Science Inventory

Refine Your Search

Search Again

or try advanced search

Search Within

Search Results

Search Criteria:

Records with

  • Person's Name = Thomas Knudsen,
  • Person's Role = Any.
  (Sorted by Title)
Records 26 to 50 of 363

Adverse Outcome Pathway (AOP) framework for embryonic vascular disruption and developmental defects (SOT)
(PRESENTATION) [Presented : Mar 16, 2017]
Vascular development commences with de novo assembly of a primary capillary plexus (vasculogenesis) followed by its expansion (angiogenesis) and maturation (angio-adaptation) into a hierarchical system of arteries and veins. These processes are tightly regulated by genetic signal...
Adverse Outcome Pathway for Embryonic Vascular Disruption and Alternative Methods to Identify Chemical Vascular Disruptors During Development
(PRESENTATION) [Presented : Mar 27, 2014]
Chemically induced vascular toxicity during embryonic development can result in a wide range of adverse prenatal outcomes. We used information from genetic mouse models linked to phenotypic outcomes and a vascular toxicity knowledge base to construct an embryonic vascular disrupt...
Adverse Outcome Pathways and Computational Toxicology Applications of a Multi-database Review of Retinoid Signaling in Skeletal Development
(PRESENTATION) [Presented : Mar 26, 2021]
Locally-regulated all-trans retinoic acid (ATRA) gradients are important determinants of skeletal morphogenesis and can be disrupted by diverse genetic or environmental factors, leading to homeotic transformations and malformations of skeletal structures. Adverse Outcome Pathway ...
Agent-Based Computational Modeling to Examine How Individual Cell Morphology Affects Dosimetry
(PRESENTATION) [Presented : Nov 18, 2016]
Cell-based models utilizing high-content screening (HCS) data have applications for predictive toxicology. Evaluating concentration-dependent effects on cell fate and state response is a fundamental utilization of HCS data.Although HCS assays may capture quantitative readouts at ...
Agent-based Modeling with Embryonic Stem Cells During Gastrulation
(PRESENTATION) [Presented : Oct 22, 2020]
New approach methodologies (NAMs) that enable in vitro profiling of chemical-biological interactions come with the need for in silico models that translate vast amounts of data and information into toxicological prediction. We are building and testing a dynamic agent-based model ...
An AOP-based Ontology for Neural Tube Closure Caused by Disturbance in Retinoic Acid Signaling
(PRESENTATION) [Presented : Sep 05, 2018]
Retinoid signaling plays an important role in embryo- fetal development and its disruption is teratogenic. The biology of the RA pathway, leading to defects in neural tube closure was the basis for the construction of an ontology for developmental toxicity.
An AOP-based Ontology for Neural Tube Closure Caused by Disturbance in Retinoic Acid Signaling (EuroTox 2018)
(PRESENTATION) [Presented : Sep 05, 2018]
Retinoid signaling plays an important role in embryo-fetal development and its disruption is teratogenic. The retinoic acid (RA) pathway includes elements in retinoid metabolism and nuclear receptor (RAR, RXR) activation and thus serves as an excellent prototype for adverse outco...
An AOP-based Ontology for Spina Bifida Caused by Disturbance in Retinoic Acid Signaling
(PRESENTATION) [Presented : Sep 13, 2018]
Retinoid signaling plays an important role in embryo-fetal development and its disruption is teratogenic. The retinoic acid (RA) pathway includes elements in retinoid metabolism and nuclear receptor (RAR, RXR) activation and thus serves as an excellent prototype for adverse outco...
An Evaluation of ToxCast Angiogenic Disruptors for Effects on Mitochondrial Bioactivity Profiles (Teratology Society Annual Meeting)
(PRESENTATION) [Presented : Jun 29, 2016]
Angiogenesis is a critical developmental process and a potential target for chemical teratogenesis. Over one-tenth of the Tox21 library of 10,000 compounds have been shown to disrupt mitochondrial function [Attene-Ramos et al., 2015]. Previous studies utilizing ToxCast chemicals ...
An Integrative Systems Toxicology Model for Neurovascular Developmental Toxicity
(PRESENTATION) [Presented : Mar 15, 2018]
The blood-brain barrier (BBB) limits passage of toxicants into brain tissue and may be an important tissue interface for developmental neurotoxicity, although the extent to which drugs and chemicals interact with BBB anatomical development is not well known. We utilized a computa...
Analysis of Eight Oil Spill Dispersants Using Rapid, In Vitro Tests for Endocrine and Other Biological Activity
(JOURNAL) [Published : Aug 01, 2010]
The Deepwater Horizon oil spill has led to the use of >1 M gallons of oil spill dispersants, which are mixtures of surfactants and solvents. Because of this large scale use there is a critical need to understand the potential for toxicity of the currently used dispersant and pote...
Analysis of a ToxCast™ HTS Toxicity Signature for putative Vascular Disruptor Compounds
(PRESENTATION) [Presented : Oct 07, 2010]
Recent studies have shown the importance of blood vessel formation during embryo development and the strong correlation to developmental toxicity. Several developmental toxicants, such as thalidomide, have been identified which specifically target the forming embryonic vasculatur...
Analysis of the Effects of Cell Stress and Cytotoxicity on In Vitro Assay Activity Across a Diverse Chemical and Assay Space
(JOURNAL) [Published : Aug 01, 2016]
Chemical toxicity can arise from disruption of specific biomolecular functions or through more generalized cell stress and cytotoxicity-mediated processes. Here, concentration-dependent responses of 1063 chemicals including pharmaceuticals, natural products, pesticidals, consumer...
Application of AOPs to Developmental Outcomes
(PRESENTATION) [Presented : Jun 26, 2019]
AOP-based ontologies provide the necessary structure for quantitative prediction of cellular and tissue responses to molecular perturbation(s). For DevTox, this can be demonstrated by an AOP framework for embryonic vascular disruption represented in the OECD AOP-KB (Aop43). Becau...
Application of Signaling Pathway-Based Adverse Outcome Pathways and High Throughput Toxicokinetic-PBPK for Developmental Cardiac Malformations
(PRESENTATION) [Presented : Mar 18, 2017]
Associating putative molecular initiating events (MIE) with downstream cell signaling pathways and modeling fetal exposure kinetics is an important challenge for integration in developmental systems toxicology. Here, we describe an integrative systems toxicology model for develop...
Application of Targeted Functional Assays to Assess a Putative Vascular Disruption Developmental Toxicity Pathway Informed By ToxCast High-Throughput Screening Data
(PRESENTATION) [Presented : Mar 15, 2012]
Chemical perturbation of vascular development is a putative toxicity pathway which may result in developmental toxicity. EPA’s high-throughput screening (HTS) ToxCast program contains assays which measure cellular signals and biological processes critical for blood vessel develop...
Biochemical Activities of 320 ToxCast Chemicals Evaluated Across 239 Functional Targets
(PRESENTATION) [Presented : Mar 18, 2009]
EPA’s ToxCast research program is profiling chemical bioactivity in order to generate predictive signatures of toxicity. The present study evaluated 320 chemicals across 239 biochemical assays. ToxCast phase I chemicals include 309 unique structures, most of which are pesticide ...
Biological Profiling of Endocrine Related Effects of Chemicals Using ToxCast
(PRESENTATION) [Presented : Mar 18, 2009]
The Food Quality Protection Act of 1996 mandates that EPA implement a validated screening program for detecting estrogenic chemicals, as well as other endocrine targets deemed appropriate by the Administrator. EPA’s Endocrine Disruptor Screening Program (EDSP) has been developing...
Biological Profiling of Endocrine Related Effects of Chemicals in ToxCast
(PRESENTATION) [Presented : Mar 18, 2009]
The Food Quality Protection Act of 1996 mandates that EPA implement a validated screening program for detecting estrogenic chemicals, as well as other endocrine targets deemed appropriate by the Administrator. EPA’s Endocrine Disruptor Screening Program (EDSP) has been developing...
Biological profiling of the ToxCast Phase II Chemical Library in Primary Human Cell Co-Culture Systems
(PRESENTATION) [Presented : Mar 15, 2012]
The U.S. EPA’s ToxCast research project was developed to address the need for high-throughput testing of chemicals and a pathway-based approach to hazard screening. Phase I of ToxCast tested over 300 unique compounds (mostly pesticides and antimicrobials). With the addition of Ph...
Blood-Brain Barrier Development: Systems Modeling and Predictive Toxicology
(JOURNAL) [Published : Dec 18, 2017]
The blood-brain barrier (BBB) serves as a gateway for passage of drugs, chemicals, nutrients, metabolites and hormones between vascular and neural compartments. Here, we review the current understanding of BBB development with regard to microphysiology of the neurovascular unit (...
Building a Developmental Toxicity Ontology
(JOURNAL) [Published : Apr 03, 2018]
This report outlines an approach to construct a developmental toxicity ontology. Such an ontology will facilitate computer-based prediction of substances likely to induce human developmental toxicity.
Building an Adverse Outcome Pathway Framework through HTS Data and Literature Mining Integration (FutureToxII)
(PRESENTATION) [Presented : Jan 17, 2014]
Interpreting EPA’s ToxCast in vitro assay data in the context of Adverse Outcome Pathway (AOP) development is a significant challenge. While chemical activation in these assays may shed light on the molecular initiating event, the downstream effect of these activities at higher ...
Building predictive models of developmental toxicity from ToxRefDB and ToxCast
(PRESENTATION) [Presented : Oct 07, 2010]
EPA’s ToxCast™ project is profiling the in vitro bioactivity of chemical compounds to assess pathway-level and cell-based signatures that are highly correlated with observed in vivo toxicity. We hypothesize that cell signaling pathways underlying development are primary targets f...
Can Computational Models Be Used to Assess the Developmental Toxicity of Environmental Exposures?
(BOOK CHAPTER) [Published : Jul 09, 2010]
Environmental causes of birth defects include maternal exposure to drugs, chemicals, or physical agents. Environmental factors account for an estimated 3–7% of birth defects although a broader contribution is likely based on the mother’s general health status and genetic blueprin...