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Yan F.,00 W. 12th Ave | Alinari L.,00 W. 12th Ave | Martin L.K.,00 W. 12th Ave | Cordero-Nieves H.M.,00 W. 12th Ave | And 19 more authors.
Cancer Research | Year: 2014

Glioblastoma is the most common and aggressive histologic subtype of brain cancer with poor outcomes and limited treatment options. Here, we report the selective overexpression of the protein arginine methyltransferase PRMT5 as a novel candidate theranostic target in this disease. PRMT5 silences the transcription of regulatory genes by catalyzing symmetric dimethylation of arginine residues on histone tails. PRMT5 overexpression in patient-derived primary tumors and cell lines correlated with cell line growth rate and inversely with overall patient survival. Genetic attenuation of PRMT5 led to cell-cycle arrest, apoptosis, and loss of cell migratory activity. Cell death was p53-independent but caspase-dependent and enhanced with temozolomide, a chemotherapeutic agent used as a present standard of care. Global gene profiling and chromatin immunoprecipitation identified the tumor suppressor ST7 as a key gene silenced by PRMT5. Diminished ST7 expression was associated with reduced patient survival. PRMT5 attenuation limited PRMT5 recruitment to the ST7 promoter, led to restored expression of ST7 and cell growth inhibition. Finally, PRMT5 attenuation enhanced glioblastoma cell survival in a mouse xenograft model of aggressive glioblastoma. Together, our findings defined PRMT5 as a candidate prognostic factor and therapeutic target in glioblastoma, offering a preclinical justification for targeting PRMT5-driven oncogenic pathways in this deadly disease.©2014 American Association for Cancer Research. Source


Sirigir V.K.,CWRU | Alzoubi K.,CWRU | Saab D.G.,CWRU | Kocan F.,University of Umm Al - Qura | Tabib-Azar M.,University of Utah
Proceedings - 2010 International Conference on Field Programmable Logic and Applications, FPL 2010 | Year: 2010

Energy efficiency and idle power consumption are becoming important parameters in the design of embedded systems that are realized with nanometer-scale CMOS devices. In nanometer-scale CMOS, Excessive quiescent power dissipation can lead to excessive heat generation and reliability issues. To address energy efficiency and idle power consumption, we present a novel Complementary Nano-Electro-Mechanical (CNEM) switch that we manufactured which operates with virtually zero leakage current, has 1 to 2 Volts operation voltage, > 1 GHZ fundamental resonant frequency, and nanometer-scale footprint. These CNEM switches can be dropped in and hybridized with CMOS at the metallization or device levels to manage leakage current and power. In this paper, we present a hybrid CMOS/CNEMS FPGA. The hybrid FPGA is based on using the CNEM switching device as a replacement of CMOS devices in the switch and connection block components found in FPGA architectures. We analyzed the impact of the CNEM substitution on power and delay using VPR and the MCNC benchmark circuits. We present experimental results showing an average 98%, 85%, 71%, and 99.99% reduction in critical path delay, routing energy, total energy, leakage power when comparisons are made between FPGA design using pure CMOS (180nm technology and hybrid CNEMS and CMOS (180nm) technology. © 2010 IEEE. Source


Harris J.P.,CWRU | Harris J.P.,Rehabilitation Research and Development | Capadona J.R.,CWRU | Capadona J.R.,Rehabilitation Research and Development | And 10 more authors.
Journal of Neural Engineering | Year: 2011

The hypothesis is that the mechanical mismatch between brain tissue and microelectrodes influences the inflammatory response. Our unique, mechanically adaptive polymer nanocomposite enabled this study within the cerebral cortex of rats. The initial tensile storage modulus of 5 GPa decreases to 12 MPa within 15 min under physiological conditions. The response to the nanocomposite was compared to surface-matched, stiffer implants of traditional wires (411 GPa) coated with the identical polymer substrate and implanted on the contralateral side. Both implants were tethered. Fluorescent immunohistochemistry labeling examined neurons, intermediate filaments, macrophages, microglia and proteoglycans. We demonstrate, for the first time, a system that decouples the mechanical and surface chemistry components of the neural response. The neuronal nuclei density within 100 νm of the device at four weeks post-implantation was greater for the compliant nanocomposite compared to the stiff wire. At eight weeks post-implantation, the neuronal nuclei density around the nanocomposite was maintained, but the density around the wire recovered to match that of the nanocomposite. The glial scar response to the compliant nanocomposite was less vigorous than it was to the stiffer wire. The results suggest that mechanically associated factors such as proteoglycans and intermediate filaments are important modulators of the response of the compliant nanocomposite. © 2011 IOP Publishing Ltd. Source


Fujioka H.,Case Western Reserve University | Phelix C.F.,The University of Texas at SanAntonio | Friedland R.P.,University of Louisville | Zhu X.,CWRU | And 2 more authors.
Journal of Health Care for the Poor and Underserved | Year: 2013

ApolipoproteinE 4 (ApoE 4) has been linked to pathogenesis of Alzheimer's disease and has been suggested to be maintained through evolutionary pressure via a protective role in malaria infection. We evaluated Plasmodium falciparum viability at the intraeryth-rocyte stage by exposure to plasma from human subjects with ApoE 4/4 or ApoE 3/3. Plasma samples from ApoE 4/4 but not ApoE 3/3 donors inhibited growth and disrupted morphology of P. falciparum. Evolutionary history is characterized by war between pathogenic microorganisms and defense mechanisms countering their pathogenicities. ApoE 4 frequency is highest in sub- Saharan Africa and other isolated populations (e.g., Papua New Guinea) that exhibit endemic malaria. High ApoE frequency may of er selective advantage protecting against some infectious diseases (e.g., Plasmodium falciparum). These results implicate evolutionary pressure by malaria selecting humans with ApoE 4/4, even considering lower survival in late life. These selective advantages may be relevant in the exploration of possible disparities between Black and Whites in the incidence of Alzheimer's Disease. © Meharry Medical College. Source


News Article
Site: http://phys.org/technology-news/

In addition to audits, the computer program will enable a building owner to assess energy efficiency and elicit the most cost-effective solutions to energy waste. "Before big data analytics, to pinpoint a building's efficiency problems, we had to walk through a building, read sensors and conduct blower door and smoke tests," said Alexis Abramson, a professor of mechanical and aerospace engineering and director of the Great Lakes Energy Institute at Case Western Reserve. "By analyzing at least two years of whole building energy use data, we can uncover some of the same information." Large industrial buildings are often wired to provide owners details of energy consumption, but the practice is uncommon in light commercial buildings, particularly older structures. The national goals of the project are to help ensure that the United States maintains a technological lead in developing and deploying energy efficient technologies, enhance the nation's economic and energy security by improving the energy efficiency of buildings and reduce energy imports as well as harmful emissions. The funding comes from the Advanced Research Projects Agency-Energy (ARPA-E) program. Abramson and Roger French, the F. Alex Nason professor of materials science and engineering at the Case School of Engineering, and Jiayang Sun, professor of epidemiology and biostatistics at the Case Western Reserve School of Medicine, will work with Milwaukee-based Johnson Controls Inc., a world leader in building-efficiency equipment, controls and services, to develop the software over the next three years. The software will assess and analyze multiple streams of data, including climate, weather, the amount of sunshine each day and utility meter records. "The data streams are like DNA, which has codes imbedded in it. It took us a while to understand what these codes meant," Abramson said. "Similarly, we can find out what's going on inside a building by uncovering the codes in the data." The researchers are looking for patterns and correlations in the data that reveal if the heating and ventilation systems are oversized or undersized, when the lights come on, if the building needs better insulation and windows, and more. Using this information, a predictive model, developed from the building's data, can then be created and tested. For example, a building's electric meter may show substantial fluctuation in energy use. If the fluctuation, when tied to many days worth of weather records, is statistically significant, it could signal a leaky building. With that information, the software could build models that would suggest high return-on-investment, energy-efficiency solutions based on predicted performance. The CWRU project is one of 41 nationally to receive funding under ARPA-E OPEN this year. Following contract negotiations, the researchers begin their work this winter. Explore further: Updating building energy codes: How much can your state save?

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