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Search Results: 1 - 10 of 212465 matches for " Amy L. Bauer "
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Topography of Extracellular Matrix Mediates Vascular Morphogenesis and Migration Speeds in Angiogenesis
Amy L. Bauer,Trachette L. Jackson,Yi Jiang
PLOS Computational Biology , 2009, DOI: 10.1371/journal.pcbi.1000445
Abstract: The extracellular matrix plays a critical role in orchestrating the events necessary for wound healing, muscle repair, morphogenesis, new blood vessel growth, and cancer invasion. In this study, we investigate the influence of extracellular matrix topography on the coordination of multi-cellular interactions in the context of angiogenesis. To do this, we validate our spatio-temporal mathematical model of angiogenesis against empirical data, and within this framework, we vary the density of the matrix fibers to simulate different tissue environments and to explore the possibility of manipulating the extracellular matrix to achieve pro- and anti-angiogenic effects. The model predicts specific ranges of matrix fiber densities that maximize sprout extension speed, induce branching, or interrupt normal angiogenesis, which are independently confirmed by experiment. We then explore matrix fiber alignment as a key factor contributing to peak sprout velocities and in mediating cell shape and orientation. We also quantify the effects of proteolytic matrix degradation by the tip cell on sprout velocity and demonstrate that degradation promotes sprout growth at high matrix densities, but has an inhibitory effect at lower densities. Our results are discussed in the context of ECM targeted pro- and anti-angiogenic therapies that can be tested empirically.
Stochastic Network Model of Receptor Cross-Talk Predicts Anti-Angiogenic Effects
Amy L. Bauer,Trachette L. Jackson,Yi Jiang,Thimo Rohlf
Physics , 2008,
Abstract: Cancer invasion and metastasis depend on angiogenesis. The cellular processes (growth, migration, and apoptosis) that occur during angiogenesis are tightly regulated by signaling molecules. Thus, understanding how cells synthesize multiple biochemical signals initiated by key external stimuli can lead to the development of novel therapeutic strategies to combat cancer. In the face of large amounts of disjoint experimental data generated from multitudes of laboratories using various assays, theoretical signal transduction models provide a framework to distill this vast amount of data. Such models offer an opportunity to formulate and test new hypotheses, and can be used to make experimentally verifiable predictions. This study is the first to propose a network model that highlights the cross-talk between the key receptors involved in angiogenesis, namely growth factor, integrin, and cadherin receptors. From available experimental data, we construct a stochastic Boolean network model of receptor cross-talk, and systematically analyze the dynamical stability of the network under continuous-time Boolean dynamics with a noisy production function. We find that the signal transduction network exhibits a robust and fast response to external signals, independent of the internal cell state. We derive an input-output table that maps external stimuli to cell phenotypes, which is extraordinarily stable against molecular noise with one important exception: an oscillatory feedback loop between the key signaling molecules RhoA and Rac1 is unstable under arbitrarily low noise, leading to erratic, dysfunctional cell motion. Finally, we show that the network exhibits an apoptotic response rate that increases with noise, suggesting that the probability of programmed cell death depends on cell health.
Agent-Based Modeling of Host-Pathogen Systems: The Successes and Challenges
Amy L. Bauer,Catherine A. A. Beauchemin,Alan S. Perelson
Quantitative Biology , 2008,
Abstract: Agent-based models have been employed to describe numerous processes in immunology. Simulations based on these types of models have been used to enhance our understanding of immunology and disease pathology. We review various agent-based models relevant to host-pathogen systems and discuss their contributions to our understanding of biological processes. We then point out some limitations and challenges of agent-based models and encourage efforts towards reproducibility and model validation.
Using Sequence-Specific Chemical and Structural Properties of DNA to Predict Transcription Factor Binding Sites
Amy L. Bauer,William S. Hlavacek,Pat J. Unkefer,Fangping Mu
PLOS Computational Biology , 2010, DOI: 10.1371/journal.pcbi.1001007
Abstract: An important step in understanding gene regulation is to identify the DNA binding sites recognized by each transcription factor (TF). Conventional approaches to prediction of TF binding sites involve the definition of consensus sequences or position-specific weight matrices and rely on statistical analysis of DNA sequences of known binding sites. Here, we present a method called SiteSleuth in which DNA structure prediction, computational chemistry, and machine learning are applied to develop models for TF binding sites. In this approach, binary classifiers are trained to discriminate between true and false binding sites based on the sequence-specific chemical and structural features of DNA. These features are determined via molecular dynamics calculations in which we consider each base in different local neighborhoods. For each of 54 TFs in Escherichia coli, for which at least five DNA binding sites are documented in RegulonDB, the TF binding sites and portions of the non-coding genome sequence are mapped to feature vectors and used in training. According to cross-validation analysis and a comparison of computational predictions against ChIP-chip data available for the TF Fis, SiteSleuth outperforms three conventional approaches: Match, MATRIX SEARCH, and the method of Berg and von Hippel. SiteSleuth also outperforms QPMEME, a method similar to SiteSleuth in that it involves a learning algorithm. The main advantage of SiteSleuth is a lower false positive rate.
Calcium and Vitamin D increase mRNA levels for the growth control hIK1 channel in human epidermal keratinocytes but functional channels are not observed
Vlasios Manaves, Wuxuan Qin, Amy L Bauer, Sandra Rossie, Masakazu Kobayashi, Stanley G Rane
BMC Dermatology , 2004, DOI: 10.1186/1471-5945-4-7
Abstract: Real-time PCR, patch clamp electrophysiology, and proliferation assays were used to determine if human IK1 (hIK1) expression and function are correlated with either proliferation or differentiation in cultured human skin epidermal keratinocytes, and skin biopsies grown in explant culture.hIK1 mRNA expression in human keratinocytes and skin was increased in response to anti-proliferative/pro-differentiating stimuli (elevated calcium and Vitamin D). Correspondingly, the hIK1 agonist 1-EBIO inhibited keratinocyte proliferation suggesting that the channel could be anti-proliferative and pro-differentiating. However, this proliferative inhibition by 1-EBIO was not reversed by a panel of hIK1 blockers, calling into question the mechanism of 1-EBIO action. Subsequent patch clamp electrophysiological analysis failed to detect hIK1 channel currents in keratinocytes, even those expressing substantial hIK1 mRNA in response to calcium and Vitamin D induced differentiation. Identical electrophysiological recording conditions were then used to observe robust IK1 currents in fibroblasts which express IK1 mRNA levels comparable to those of keratinocytes. Thus, the absence of observable hIK1 currents in keratinocytes was not a function of the electrophysiological techniques.Human keratinocyte differentiation is stimulated by calcium mobilization and influx, and differentiation stimuli coordinately upregulate mRNA levels of the calcium-activated hIK1 channel. This upregulation is paradoxical in that functional hIK1 channels are not observed in cultured keratinocytes. It appears, therefore, that hIK1 does not contribute to the functional electrophysiology of primary human keratinocytes, nor intact human skin. Further, the results indicate caution is required when interpreting experiments utilizing pharmacological hIK1 modulators in human keratinocytes.Intermediate conductance, calcium-activated potassium channels (IKs) stimulate proliferative growth in T-cells and fibroblasts [1,2], v
Identification of N-acetylglucosaminyltranferase-IV as a modifier of Epstein-Barr virus BZLF1 activity  [PDF]
Amy L. Adamson
Open Journal of Genetics (OJGen) , 2013, DOI: 10.4236/ojgen.2013.31001
Abstract:

Epstein-Barr virus is a prevalent human herpesvirus, with about 95% of the world’s adult population positive for anti-EBV antigen antibodies. After the initial infection and production of new virus particles, the virus may enter a latent state within a subset of cells, and therefore can remain within the host indefinitely. Epstein-Barr virus contributes to a variety of diseases, including many types of cancers. We have created a model system in Drosophila melanogaster to study the effect of expression of the Epstein-Barr virus protein BZLF1, and to identify cellular proteins that mediate BZLF1 activity. Here we present the results of a genetic screen that determined that the Drosophila melanogaster CG9384 gene (an N-acetylglucosaminyl-transferase) is a significant modulator of BZLF1 activity and EBV early lytic replication.

An ultrasound elastography method for examining the anterior cruciate ligament  [PDF]
Amy L. Cochran, Yingxin Gao
Natural Science (NS) , 2013, DOI: 10.4236/ns.2013.58A2004
Abstract:

We introduce an ultrasound elastography method for examining the ACL. It consisted of imaging the distal ACL while applying a drawer test and analyzing the resulting displacement and strain maps, where a map refers to how a variable is distributed spatially throughout an image. Our method was applied to healthy knees of cadaveric sheep to determine whether 1) our method can consistently generate displacements and strain maps in healthy ACLs; 2) displacement and strain maps are repeatable; and 3) healthy ACLs experience similar maps. We found that our method could consistently provide displacements and strain maps of the distal ACL region. Moreover, these ACLs experienced displacement and strain maps that were positively-correlated between trials, knees, and specimens. This correlation was statistically significant between pairs of trials and between left and right knees (p < 0.05). These results suggest that the maps are indeed repeatable and similar for healthy ACLs.

Binding of Nucleoid-Associated Protein Fis to DNA Is Regulated by DNA Breathing Dynamics
Kristy Nowak-Lovato,Ludmil B. Alexandrov,Afsheen Banisadr,Amy L. Bauer,Alan R. Bishop,Anny Usheva,Fangping Mu,Elizabeth Hong-Geller,Kim ?. Rasmussen,William S. Hlavacek ,Boian S. Alexandrov
PLOS Computational Biology , 2013, DOI: 10.1371/journal.pcbi.1002881
Abstract: Physicochemical properties of DNA, such as shape, affect protein-DNA recognition. However, the properties of DNA that are most relevant for predicting the binding sites of particular transcription factors (TFs) or classes of TFs have yet to be fully understood. Here, using a model that accurately captures the melting behavior and breathing dynamics (spontaneous local openings of the double helix) of double-stranded DNA, we simulated the dynamics of known binding sites of the TF and nucleoid-associated protein Fis in Escherichia coli. Our study involves simulations of breathing dynamics, analysis of large published in vitro and genomic datasets, and targeted experimental tests of our predictions. Our simulation results and available in vitro binding data indicate a strong correlation between DNA breathing dynamics and Fis binding. Indeed, we can define an average DNA breathing profile that is characteristic of Fis binding sites. This profile is significantly enriched among the identified in vivo E. coli Fis binding sites. To test our understanding of how Fis binding is influenced by DNA breathing dynamics, we designed base-pair substitutions, mismatch, and methylation modifications of DNA regions that are known to interact (or not interact) with Fis. The goal in each case was to make the local DNA breathing dynamics either closer to or farther from the breathing profile characteristic of a strong Fis binding site. For the modified DNA segments, we found that Fis-DNA binding, as assessed by gel-shift assay, changed in accordance with our expectations. We conclude that Fis binding is associated with DNA breathing dynamics, which in turn may be regulated by various nucleotide modifications.
NEOWISE-R Observation of the Coolest Known Brown Dwarf
Edward L. Wright,Amy Mainzer,J. Davy Kirkpatrick,Frank Masci,Michael C. Cushing,James Bauer,Sergio Fajardo-Acosta,Christopher R. Gelino,Charles A. Beichman,M. F. Skrutskie,T. Grav,Peter R. M. Eisenhardt,Roc Cutri
Physics , 2014, DOI: 10.1088/0004-6256/148/5/82
Abstract: The Wide-field Infrared Survey Explorer (WISE) spacecraft has been reactivated as NEOWISE-R to characterize and search for Near Earth Objects. The brown dwarf WISE J085510.83-071442.5 has now been reobserved by NEOWISE-R, and we confirm the results of Luhman (2014b), who found a very low effective temperature ($\approx 250$ K), a very high proper motion (8.1 +/- 0.1 arcsec/yr) , and a large parallax (454 +/- 45 mas). The large proper motion has separated the brown dwarf from the background sources that influenced the 2010 WISE data, allowing a measurement of a very red WISE color of W1-W2 $> 3.9$ mag. A re-analysis of the 2010 WISE astrometry using only the W2 band, combined with the new NEOWISE-R 2014 position, gives an improved parallax of 448 +/- 33 mas and proper motion of 8.08 +/- 0.05\; arcsec/yr. These are all consistent with Luhman (2014b).
Motivational Priming Predicts How Noxious Unconditioned Stimuli Influence Affective Reactions to Emotional Pictures  [PDF]
Amy E. Williams, Jamie L. Rhudy
Psychology (PSYCH) , 2012, DOI: 10.4236/psych.2012.310133
Abstract: Motivational priming theory (MPT) and preparedness theory generate competing hypotheses about the impact of an aversive US on responses to an affective foreground. MPT predicts the aversive US will facilitate negative emotional reactions to unpleasant pictures and inhibit positive emotional reactions to pleasant pictures. Preparedness theory predicts an aversive US will increase negative emotional reactions to unpleasant pictures, but will not impact responses to pleasant pictures. The present study (N = 125) compared these competing hypotheses by assessing how noxious shocks and non-noxious noises influence responses to emotional pictures. Following each picture, participants rated how the picture made them feel using the Self Assessment Manikin. Results supported MPT - noxious USs, but not non-noxious USs, facilitated negative emotional reactions to unpleasant pictures and inhibited positive emotional reactions to pleasant pictures.
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