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Cooper, O.,Seo, H.,Andrabi, S.,Guardia-Laguarta, C.,Graziotto, J.,Sundberg, M.,McLean, J. R.,Carrillo-Reid, L.,Xie, Z.,Osborn, T.,Hargus, G.,Deleidi, M.,Lawson, T.,Bogetofte, H.,Perez-Torres, E.,Clark American Association for the Advancement of Scienc 2012 Science Translational Medicine Vol.4 No.141
<P>Parkinson's disease (PD) is a common neurodegenerative disorder caused by genetic and environmental factors that results in degeneration of the nigrostriatal dopaminergic pathway in the brain. We analyzed neural cells generated from induced pluripotent stem cells (iPSCs) derived from PD patients and presymptomatic individuals carrying mutations in the PINK1 (PTEN-induced putative kinase 1) and LRRK2 (leucine-rich repeat kinase 2) genes, and compared them to those of healthy control subjects. We measured several aspects of mitochondrial responses in the iPSC-derived neural cells including production of reactive oxygen species, mitochondrial respiration, proton leakage, and intraneuronal movement of mitochondria. Cellular vulnerability associated with mitochondrial dysfunction in iPSC-derived neural cells from familial PD patients and at-risk individuals could be rescued with coenzyme Q(10), rapamycin, or the LRRK2 kinase inhibitor GW5074. Analysis of mitochondrial responses in iPSC-derived neural cells from PD patients carrying different mutations provides insight into convergence of cellular disease mechanisms between different familial forms of PD and highlights the importance of oxidative stress and mitochondrial dysfunction in this neurodegenerative disease.</P>
Jeremy M. Osborn,Kevin J. Glennon,Evans D. Kitcher,Jonathan D. Burns,Charles M. Folden III,Sunil S. Chirayath 한국원자력학회 2019 Nuclear Engineering and Technology Vol.51 No.2
An experimental validation of a nuclear forensics methodology for the source reactor-type discriminationof separated weapons-useable plutonium is presented. The methodology uses measured values of intraelementisotope ratios of plutonium and fission product contaminants. MCNP radiation transport codeswere used for various reactor core modeling and fuel burnup simulations. A reactor-dependent library ofintra-element isotope ratio values as a function of burnup and time since irradiation was created fromthe simulation results. The experimental validation of the methodology was achieved by performing twolow-burnup experimental irradiations, resulting in distinct fuel samples containing sub-milligramquantities of weapons-useable plutonium. The irradiated samples were subjected to gamma and massspectrometry to measure several intra-element isotope ratios. For each reactor in the library, a maximumlikelihood calculation was utilized to compare the measured and simulated intra-element isotope ratiovalues, producing a likelihood value which is proportional to the probability of observing the measuredratio values, given a particular reactor in the library. The measured intra-element isotope ratio values ofboth irradiated samples and its comparison with the simulation predictions using maximum likelihoodanalyses are presented. The analyses validate the nuclear forensics methodology developed
Jeremy M. Osborn,Kevin J. Glennon,Evans D. Kitcher,Jonathan D. Burns,Charles M. Folden III,Sunil S. Chirayath 한국원자력학회 2018 Nuclear Engineering and Technology Vol.50 No.6
The growing nuclear threat has amplified the need for developing diverse and accurate nuclear forensicsanalysis techniques to strengthen nuclear security measures. The work presented here is part of aresearch effort focused on developing a methodology for reactor-type discrimination of weapons-gradeplutonium. To verify the developed methodology, natural UO2 fuel samples were irradiated in a thermalneutron spectrum at the University of Missouri Research Reactor (MURR) and produced approximately20 mg of weapons-grade plutonium test material. Radiation transport simulations of common thermalreactor types that can produce weapons-grade plutonium were performed, and the results are presentedhere. These simulations were needed to verify whether the plutonium produced in the natural UO2 fuelsamples during the experimental irradiation at MURR was a suitable representative to plutonium producedin common thermal reactor types. Also presented are comparisons of fission product and plutoniumconcentrations obtained from computational simulations of the experimental irradiation at MURRto the nondestructive and destructive measurements of the irradiated natural UO2 fuel samples. Gammaspectroscopy measurements of radioactive fission products were mostly within 10%, mass spectroscopymeasurements of the total plutonium mass were within 4%, and mass spectroscopy measurements ofstable fission products were mostly within 5%.
Evans D. Kitcher,Jeremy M. Osborn,Sunil S. Chirayath 한국원자력학회 2019 Nuclear Engineering and Technology Vol.51 No.5
A recently published nuclear forensics methodology for source discrimination of separated weaponsgradeplutonium utilizes intra-element isotope ratios and a maximum likelihood formulation to identifythe most likely source reactor-type, fuel burnup and time since irradiation of unknown material. Sensitivity studies performed here on the effects of random measurement error and the uncertainty inintra-element isotope ratio values show that different intra-element isotope ratios have disproportionatecontributions to the determination of the reactor parameters. The methodology is robust to individualerrors in measured intra-element isotope ratio values and even more so for uniform systematic errorsdue to competing effects on the predictions from the selected intra-element isotope ratios suite. For aunique sample-model pair, simulation uncertainties of up to 28% are acceptable without impedingsuccessful source-reactor discrimination. However, for a generic sample with multiple plausible sourceswithin the reactor library, uncertainties of 7% or less may be required. The results confirm the critical roleof accurate reactor core physics, fuel burnup simulations and experimental measurements in the proposedmethodology where increased simulation uncertainty is found to significantly affect the capabilityto discriminate between the reactors in the library.
THESEUS: A key space mission concept for Multi-Messenger Astrophysics
Stratta, G.,Ciolfi, R.,Amati, L.,Bozzo, E.,Ghirlanda, G.,Maiorano, E.,Nicastro, L.,Rossi, A.,Vinciguerra, S.,Frontera, F.,Gö,tz, D.,Guidorzi, C.,O’Brien, P.,Osborne, J.P.,Tanvir, N.,Branchesi, M. Elsevier 2018 ADVANCES IN SPACE RESEARCH Vol.62 No.3
<P><B>Abstract</B></P> <P>The recent discovery of the electromagnetic counterpart of the gravitational wave source GW170817, has demonstrated the huge informative power of multi-messenger observations. During the next decade the nascent field of multi-messenger astronomy will mature significantly. Around 2030 and beyond, third generation ground-based gravitational wave detectors will be roughly ten times more sensitive than the current ones. At the same time, neutrino detectors currently upgrading to multi km<SUP>3</SUP> telescopes, will include a 10 km<SUP>3</SUP> facility in the Southern hemisphere. In this review, we describe the most promising sources of high frequency gravitational waves and neutrinos that will be detected in the next two decades. In this context, we show the important role of the <I>Transient High Energy Sky and Early Universe Surveyor</I> (THESEUS), a mission concept accepted by ESA for phase A study and proposed by a large international collaboration in response to the call for the Cosmic Vision Programme M5 missions. THESEUS aims at providing a substantial advancement in early Universe science as well as in multi–messenger and time–domain astrophysics, operating in strong synergy with future gravitational wave and neutrino detectors as well as major ground- and space-based telescopes. This review is an extension of the THESEUS white paper (Amati et al., 2017), also in light of the discovery of GW170817/GRB170817A that was announced on October 16th, 2017.</P>