TGFβ inhibition stimulates collagen maturation to enhance bone repair and fracture resistance in a murine myeloma model

Multiple myeloma is a plasma cell malignancy that causes debilitating bone disease and fractures, in which TGFβ plays a central role. Current treatments do not repair existing damage and fractures remain a common occurrence. We developed a novel low tumour phase murine model mimicking the plateau phase in patients, as we hypothesized this would be an ideal time to treat with a bone anabolic. Using in vivo microCT we show substantial and rapid bone lesion repair (and prevention) driven by SD‐208 (TGFβ receptor I kinase inhibitor) and chemotherapy (bortezomib and lenalidomide) in mice with human U266‐GFP‐luc myeloma. We discovered that lesion repair occurred via an intramembranous fracture repair‐like mechanism and that SD‐208 enhanced collagen matrix maturation to significantly improve fracture resistance. Lesion healing was associated with VEGFA expression in woven bone, reduced osteocyte‐derived PTHrP, increased osteoblasts, decreased osteoclasts and lower serum TRACP‐5b. SD‐208 also completely prevented bone lesion development mice with aggressive JJN3 tumors, and was more effective than an anti‐TGFβ neutralizing antibody (1D11). We also discovered that SD‐208 promoted osteoblastic differentiation (and overcame the TGFβ‐induced block in osteoblastogenesis) in myeloma patient bone marrow stromal cells in vitro, comparable to normal donors. The improved bone quality and fracture‐resistance with SD‐208 provides incentive for clinical translation to improve myeloma patient quality of life by reducing fracture risk and fatality

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

A Measurement of the KL Charge Asymmetry

We present a measurement of the charge asymmetry $\delta_L$ in the mode $K_L \to \pi^{\pm}e^{\mp}\nu$ based on 298 million analyzed decays. We measure a value of $\delta_L = (3322 \pm 58(stat) \pm 47(sys))\cdot 10^{-6}$, in good agreement with previous measurements and 2.4 times more precise than the current best published result. The result is used to place more stringent limits on CPT and $\Delta S = \Delta Q$ violation in the neutral kaon system.Comment: Submitted to Physical Review Letters, Dec 31, 2001. 4 pages, 4 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

Observation of CP Violation in K(L)->pi+pi-e+e- Decays

We report the first observation of a manifestly CP violating effect in the K(L)->pi+pi-e+e- decay mode. A large asymmetry was observed in the distribution of these decays in the CP-odd and T-odd angle phi between the decay planes of the e+e- and pi+pi- pairs in the K(L) center of mass system. After acceptance corrections, the overall asymmetry is found to be 13.6+-2.5 (stat) +-1.2 (syst)%. This is the largest CP-violating effect yet observed integrating over the entire phase space of a mode and the first such effect observed in an angular variable.Comment: 4 pages 4 figures submitted to pr

New Particles Working Group Report of the Snowmass 2013 Community Summer Study

This report summarizes the work of the Energy Frontier New Physics working group of the 2013 Community Summer Study (Snowmass)

Measurement of the branching ratio of pi^0 -> e^+e^- using K_L -> 3 pi^0 decays in flight

The branching ratio of the rare decay pi^0 -> e^+e^- has been measured in E799-II, a rare kaon decay experiment using the KTeV detector at Fermilab. The pi^0's were produced in fully-reconstructed K_L -> 3 pi^0 decays in flight. We observed 275 candidate pi^0 -> e^+e^- events, with an expected background of 21.4 +- 6.2 events which includes the contribution from Dalitz decays. We measured BR(pi^0 -> e^+e^-, x>0.95) = (6.09 +- 0.40 +- 0.24) times 10^{-8}, where the first error is statistical and the second systematic. This result is the first significant observation of the excess rate for this decay above the unitarity lower bound.Comment: New version shortened to PRL length limit. 5 pages, 4 figures. Published in Phys. Rev. Let