1,518 research outputs found
Causal graphical models in systems genetics: A unified framework for joint inference of causal network and genetic architecture for correlated phenotypes
Causal inference approaches in systems genetics exploit quantitative trait
loci (QTL) genotypes to infer causal relationships among phenotypes. The
genetic architecture of each phenotype may be complex, and poorly estimated
genetic architectures may compromise the inference of causal relationships
among phenotypes. Existing methods assume QTLs are known or inferred without
regard to the phenotype network structure. In this paper we develop a
QTL-driven phenotype network method (QTLnet) to jointly infer a causal
phenotype network and associated genetic architecture for sets of correlated
phenotypes. Randomization of alleles during meiosis and the unidirectional
influence of genotype on phenotype allow the inference of QTLs causal to
phenotypes. Causal relationships among phenotypes can be inferred using these
QTL nodes, enabling us to distinguish among phenotype networks that would
otherwise be distribution equivalent. We jointly model phenotypes and QTLs
using homogeneous conditional Gaussian regression models, and we derive a
graphical criterion for distribution equivalence. We validate the QTLnet
approach in a simulation study. Finally, we illustrate with simulated data and
a real example how QTLnet can be used to infer both direct and indirect effects
of QTLs and phenotypes that co-map to a genomic region.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS288 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Pax3:Fkhr interferes with embryonic Pax3 and Pax7 function: implications for alveolar rhabdomyosarcoma cell of origin.
Journal ArticleTo investigate the role of the translocation-associated gene Pax3:Fkhr in alveolar rhabdomyosarcomas, we generated a Cre-mediated conditional knock-in of Pax3:Fkhr into the mouse Pax3 locus. Exploring embryonic tumor cell origins, we replaced a Pax3 allele with Pax3:Fkhr throughout its expression domain, causing dominant-negative effects on Pax3 and paradoxical activation of the Pax3 target gene, c-Met. Ectopic neuroprogenitor cell proliferation also occurs. In contrast, activation later in embryogenesis in cells that express Pax7 results in viable animals with a postnatal growth defect and a moderately decreased Pax7+ muscle satellite cell pool, phenocopying Pax7 deficiency but remarkably not leading to tumors
Show Me the Data: Statistical Representation
Statistical representation is the science and art of using data to describe the world around us. Statistical representation is based on the fundamental concept that data consists of structure plus noise. The challenge facing the statistician is to use the noisy data to learn about the underlying structure. This framework accommodates the analysis of data generated by almost all other scientific disciplines. There are numerous ways of constructing statistical representations. The methods discussed here include tables, graphs, and models. The proper representation depends on the nature of the data and the particular issues being addressed. A combination of methods is often appropriate
Measurement of Subcellular CA2+ Redistribution in Cardiac Muscle In Situ: Time Resolved Rapid Freezing and Electron Probe Microanalysis
To directly assess the physiological roles of sarcoplasmic reticulum (SR) and miitochondria (MT), we have utilized energy dispersive electron probe microanalysis (EPMA) on ultrathin freeze-dried cryosections from isolated papillary muscles, rapidly frozen at precise time points of the contractile cycle. Using this approach, we can detect redistribution of subcellular Ca2+ during the cardiac contractile cycle. Changes in Ca2+ of less than 1.0 mmol/kg dry wt can be detected. By determining the variability of the Ca2+ measurements in preliminary experiments, we have also demonstrated that it is possible to optimize experimental design, i.e., to predict the number of animals per treatment group and the number of X-ray spectra per animal that are required in order to detect a specified Ca2+ difference. Quantitative EPMA of rapidly frozen contracting papillary muscle has also allowed us to correlate the Ca2+ content of SR and MT with the contractile state of the muscle. Our results show a decrease of 40% in the amount of Ca2+ stored in the junctional SR during a cardiac muscle twitch, thus providing direct evidence for a role of the SR as a primary site of Ca2+ release. In addition, we have demonstrated dissociation between MT Ca2+ uptake and activation of regulatory enzymes, such as pyruvate dehydrogenase, indicating that MT Ca2+ uptake is not required for activation of MT metabolism
Midwest Evaluation of the Adult Functioning of Former Foster Youth
The Midwest Evaluation of the Adult Functioning of Former Foster Youth (Midwest Study) is a prospective study that has been following a sample of young people from Iowa, Wisconsin, and Illinois as they transition out of foster care into adulthood. It is a collaborative effort involving Chapin Hall at the University of Chicago; Partners for Our Children at the University of Washington, Seattle; the University of Wisconsin Survey Center; and the public child welfare agencies in Illinois, Iowa, and Wisconsin.The Midwest Study provides a comprehensive picture of how foster youth are faring during this transition since the Foster Care Independence Act of 1999 became law. Foster youth in Iowa, Wisconsin, and Illinois were eligible to participate in the study if they had entered care before their 16th birthday, were still in care at age 17, and had been removed from home for reasons other than delinquency. Baseline survey data were collected from 732 study participants when they were 17 or 18 years old. Study participants were re-interviewed at ages 19 (n = 603), 21 (n = 591), and 23 or 24 (n = 602). A fifth wave of survey data will be collected when study participants are 25 or 26 years old.Because many of the questions Midwest Study participants were also asked as part of the National Longitudinal Study of Adolescent Health, it is possible to make comparisons between this sample of former foster youth and a nationally representative sample of young people in the general population. These comparisons indicate that young people who have aged out of foster care are faring poorly as a group relative to their peers across a variety of domains.The Midwest Study also presents a unique opportunity to compare the outcomes of young people from one state (i.e., Illinois) that allows foster youth to remain in care until their 21st birthday to the outcomes of young people from two other states (i.e., Iowa and Wisconsin) in which foster youth generally age out when they are 18 years old. The data suggest that extending foster care until age 21 may be associated with better outcomes, at least in some domains
Perilipin 5 and liver fatty acid binding protein function to restore quiescence in mouse hepatic stellate cells
Behavior of the Escape Rate Function in Hyperbolic Dynamical Systems
For a fixed initial reference measure, we study the dependence of the escape
rate on the hole for a smooth or piecewise smooth hyperbolic map. First, we
prove the existence and Holder continuity of the escape rate for systems with
small holes admitting Young towers. Then we consider general holes for Anosov
diffeomorphisms, without size or Markovian restrictions. We prove bounds on the
upper and lower escape rates using the notion of pressure on the survivor set
and show that a variational principle holds under generic conditions. However,
we also show that the escape rate function forms a devil's staircase with jumps
along sequences of regular holes and present examples to elucidate some of the
difficulties involved in formulating a general theory.Comment: 21 pages. v2 differs from v1 only by additions to the acknowledgment
- …