An imaging neutron/gamma-ray spectrometer

We present the test results of a neutron/gamma-ray imaging spectrometer for the identification and location of radioactive and special nuclear materials. Radioactive materials that could be fashioned into a radiation dispersal device typically emit gamma rays, while fissile materials such as uranium and plutonium emit both neutrons and gamma rays via spontaneous or induced fission. The simultaneous detection of neutrons and gamma rays is a clear indication of the presence of fissile material. The instrument works as a double-scatter telescope, requiring a neutron or gamma ray to undergo an interaction in two detectors to be considered a valid event. While this requirement reduces the detector efficiency, it yields information about the direction and energy of the incident particle, which is then used to reconstruct an image of the emitting source. Because of this imaging capability background events can be rejected, decreasing the number of events required for high confidence detection and thereby greatly improving its sensitivity. The instrument is optimized for the detection of neutrons with energies from 1-20 MeV and gamma rays from 0.4 to 10 MeV. Images and energy spectra for neutron and gamma rays are reported for several sources including depleted uranium and plutonium. In addition, the effect of neutron source shielding is investigated

Novel Analogue of Colchicine Induces Selective Pro-Death Autophagy and Necrosis in Human Cancer Cells

Colchicine, a natural product of Colchicum autumnae currently used for gout treatment, is a tubulin targeting compound which inhibits microtubule formation by targeting fast dividing cells. This tubulin-targeting property has lead researchers to investigate the potential of colchicine and analogs as possible cancer therapies. One major study conducted on an analogue of allocolchicine, ZD 6126, was halted in phase 2 clinical trials due to severe cardio-toxicity associated with treatment. This study involves the development and testing of novel allocolchicine analogues that hold non-toxic anti-cancer properties. Currently we have synthesized and evaluated the anti-cancer activities of two analogues; N-acetyl-O-methylcolchinol (NSC 51046 or NCME), which is structurally similar to ZD 6126, and (S)-3,8,9,10-tetramethoxyallocolchicine (Green 1), which is a novel derivative of allocolchicine that is isomeric in the A ring. NSC 51046 was found to be non-selective as it induced apoptosis in both BxPC-3 and PANC-1 pancreatic cancer cells and in normal human fibroblasts. Interestingly, we found that Green 1 was able to modestly induce pro-death autophagy in these pancreatic cancer cells and E6-1 leukemia cells but not in normal human fibroblasts. Unlike colchicine and NSC 51046, Green 1 does not appear to affect tubulin polymerization indicating that it has a different molecular target. Green 1 also caused increased reactive oxygen species (ROS) production in mitochondria isolated from pancreatic cancer cells. Furthermore, in vivo studies revealed that Green 1 was well tolerated in mice. Our findings suggest that a small change in the structure of colchicine has apparently changed the mechanism of action and lead to improved selectivity. This may lead to better selective treatments in cancer therapy

An imaging neutron/gamma-ray spectrometer

We present the design and development of a dual-species, neutron/γ-ray imaging spectrometer for the identification and location of radioactive and special nuclear materials (SNM). Real-time detection and identification is important for locating fissile materials. These materials, specifically uranium and plutonium, emit neutrons and γ rays via spontaneous or induced fission. Co-located neutron and γ-ray emissions are a sure sign of fissile material, requiring very few spatially correlated events for a significant detection. Our instrument design detects neutrons and γ rays from all sources in its field of view, constructs images of the emission pattern, and reports the spectra for both species. The detection principle is based upon multiple elastic neutron-proton scatters in organic scintillator for neutrons, and Compton scattering in organic scintillator followed by photoelectric absorption in inorganic scintillator for γ rays. The instrument is optimized for neutron imaging and spectroscopy in the 1-20 MeV range. We recorded images and spectra of a Cf-252 source from 0.5 - 10 MeV, and have done similarly for several γ-ray sources. We report the results of laboratory testing of this expanded instrument and compare them to detailed Monte Carlo simulations using Geant4

A portable neutron spectroscope (NSPECT) for detection, imaging and identification of nuclear material

We have developed, fabricated and tested a prototype imaging neutron spectrometer designed for real-time neutron source location and identification. Real-time detection and identification is important for locating materials. These materials, specifically uranium and transuranics, emit neutrons via spontaneous or induced fission. Unlike other forms of radiation (e.g. gamma rays), penetrating neutron emission is very uncommon. The instrument detects these neutrons, constructs images of the emission pattern, and reports the neutron spectrum. The device will be useful for security and proliferation deterrence, as well as for nuclear waste characterization and monitoring. The instrument is optimized for imaging and spectroscopy in the 1-20 MeV range. The detection principle is based upon multiple elastic neutron-proton scatters in organic scintillator. Two detector panel layers are utilized. By measuring the recoil proton and scattered neutron locations and energies, the direction and energy spectrum of the incident neutrons can be determined and discrete and extended sources identified. Event reconstruction yields an image of the source and its location. The hardware is low power, low mass, and rugged. Its modular design allows the user to combine multiple units for increased sensitivity. We will report the results of laboratory testing of the instrument, including exposure to a calibrated Cf-252 source. Instrument parameters include energy and angular resolution, gamma rejection, minimum source identification distances and times, and projected effective area for a fully populated instrument

Precise U-Pb zircon ages and geochemistry of Jurassic granites, Ellsworth-Whitmore terrane, central Antarctica

The Ellsworth-Whitmore Mountain terrane of central Antarctica was part of the early Paleozoic amalgamation of Gondwana, including a 13,000 m section of Cambrian–Permian sediments in the Ellsworth Mountains deposited on Grenville-age crust. The Jurassic breakup of Gondwana involved a regional, bimodal magmatic event during which the Ellsworth-Whitmore terrane was intruded by intraplate granites before translation of the terrane to its present location in central Antarctica. Five widely separated granitic plutons in the Ellsworth-Whitmore terrane were analyzed for their whole-rock geochemistry (X-ray fluorescence), Sr, Nd, and Pb isotopic compositions, and U-Pb zircon ages to investigate the origins of the terrane magmas and their relationships to mafic magmatism of the 183 Ma Karoo-Ferrar large igneous province (LIP). We report high-precision (±0.1 m.y.) isotope dilution–thermal ionization mass spectrometry (ID-TIMS) U-Pb zircon ages from granitic rocks from the Whitmore Mountains (208.0 Ma), Nash Hills (177.4–177.3 Ma), Linck Nunatak (175.3 Ma), Pagano Nunatak (174.8 Ma), and the Pirrit Hills (174.3–173.9 Ma), and U-Pb sensitive high-resolution ion microprobe (SHRIMP) ages from the Whitmore Mountains (200 ± 5 Ma), Linck Nunatak (180 ± 4 Ma), Pagano Nunatak (174 ± 4 Ma), and the Pirrit Hills (168 ± 4 Ma). We then compared these results with existing K-Ar ages and Nd model ages, and used initial Sr, Nd, and Pb isotope ratios, combined with xenocrystic zircon U-Pb inheritance, to infer characteristics of the source(s) of the parent magmas. We conclude that the Jurassic plutons were not derived exclusively from crustal melts, but rather they are hybridized magmas composed of convecting mantle, subcontinental lithospheric mantle, and lower continental crustal contributions. The mantle contributions to the granites share isotopic similarities to the sources of other Jurassic LIP mafic magmas, including radiogenic 87Sr/86Sr (0.706–0.708), unradiogenic 143Nd/144Nd (εNd < –5), and Pb isotopes consistent with a low-µ source (where μ = 238U/204Pb). Isotopes and zircon xenocrysts point toward a crustal end member of predominantly Proterozoic provenance (0.5–1.0 Ga; Grenville crust), extending the trends illustrated by Ferrar mafic intrusive rocks, but contrasting with the inferred Archean crustal and/or lithospheric mantle contributions to some basalts of the Karoo sector of the LIP. The Ellsworth-Whitmore terrane granites are the result of mafic rocks underplating the hydrous crust, causing crustal melting, hybridization, and fractionation to produce granitic magmas that were eventually emplaced as post-Ferrar, within-plate melts at higher crustal levels as the Ellsworth-Whitmore terrane rifted off Gondwana (47°S) before migrating to its current position (82°S) in central Antarctica

Three-dimensional mapping of fluorescent dye using a scanning, depth-resolving airborne lidar

Author Posting. © American Meteorological Society, 2007. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Atmospheric and Oceanic Technology 24 (2007): 1050-1065, doi:10.1175/JTECH2027.1.Results are presented from a pilot study using a fluorescent dye tracer imaged by airborne lidar in the ocean surface layer on spatial scales of meters to kilometers and temporal scales of minutes to hours. The lidar used here employs a scanning, frequency-doubled Nd:YAG laser to emit an infrared (1064 nm) and green (532 nm) pulse 6 ns in duration at a rate of 1 kHz. The received signal is split to infrared, green, and fluorescent (nominally 580–600 nm) channels, the latter two of which are used to compute absolute dye concentration as a function of depth and horizontal position. Comparison of dye concentrations inferred from the lidar with in situ fluorometry measurements made by ship shows good agreement both qualitatively and quantitatively for absolute dye concentrations ranging from 1 to >10 ppb. Uncertainties associated with horizontal variations in the natural seawater attenuation are approximately 1 ppb. The results demonstrate the ability of airborne lidar to capture high-resolution three-dimensional “snapshots” of the distribution of the tracer as it evolves over very short time and space scales. Such measurements offer a powerful observational tool for studies of transport and mixing on these scales.Support was provided by the Cecil H. and Ida M. Green Technology Innovation Fund under Grant 27001545, the Office of Naval Research Grant N00014-01-1-0984, and the Woods Hole Oceanographic Institution Coastal Ocean Institute

Artemis inhibition as a therapeutic strategy for acute lymphoblastic leukemia

As effective therapies for relapse and refractory B-cell acute lymphoblastic leukemia (B-ALL) remain problematic, novel therapeutic strategies are needed. Artemis is a key endonuclease in V(D)J recombination and nonhomologous end joining (NHEJ) of DNA double-strand break (DSB) repair. Inhibition of Artemis would cause chromosome breaks during maturation of RAG-expressing T- and B-cells. Though this would block generation of new B- and T-cells temporarily, it could be oncologically beneficial for reducing the proliferation of B-ALL and T-ALL cells by causing chromosome breaks in these RAG-expressing tumor cells. Currently, pharmacological inhibition is not available for Artemis. According to gene expression analyses from 207 children with high-risk pre-B acute lymphoblastic leukemias high Artemis expression is correlated with poor outcome. Therefore, we evaluated four compounds (827171, 827032, 826941, and 825226), previously generated from a large Artemis targeted drug screen. A biochemical assay using a purified Artemis:DNA-PKcs complex shows that the Artemis inhibitors 827171, 827032, 826941, 825226 have nanomolar IC50 values for Artemis inhibition. We compared these 4 compounds to a DNA-PK inhibitor (AZD7648) in three patient-derived B-ALL cell lines (LAX56, BLQ5 and LAX7R) and in two mature B-cell lines (3301015 and 5680001) as controls. We found that pharmacological Artemis inhibition substantially decreases proliferation of B-ALL cell lines while normal mature B-cell lines are not markedly affected. Inhibition of DNA-PKcs (which regulates Artemis) using the DNA-PK inhibitor AZD7648 had minor effects on these same primary patient-derived ALL lines, indicating that inhibition of V(D)J hairpin opening requires direct inhibition of Artemis, rather than indirect suppression of the kinase that regulates Artemis. Our data provides a basis for further evaluation of pharmacological Artemis inhibition of proliferation of B- and T-ALL