Unraveling the Allosteric Mechanism of Serine Protease Inhibition by an Antibody

SummaryRecent structural studies have outlined the mechanism of protease inhibition by active site-directed antibodies. However, the molecular basis of allosteric inhibition by antibodies has been elusive. Here we report the 2.35 Å resolution structure of the trypsin-like serine protease hepatocyte growth factor activator (HGFA) in complex with the allosteric antibody Ab40, a potent inhibitor of HGFA catalytic activity. The antibody binds at the periphery of the substrate binding cleft and imposes a conformational change on the entire 99-loop (chymotrypsinogen numbering). The altered conformation of the 99-loop is incompatible with substrate binding due to the partial collapse of subsite S2 and the reorganization of subsite S4. Remarkably, a single residue deletion of Ab40 abolished inhibition of HGFA activity, commensurate with the reversal of the 99-loop conformation to its “competent” state. The results define an “allosteric switch” mechanism as the basis of protease inhibition by an allosteric antibody

Limits on dark matter WIMPs using upward-going muons in the MACRO detector

We perform an indirect search for Weakly Interacting Massive Particles (WIMPs) using the MACRO detector to look for neutrino-induced upward-going muons resulting from the annihilation of WIMPs trapped in the Sun and Earth. The search is conducted in various angular cones centered on the Sun and Earth to accommodate a range of WIMP masses. No significant excess over the background from atmospheric neutrinos is seen and limits are placed on the upward-going muon fluxes from Sun and Earth. These limits are used to constrain neutralino particle parameters from supersymmetric theory, including those suggested by recent results from DAMA/NaI.Comment: 14 pages, 7 figures, submitted to Phys. Rev.

Measurement of the residual energy of muons in the Gran Sasso underground Laboratories

The MACRO detector was located in the Hall B of the Gran Sasso underground Laboratories under an average rock overburden of 3700 hg/cm^2. A transition radiation detector composed of three identical modules, covering a total horizontal area of 36 m^2, was installed inside the empty upper part of the detector in order to measure the residual energy of muons. This paper presents the measurement of the residual energy of single and double muons crossing the apparatus. Our data show that double muons are more energetic than single ones. This measurement is performed over a standard rock depth range from 3000 to 6500 hg/cm^2.Comment: 28 pages, 9 figure

Neutral currents and tests of three-neutrino unitarity in long-baseline experiments

We examine a strategy for using neutral current measurements in long-baseline neutrino oscillation experiments to put limits on the existence of more than three light, active neutrinos. We determine the relative contributions of statistics, cross section uncertainties, event misidentification and other systematic errors to the overall uncertainty of these measurements. As specific case studies, we make simulations of beams and detectors that are like the K2K, T2K, and MINOS experiments. We find that the neutral current cross section uncertainty and contamination of the neutral current signal by charge current events allow a sensitivity for determining the presence of sterile neutinos at the 0.10--0.15 level in probablility.Comment: 24 pages, Latex2e, uses graphicx.sty, 2 postscript figures. Submitted to the Neutrino Focus Issue of New Journal Physics at http://www.njp.or

Low energy atmospheric muon neutrinos in MACRO

We present the measurement of two event samples induced by atmospheric $\nu_\mu$ of average energy $\bar {E}_\nu \sim 4 GeV$. In the first sample, the neutrino interacts inside the MACRO detector producing an upward-going muon leaving the apparatus. The ratio of the number of observed to expected events is $0.57 \pm0.05_{stat} \pm0.06_{syst} \pm0.14_{theor}$ with an angular distribution similar to that expected from the Bartol atmospheric neutrino flux. The second is a mixed sample of internally produced downward-going muons and externally produced upward-going muons stopping inside the detector. These two subsamples are selected by topological criteria; the lack of timing information makes it impossible to distinguish stopping from downgoing muons. The ratio of the number of observed to expected events is $0.71 \pm 0.05_{stat} \pm0.07_{syst} \pm0.18_{theor}$ . Using the ratio of the two subsamples (for which most theoretical uncertainties cancel) we can test the pathlength dependence of the oscillation hypothesis. The probability of agreement with the no-oscillation hypothesis is 5% . The deviations of our observations from the expectations has a preferred interpretation in terms of $\nu_\mu$ oscillations with maximal mixing and $\Delta m^2 \sim 10^{-3} \div 10^{-2} eV^2$. These parameters are in agreement with our results from upward throughgoing muons, induced by $\nu_\mu$ of much higher energies.Comment: 7 pages, 6 figures. Submitted to Phys. Lett.

Measurement of the atmospheric neutrino-induced upgoing muon flux using MACRO

We present a measurement of the flux of neutrino-induced upgoing muons (~100 GeV) using the MACRO detector. The ratio of the number of observed to expected events integrated over all zenith angles is 0.74 +/- 0.036 (stat) +/- 0.046(systematic) +/- 0.13 (theoretical). The observed zenith distribution for -1.0 < cos(theta) < -0.1 does not fit well with the no oscillation expectation, giving a maximum probability for chi^2 of 0.1%. The acceptance of the detector has been extensively studied using downgoing muons, independent analyses and Monte-Carlo simulations. The other systematic uncertainties cannot be the source of the discrepancies between the data and expectations. We have investigated whether the observed number of events and the shape of the zenith distribution can be explained by a neutrino oscillation hypothesis. Fitting either the flux or zenith distribution independently yields mixing parameters of sin^2 (2theta)=1.0 and delta m^2 of a few times 10^-3 eV^2. However, the observed zenith distribution does not fit well with any expectations giving a maximum probability for chi^2 of 5% for the best oscillation hypothesis, and the combined probability for the shape and number of events is 17%. We conclude that these data favor a neutrino oscillation hypothesis, but with unexplained structure in the zenith distribution not easily explained by either the statistics or systematics of the experiment.Comment: 7 pages (two-column) with 4 figure

Neutrino astronomy with the MACRO detector

High energy gamma ray astronomy is now a well established field and several sources have been discovered in the region from a few GeV up to several TeV. If sources involving hadronic processes exist, the production of photons would be accompanied by neutrinos too. Other possible neutrino sources could be related to the annihilation of WIMPs at the center of galaxies with black holes. We present the results of a search for point-like sources using 1100 upward-going muons produced by neutrino interactions in the rock below and inside the MACRO detector in the underground Gran Sasso Laboratory. These data show no evidence for a possible neutrino point-like source or for possible correlations between gamma ray bursts and neutrinos. They have been used to set flux upper limits for candidate point-like sources which are in the range 10^-14-10^-15 cm-2 s-1.Comment: 37 pages, 15 figures, replacement due to a typo in tab. 6, AASLaTex, submitted to Ap

Final results of magnetic monopole searches with the MACRO experiment

We present the final results obtained by the MACRO experiment in the search for GUT magnetic monopoles in the penetrating cosmic radiation, for the range $4\times 10^{-5}< \beta < 1$. Several searches with all the MACRO sub-detectors (i.e. scintillation counters, limited streamer tubes and nuclear track detectors) were performed, both in stand alone and combined ways. No candidates were detected and a 90% Confidence Level (C.L.) upper limit to the local magnetic monopole flux was set at the level of $1.4\times 10^{-16}$ cm$^{-2}$ s$^{-1}$ sr$^{-1}$. This result is the first experimental limit obtained in direct searches which is well below the Parker bound in the whole $\beta$ range in which GUT magnetic monopoles are expected.Comment: 12 pages, Latex, 9 figures and 2 Table

Search for Nucleon Decays induced by GUT Magnetic Monopoles with the MACRO Experiment

The interaction of a Grand Unification Magnetic Monopole with a nucleon can lead to a barion-number violating process in which the nucleon decays into a lepton and one or more mesons (catalysis of nucleon decay). In this paper we report an experimental study of the effects of a catalysis process in the MACRO detector. Using a dedicated analysis we obtain new magnetic monopole (MM) flux upper limits at the level of $\sim 3\cdot 10^{-16} cm^{-2} s^{-1} sr^{-1}$ for $1.1\cdot 10^{-4} \le |\beta| \le 5\cdot 10^{-3}$, based on the search for catalysis events in the MACRO data. We also analyze the dependence of the MM flux limit on the catalysis cross section.Comment: 12 pages, Latex, 10 figures and 2 Table

Nuclearite search with the MACRO detector at Gran Sasso

In this paper we present the results of a search for nuclearites in the penetrating cosmic radiation using the scintillator and track-etch subdetectors of the MACRO apparatus. The analyses cover the beta =v/c range at the detector depth (3700 hg/cm^2) 10^-5 < beta < 1; for beta = 2 x 10^-3 the flux limit is 2.7 x 10^-16 cm^-2 s^-1 sr^-1 for an isotropic flux of nuclearites, and twice this value for a flux of downgoing nuclearites.Comment: 16 pages, 4 Encapsulated Postscript figures, uses article.sty. Submitted to The European Physical Journal