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Modafinil is an increasingly popular wake-promoting drug used for the treatment of narcolepsy, but its precise mechanism of action is unknown. To determine potential pathways via which modafinil acts, we administered a range of doses of modafinil to rats, recorded sleep/wake activity, and studied the pattern of neuronal activation using Fos(More)
Mammalian cells are constantly exposed to a wide variety of genotoxic agents from both endogenous and exogenous sources. Genetic variability in DNA repair may contribute to human cancer risk. We used a case-control study design (162 cases and 302 controls) to test the association between three amino acid substitution variants of DNA repair genes (XRCC1(More)
Mammalian cells are constantly exposed to genotoxic agents from both endogenous and exogenous sources. Genetic variability in DNA repair contributes to deficient repair and breast cancer risk. Using samples collected in an ongoing, clinic-based, case-control study (253 cases and 268 controls), we tested whether breast cancer risk is associated with four(More)
We examined the neuronal targets in the rat brain for the novel wakefulness-promoting agent modafinil and for amphetamine using c-Fos immunohistochemistry. Both modafinil and amphetamine induced neuronal expression of c-Fos-like immunoreactivity in the paraventricular nucleus of the hypothalamus, anterior hypothalamus and central nucleus of the amygdala.(More)
Polycystic kidney disease (PKD) is a common human genetic illness. It is characterized by the formation of multiple kidney cysts that are thought to result from over-proliferation of epithelial cells. Zebrafish larvae can also develop kidney cysts. In an insertional mutagenesis screen in zebrafish, we identified 12 genes that can cause cysts in the(More)
The transport of flagellar precursors and removal of turnover products from the flagellar tip is mediated by intraflagellar transport (IFT) , which is essential for both flagellar assembly and maintenance . Large groups of IFT particles are moved from the flagellar base to the tip by kinesin-2, and smaller groups are returned to the base by cytoplasmic(More)
We address three common misconceptions about capability-based systems: the Equivalence Myth (access control list systems and capability systems are formally equivalent), the Confinement Myth (capability systems cannot enforce confinement), and the Irrevocability Myth (capability-based access cannot be revoked). The Equivalence Myth obscures the benefits of(More)
Proxies are a powerful approach to implement meta-objects in object-oriented languages without having to resort to metacircular interpretation. We introduce such a meta-level API based on proxies for Javascript. We simultaneously introduce a set of design principles that characterize such APIs in general, and compare similar APIs of other languages in terms(More)
Systemic administration of capsaicin and dihydrocapsaicin to adult rats of two different strains and of capsaicin to neonatal rats, depleted substance P levels in dorsal roots plus ganglia and in dorsal spinal cord. In no case was this depletion accompanied by substantially altered tail-flick latencies. The results are not consistent with a role of the(More)
We have identified a bis-ethylthiomethyl analog of K-252a, CEP-1347/KT-7515, that promotes neuronal survival in culture and in vivo. The neuronal survival properties of CEP-1347/KT-7515 may be related to its ability to inhibit the activation of c-jun N-terminal kinase, a key kinase in some forms of stress-induced neuronal death and perhaps apoptosis. There(More)