Closing the Window on Strongly Interacting Dark Matter with IceCube

We use the recent results on dark matter searches of the 22-string IceCube detector to probe the remaining allowed window for strongly interacting dark matter in the mass range 10^4<m_X<10^15 GeV. We calculate the expected signal in the 22-string IceCube detector from the annihilation ofsuch particles captured in the Sun and compare it to the detected background. As a result, the remaining allowed region in the mass versus cross sectionparameter space is ruled out. We also show the expected sensitivity of the complete IceCube detector with 86 strings.Comment: 5 pages, 7 figures. Uppdated figures 2 and 3 (y-axis normalization and label) . Version accepted for publication in PR

Constraints on Enhanced Dark Matter Annihilation from IceCube Results

Excesses on positron and electron fluxes measured by ATIC, and the PAMELA and Fermi--LAT telescopes can be explained by dark matter annihilation in our Galaxy. However, this requires large boosts on the dark matter annihilation rate. There are many possible enhancement mechanisms, such as the Sommerfeld effect or the existence of dark matter clumps in our halo. If enhancements on the dark matter annihilation cross section are taking place, the dark matter annihilation in the core of the Earth should also be enhanced. Here we use recent results from the IceCube 40-string configuration to probe generic enhancement scenarios. We present results as a function of the dark matter-proton interaction cross section, $\sigma_{\chi p}$ weighted by the branching fraction into neutrinos, $f_{\nu\bar{\nu}}$, as a function of a generic boost factor, $B_F$, which parametrizes the expected enhancement of the annihilation rate. We find that dark matter models which require annihilation enhancements of $\mathcal{O}(100)$ or more and that annihilate significantly into neutrinos are excluded as the explanation for these excesses. We also determine the boost range that can be probed by the full IceCube telescope.Comment: 6 pages, 3 figures; version accepted for publicatio

Including Systematic Uncertainties in Confidence Interval Construction for Poisson Statistics

One way to incorporate systematic uncertainties into the calculation of confidence intervals is by integrating over probability density functions parametrizing the uncertainties. In this note we present a development of this method which takes into account uncertainties in the prediction of background processes, uncertainties in the signal detection efficiency and background efficiency and allows for a correlation between the signal and background detection efficiencies. We implement this method with the Feldman & Cousins unified approach with and without conditioning. We present studies of coverage for the Feldman & Cousins and Neyman ordering schemes. In particular, we present two different types of coverage tests for the case where systematic uncertainties are included. To illustrate the method we show the relative effect of including systematic uncertainties the case of dark matter search as performed by modern neutrino tel escopes.Comment: 23 pages, 10 figures, replaced to match published versio

The WNK-regulated SPAK/OSR1 kinases directly phosphorylate and inhibit the K+-Cl- co-transporters

This is the final version of the article. Available from Portland Press via the DOI in this record.There is another ORE record for this publication: http://hdl.handle.net/10871/32310Precise homoeostasis of the intracellular concentration of Cl- is achieved via the co-ordinated activities of the Cl- influx and efflux. We demonstrate that the WNK (WNK lysine-deficient protein kinase)-activated SPAK (SPS1-related proline/alanine-rich kinase)/OSR1 (oxidative stress-responsive kinase 1) known to directly phosphorylate and stimulate the N[K]CCs (Na+-K+ ion co-transporters), also promote inhibition of the KCCs (K+-Cl- co-transporters) by directly phosphorylating a recently described C-terminal threonine residue conserved in all KCC isoforms [Site-2 (Thr1048)]. First, we demonstrate that SPAK and OSR1, in the presence of the MO25 regulatory subunit, robustly phosphorylates all KCC isoforms at Site-2 in vitro. Secondly, STOCK1S-50699, a WNK pathway inhibitor, suppresses SPAK/OSR1 activation and KCC3A Site-2 phosphorylation with similar efficiency. Thirdly, in ES (embryonic stem) cells lacking SPAK/OSR1 activity, endogenous phosphorylation of KCC isoforms at Site-2 is abolished and these cells display elevated basal activity of 86Rb+ uptake that was not markedly stimulated further by hypotonic high K+ conditions, consistent with KCC3A activation. Fourthly, a tight correlation exists between SPAK/OSR1 activity and the magnitude of KCC3A Site-2 phosphorylation. Lastly, a Site-2 alanine KCC3A mutant preventing SPAK/OSR1 phosphorylation exhibits increased activity. We also observe that KCCs are directly phosphorylated by SPAK/OSR1, at a novel Site-3 (Thr5 in KCC1/KCC3 and Thr6 in KCC2/KCC4), and a previously recognized KCC3-specific residue, Site-4 (Ser96). These data demonstrate that the WNK-regulated SPAK/OSR1 kinases directly phosphorylate the N[K]CCs and KCCs, promoting their stimulation and inhibition respectively. Given these reciprocal actions with anticipated net effects of increasing Cl- influx, we propose that the targeting of WNK-SPAK/OSR1 with kinase inhibitors might be a novel potent strategy to enhance cellular Cl- extrusion, with potential implications for the therapeutic modulation of epithelial and neuronal ion transport in human disease states.This work was supported by the Medical Research Council and the Wellcome Trust [grant number 091415] as well as the pharmaceutical companies supporting the Division of Signal Transduction Therapy Unit (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck KgaA, Janssen Pharmaceutica and Pfizer). K.T.K. is supported by the Manton Center for Orphan Diseases at Children's Hospital Boston at Harvard Medical School, and the Harvard/MIT Joint Research Grants Program in Basic Neuroscience

Low-mass e+e- pair production in 158 A GeV Pb-Au collisions at the CERN SPS, its dependence on multiplicity and transverse momentum

We report a measurement of low-mass electron pairs observed in 158 GeV/nucleon Pb-Au collisions. The pair yield integrated over the range of invariant masses 0.2 < m < 2.0 GeV is enhanced by a factor of 3.5 +/- 0.4 (stat) +/- 0.9 (syst) over the expectation from neutral meson decays. As observed previously in S-Au collisions, the enhancement is most pronounced in the invariant-mass region 300-700 MeV. For Pb-Au we find evidence for a strong increase of the enhancement with centrality. In addition, we show that the enhancement covers a wide range in transverse momentum, but is largest at the lowest observed pt.Comment: 17 pages, 4 figures, submitted to Phys.Lett.

Core patient-reported outcome measures for chronic pain patients treated with spinal cord stimulation or dorsal root ganglia stimulation

Background: Neurostimulation is a highly effective therapy for the treatment of chronic Intractable pain, however, due to the complexity of pain, measuring a subject’s long-term response to the therapy remains difficult. Frequent measurement of patient-reported outcomes (PROs) to reflect multiple aspects of subjects’ pain is a crucial step in determining therapy outcomes. However, collecting full-length PROs is burdensome for both patients and clinicians. The objective of this work is to identify the reduced set of questions from multiple validated PROs that can accurately characterize chronic pain patients’ responses to neurostimulation therapies. Methods: Validated PROs were used to capture pain, physical function and disability, as well as psychometric, satisfaction, and global health metrics. PROs were collected from 509 patients implanted with Spinal Cord Stimulation (SCS) or Dorsal Root Ganglia (DRG) neurostimulators enrolled in the prospective, international, post-market REALITY study (NCT03876054, Registration Date: March 15, 2019). A combination of linear regression, Pearson’s correlation, and factor analysis were used to eliminate highly correlated questions and find the minimal meaningful set of questions within the predefined domains of each scale. Results: The shortened versions of the questionnaires presented almost identical accuracy for classifying the therapy outcomes as compared to the validated full-length versions. In addition, principal component analysis was performed on all the PROs and showed a robust clustering of pain intensity, psychological factors, physical function, and sleep across multiple PROs. A selected set of questions captured from multiple PROs can provide adequate information for measuring neurostimulation therapy outcomes. Conclusions: PROs are important subjective measures to evaluate the physiological and psychological aspects of pain. However, these measures are cumbersome to collect. These shorter and more targeted PROs could result in better patient engagement, and enhanced and more frequent data collection processes for digital health platforms that minimize patient burden while increasing therapeutic benefits for chronic pain patients.</p

e+e--pair production in Pb-Au collisions at 158 GeV per nucleon

We present the combined results on electron-pair production in 158 GeV/n {Pb-Au} ($\sqrt{s}$= 17.2 GeV) collisions taken at the CERN SPS in 1995 and 1996, and give a detailed account of the data analysis. The enhancement over the reference of neutral meson decays amounts to a factor of 2.31$\pm0.19 (stat.)\pm0.55 (syst.)\pm0.69 (decays)$ for semi-central collisions (28% $\sigma/\sigma_{geo}$) when yields are integrated over $m>$ 200 MeV/$c^2$ in invariant mass. The measured yield, its stronger-than-linear scaling with $N_{ch}$, and the dominance of low pair $p_t$ strongly suggest an interpretation as {\it thermal radiation} from pion annihilation in the hadronic fireball. The shape of the excess centring at $m\approx$ 500 MeV/$c^2$, however, cannot be described without strong medium modifications of the $\rho$ meson. The results are put into perspective by comparison to predictions from Brown-Rho scaling governed by chiral symmetry restoration, and from the spectral-function many-body treatment in which the approach to the phase boundary is less explicit.Comment: 39 pages, 40 figures, to appear in Eur.Phys.J.C. (2005