of previous biological knowledge. The challenge of cancer treatment has been to target specific therapies to pathogenetically distinct tumor types, to maximize efficacy

based on Recursive Feature Elimination (RFE). We demonstrate experimentally that the genes selected by our techniques yield better classification performance and are biologically relevant to cancer. In contrast with the baseline method, our method eliminates gene redundancy automatically and yields

. National Cancer Institute, Frederick Cancer Research and Development Center, Laboratory of Mathematical Biology, P. O. Box B, Frederick, MD 21701. Internet addresses: toms@ncifcrf.gov and stephens@ncifcrf.gov. y corresponding author 1 2. The order of predominance of the residues at every position. 3

and of radiobiology, it seems possible that one factor in aging may be related to deleterious side attacks of free radicals (which are normally produced in the course of cellular metabolism) on cell constituents.' Irradiation of living things induces mutation, cancer, and aging (9). Inasmuch as these also arise

LC–MS/MS glycomic analyses of free and conjugated forms of the sialic acids, Neu5Ac, Neu5Gc and KDN in human throat cancers

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Abstract not found

iii Acknowledgement I would like to thank my mentor Michelle Kelliher for her guidance and support throughout my graduate career. I also appreciate the support, advice and criticism of my committee members, Steven Grossman, Kate Fitzgerald, Tony Ip, Stephen Jones and Adrian Ting. I am grateful to the members of the Kelliher laboratory for their support, encouragement and for helping to provide a fun atmosphere in which to work and learn. I would like to thank Amit Pandey and Christopher Sassetti for their great collaboration in Mycobacterium Tuberculosis work. I would like to thank Zhaozhao Jiang in Kate Fitzgerald’s laboratory for providing the data in Figure 21B and the irf3-/-, irf5-/-, tbk1+/+tnfr1-/- and tbk1-/-tnfr1-/- mice and their littermate controls, Catherine Yin for contributing to the work on Figure 6, and Nicole Hermance and Sarah Morrissey for their help and support with many of the mouse studies.

Survival and maturation of dorsal root ganglia sensory neurons during development depend on target-derived neurotrophins. These target-derived signals must be transmitted across long distances to alter gene expression. Here, we address the possibility that long-range retrograde signals initiated by target-derived neurotrophins activate a specialized transcriptional program. The transcription factor MEF2D is expressed in sensory neurons; we show that expression of this factor is induced in response to target-derived neurotrophins that stimulate the distal axons. We demonstrate that MEF2D regulates expression of an anti-apoptotic bcl-2 family member, bcl-w. Expression of mef2d and bcl-w is stimulated in response to activation of a Trk-dependent ERK5/MEF2 pathway, and our data indicate that this pathway promotes sensory neuron survival. We find that mef2d and bcl-w are members of a larger set of retrograde response genes, which are preferentially induced by neurotrophin stimulation of distal axons. Thus, activation of an ERK5/MEF2D transcriptional program establishes and maintains the cellular constituents of functional sensory circuits.

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