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Search Results: 1 - 10 of 208638 matches for " Lyle L Moldawer "
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A dynamic network of transcription in LPS-treated human subjects
Junhee Seok, Wenzhong Xiao, Lyle L Moldawer, Ronald W Davis, Markus W Covert
BMC Systems Biology , 2009, DOI: 10.1186/1752-0509-3-78
Abstract: In this study, we analyzed a gene expression data set in blood leukocytes from human subjects administered with lipopolysaccharide (LPS), a prototypical inflammatory challenge, in the context of a reconstructed regulatory network including 10 transcription factors, 99 target genes and 149 regulatory interactions. We found that the computationally estimated activities were well correlated to their coordinated action. Furthermore, we found that clustering the genes in the context of regulatory influences greatly facilitated interpretation of the expression data, as clusters of gene expression corresponded to the activity of specific factors or more interestingly, factor combinations which suggest coordinated regulation of gene expression. The resulting clusters were therefore more biologically meaningful, and also led to identification of additional genes under the same regulation.Using NCA, we were able to build a network that accounted for between 8–11% genes in the known transcriptional response to LPS in humans. The dynamic network illustrated changes of transcription factor activities and gene expressions as well as interactions of signaling proteins, transcription factors and target genes.An achievement that would have a major impact on our understanding of transcriptional regulatory networks would be to map out the coordinated dynamic responses of signaling proteins, transcription factors and target genes over time. The primary challenges to such an effort are development of high-throughput technologies to measure transcription factor activities at the genome-scale, and computational tools to interpret the data and predict the structure and dynamics of the underlying networks.Recent development of high-throughput technologies has enabled large-scale measurements of biological signals related to transcription, such as the expression of target genes and the activities of transcription factors. For target gene expression, microarrays measure the expression levels
Identification and Interpretation of Longitudinal Gene Expression Changes in Trauma
Natasa Rajicic,Joseph Cuschieri,Dianne M. Finkelstein,Carol L. Miller-Graziano,Douglas Hayden,Lyle L. Moldawer,Ernest Moore,Grant O'Keefe,Kimberly Pelik,H. Shaw Warren,David A. Schoenfeld
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0014380
Abstract: The relationship between leukocyte gene expression and recovery of respiratory function after injury may provide information on the etiology of multiple organ dysfunction.
Host Responses to Sepsis Vary in Different Low-Lethality Murine Models
Lori F. Gentile, Dina C. Nacionales, M. Cecilia Lopez, Erin Vanzant, Angela Cuenca, Benjamin E. Szpila, Alex G. Cuenca, Anna Joseph, Frederick A. Moore, Christiaan Leeuwenburgh, Henry V. Baker, Lyle L. Moldawer, Philip A. Efron
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0094404
Abstract: Introduction Animal models for the study of sepsis are being increasingly scrutinized, despite their essential role for early translational research. In particular, recent studies have suggested that at the level of the leukocyte transcriptome, murine models of burns, trauma and endotoxemia markedly differ from their human equivalents, and are only weakly similar amongst themselves. We compared the plasma cytokine and leukocyte transcriptome responses between two different low-lethality murine models of polymicrobial intra-abdominal sepsis. Methods Six to ten week male C57BL/6j mice underwent either the ‘gold standard’ cecal ligation and puncture (CLP) model of intra-abdominal sepsis or administration of a cecal slurry (CS), where cecal contents are injected intraperitoneally. Surviving mice were euthanized at two hours, one or three days after sepsis. Results The murine leukocyte transcriptomic response to the CLP and CS models of sepsis was surprisingly dissimilar at two hours, one, and three days after sepsis. The Pearson correlation coefficient for the maximum change in expression for the entire leukocyte transcriptome that changed significantly over time (n = 19,071) was R = 0.54 (R2 = 0.297). The CS model resulted in greater magnitude of early inflammatory gene expression changes in response to sepsis with associated increased production of inflammatory chemokines and cytokines. Two hours after sepsis, CLP had more significant expression of genes associated with IL-10 signaling pathways, whereas CS had greater expression of genes related to CD28, apoptosis, IL-1 and T-cell receptor signaling. By three days, the changes in gene expression in both sepsis models were returning to baseline in surviving animals. Conclusion These analyses reveal that the murine blood leukocyte response to sepsis is highly dependent on which model of intra-abdominal sepsis is employed, despite their similar lethality. It may be difficult to extrapolate findings from one murine model to another, let alone to human sepsis.
The Potential Influence of Common Viral Infections Diagnosed during Hospitalization among Critically Ill Patients in the United States
Makesha Miggins,Anjum Hasan,Samuel Hohmann,Frederick Southwick,George Casella,Denise Schain,Huazhi Liu,Azra Bihorac,Lyle Moldawer,Philip Efron,Darwin Ang
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0018890
Abstract: Viruses are the most common source of infection among immunocompetent individuals, yet they are not considered a clinically meaningful risk factor among the critically ill. This work examines the association of viral infections diagnosed during the hospital stay or not documented as present on admission to the outcomes of ICU patients with no evidence of immunosuppression on admission. This is a population-based retrospective cohort study of University HealthSystem Consortium (UHC) academic centers in the U.S. from the years 2006 to 2009. The UHC is an alliance of over 90% of the non-profit academic medical centers in the U.S. A total of 209,695 critically ill patients were used in this analysis. Eight hospital complications were examined. Patients were grouped into four cohorts: absence of infection, bacterial infection only, viral infection only, and bacterial and viral infection during same hospital admission. Viral infections diagnosed during hospitalization significantly increased the risk of all complications. There was also a seasonal pattern for viral infections. Specific viruses associated with poor outcomes included influenza, RSV, CMV, and HSV. Patients who had both viral and bacterial infections during the same hospitalization had the greatest risk of mortality RR 6.58, 95% CI (5.47, 7.91); multi-organ failure RR 8.25, 95% CI (7.50, 9.07); and septic shock RR 271.2, 95% CI (188.0, 391.3). Viral infections may play a significant yet unrecognized role in the outcomes of ICU patients. They may serve as biological markers or play an active role in the development of certain adverse complications by interacting with coincident bacterial infection.
Effect of Terrestrial LiDAR Point Sampling Density in Ephemeral Gully Characterization  [PDF]
Henrique G. Momm, Ronald L. Bingner, Robert R. Wells, Seth M. Dabney, Lyle D. Frees
Open Journal of Modern Hydrology (OJMH) , 2013, DOI: 10.4236/ojmh.2013.31006
Abstract:

Gully erosion can account for significant volumes of sediment exiting agricultural landscapes, but is difficult to monitor and quantify its evolution with traditional surveying technology. Scientific investigations of gullies depend on accurate and detailed topographic information to understand and evaluate the complex interactions between field topography and gully evolution. Detailed terrain representations can be produced by new technologies such as terrestrial LiDAR systems. These systems are capable of collecting information with a wide range of ground point sampling densities as a result of operator controlled factors. Increasing point density results in richer datasets at a cost of increased time needed to complete field surveys. In large research watersheds, with hundreds of sites being monitored, data collection can become costly and time consuming. In this study, the effect of point sampling density on the capability to collect topographic information was investigated at individual gully scale. This was performed through the utilization of semi-variograms to produce overall guiding principles for multi-temporal gully surveys based on various levels of laser sampling points and relief variation (low, moderate, and high). Results indicated the existence of a point sampling density threshold that produces little or no additional topographic information when exceeded. A reduced dataset was created using the density thresholds and compared to the original dataset with no major discrepancy. Although variations in relief and soil roughness can lead to different point sampling density requirements, the outcome of this study serves as practical guidance for future field surveys of gully evolution and erosion.

Leptin in Teleost Fishes: An Argument for Comparative Study
Donald L. Copeland,Richard Lyle Londraville
Frontiers in Physiology , 2011, DOI: 10.3389/fphys.2011.00026
Abstract: All organisms face tradeoffs with regard to how limited energy resources should be invested. When is it most favorable to grow, to reproduce, how much lipid should be allocated to storage in preparation for a period of limited resources (e.g., winter), instead of being used for growth or maturation? These are a few of the high consequence fitness “decisions” that represent the balance between energy acquisition and allocation. Indeed, for animals to make favorable decisions about when to grow, eat, or reproduce, they must integrate signals among the systems responsible for energy acquisition, storage, and demand. We make the argument that leptin signaling is a likely candidate for an integrating system. Great progress has been made understanding the leptin system in mammals, however our understanding in fishes has been hampered by difficulty in cloning fish orthologs of mammalian proteins and (we assert), underutilization of the comparative approach.
MIPHENO: data normalization for high throughput metabolite analysis
Shannon M Bell, Lyle D Burgoon, Robert L Last
BMC Bioinformatics , 2012, DOI: 10.1186/1471-2105-13-10
Abstract: Here we describe MIPHENO (Mutant Identification by Probabilistic High throughput-Enabled Normalization), an approach for post-hoc normalization of quantitative first-pass screening data in the absence of explicit in-group controls. This approach includes a quality control step and facilitates cross-experiment comparisons that decrease the false non-discovery rates, while maintaining the high accuracy needed to limit false positives in first-pass screening. Results from simulation show an improvement in both accuracy and false non-discovery rate over a range of population parameters (p < 2.2 × 10-16) and a modest but significant (p < 2.2 × 10-16) improvement in area under the receiver operator characteristic curve of 0.955 for MIPHENO vs 0.923 for a group-based statistic (z-score). Analysis of the high throughput phenotypic data from the Arabidopsis Chloroplast 2010 Project (http://www.plastid.msu.edu/ webcite) showed ~ 4-fold increase in the ability to detect previously described or expected phenotypes over the group based statistic.Results demonstrate MIPHENO offers substantial benefit in improving the ability to detect putative mutant phenotypes from post-hoc analysis of large data sets. Additionally, it facilitates data interpretation and permits cross-dataset comparison where group-based controls are missing. MIPHENO is applicable to a wide range of high throughput screenings and the code is freely available as Additional file 1 as well as through an R package in CRAN.High-throughput screening studies in biology and other fields are increasingly popular due to ease of sample tracking and decreasing technology costs. These experimental setups enable researchers to obtain numerous measurements across multiple individuals in parallel (e.g. gene expression and diverse plate-based assays) or in series (e.g. metabolomics and proteomics platforms). The large number of measurements collected often comes at the cost of measurement precision or the overall power of detect
Epidemic Intelligence. Langmuir and the Birth of Disease Surveillance
Lyle Fearnley
Behemoth : a Journal on Civilisation , 2010,
Abstract: In the wake of the SARS and influenza epidemics of the past decade, one public health solution has become a refrain: surveillance systems for detection of disease outbreaks. This paper is an effort to understand how disease surveillance for outbreak detection gained such paramount rationality in contemporary public health. The epidemiologist Alexander Langmuir is well known as the creator of modern disease surveillance. But less well known is how he imagined disease surveillance as one part of what he called “epidemic intelligence.” Langmuir developed the practice of disease surveillance during an unprecedented moment in which the threat of biological warfare brought civil defense experts and epidemiologists together around a common problem. In this paper, I describe how Langmuir navigated this world, experimenting with new techniques and rationales of epidemic control. Ultimately, I argue, Langmuir′s experiments resulted in a set of techniques and infrastructures – a system of epidemic intelligence – that transformed the epidemic as an object of human art.
Narrative Form and the Structure of Myth
Emily Lyle
Folklore : Electronic Journal of Folklore , 2006,
Abstract: At each stage in transmission of a tale from generation to generation, modifications take place but something remains. Thus there is a potential for material to be retained from a time in the distant past when the narrative was embedded in a total oral worldview or cosmology. This article introduces the analogical discovery method and uses it to build up a structure based on a group of tales from Greece , Ireland and Wales. It draws the conc lusion that the structure of myth that is indirectly discernible through them deals with four generations, both of gods and of humans, the last of which contains the king. It agrees with the view proposed by Georges Dumézil that myth reflects human social organisation and argues in addition that matrilineal succession to kingship provides a good fit with the tales. The suggestion is put forward that there was a total, quite complex, cosmological code of which narratives retain traces and that scholars today have the opportunity of decipheringit.
Vaenulike kaksikute positsioon etteantud teogoonilises struktuuris
Emily Lyle
M?etagused. Hüperajakiri , 2002,
Abstract: Comparative mythology needs to consider two parallel pairs of twins. One is the pair of antagonistic twins, the other the Ashvin pair of twins found in the Vedas. Often they are treated only as simply a pair, the personification of fertility and prosperity. One of them is the cattle-breeder-twin and the other horseman-twin. In Roman mythology, the Ashvin twins are Castor and Pollux; in the Jewish legend, Esav and Jacob. The topic of the first birth of the twins is more clearly treated in the versions of the antagonistic twins. E.g. the zervanistic god of light Ohrmazd and god of darkness Ahriman; in Roman mythology, Romulus and Remus. Characteristic of the story of the antagonistic twins is the argument over which will become the ruler, i.e. they are royal twins and their royal descent is as important in their identification as their antagonism. Thus, the theogony peaking with the birth of the antagonistic twins is only applicable in a society ruled by a king.
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