DNA damaging agents such as cisplatin arrest cell cycle progression at either G1, S, or G2 phase, although the G1 arrest is only seen in cells expressing the wild-type p53 tumor suppressor protein. We have reported that 7-hydroxystaurosporine (UCN-01) overcomes S and G2 phase arrest and enhances the cytotoxicity of cisplatin. Abrogation of arrest appears to be selective for cells defective in p...

Corticotropin releasing factor-binding protein (CRF-BP) binds CRF and urocortin 1 (Ucn 1) with high affinity, thus preventing CRF receptor (CRFR) activation. Despite recent progress on the molecular details that govern interactions between CRF family neuropeptides and their cognate receptors, little is known concerning the mechanisms that allow CRF-BP to bind CRF and Ucn 1 with picomolar affini...

Gemcitabine (dFdC) is an anti-cancer agent that is affected by cell cycle modulation. Staurosporine and 7-hydroxystaurosporine (UCN-01) are potent protein kinase C (PKC) inhibitors as well as inhibitors of cyclin dependent kinase 2 (cdk2) and were therefore investigated for potential synergism, cell cycle modulation, cell death induction, and the role of the p53 protein. Lovo colon cancer cell ...

We study the minimal recurrent spiking neural network of a single neuron with an autaptic synapse. implement system in solid state recently introduced ultracompact (UCN) model, which is based on memristive properties thyristor. The UCN supplemented by self-synaptic, autaptic, connection, where we control feedback. Both excitatory and inhibitory cases are considered. explore systematic behavior ...

The UCNA collaboration is making a precision measurement of the β asymmetry (A) in free neutron decay using polarized ultracold neutrons (UCN). A critical component of this experiment is an adiabatic fast passage neutron spin flipper capable of efficient operation in ambient magnetic fields on the order of 1 T. The requirement that it operate in a high field necessitated the construction of a f...

We present a conceptual design for an experiment to measure the neutron lifetime (~886 s) with an accuracy of 10(-4). The lifetime will be measured by observing the decay rate of a sample of ultracold neutrons (UCN) confined in vacuum in a magnetic trap. The UCN collaboration at Los Alamos National Laboratory has developed a prototype UCN source that is expected to produce a bottled UCN density...

Stress is a perceived perturbation in the environment of the organism that affects numerous extrahypothalamic brain regions including the hippocampus, a limbic structure critical for learning, spatial memory and the regulation of stress hormones. Though many effects of stress on the hippocampus are mediated via local glucocorticoid action, there is now ample evidence for the contributions of th...

The investigational anticancer agent 7-hydroxystaurosporine (UCN-01) abrogates the G2 checkpoint in tumor cells and sensitizes them to the lethal effects of genotoxic anticancer agents. On the basis of the role of the Cdc25C phosphatase in maintenance of this damage-inducible checkpoint, we hypothesized that UCN-01 inhibits a component of the signal transduction pathway that modulates Cdc25C ph...

In response to DNA damage, cells arrest progression through the cell cycle at either G(1), S, or G(2). We have reported that UCN-01 (7-hydroxystaurosporine) abrogates DNA damage-induced S and G(2) arrest and enhances cytotoxicity selectively in p53 mutant cells, thus providing a potential, tumor-targeted therapy. Unfortunately, UCN-01 binds avidly to human plasma proteins, limiting bioavailabil...

We report the full genomic organization of the human gene for the corticotropin-releasing factor (CRF) receptor type 1 (CRFR1), with complete mapping of exons 1-14. The 5' flanking region (2.4 kb) of the gene encoding for human CRFR1 was isolated, sequenced, and characterized. Two major transcriptional start sites were determined at -265 and -238, relative to the ATG start site (+1). Transient ...