Aminobisphosphonates (NBPs) are used widely against excessive bone resorption in osteoporosis and Paget's disease as well as in metastatic bone disease and multiple myeloma. Intravenous NBP administration often causes mild to severe acute-phase responses (APRs) that may require intervention with analgesics and antipyretics and lead to treatment noncompliance and nonadherence. We here undertook a phase IV safety trial in patients with osteoporosis to investigate the APR of otherwise healthy individuals to first-time intravenous treatment with the NBP zoledronate. This study provides unique insight into sterile acute inflammatory responses in vivo, in the absence of confounding factors such as infection or cancer. Our data show that both peripheral gd T cells and monocytes become rapidly activated after treatment with zoledronate, which ultimately determines the clinical severity of the APR. Our study highlights a key role for IFN-g in the zoledronate-induced APR and identifies pretreatment levels of monocytes and central/memory Vg9/Vd2 T cells as well as their responsiveness to zoledronate in vitro as predictive risk factors for the occurrence of subclinical and clinical symptoms. These findings have diagnostic and prognostic implications for patients with and without malignancy and are relevant for Vg9/Vd2 Tcell-based immunotherapy approaches. ß

We consider the production of heavy quark jets at the Z pole at next-to-leading order ͑NLO͒ using the Cambridge jet algorithm. We study the effects of the quark mass in two-and three-jet observables and the uncertainty due to unknown higher-order corrections as well as due to fragmentation. We find that the three-jet observable has remarkably small NLO corrections, which are stable with respect to the change of the renormalization scale, when expressed in terms of the running quark mass at the m Z scale. The size of the hadronization uncertainty for this observable remains reasonably small and is very stable with respect to changes in the jet resolution parameter y c . ͓S0556-2821͑99͒01921-9͔

General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Paris-Sud, Lab. de l'Accdlgrateur Lingaire, IN2P3-CNRS, Bat 200, F-91405 Orsay, France s School of Physics and Materials, University of Lancaster, Lancaster LA1 4YB, UK t LIP, IST, FCUL -Av. Elias Garcia, 14-1(o), P-IO00 Lisboa Codex, Portugal u Department of Physics, University of Liverpool, P.O. Box 147, Liverpool L69 3BX, UK v LPNHE, IN2P3-CNRS, Universitds Paris VI et VII, Tour 33 (RdC), 4 place Jussieu, F-75252 Paris Cedex 05, France w Department of Physics, University of Lund, SOlvegatan 14, S-22363 Lund, Sweden DELPHI Collaboration/Physics Letters B 332 (1994)

From measurements of the cross sections for eẽ-~hadrons and the cross sections and forward-backward charge-asymmetries for e e-~e + e-,~+-and s-r at several centreof-mass energies around the Z" pole with the DELPHI apparatus, using approximately 150000 2 = 0.0003±0.0010and A~= 0.2508±1)0027. These values correspond to the electroweak parameters: PCV = 1.003±0.011and sin20~j 0.241±0.009.Within the Minimal Standard Model (MSM). the results can he expressed in terms of a single parameter: sin20~=0.2338±0.0027.All these values are in good agreement with the predictions ot the MSM. Fits yield 43< m 115, < 215 0eV at the 95Vr level. Finally, the measured values of "z and arc used to derive lower mass bounds for possible new particles. * The VD, which was operated during most of the 1990 data collection period, was used in the alignment procedure of the barrel tracking detectors, but was not used directly in the analysis described here. * Fits with the formula of ref. [26] tend to underestimate M~and T~by about 2 MeV and to overestimate a'1~by approximately 0.1%.

Engagement of major histocompatibility complex (MHC) class I molecules on immune cells, where they are usually highly expressed, induces signal transduction events of unclear significance. We show here that antibody-mediated cross-linking of MHC-I molecules on human natural killer (NK) cells inhibits their cytotoxic activity against tumor target cells. Inhibition by anti-MHC class I monoclonal antibody exhibits molecular specificity and is an isotype and Fc-independent process. Physical hindrance of specific molecular recognition, induction of apoptosis, or reciprocal NK cell killing, which could be induced by cross-linking of MHC I molecules, has also been ruled out as putative mechanisms of inhibition. Confocal microscopy analysis revealed that MHC class I molecules on the surface of NK cells colocalize constitutively with GM1, a marker of lipid rafts. Cross-linking of MHC class I resulted in the asymmetric redistribution of GM1-enriched raft domains, which are concentrated to the immunological synapse, and MHC I molecules, which segregate to the opposite pole. Also, the cross-linking of MHC I on NK cells induced intracellular tyrosine phosphorylations. These results suggest that MHC I molecules on NK cells could transmit inhibitory signals upon engagement with putative ligands expressed on the surface of those cells that need to be protected from natural cytotoxicity.