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Search Results: 1 - 10 of 301029 matches for " Timothy J Sendera "
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Performance evaluation of commercial short-oligonucleotide microarrays and the impact of noise in making cross-platform correlations
Richard Shippy, Timothy J Sendera, Randall Lockner, Chockalingam Palaniappan, Tamma Kaysser-Kranich, George Watts, John Alsobrook
BMC Genomics , 2004, DOI: 10.1186/1471-2164-5-61
Abstract: In this study, expression measurements for 10,763 genes uniquely represented on Affymetrix U133A/B GeneChips? and Amersham CodeLink? UniSet Human 20 K microarrays were compared. For each microarray platform, five technical replicates, derived from the same total RNA samples, were labeled, hybridized, and quantified according to each manufacturers' standard protocols. The correlation coefficient (r) of differential expression ratios for the entire set of 10,763 overlapping genes was 0.62 between platforms. However, the correlation improved significantly (r = 0.79) when genes within noise were excluded. In addition to levels of inter-platform correlation, we evaluated precision, statistical-significance profiles, power, and noise levels for each microarray platform. Accuracy of differential expression was measured against real-time PCR for 25 genes and both platforms correlated well with r values of 0.92 and 0.79 for CodeLink and GeneChip, respectively.As a result of this study, we recommend using only genes called 'present' in cross-platform correlations. However, as in this study, a large number of genes may be lost from the correlation due to differing levels of noise between platforms. This is an important consideration given the apparent difference in sensitivity of the two platforms. Data from microarray analysis need to be interpreted cautiously and therefore, we provide guidelines for making cross-platform correlations. In all, this study represents the most comprehensive and specifically designed comparison of short-oligonucleotide microarray platforms to date using the largest set of overlapping genes.There are several commercial microarray systems currently available on the market for genome-scale gene expression analysis. Different microarray manufacturers provide distinct underlying technologies, protocols and reagents specific to each system [1]. Despite the widespread use of microarrays, much ambiguity regarding data analysis, interpretation and correla
Combined histomorphometric and gene-expression profiling applied to toxicology
Andres Kriete, Mary K Anderson, Brad Love, John Freund, James J Caffrey, M Brook Young, Timothy J Sendera, Scott R Magnuson, J Mark Braughler
Genome Biology , 2003, DOI: 10.1186/gb-2003-4-5-r32
Abstract: Recent reports describe the use of gene-expression profiling for the identification of molecular markers of toxicity [1-3]. This technique alone does not account for morphological changes in tissues that have traditionally been used by pathologists to discriminate between types and severity of toxicological responses [4-6]. For a comprehensive approach to toxicological evaluation, we developed a unique methodology that uses histomorphometric profiles, derived from machine vision, in conjunction with gene-expression profiles, termed extensible morphometric relational gene-expression analysis (EMeRGE). This novel method was evaluated on an established, extreme model of liver toxicity using carbon tetrachloride (CCl4) in rats that were dosed for 3 days and allowed to recover. Liver is relevant in toxicology as the primary organ of metabolism and detoxification; it is a recurrent target of chronic drug toxicity.A fully automated analytical microscope equipped with machine-vision hardware and software was used to generate quantitative information about the structure and heterogeneity of liver. The histomorphometric profiles could be used to evaluate tissue heterogeneity across the tissue including regions of hepatocellular necrosis. Representative images of tissue sections from control and treated tissues are shown in Figure 1. Examples of processed sample image tiles are shown in Figure 2, where a control liver (Figure 2a) can be compared to a treated liver (Figure 2b), illustrating the significant structural damage induced by treatment with CCl4. Gene-expression profiles were generated from the same livers using DNA microarrays. The microarrays measured mRNA transcription levels of genes important in adsorption, distribution, metabolism and excretion (ADME). Previous studies of these genes, including markers of toxic stress, apoptosis, growth regulation and repair, were consistent with documented toxicologic responses to CCl4, where expression of components of cytochro
Oligodeoxyribonucleotide probe accessibility on a three-dimensional DNA microarray surface and the effect of hybridization time on the accuracy of expression ratios
David R Dorris, Allen Nguyen, Linn Gieser, Randall Lockner, Anna Lublinsky, Marcus Patterson, Edward Touma, Timothy J Sendera, Robert Elghanian, Abhijit Mazumder
BMC Biotechnology , 2003, DOI: 10.1186/1472-6750-3-6
Abstract: We demonstrate solution-phase hybridization behavior of probe:target interactions by showing a strong correlation between the effect of mismatches in probes attached to a three dimensional matrix of a microarray and solution-based, thermodynamic duplex melting studies. The effects of mismatches in the probes attached to the microarray also demonstrate that most, if not all, of the oligodeoxyribonucleotide is available for hybridization. Kinetic parameters were also investigated. As anticipated, hybridization signals increased in a transcript concentration-dependent manner, and mismatch specificity increased with hybridization time. Unexpectedly, hybridization time increased the accuracy of fold changes by relieving the compression observed in expression ratios, and this effect may be more dramatic for larger fold changes.Taken together, these studies demonstrate that a three-dimensional surface may enable use of shorter oligodeoxyribonucleotide probes and that hybridization time may be critical in improving the accuracy of microarray data.DNA microarrays have emerged as a powerful tool to monitor the transcript levels of thousands of genes simultaneously [1,2]. This parallel analysis permits tumor prognosis and classification [3,4], drug target validation [5], toxicology evaluations [6,7], and functional discovery [8,9].The microarray fabrication method can play a key role in the performance of a DNA microarray platform. For example, oligodeoxyribonucleotide probes can be covalently attached to a surface [10], synthesized in situ [11-13], or retained via electrostatic interactions with a positively charged surface [14]. A recent study examining the effect of mismatches along the length of in situ synthesized 60 mer oligodeoxyribonucleotides demonstrated a lack of an effect of mismatches for the first ten to fifteen bases at the 3' (surface) end of the oligodeoxyribonucleotide, suggesting that these bases may not be accessible during the hybridization reaction [12].
Powder River Basin Coal: Powering America  [PDF]
Timothy J. Considine
Natural Resources (NR) , 2013, DOI: 10.4236/nr.2013.48063

Powder River Basin (PRB) coal in Wyoming and Montana is used to produce 18 percent of the electricity consumed in the United States. Coal production from the PRB more than doubled between 1994 and 2009. PRB coal companies produced greater amounts of coal at declining real prices over much of this period through investment in equipment and production systems that achieved massive economies of scale. The bulk of PRB coal is shipped to the middle part of America from Texas in the south to Michigan in the north and New York in the east. States that consume significant amounts of PRB coal have electricity rates well below the national average. The largest industrial users of electricity are in these regions. Replacing PRB coal would require almost 5.5 trillion cubic feet of natural gas per year, representing a 26 percent increase in demand. Such an increase in gas consumption would increase prices for natural gas by roughly 76 percent. In such a world, U.S. energy users would pay $107 billion more each year for electricity and natural gas. Hence, by using PRB coal, the U.S. economy avoids $107 billion per year in higher energy costs. Estimates reported in the literature indicate that the gross environmental damages from PRB coal production are $27 billion. Hence, the net social benefits of PRB coal are $80 billion per year. Given the large size and low cost of these reserves, PRB coal will likely supply societal energy needs well into the future as long as the public and their elected officials are willing to accept the environmental impacts in return for the substantial economic benefits from using PRB coal.

An Integrative Socio-Technical Enterprise Approach to Urban Design/Planning for Sustainable Development  [PDF]
Timothy J. Downs
Open Journal of Civil Engineering (OJCE) , 2018, DOI: 10.4236/ojce.2018.82015
Abstract: Human society locally and globally needs to better understand and respond to ever-more complex, interwoven problems: environmental degradation; climate instability; persistent poverty; disparities in human health; growing income/wealth inequality; economies and infrastructures vulnerable to climate shock; and mounting socio-political unrest. Cities are where most people live, urbanization is a strong upward global trend, and cities bring all these problems into sharp, compelling focus. Since outcomes stem from processes and systems, we argue transformative changes depend on re-imagining the Urban Design, Urban Planning and Urban Development Practice (UD/UP/UDP) process. While there has been insufficient attention to process innovation— with technological aspects tending to dominate UD/UP/UDP work—emerging systems views of cities, and disenchantment with existing modes are enabling. We propose an empirically based integrative frame to tackle recognized conundrums, and inform an adaptive UD/UP/UDP process—from concept through design, assessment, planning, implementation, project functioning and monitoring. The frame contemplates six domains (6-D): 1) Project ethos, concept, and framing; 2) sectors, topics, and issues; 3) Varying spatial and temporal scales; 4) Stakeholder interests, relationships and capacities; 5) Knowledge types, modes and methods; and 6) Socio-technical capacities and networks. The frame, process and outcomes constitute a socio-technical enterprise (STE) approach to UD/UP/UDP work, with implications for education, training, and professional practice. We highlight the pivotal role Integrators and Universities play, and the scalability of STE knowledge/capacity networks. The case of Greater Mexico City/Central Mexico Urban Region illustrates the utility of the approach in a hyper-complex, climate-change vulnerable regional context.
The Economic Impacts of Restrictions on the Transportation of Petroleum Coke  [PDF]
Timothy J. Considine
Natural Resources (NR) , 2019, DOI: 10.4236/nr.2019.103005
Abstract: Petroleum coke is the?third?leading refined petroleum product export from the US behind distillate fuel oil. Legal challenges and proposals could either increase the cost or restrict the transportation of petroleum coke. This paper develops an econometric model of world markets for refined petroleum markets to estimate the effects of such restrictions. The model is used to estimate how supply, demand, trade flows, and prices would adjust under a shutdown of US petroleum coke production. The market impacts are significant, withsubstantially higher prices for jet fuel and petroleum coke, significantly higher prices for gasoline and other products, and sharply lower prices for residual fuel oil. Over a four-year simulation of the model, the US petroleum trade balance deteriorates by $85 billion and consumers pay over $187 and $376 billion more for refined petroleum products in the US and the rest of the world respectively.
The Sociological Determination: A Reflexive Look at Conducting Local Disaster Research after Hurricane Katrina  [PDF]
Timothy J. Haney, James R. Elliott
Sociology Mind (SM) , 2013, DOI: 10.4236/sm.2013.31002

This paper examines the process of collecting data on New Orleanians affected by Hurricane Katrina. It does so by focusing upon the experiences of local researchers who were simultaneously conducting research on and within the disaster. It also documents one research team’s attempt to generate a random sample of residents from several New Orleans neighborhoods, stratified both by racial composition and level of damage. Further, it describes the challenges associated with navigating complex bureaucracies that are themselves affected by the disaster. Results demonstrate that our methods for drawing samples from six New Orleans neighborhoods yielded highly representative samples, even in heavily damaged neighborhoods where the long-term displacement required a multi-pronged strategy that involved contact by mail, telephone, and visits to local churches. The paper concludes by making recommendations for facilitating future research by locally affected researchers.


System for High Throughput Water Extraction from Soil Material for Stable Isotope Analysis of Water  [PDF]
Timothy S. Goebel, Robert J. Lascano
Journal of Analytical Sciences, Methods and Instrumentation (JASMI) , 2012, DOI: 10.4236/jasmi.2012.24031

A major limitation in the use of stable isotope of water in ecological studies is the time that is required to extract water from soil and plant samples. Using vacuum distillation the extraction time can be less than one hour per sample. Therefore, assembling a distillation system that can process multiple samples simultaneously is advantageous and necessary for ecological or hydrological investigations. Presented here is a vacuum distillation apparatus, having six ports, that can process up to 30 samples per day. The distillation system coupled with the Los Gatos Research DLT-100 Liquid Water Isotope Analyzer is capable of analyzing all of the samples that are generated by vacuum distillation. These two systems allow larger sampling rates making investigations into water movement through an ecological system possible at higher temporal and spatial resolution.

Time for cotton to uptake water of a known isotopic signature as measured in leaf petioles  [PDF]
Timothy S. Goebel, Robert J. Lascano
Agricultural Sciences (AS) , 2014, DOI: 10.4236/as.2014.52021

While stable isotopes of water have been used to study water movement through the environment, they generally have not been used to examine shorter, more transient events, e.g., rainfall of <25 mm. With the development of robust methods that use isotope ratio infrared spectrometry, evaluating samples has become faster and simpler, allowing more soil and plant samples to be collected and analyzed. Using larger sampling rates can therefore increase the resolution of changes in stable isotopes within an ecosystem, and allows for a better understanding of how quickly rainwater that enters the soil by infiltration is transpired by a plant via root-water uptake. Quantifying rainwater uptake by plants is essential to increase crop production in rainfed agriculture. Thus the objective of this study was to measure the time required by a plant to transpire water from a source of water with a different isotopic signature than the water that the plant was irrigated. To this end, cotton (Gossypium hirsutum (L.)) plants were grown in a greenhouse and the time required for the enriched water added the soil to show up in the meristematic petioles of cotton leaves was measured. The initial divergence from the irrigation water signature occurred as quickly as 4 hours. The water from the sampled petioles then reached equilibrium with the new source water within 12 hours.

Changes in the Threshold Uncertainty in a Simultaneous Subscription Game  [PDF]
Timothy J. Gronberg, Hui-Chun Peng
Theoretical Economics Letters (TEL) , 2014, DOI: 10.4236/tel.2014.44036

This paper considers a discrete public good subscription game under threshold uncertainty and private information on valuations and analyzes the effect of change in cost uncertainty on the private contribution equilibrium under a simultaneous institution. Comparative statics with respect to the changes in the cost distribution are derived. We find that if the cost distribution becomes more dispersed, in the sense of a mean-preserving spread, the expected total contributions to the public good will decrease. Our proposition provides a policy implication that if the suppliers are able to reduce the uncertainty of the cost distribution, the private contribution to the public good will increase.

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