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BACKGROUND Cutaneous squamous-cell carcinomas and keratoacanthomas are common findings in patients treated with BRAF inhibitors. METHODS We performed a molecular analysis to identify oncogenic mutations (HRAS, KRAS, NRAS, CDKN2A, and TP53) in the lesions from patients treated with the BRAF inhibitor vemurafenib. An analysis of an independent validation(More)
The grass genus Zea contains the domesticate maize and several wild taxa indigenous to Central and South America. Here we study the genetic consequences of speciation and domestication in this group by sampling DNA sequences from four taxa-maize (Zea mays ssp. mays), its wild progenitor (Z. mays ssp. parviglumis), a more distant species within the genus (Z.(More)
Maize (Zea mays ssp. mays) is genetically diverse, yet it is also morphologically distinct from its wild relatives. These two observations are somewhat contradictory: the first observation is consistent with a large historical population size for maize, but the latter observation is consistent with strong, diversity-limiting selection during maize(More)
The virilis phylad of the Drosophila virilis group consists of five closely related taxa: D. virilis, D. lummei, D. novamexicana, D. americana americana and D. americana texana. DNA sequences from a 2.1-kb pair portion of the period locus were generated in four to eight individuals from each of the five taxa. We found evidence of recombination and high(More)
The p53 tumor suppressor retains its wild-type conformation and transcriptional activity in half of all human tumors, and its activation may offer a therapeutic benefit. However, p53 function could be compromised by defective signaling in the p53 pathway. Using a small-molecule MDM2 antagonist, nutlin-3, to probe downstream p53 signaling we find that the(More)
The historical population genetic processes associated with the divergence of members of the Drosophila irilis species group were examined using DNA sequence variation from two loci. New data on DNA sequence variation from the oskar locus, taken from within and among all five closely related taxa in the irilis phylad of the D. irilis species group, were(More)
Exosomes are bioactive vesicles derived from the cell's endosomal membrane system and secreted into surrounding body fluids. Exosomes contain cell and cell-state specific cargos of protein, mRNA and miRNA. Exosome formation, cargo content, and delivery to surrounding cells is of immense biological interest considering the role that exosomes are believed to(More)
Several studies of intraspecific and interspecific DNA sequence variation from Drosophila loci have revealed a pattern of low intraspecific variation from genomic regions of low recombination. The mechanisms consistently invoked to explain these patterns are the selective sweep of advantageous mutations together with genetic hitchhiking of linked loci. To(More)
The identification and validation of biomarkers to support the assessment of novel therapeutics for COPD continues to be an important area of research. The aim of the current study was to identify systemic protein biomarkers correlated with measures of COPD severity, as well as specific protein signatures associated with comorbidities such as metabolic(More)
Notch signaling is an area of great interest in oncology. RO4929097 is a potent and selective inhibitor of gamma-secretase, producing inhibitory activity of Notch signaling in tumor cells. The RO4929097 IC50 in cell-free and cellular assays is in the low nanomolar range with >100-fold selectivity with respect to 75 other proteins of various types(More)