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Acknowledgments Many agencies, organizations, and individuals contributed their time, energy, and expertise to the completion of this report. The author would like to specifically recognize the following individuals for their contributions. Peer review of the manuscript was provided by the following technical experts: Ms. This report is the culmination of(More)
Although DNA damaging agents have revolutionized chemotherapy against solid tumors, a narrow therapeutic window combined with severe side effects has limited their broader use. Here we show that RAD001 (everolimus), a rapamycin derivative, dramatically enhances cisplatin-induced apoptosis in wild-type p53, but not mutant p53 tumor cells. The use of isogenic(More)
Double stranded, short interfering RNAs (siRNA) of 21-22 nt length initiate a sequence-specific, post-trancriptional gene silencing in animals and plants known as RNA interference (RNAi). Here we show that RNAi can block a pathophysiological pain response and provide relief from neuropathic pain in a rat disease model by down regulating an endogenous,(More)
The excitation of nociceptive sensory neurons by ATP released in injured tissue is believed to be mediated partly by P2X3 receptors. Although an analysis of P2X3 knock-out mice has revealed some deficits in nociceptive signaling, detailed analysis of the role of these receptors is hampered by the lack of potent specific pharmacological tools. Here we have(More)
Human cells have evolved complex signaling networks to coordinate the cell cycle. A detailed understanding of the global regulation of this fundamental process requires comprehensive identification of the genes and pathways involved in the various stages of cell-cycle progression. To this end, we report a genome-wide analysis of the human cell cycle, cell(More)
BACKGROUND The mitotic spindle is a complex mechanical apparatus required for accurate segregation of sister chromosomes during mitosis. We designed a genetic screen using automated microscopy to discover factors essential for mitotic progression. Using a RNA interference library of 49,164 double-stranded RNAs targeting 23,835 human genes, we performed a(More)
Synthetic 21-bp-long short interfering RNAs (siRNA) can stimulate sequence-specific mRNA degradation in mammalian cell cultures, a process referred to as RNA interference (RNAi). In the present study, the potential of RNAi was compared to the traditional antisense approach, acting mainly via RnaseH, for targeting the recombinant rat pain-related(More)
Prefetching is a widely used consumer-initiated mechanism to hide communication latency in shared-memory multiprocessors. However, prefetching is inapplicable or insuucient for some communication patterns such as irregular communication, pipelined loops, and synchronization. For these cases, a combination of two ne-grain, producer-initiated primitives(More)
Microarrays to examine the global expression levels of microRNAs (miRNAs) in a systematic in-parallel manner have become important tools to help unravel the functions of miRNAs and to understand their roles in RNA-based regulation and their implications in human diseases. We have established a novel miRNA-specific microarray platform that enables the(More)
nucleotide sequence. This has not presented a hurdle for the routine laboratory use of siRNAs as a biological tool, as reagents are usually characterized before initiating extensive experimentation. Reagents that perform unsatisfactorily are simply replaced. However, genome-wide libraries of human RNAi reagents for high-throughput gene screening will(More)