Cosmic Ray Energy Spectra and Mass Composition at the Knee - Recent Results from KASCADE -

Recent results from the KASCADE experiment on measurements of cosmic rays in the energy range of the knee are presented. Emphasis is placed on energy spectra of individual mass groups as obtained from an two-dimensional unfolding applied to the reconstructed electron and truncated muon numbers of each individual EAS. The data show a knee-like structure in the energy spectra of light primaries (p, He, C) and an increasing dominance of heavy ones (A > 20) towards higher energies. This basic result is robust against uncertainties of the applied interaction models QGSJET and SIBYLL which are used in the shower simulations to analyse the data. Slight differences observed between experimental data and EAS simulations provide important clues for further improvements of the interaction models. The data are complemented by new limits on global anisotropies in the arrival directions of CRs and by upper limits on point sources. Astrophysical implications for discriminating models of maximum acceleration energy vs galactic diffusion/drift models of the knee are discussed based on this data.Comment: 8 pages, 7 figures, to appear in Nuclear Physics B, Proceedings Supplements, as part of the volume for the CRIS 2004, Cosmic Ray International Seminar: GZK and Surrounding

Cosmic Neutrinos and the Energy Budget of Galactic and Extragalactic Cosmic Rays

Although kilometer-scale neutrino detectors such as IceCube are discovery instruments, their conceptual design is very much anchored to the observational fact that Nature produces protons and photons with energies in excess of 10^{20} eV and 10^{13} eV, respectively. The puzzle of where and how Nature accelerates the highest energy cosmic particles is unresolved almost a century after their discovery. We will discuss how the cosmic ray connection sets the scale of the anticipated cosmic neutrino fluxes. In this context, we discuss the first results of the completed AMANDA detector and the science reach of its extension, IceCube.Comment: 13 pages, Latex2e, 3 postscript figures included. Talk presented at the International Workshop on Energy Budget in the High Energy Universe, Kashiwa, Japan, February 200

UHECR as Decay Products of Heavy Relics? The Lifetime Problem

The essential features underlying the top-down scenarii for UHECR are discussed, namely, the stability (or lifetime) imposed to the heavy objects (particles) whatever they be: topological and non-topological solitons, X-particles, cosmic defects, microscopic black-holes, fundamental strings. We provide an unified formula for the quantum decay rate of all these objects as well as the particle decays in the standard model. The key point in the top-down scenarii is the necessity to adjust the lifetime of the heavy object to the age of the universe. This ad-hoc requirement needs a very high dimensional operator to govern its decay and/or an extremely small coupling constant. The natural lifetimes of such heavy objects are, however, microscopic times associated to the GUT energy scale (sim 10^{-28} sec. or shorter). It is at this energy scale (by the end of inflation) where they could have been abundantly formed in the early universe and it seems natural that they decayed shortly after being formed.Comment: 11 pages, LaTex, no figures, updated versio

Cosmic Neutrinos from the Sources of Galactic and Extragalactic Cosmic Rays

Although kilometer-scale neutrino detectors such as IceCube are discovery instruments, their conceptual design is very much anchored to the observational fact that Nature produces protons and photons with energies in excess of 10^20 eV and 10^13 eV, respectively. The puzzle of where and how Nature accelerates the highest energy cosmic particles is unresolved almost a century after their discovery. From energetics considerations we anticipate order 10~100 neutrino events per kilometer squared per year pointing back at the source(s) of both galactic and extragalactic cosmic rays. In this context, we discuss the results of the AMANDA and IceCube neutrino telescopes which will deliver a kilometer-square-year of data over the next 3 years.Comment: 8 pages, 4 figure

Differential effect of lacosamide on Na(v)1.7 varients from responsive and non-responsive patients with small fibre neuropathy

Small fibre neuropathy is a common pain disorder, which in many cases fails to respond to treatment with existing medications. Gain-of-function mutations of voltage-gated sodium channel Nav1.7 underlie dorsal root ganglion neuronal hyperexcitability and pain in a subset of patients with small fibre neuropathy. Recent clinical studies have demonstrated that lacosamide, which blocks sodium channels in a use-dependent manner, attenuates pain in some patients with Nav1.7 mutations; however, only a subgroup of these patients responded to the drug. Here, we used voltage-clamp recordings to evaluate the effects of lacosamide on five Nav1.7 variants from patients who were responsive or non-responsive to treatment. We show that, at the clinically achievable concentration of 30 \u3bcM, lacosamide acts as a potent sodium channel inhibitor of Nav1.7 variants carried by responsive patients, via a hyperpolarizing shift of voltage-dependence of both fast and slow inactivation and enhancement of use-dependent inhibition. By contrast, the effects of lacosamide on slow inactivation and use-dependence in Nav1.7 variants from non-responsive patients were less robust. Importantly, we found that lacosamide selectively enhances fast inactivation only in variants from responders. Taken together, these findings begin to unravel biophysical underpinnings that contribute to responsiveness to lacosamide in patients with small fibre neuropathy carrying select Nav1.7 variants