Novel Simulation to Avoid Bias in Measurement of Hyperpolarized Pyruvate: Demonstrated in Phantom and In Vivo

Dynamic nuclear polarization creates a transient hyperpolarized nuclear state that can dramatically increase the signal detected by magnetic resonance imaging. This signal increase allows real-time spectroscopic imaging of specific metabolites in vivo by magnetic resonance. Real-time imaging of both the spatial and chemical fate of hyperpolarized metabolites is showing great promise to meaningfully benefit clinical care of cancer patients. Imaging of hyperpolarized agents will have a larger clinical impact if it can function as a quantitative modality upon which clinical decisions can be made. However, quantitative measurement of hyperpolarized agents is currently difficult due to the restrictions imposed by the transient hyperpolarized state and the complexity inherent in biological systems. As more advanced imaging and measurement techniques are developed for imaging hyperpolarized substrates, it is critical to characterize their effect on any relevant quantitative measure. To assist in accurate quantitative measurement of hyperpolarized agents, an infrastructure where acquisition strategies can be developed, compared, optimized and validated was critically need. A novel simulation architecture was developed that combines classical chemical kinetics with the basic physics of nuclear magnetic resonance and couples them to multiple perfusion models. Simulation results showed that changes in the acquisition strategy used will affect the resulting quantification of chemical exchange rates and suggested that any bias that is imposed by the acquisition strategy can be avoided by using optimized pulse sequences. To validate these predictions, a phantom system was developed that allows controllable chemical conversion of hyperpolarized pyruvate into lactate with a variability less than 20%. Using this phantom system, studies showed that poorly optimized pulse sequences significantly reduced the measured value of the chemical exchange rates, whereas optimized pulse sequences showed no significant difference in chemical exchange measurements. In order to test simulation predictions for a perfused system, an animal cohort with orthotropic anaplastic thyroid cancer was scanned with multiple sequences. Again, optimized sequences showed no significant difference in measured exchange rates while poorly designed sequences significantly underestimated the exchange rates, which is consistent with the simulation results. These validation studies suggest that this simulation architecture will be a powerful tool for developing and optimizing acquisition and quantization methods for hyperpolarized magnetic resonance imaging

Millimeter and Submillimeter Survey of the R Corona Australis Region

Using a combination of data from the Antarctic Submillimeter Telescope and Remote Observatory (AST/RO), the Arizona Radio Observatory Kitt Peak 12m telescope and the Arizona Radio Observatory 10m Heinrich Hertz Telescope, we have studied the most active part of the R CrA molecular cloud in multiple transitions of Carbon Monoxide, HCO$^+$ and 870\micron continuum emission. Since R CrA is nearby (130 pc), we are able to obtain physical spatial resolution as high as 0.01pc over an area of 0.16 pc$^2$, with velocity resolution finer than 1 km/s. Mass estimates of the protostar driving the mm-wave emission derived from HCO$^+$, dust continuum emission and kinematic techniques point to a young, deeply embedded protostar of $\sim$0.5-0.75 M$_\odot$, with a gaseous envelope of similar mass. A molecular outflow is driven by this source that also contains at least 0.8 M$_\odot$ of molecular gas with $\sim$0.5 L$_\odot$ of mechanical luminosity. HCO$^+$ lines show the kinematic signature of infall motions as well as bulk rotation. The source is most likely a Class 0 protostellar object not yet visible at near-IR wavelengths. With the combination of spatial and spectral resolution in our data set, we are able to disentangle the effects of infall, rotation and outflow towards this young object.Comment: 29 pages, 9 figures. Accepted for publication in the Astrophysical Journa

The Relationship Between Gambling Behavior and Binge Drinking, Hard Drug Use, and Paying for Sex

We examine the relationship between gambling behavior and other vices : hard drug use, binge drinking, and paying for sex. We utilize survey data from the National Longitudinal Study of Adolescent Health, a comprehensive survey of a representative sample of young adults in the US. We analyze survey data on the behavior of 6,145 respondents using linear probability modeling and a comprehensive set of control variables. Our results indicate that individuals who exhibit signs of problem gambling behavior are significantly more likely to use hard drugs, to binge drink, and to pay for sex. These findings, based on data collected on the general public, provide an interesting contribution to the gambling literature

The Chimpanzee Model of Viral Hepatitis: Advances in Understanding the Immune Response and Treatment of Viral Hepatitis

Chimpanzees (Pan troglodytes) have contributed to diverse fields of biomedical research due to their close genetic relationship to humans and in many instances due to the lack of any other animal model. This review focuses on the contributions of the chimpanzee model to research on hepatitis viruses where chimpanzees represented the only animal model (hepatitis B and C) or the most appropriate animal model (hepatitis A). Research with chimpanzees led to the development of vaccines for HAV and HBV that are used worldwide to protect hundreds of millions from these diseases and, where fully implemented, have provided immunity for entire generations. More recently, chimpanzee research was instrumental in the development of curative therapies for hepatitis C virus infections. Over a span of 40 years, this research would identify the causative agent of NonA,NonB hepatitis, validate the molecular tools for drug discovery, and provide safety and efficacy data on the therapies that now provide a rapid and complete cure of HCV chronic infections. Several cocktails of antivirals are FDA approved that eliminate the virus following 12 weeks of once-per-day oral therapy. This represents the first cure of a chronic viral disease and, once broadly implemented, will dramatically reduce the occurrence of cirrhosis and liver cancer. The recent contributions of chimpanzees to our current understanding of T cell immunity for HCV, development of novel therapeutics for HBV, and the biology of HAV are reviewed. Finally, a perspective is provided on the events leading to the cessation of the use of chimpanzees in research and the future of the chimpanzees previously used to bring about these amazing breakthroughs in human healthcare

Mutational escape from CD8+ T cell immunity: HCV evolution, from chimpanzees to man

The mechanisms by which the hepatitis C virus (HCV) establishes persistence are not yet fully understood. Previous chimpanzee and now human studies suggest that mutations within MHC class I–restricted HCV epitopes might contribute to viral escape from cytotoxic T lymphocyte (CTL) responses. However, there are several outstanding questions regarding the role of escape mutations in viral persistence and their fate in the absence of immune selection pressure

Catalysis and evolution on cycling of nano-structured magnesium multilayer thin films

This paper explores the hydrogen cycling properties of Mg/Cr and Mg/V multilayer thin films and studies the effect of chromium and vanadium transition metal catalysts on the cycling properties of thick magnesium coatings. Two transition-metal catalysed magnesium-based multilayer PVD coatings are compared with a non-catalysed magnesium control sample. The (micro-)structural evolution of the thin film coatings into fine, flakey powders is studied in depth using XRD, SEM and TEM and the hydrogen storage properties of all three materials are assessed using volumetric, gravimetric and calorimetric methods focussing on the effect of the microstructure and composition of the coatings on the hydrogen storage kinetics. It was found that the chromiumcatalysed coating had the most favourable hydrogen storage kinetics with an activation energy for the dehydrogenation reaction of 65.7±2.5 kJ mol-1 and a hydrogen capacity of 6.1±0.3 wt%. The mechanism of the dehydrogenation reaction of the catalysed samples was studied using the CV and JMAK kinetic models and it was found that the catalyst material influenced not only the hydrogen storage kinetics but also the mechanism of the reaction

Star Formation in the Northern Cloud Complex of NGC 2264

We have made continuum and spectral line observations of several outflow sources in the Mon OB1 dark cloud (NGC 2264) using the Heinrich Hertz Telescope (HHT) and ARO 12m millimeter-wave telescope. This study explores the kinematics and outflow energetics of the young stellar systems observed and assesses the impact star formation is having on the surrounding cloud environment. Our data set incorporates 12CO(3-2), 13CO(3-2), and 12CO(1-0) observations of outflows associated with the sources IRAS 06382+1017 and IRAS 06381+1039, known as IRAS 25 and 27, respectively, in the northern cloud complex. Complementary 870 micron continuum maps were made with the HHT 19 channel bolometer array. Our results indicate that there is a weak (approximately less than 0.5%) coupling between outflow kinetic energy and turbulent energy of the cloud. An analysis of the energy balance in the IRAS 25 and 27 cores suggests they are maintaining their dynamical integrity except where outflowing material directly interacts with the core, such as along the outflow axes.Comment: 28 pages including 6 figures, to be published in ApJ 01 July 2006, v645, 1 issu