JZL184, a monoacylglycerol lipase inhibitor, induces bone loss in a multiple myeloma model of immunocompetent mice

Multiple myeloma (MM) patients develop osteolysis characterised by excessive osteoclastic bone destruction and lack of osteoblast bone formation. Pharmacological manipulation of monoacylglycerol lipase (MAGL), an enzyme responsible for the degradation of the endocannabinoid 2-arachidonoyl glycerol (2-AG), reduced skeletal tumour burden and osteolysis associated with osteosarcoma and advanced breast and prostate cancers. MM and hematopoietic, immune and bone marrow cells express high levels of type 2 cannabinoid receptor and osteoblasts secrete 2-AG. However, the effects of MAGL manipulation on MM have not been investigated. Here, we report that treatment of pre-osteoclasts with non-cytotoxic concentrations of JZL184, a verified MAGL inhibitor, enhanced MM- and RANKL-induced osteoclast formation and size in vitro. Exposure of osteoblasts to JZL184 in the presence of MM cell-derived factors reduced osteoblast growth but had no effect on the ability of these cells to mature or form bone nodules. In vivo, administration of JZL184 induced a modest, yet significant, bone loss at both trabecular and cortical compartments of long bones of immunocompetent mice inoculated with the syngeneic 5TGM1-GFP MM cells. Notably, JZL184 failed to inhibit the in vitro growth of a panel of mouse and human MM cell lines, or reduce tumour burden in mice. Thus, MAGL inhibitors such as JZL184 can exacerbate MM-induced bone loss

Observation of Target Electron Momentum Effects in Single-Arm M\o ller Polarimetry

In 1992, L.G. Levchuk noted that the asymmetries measured in M\o ller scattering polarimeters could be significantly affected by the intrinsic momenta of the target electrons. This effect is largest in devices with very small acceptance or very high resolution in laboratory scattering angle. We use a high resolution polarimeter in the linac of the polarized SLAC Linear Collider to study this effect. We observe that the inclusion of the effect alters the measured beam polarization by -14% of itself and produces a result that is consistent with measurements from a Compton polarimeter. Additionally, the inclusion of the effect is necessary to correctly simulate the observed shape of the two-body elastic scattering peak.Comment: 29 pages, uuencoded gzip-compressed postscript (351 kb). Uncompressed postscript file (898 kb) available to DECNET users as SLC::USER_DISK_SLC1:[MORRIS]levpre.p

Search for Light Gluinos via the Spontaneous Appearance of pi+pi- Pairs with an 800 GeV/c Proton Beam at Fermilab

We searched for the appearance of pi+pi- pairs with invariant mass greater than 648 MeV in a neutral beam. Such an observation could signify the decay of a long-lived light neutral particle. We find no evidence for this decay. Our null result severely constrains the existence of an R0 hadron, which is the lightest bound state of a gluon and a light gluino, and thereby also the possibility of a light gluino. Depending on the photino mass, we exclude the R0 in the mass and lifetime ranges of 1.2 -- 4.6 GeV and 2E-10 -- 7E-4 seconds, respectively. (To Appear in Phys. Rev. Lett.)Comment: Documentstyle aps,epsfig,prl (revtex), 6 pages, 7 figure

Search for the Decay K_L -> pi^0 nu nubar using pi^0 -> e^+ e^- gamma

We report on a search for the decay K_L -> pi^0 nu nubar, carried out as a part of E799-II, a rare K_L decay experiment at Fermilab. Within the Standard Model, the K_L -> pi^0 nu nubar decay is dominated by direct CP violating processes, and thus an observation of the decay implies confirmation of direct CP violation. Due to theoretically clean calculations, a measurement of B(K_L -> pi^0 nu nubar) is one of the best ways to determine the CKM parameter eta. No events were observed, and we set an upper limit B(K_L -> pi^0 nu nubar) < 5.9 times 10^-7 at the 90% confidence level.Comment: 5 pages, 4 figure

Observation of the Decay KL→μ+μ−γγK_L\to \mu^+\mu^- \gamma \gamma

We have observed the decay $K_L\to \mu^+\mu^- \gamma \gamma$ at the KTeV experiment at Fermilab. This decay presents a formidable background to the search for new physics in $K_L\to\pi^0\mu^+\mu^-$. The 1997 data yielded a sample of 4 signal events, with an expected background of 0.155 $\pm$ 0.081 events. The branching ratio is ${\mathcal B}(K_L\to \mu^+\mu^- \gamma \gamma$) $= (10.4^{+7.5}_{-5.9} {\rm (stat)} \pm 0.7 {\rm (sys)})\times 10^{-9}$ with $m_{\gamma\gamma} \geq 1 {\rm MeV/c}^2$, consistent with a QED calculation which predicts $(9.1\pm 0.8)\times 10^{-9}$.Comment: See also the paper "Search for the Decay $K_L \to \pi^0 \mu^+ \mu^-$", also by the KTeV collaboratio

First Observation of the decay KL -> pi0 e e gamma

We report on the first observation of the decay KL -> pi0 ee gamma by the KTeV E799 experiment at Fermilab. Based upon a sample of 48 events with an estimated background of 3.6 +/- 1.1 events, we measure the KL -> pi0 ee gamma branching ratio to be (2.34 +/- 0.35 +/- 0.13)x10^{-8}. Our data agree with recent O(p^6) calculations in chiral perturbation theory that include contributions from vector meson exchange through the parameter a_V. A fit was made to the KL -> pi0 ee gamma data for a_V with the result -0.67 +/- 0.21 +/- 0.12, which is consistent with previous results from KTeV.Comment: Submitted to Physical Review Letters, 5 pages, 5 figure

Search for the Decay Kl -> pi0 e+ e-

We report on a search for the decay Kl -> pi0 e+ e- carried out by the KTeV/E799 experiment at Fermilab. This decay is expected to have a significant CP violating contribution and the measurement of its branching ratio could support the CKM mechanism for CP violation or could point to new physics. Two events were observed in the 1997 data with an expected background of 1.06 +-0.41 events, and we set an upper limit Br(Kl -> pi0 e+ e-) < 5.1 x 10^-10 at the 90% confidence level.Comment: 13 pages, 2 figure

Search for the Decay KL→π0μ+μ−K_L \to \pi^0 \mu^+ \mu^-

We report on a search for the decay \klpimumu carried out as a part of the KTeV experiment at Fermilab. This decay is expected to have a significant $CP$ violating contribution and a direct measurement will either support the CKM mechanism for CP violation or point to new physics. Two events were observed in the 1997 data with an expected background of $0.87 \pm 0.15$ events, and we set an upper limit \BR{\klpimumu} $<3.8 \times 10^{-10}$ at the 90% confidence level.Comment: See also "Observation of the Decay $K_L\to \mu^+\mu^- \gamma \gamma$", also by the KTeV collaboratio