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Search Results: 1 - 10 of 462429 matches for " Chad A. Glazer "
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Dose-Dependent Activation of Putative Oncogene SBSN by BORIS
Daria Gaykalova, Rajita Vatapalli, Chad A. Glazer, Sheetal Bhan, Chunbo Shao, David Sidransky, Patrick K. Ha, Joseph A. Califano
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0040389
Abstract: Testis-specific transcription factor BORIS (Brother of the Regulator of Imprinted Sites), a paralog and proposed functional antagonist of the widely expressed CTCF, is abnormally expressed in multiple tumor types and has been implicated in the epigenetic activation of cancer-testis antigens (CTAs). We have reported previously that suprabasin (SBSN), whose expression is restricted to the epidermis, is epigenetically derepressed in lung cancer. In this work, we establish that SBSN is a novel non-CTA target of BORIS epigenetic regulation. With the use of a doxycycline-inducible BORIS expressing vector, we demonstrate that relative BORIS dosage is critical for SBSN activation. At lower concentrations, BORIS induces demethylation of the SBSN CpG island and disruption and activation of chromatin around the SBSN transcription start site (TSS), resulting in a 35-fold increase in SBSN expression in the H358 human lung cancer cell line. Interestingly, increasing BORIS concentrations leads to a subsequent reduction in SBSN expression via chromatin repression. In a similar manner, increase in BORIS concentrations leads to eventual decrease of cell growth and colony formation. This is the first report demonstrating that different amount of BORIS defines its varied effects on the expression of a target gene via chromatin structure reorganization.
Integrative Discovery of Epigenetically Derepressed Cancer Testis Antigens in NSCLC
Chad A. Glazer,Ian M. Smith,Michael F. Ochs,Shahnaz Begum,William Westra,Steven S. Chang,Wenyue Sun,Sheetal Bhan,Zubair Khan,Steven Ahrendt,Joseph A. Califano
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0008189
Abstract: Cancer/testis antigens (CTAs) were first discovered as immunogenic targets normally expressed in germline cells, but differentially expressed in a variety of human cancers. In this study, we used an integrative epigenetic screening approach to identify coordinately expressed genes in human non-small cell lung cancer (NSCLC) whose transcription is driven by promoter demethylation.
MAGEB2 is Activated by Promoter Demethylation in Head and Neck Squamous Cell Carcinoma
Kavita M. Pattani, Ethan Soudry, Chad A. Glazer, Michael F. Ochs, Hao Wang, Juliana Schussel, Wenyue Sun, Patrick Hennessey, Wojciech Mydlarz, Myriam Loyo, Semra Demokan, Ian M. Smith, Joseph A. Califano
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0045534
Abstract: Purpose Although promoter hypermethylation has been an accepted means of tumor suppressor gene inactivation, activation of otherwise normally repressed proto-oncogenes by promoter demethylation has been infrequently documented. Experimental Design In this study we performed an integrative, whole-genome analysis for discovery of epigenetically activated proto-oncogenes in head and neck cancer tumors. We used the 47K GeneChip U133 Plus 2.0 Affymetrix expression microarray platform to obtain re-expression data from 5-aza treated normal cell line and expression data from primary head and neck squamous cell carcinoma (HNSCC) tumor tissues and normal mucosa tissues. We then investigated candidate genes by screening promoter regions for CpG islands and bisulfite sequencing followed by QUMSP and RT PCR for the best candidate genes. Finally, functional studies were performed on the top candidate gene. Results From the top 178 screened candidates 96 had CpG islands in their promoter region. Seven candidate genes showed promoter region methylation in normal mucosa samples and promoter demethylation in a small cohort of primary HNSCC tissues. We then studied the demethylation of the top 3 candidate genes in an expanded cohort of 76 HNSCC tissue samples and 17 normal mucosa samples. We identified MAGEB2 as having significant promoter demethylation in primary head and neck squamous cell carcinoma tissues. We then found significantly higher expression of MAGEB2 in tumors in a separate cohort of 73 primary HNSCC tissues and 31 normal tissues. Finally, we found that MAGEB2 has growth promoting effects on minimally transformed oral keratinocyte cell lines but not a definite effect on HNSCC cell lines. Conclusion In conclusion, we identified MAGEB2 as activated by promoter demethylation in HNSCCand demonstrates growth promoting effects in a minimally transformed oral keratinocyte cell line. More studies are needed to evaluate MAGBE2's exact role in HNSCC.
Coordinated Activation of Candidate Proto-Oncogenes and Cancer Testes Antigens via Promoter Demethylation in Head and Neck Cancer and Lung Cancer
Ian M. Smith, Chad A. Glazer, Suhail K. Mithani, Michael F. Ochs, Wenyue Sun, Sheetal Bhan, Alexander Vostrov, Ziedulla Abdullaev, Victor Lobanenkov, Andrew Gray, Chunyan Liu, Steven S. Chang, Kimberly L. Ostrow, William H. Westra, Shahnaz Begum, Mousumi Dhara, Joseph Califano
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0004961
Abstract: Background Epigenetic alterations have been implicated in the pathogenesis of solid tumors, however, proto-oncogenes activated by promoter demethylation have been sporadically reported. We used an integrative method to analyze expression in primary head and neck squamous cell carcinoma (HNSCC) and pharmacologically demethylated cell lines to identify aberrantly demethylated and expressed candidate proto-oncogenes and cancer testes antigens in HNSCC. Methodology/Principal Findings We noted coordinated promoter demethylation and simultaneous transcriptional upregulation of proto-oncogene candidates with promoter homology, and phylogenetic footprinting of these promoters demonstrated potential recognition sites for the transcription factor BORIS. Aberrant BORIS expression correlated with upregulation of candidate proto-oncogenes in multiple human malignancies including primary non-small cell lung cancers and HNSCC, induced coordinated proto-oncogene specific promoter demethylation and expression in non-tumorigenic cells, and transformed NIH3T3 cells. Conclusions/Significance Coordinated, epigenetic unmasking of multiple genes with growth promoting activity occurs in aerodigestive cancers, and BORIS is implicated in the coordinated promoter demethylation and reactivation of epigenetically silenced genes in human cancers.
Rapid Lab-Scale Microwave-Assisted Extraction and Analysis of Anthropogenic Organic Chemicals in River Sediments  [PDF]
Thomas J Brown, Chad A Kinney
International Journal of Geosciences (IJG) , 2011, DOI: 10.4236/ijg.2011.23029
Abstract: An Ethos EZ Microwave Lab Station is employed in the development of a robust and efficient microwave extraction method for organic contaminants of anthropogenic origin in river sediments. The extraction method is designed for a small, representative set of target compounds encompassing a range of physicochemical properties. Listed in order of gas chromatography elution they are para-cresol, indole, 4-tert-octylphenol, phenanthrene, triclosan, bisphenol-A, carbamazepine, and benzo [a] pyrene. The sediments samples are extracted wet, which reduces preparation time, and allows the ambient moisture of the sediments to aid in microwave energy absorption and the extraction process. The microwave can hold up to 12 samples that can be simultaneously extracted allowing for rapid sample preparation. Utilizing the pressurized vessels, microwave energy, and a unique mixture of three organic solvents allows for multiple samples to be extracted rapidly with minimal solvent consumption. The final extracts are quantified by gas chromatography/mass spectrometry. Recoveries of the 8 target compounds in sediment range from 49% to 113%, and method detection limits range between 14 and 114 μg kg–1, which are comparable with other more time consuming methods.
The 2D surfaces that generate Newtonian and general relativistic orbits with small eccentricities
Chad A. Middleton
Physics , 2015,
Abstract: Embedding diagrams prove to be quite useful when learning general relativity as they offer a way of visualizing spacetime curvature through warped two dimensional (2D) surfaces. In this manuscript we present a different 2D construct that also serves as a useful conceptual tool for gaining insight into gravitation, in particular, orbital dynamics - namely the cylindrically symmetric surfaces that generate Newtonian and general relativistic orbits with small eccentricities. Although we first show that no such surface exists that can exactly reproduce the arbitrary bound orbits of Newtonian gravitation or of general relativity (or, more generally, of any spherically symmetric potential), surfaces do exist that closely approximate the resulting orbital motion for small eccentricities; exactly the regime that describes the motion of the solar system planets. These surfaces help to illustrate the similarities, as well as the differences, between the two theories of gravitation (i.e. stationary elliptical orbits in Newtonian gravitation and precessing elliptical-like orbits in general relativity) and offer, in this age of 3D printing, an opportunity for students and instructors to experimentally explore the predictions made by each.
A Class of Curves In Every Knot Type Where Chords of High Distortion are Common
Chad A. S. Mullikin
Mathematics , 2006,
Abstract: The distortion of a curve is the supremum, taken over distinct pairs of points of the curve, of the ratio of arclength to spatial distance between the points. Gromov asked in 1981 whether a curve in every knot type can be constructed with distortion less than a universal constant C. Answering Gromov's question seems to require the construction of lower bounds on the distortion of knots in terms of some topological invariant. We attempt to make such bounds easier to construct by showing that pairs of points with high distortion are very common on curves of minimum length in the set of curves in a given knot type with distortion bounded above and distortion thickness bounded below.
A Comparative Study of the Economic Feasibility of Employing CHP Systems in Different Industrial Manufacturing Applications  [PDF]
Chad A. Wheeley, Pedro J. Mago, Rogelio Luck
Energy and Power Engineering (EPE) , 2011, DOI: 10.4236/epe.2011.35079
Abstract: Extensive research work including multiple methodologies and numerous simulations have been completed in order to determine the economic effectiveness of employing CHP at commercial and residential sites. In contrast to the above, very few attempts have been made to develop methodologies to study the feasibility of CHP systems at industrial manufacturing facilities. As a result, practical opportunities for CHP at industrial sites are often not realized or even investigated. It follows that there is a need in the CHP related literature for an analysis that is explicit and yet general enough to determine the economic viability and potential for success of CHP systems at industrial manufacturing facilities. Therefore, the purpose of this paper is to clearly outline a methodology to determine the economic effectiveness of installation and operation of a CHP system at industrial facilities that have a need for space or process heating in the form of steam. The effect on the CHP system economic performance of several parameters, such as the project payback, internal rate of return, net present value, etc., are considered in the proposed methodology. The applicability and generality of the methodology is illustrated by examples including four different manufacturing facilities. The effects of the variability of factors such as annual facility operational hours during which both process heat and electricity are needed, facility average hourly thermal load, cost of utility supplied electricity, and CHP fuel type and associated fuel cost, on the outcome of the economic analysis are also examined.
Post-metabolic response to passive normobaric hypoxic exposure in sedendary overweight males: a pilot study
Workman Chad,Basset Fabien A
Nutrition & Metabolism , 2012, DOI: 10.1186/1743-7075-9-103
Abstract: Background The present pilot study was designed to test the impact of passive acute normobaric hypoxic exposure (PAH) and passive short-term normobaric hypoxic exposure (PSH) conditions on energy expenditure (EE) and substrates utilisation (glucose and lipid oxidation). Methods Eleven participants have completed the PAH session while the control group (CG) underwent a simulated experimental condition in normobaric normoxic condition. A subset of 6 participants underwent an additional six 3-hour sessions on consecutive days. Metabolic rates were obtained pre- and post-treatments on the morning following an overnight (12 hours) fast in PAH, PSH, and CG groups. Results The statistical outcomes showed a significant increase in EE for PAH, control, and PSH while a shift in substrate utilization towards lipid sources was only detected for PAH and PSH, respectively. Conclusion This pilot study showed that passive acute normobaric hypoxic exposure did affect EE and fuel utilization in sedentary overweight males and that further passive normobaric hypoxic exposures (PSH) magnified these metabolic adjustments. These outcomes provide valuable information for further research in the area of hypoxia as a new therapeutic strategy to improve the management of weight loss.
Anisotropic evolution of 5D Friedmann-Robertson-Walker spacetime
Chad A. Middleton,Ethan Stanley
Physics , 2011, DOI: 10.1103/PhysRevD.84.085013
Abstract: We examine the time evolution of the five-dimensional Einstein field equations subjected to a flat, anisotropic Robertson-Walker metric, where the 3D and higher-dimensional scale factors are allowed to dynamically evolve at different rates. By adopting equations of state relating the 3D and higher-dimensional pressures to the density, we obtain an exact expression relating the higher-dimensional scale factor to a function of the 3D scale factor. This relation allows us to write the Friedmann-Robertson-Walker field equations exclusively in terms of the 3D scale factor, thus yielding a set of 4D effective Friedmann-Robertson-Walker field equations. We examine the effective field equations in the general case and obtain an exact expression relating a function of the 3D scale factor to the time. This expression involves a hypergeometric function and cannot, in general, be inverted to yield an analytical expression for the 3D scale factor as a function of time. When the hypergeometric function is expanded for small and large arguments, we obtain a generalized treatment of the dynamical compactification scenario of Mohammedi [Phys.Rev.D 65, 104018 (2002)] and the 5D vacuum solution of Chodos and Detweiler [Phys.Rev.D 21, 2167 (1980)], respectively. By expanding the hypergeometric function near a branch point, we obtain the perturbative solution for the 3D scale factor in the small time regime. This solution exhibits accelerated expansion, which, remarkably, is independent of the value of the 4D equation of state parameter w. This early-time epoch of accelerated expansion arises naturally out of the anisotropic evolution of 5D spacetime when the pressure in the extra dimension is negative and offers a possible alternative to scalar field inflationary theory.
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