program (ETS)
(PRESENTATION) [Presented : Sep 20, 2019]
Morphogenesis is mediated by coordinated action of cells interacting with one another and their micro-environment through systems of genetic signals and responses that are potentially vulnerable to chemical disruption. Computer models that integrate high-dimensional data on chemi...
5.22 - Systems Toxicology and Virtual Tissue Models
(BOOK CHAPTER) [Published : May 01, 2018]
Cells in developing tissues must integrate and respond to highly dynamic information in the form of metabolic intermediates, genetic signals, and molecular gradients. Understanding the cellular decision-making process, and how these decisions may be perturbed by genetic errors or...
A Computational Framework for Systems-based Analysis of Developmental Toxicity
(PRESENTATION) [Presented : Mar 19, 2008]
Discusses the EPA/NCCT ToxRefDB database. The EPA is building capacity for multi-dimensional evaluation of toxicity using information aboout chemical properties, genome-wide responses, and cell-based assays.
A Computational Model Predicting Disruption of Blood Vessel Development
(JOURNAL) [Published : Apr 04, 2013]
Vascular development is a complex process regulated by dynamic biological networks that vary in topology and state across different tissues and developmental stages. Signals regulating de novo blood vessel formation (vasculogenesis) and remodeling (angiogenesis) come from a varie...
A Data-driven Model Analysis of Retinoid Signaling in Skeletal Dysmorphogenesis and Potential Adverse Outcome Pathways
(PRESENTATION) [Presented : Jul 01, 2021]
Homeotic transformations and malformations of the fetal skeleton can occur as locally-regulated all-trans retinoic acid (ATRA) gradients. Such gradients determine skeletal patterning morphogenesis and can be disrupted by diverse genetic or environmental factors. Adverse Outcome P...
A Roadmap for the Development of Alternative (Non-Animal) Methods for Systemic Toxicity Testing
(JOURNAL) [Published : Jan 01, 2012]
Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new prod...
A cross-platform approach to characterize and screen potential neurovascular unit toxicants
(JOURNAL) [Published : Sep 01, 2020]
Development of the neurovascular unit (NVU) is a complex, multistage process that requires orchestrated cell signaling mechanisms across several cell types and ultimately results in formation of the blood-brain barrier. Typical high-throughput screening (HTS) assays investigate s...
A developmental ontology-based computational model for mammalian neural tube closure
(PRESENTATION) [Presented : Mar 19, 2020]
Computational models of biological processes are expected to revolutionize chemical safety assessment in the not too far future. Such models provide the template for establishing quantitative adverse outcome pathway (AOP) networks that define critical key events that need monitor...
A toxicity signature for species-specific disruption of embryonic vasculogenesis derived from ToxCast in vitro profiling data
(PRESENTATION) [Presented : Jun 27, 2010]
Blood vessel formation is crucial for normal embryo development and is sensitive to disruption by diverse teratogens. Recent studies have begun to reveal the cell signaling networks underlying vasculogenesis and angiogenesis and how these pathways might be perturbed by specific c...
AN INTELLIGENT REPRODUCTIVE AND DEVELOPMENTAL TESTING PARADIGM FOR THE 21ST CENTURY
(PRESENTATION) [Presented : Mar 15, 2012]
Addressing the chemical evaluation bottleneck that currently exists can only be achieved through progressive changes to the current testing paradigm. The primary resources for addressing these issues lie in computational toxicology, a field enriched by recent advances in computer...
AOP-based ontologies for developmental toxicity
(PRESENTATION) [Presented : Sep 05, 2018]
New approach methodologies (NAMs) based on high-throughput screening (HTS) assays can test large numbers of chemicals for bioactivity but interpretation of the data remains a challenge, especially for complex processes such as developmental toxicity. A pragmatic solution is to ma...
Abstract Sifter: A literature informatics tool for chemical safety assessments
(PRESENTATION) [Presented : Dec 11, 2018]
The biomedical literature contains an abundance of information about the activity of chemicals in biological systems. Literature informatics approaches applied to chemical toxicity research can help researchers make use of this vast literature in more effective ways, including th...
Abstract Sifter: A literature informatics tool for chemical safety assessments (ASCCT 2020)
(PRESENTATION) [Presented : Oct 21, 2020]
By the year 2035, the US EPA aims to eliminate animal testing in chemical safety assessment by adopting a set of new approach methods (NAMs). These methods will rely on rich data and an understanding of the mechanisms underpinning chemical toxicity. The biomedical literature is a...
Abstract Sifter: A literature informatics tool for computational toxicology
(PRESENTATION) [Presented : Jun 10, 2021]
The biomedical literature contains an abundance of information about the activity of chemicals in biological systems. The goal of literature informatics research at the EPA’s Center for Computational Toxicology and Exposure is to use the literature more effectively in compu...
Abstract Sifter: A literature informatics tool for computational toxicology (ASCCT)
(PRESENTATION) [Presented : Sep 26, 2019]
The biomedical literature contains an abundance of information about the activity of chemicals in biological systems. The goal of literature informatics research at the EPA’s National Center for Computational Toxicology is to use the literature more effectively in computati...
Abstract Sifter: A literature informatics tool for research in developmental toxicology
(PRESENTATION) [Presented : Nov 16, 2018]
Identifying environmental chemicals that adversely affect children’s health outcomes requires assembling information from a wide variety of sources, particularly from the millions of articles in the biomedical literature. Literature informatics approaches can help researchers ma...
Abstract Sifter: a comprehensive front-end system to PubMed
(JOURNAL) [Published : Dec 21, 2017]
Summary: The Abstract Sifter is a Microsoft Excel based application that enhances the user experience associated with literature searching of PubMed. The Sifter assists researchers to search effectively, triage results, and keep track of articles of interest. The tool implements ...
Activity profiles of 309 ToxCast™ chemicals evaluated across 292 biochemical targets
(JOURNAL) [Published : Mar 28, 2011]
Understanding the potential health risks posed by environmental chemicals is a significant challenge elevated by the large number of diverse chemicals with generally uncharacterized exposures, mechanisms, and toxicities. The present study is a performance evaluation and critical ...
Activity profiles of 676 ToxCast Phase II compounds in 231 biochemical high-throughput screening assays
(PRESENTATION) [Presented : Mar 15, 2012]
Understanding potential health risks posed by environmental chemicals is a significant challenge elevated by large numbers of diverse chemicals with generally uncharacterized exposures, mechanisms and toxicities. The present study is a performance evaluation and critical analysis...