ABSTRACT
A free space collective Thomson scattering system has been developed to study pulsed power produced plasmas. While most Thomson scattering diagnostics on pulsed power machines use a bundle of fibers to couple scattered light from the plasma to the spectrometer, this system used free space coupling of the light, which enabled a spatially continuous image of the plasma. Initial experiments with this diagnostic were performed on an inverse wire array generated by a 200 kA, 1100 ns rise time pulse power generator. The capabilities of this diagnostic were demonstrated by using the low frequency ion acoustic wave feature of the Thomson scattering spectra to measure the plasma flow velocity. The diagnostic was demonstrated to measure velocities between 20 and 40 km/s with an error of 4.7 km/s when fitting with a 600 µm spatial resolution or 8.9 km/s when fitting with a 150 µm spatial resolution. In some experiments, the diagnostic observed a bow shock in the plasma flow as the scattering intensity increased and flow velocity decreased.
ABSTRACT
Caspase-2 is an atypical caspase that regulates apoptosis, cell cycle arrest and genome maintenance, although the mechanisms are not well understood. Caspase-2 has also been implicated in chemotherapy response in lung cancer, but this function has not been addressed in vivo. Here we show that Caspase-2 functions as a tumor suppressor in Kras-driven lung cancer in vivo. Loss of Caspase-2 leads to enhanced tumor proliferation and progression. Despite being more histologically advanced, Caspase-2-deficient tumors are sensitive to chemotherapy and exhibit a significant reduction in tumor volume following repeated treatment. However, Caspase-2-deficient tumors rapidly rebound from chemotherapy with enhanced proliferation, ultimately hindering long-term therapeutic benefit. In response to DNA damage, Caspase-2 cleaves and inhibits Mdm2 and thereby promotes the stability of the tumor-suppressor p53. Caspase-2 expression levels are significantly reduced in human lung tumors with wild-type p53, in agreement with the model whereby Caspase-2 functions through Mdm2/p53 regulation. Consistently, p53 target genes including p21, cyclin G1 and Msh2 are reduced in Caspase-2-deficient tumors. Finally, we show that phosphorylation of p53-induced protein with a death domain 1 leads to Caspase-2-mediated cleavage of Mdm2, directly impacting p53 levels, activity and chemotherapy response. Together, these studies elucidate a Caspase-2-p53 signaling network that impacts lung tumorigenesis and chemotherapy response in vivo.
Subject(s)
Caspase 2/metabolism , Cysteine Endopeptidases/metabolism , Lung Neoplasms , Neoplasm Proteins/metabolism , Neoplasms, Experimental , Signal Transduction , Animals , Caspase 2/genetics , Cell Line, Tumor , Cell Proliferation , Cysteine Endopeptidases/genetics , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/enzymology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mice , Neoplasm Proteins/genetics , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/enzymology , Neoplasms, Experimental/genetics , Neoplasms, Experimental/pathologyABSTRACT
Since the inception of Fort Leavenworth as Cantonment Leavenworth on May 8, 1827, there have been four hospitals located on the post. With the health care of the command being paramount, each hospital has functioned to provide health services to the command, dependents, and the retirement community of the Armed Forces within its respective era of operation.
