The Design and Application of Target-Focused Compound Libraries

Target-focused compound libraries are collections of compounds which are designed to interact with an individual protein target or, frequently, a family of related targets (such as kinases, voltage-gated ion channels, serine/cysteine proteases). They are used for screening against therapeutic targets in order to find hit compounds that might be further developed into drugs. The design of such libraries generally utilizes structural information about the target or family of interest. In the absence of such structural information, a chemogenomic model that incorporates sequence and mutagenesis data to predict the properties of the binding site can be employed. A third option, usually pursued when no structural data are available, utilizes knowledge of the ligands of the target from which focused libraries can be developed via scaffold hopping. Consequently, the methods used for the design of target-focused libraries vary according to the quantity and quality of structural or ligand data that is available for each target family. This article describes examples of each of these design approaches and illustrates them with case studies, which highlight some of the issues and successes observed when screening target-focused libraries

High Energy Cosmic Rays from Neutrinos

We discuss recent models in which neutrinos, which are assumed to have mass in the eV range, originate the highest energy cosmic rays by interaction with the enhanced density in the galactic halo of the relic cosmic neutrino background. We make an analytical calculation of the required neutrino fluxes to show that the parameter space for these models is constrained by horizontal air shower searches and by the total number of background neutrinos, so that only models which have fairly unnatural halo sizes and enhanced densities are allowed.Comment: 14 pages, 3 ps figures. To appear in Phys. Rev.

Lorentz invariance violation in top-down scenarios of ultrahigh energy cosmic ray creation

The violation of Lorentz invariance (LI) has been invoked in a number of ways to explain issues dealing with ultrahigh energy cosmic ray (UHECR) production and propagation. These treatments, however, have mostly been limited to examples in the proton-neutron system and photon-electron system. In this paper we show how a broader violation of Lorentz invariance would allow for a series of previously forbidden decays to occur, and how that could lead to UHECR primaries being heavy baryonic states or Higgs bosons.Comment: Replaced with heavily revised (see new Abstract) version accepted by Phys. Rev. D. 6 page

New hadrons as ultra-high energy cosmic rays

Ultra-high energy cosmic ray (UHECR) protons produced by uniformly distributed astrophysical sources contradict the energy spectrum measured by both the AGASA and HiRes experiments, assuming the small scale clustering of UHECR observed by AGASA is caused by point-like sources. In that case, the small number of sources leads to a sharp exponential cutoff at the energy E<10^{20} eV in the UHECR spectrum. New hadrons with mass 1.5-3 GeV can solve this cutoff problem. For the first time we discuss the production of such hadrons in proton collisions with infrared/optical photons in astrophysical sources. This production mechanism, in contrast to proton-proton collisions, requires the acceleration of protons only to energies E<10^{21} eV. The diffuse gamma-ray and neutrino fluxes in this model obey all existing experimental limits. We predict large UHE neutrino fluxes well above the sensitivity of the next generation of high-energy neutrino experiments. As an example we study hadrons containing a light bottom squark. These models can be tested by accelerator experiments, UHECR observatories and neutrino telescopes.Comment: 17 pages, revtex style; v2: shortened, as to appear in PR

Black Holes from Cosmic Rays: Probes of Extra Dimensions and New Limits on TeV-Scale Gravity

If extra spacetime dimensions and low-scale gravity exist, black holes will be produced in observable collisions of elementary particles. For the next several years, ultra-high energy cosmic rays provide the most promising window on this phenomenon. In particular, cosmic neutrinos can produce black holes deep in the Earth's atmosphere, leading to quasi-horizontal giant air showers. We determine the sensitivity of cosmic ray detectors to black hole production and compare the results to other probes of extra dimensions. With n \ge 4 extra dimensions, current bounds on deeply penetrating showers from AGASA already provide the most stringent bound on low-scale gravity, requiring a fundamental Planck scale M_D > 1.3 - 1.8 TeV. The Auger Observatory will probe M_D as large as 4 TeV and may observe on the order of a hundred black holes in 5 years. We also consider the implications of angular momentum and possible exponentially suppressed parton cross sections; including these effects, large black hole rates are still possible. Finally, we demonstrate that even if only a few black hole events are observed, a standard model interpretation may be excluded by comparison with Earth-skimming neutrino rates.Comment: 30 pages, 18 figures; v2: discussion of gravitational infall, AGASA and Fly's Eye comparison added; v3: Earth-skimming results modified and strengthened, published versio

The PHENIX Experiment at RHIC

The physics emphases of the PHENIX collaboration and the design and current status of the PHENIX detector are discussed. The plan of the collaboration for making the most effective use of the available luminosity in the first years of RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program available at http://www.rhic.bnl.gov/phenix