In Vivo Intracellular Oxygen Dynamics in Murine Brain Glioma and Immunotherapeutic Response of Cytotoxic T Cells Observed by Fluorine-19 Magnetic Resonance Imaging

Noninvasive biomarkers of anti-tumoral efficacy are of great importance to the development of therapeutic agents. Tumor oxygenation has been shown to be an important indicator of therapeutic response. We report the use of intracellular labeling of tumor cells with perfluorocarbon (PFC) molecules, combined with quantitative 19F spin-lattice relaxation rate (R1) measurements, to assay tumor cell oxygen dynamics in situ. In a murine central nervous system (CNS) GL261 glioma model, we visualized the impact of Pmel-1 cytotoxic T cell immunotherapy, delivered intravenously, on intracellular tumor oxygen levels. GL261 glioma cells were labeled ex vivo with PFC and inoculated into the mouse striatum. The R1 of 19F labeled cells was measured using localized single-voxel magnetic resonance spectroscopy, and the absolute intracellular partial pressure of oxygen (pO2) was ascertained. Three days after tumor implantation, mice were treated with 2×107 cytotoxic T cells intravenously. At day five, a transient spike in pO2 was observed indicating an influx of T cells into the CNS and putative tumor cell apoptosis. Immunohistochemistry and quantitative flow cytometry analysis confirmed that the pO2 was causally related to the T cells infiltration. Surprisingly, the pO2 spike was detected even though few (∼4×104) T cells actually ingress into the CNS and with minimal tumor shrinkage. These results indicate the high sensitivity of this approach and its utility as a non-invasive surrogate biomarker of anti-cancer immunotherapeutic response in preclinical models. © 2013 Zhong et al

Many-Body Currents and the Strange-Quark Content of 4he

Meson-exchange current (MEC) contributions to the parity-violating (PV) asymmetry for elastic scattering of polarized electrons from $^4$He are calculated over a range of momentum transfer using Monte Carlo methods and a variational $^4$He ground state wavefunction. The results indicate that MEC's generate a negligible contribution to the asymmetry at low-|\qv|, where a determination of the nucleon's mean square strangeness radius could be carried out at CEBAF. At larger values of momentum transfer -- beyond the first diffraction minimum -- two-body corrections from the $\rho$-$\pi$ \lq\lq strangeness charge" operator enter the asymmetry at a potentially observable level, even in the limit of vanishing strange-quark matrix elements of the nucleon. For purposes of constraining the nucleon's strangeness electric form factor, theoretical uncertainties associated with these MEC contributions do not appear to impose serious limitations.Comment: 32 TEX pages and 7 figures (not included, available from authors upon request), CEBAF Preprint #TH-94-1

Search for annihilating dark matter in the Sun with 3 years of IceCube data

We present results from an analysis looking for dark matter annihilation in the Sun with the IceCube neutrino telescope. Gravitationally trapped dark matter in the Sun’s core can annihilate into Standard Model particles making the Sun a source of GeV neutrinos. IceCube is able to detect neutrinos with energies >100 GeV while its low-energy infill array DeepCore extends this to >10 GeV. This analysis uses data gathered in the austral winters between May 2011 and May 2014, corresponding to 532 days of livetime when the Sun, being below the horizon, is a source of up-going neutrino events, easiest to discriminate against the dominant background of atmospheric muons. The sensitivity is a factor of two to four better than previous searches due to additional statistics and improved analysis methods involving better background rejection and reconstructions. The resultant upper limits on the spin-dependent dark matter-proton scattering cross section reach down to 1.46×10−5 pb for a dark matter particle of mass 500 GeV annihilating exclusively into τ+τ−particles. These are currently the most stringent limits on the spin-dependent dark matter-proton scattering cross section for WIMP masses above 50 GeV.M. G. Aartsen ... G. C. Hill ... S. Robertson ... A. Wallace … B. J. Whelan ... et al. (IceCube Collaboration

All-flavour search for neutrinos from dark matter annihilations in the Milky Way with IceCube/DeepCore

Published online: 28 September 2016We present the first IceCube search for a signal of dark matter annihilations in the Milky Way using all-flavour neutrino-induced particle cascades. The analysis focuses on the DeepCore sub-detector of IceCube, and uses the surrounding IceCube strings as a veto region in order to select starting events in the DeepCore volume. We use 329 live-days of data from IceCube operating in its 86-string configuration during 2011–2012. No neutrino excess is found, the final result being compatible with the background-only hypothesis. From this null result, we derive upper limits on the velocity-averaged self-annihilation cross-section, 〈σAv〉, for dark matter candidate masses ranging from 30 GeV up to 10 TeV, assuming both a cuspy and a flat-cored dark matter halo profile. For dark matter masses between 200 GeV and 10 TeV, the results improve on all previous IceCube results on 〈σAv〉 , reaching a level of 10⁻²³ cm³ s⁻¹, depending on the annihilation channel assumed, for a cusped NFW profile. The analysis demonstrates that all-flavour searches are competitive with muon channel searches despite the intrinsicallyworse angular resolution of cascades compared to muon tracks in IceCube.M.G. Aartsen … G.C. Hill … S. Robertson … A. Wallace … B.J. Whelan … et al. (IceCube Collaboration

Neutrino oscillation studies with IceCube-DeepCore

Abstract not availableM.G. Aartsen ... G.C. Hill ... S. Robertson ... A. Wallace ... B.J. Whelan ... et al. [IceCube Collaboration

Development of a general analysis and unfolding scheme and its application to measure the energy spectrum of atmospheric neutrinos with IceCube

We present the development and application of a generic analysis scheme for the measurement of neutrino spectra with the IceCube detector. This scheme is based on regularized unfolding, preceded by an event selection which uses a Minimum Redundancy Maximum Relevance algorithm to select the relevant variables and a random forest for the classification of events. The analysis has been developed using IceCube data from the 59-string configuration of the detector. 27,771 neutrino candidates were detected in 346 days of livetime. A rejection of 99.9999 % of the atmospheric muon background is achieved. The energy spectrum of the atmospheric neutrino flux is obtained using the TRUEE unfolding program. The unfolded spectrum of atmospheric muon neutrinos covers an energy range from 100 GeV to 1 PeV. Compared to the previous measurement using the detector in the 40-string configuration, the analysis presented here, extends the upper end of the atmospheric neutrino spectrum by more than a factor of two, reaching an energy region that has not been previously accessed by spectral measurements.M.G. Aartsen … G.C. Hill … S. Robertson … B. Whelan … et al. (IceCube Collaboration

First search for dark matter annihilations in the Earth with the IceCube detector

Published online: 8 February 2017We present the results of the first IceCube search for dark matter annihilation in the center of the Earth. Weakly interacting massive particles (WIMPs), candidates for dark matter, can scatter off nuclei inside the Earth and fall below its escape velocity. Over time the captured WIMPs will be accumulated and may eventually self-annihilate. Among the annihilation products only neutrinos can escape from the center of the Earth. Large-scale neutrino telescopes, such as the cubic kilometer IceCube Neutrino Observatory located at the South Pole, can be used to search for such neutrino fluxes. Data from 327 days of detector livetime during 2011/2012 were analyzed. No excess beyond the expected background from atmospheric neutrinos was detected. The derived upper limits on the annihilation rate of WIMPs in the Earth and the resulting muon flux are an order of magnitude stronger than the limits of the last analysis performed with data from IceCube’s predecessor AMANDA. The limits can be translated in terms of a spin-independent WIMP–nucleon cross section. For a WIMP mass of 50 GeV this analysis results in the most restrictive limits achieved with IceCube data.M.G. Aartsen … G.C. Hill … S. Robertson … A. Wallace … B.J. Whelan … et al. (IceCube Collaboration

Improved limits on dark matter annihilation in the Sun with the 79-string IceCube detector and implications for supersymmetry

We present an improved event-level likelihood formalism for including neutrino telescope data in global fits to new physics. We derive limits on spin-dependent dark matter-proton scattering by employing the new formalism in a re-analysis of data from the 79-string IceCube search for dark matter annihilation in the Sun, including explicit energy information for each event. The new analysis excludes a number of models in the weak-scale minimal supersymmetric standard model (MSSM) for the rst time. This work is accompanied by the public release of the 79-string IceCube data, as well as an associated computer code for applying the new likelihood to arbitrary dark matter models.M.G. Aarten ... G.C. Hill ... S. Robertson ... B.J. Whelan ... et al