Leveraging gene expression subgroups to classify DLBCL patients and select for clinical benefit from a novel agent

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, commonly described by cell-of-origin (COO) molecular subtypes. We sought to identify novel patient subgroups through an unsupervised analysis of a large public dataset of gene expression profiles from newly diagnosed de novo DLBCL patients, yielding 2 biologically distinct subgroups characterized by differences in the tumor microenvironment. Pathway analysis and immune deconvolution algorithms identified higher B-cell content and a strong proliferative signal in subgroup A and enriched T-cell, macrophage, and immune/inflammatory signals in subgroup B, reflecting similar biology to published DLBCL stratification research. A gene expression classifier, featuring 26 gene expression scores, was derived from the public dataset to discriminate subgroup A (classifier-negative, immune-low) and subgroup B (classifier-positive, immune-high) patients. Subsequent application to an independent series of diagnostic biopsies replicated the subgroups, with immune cell composition confirmed via immunohistochemistry. Avadomide, a CRL4CRBN E3 ubiquitin ligase modulator, demonstrated clinical activity in relapsed/refractory DLBCL patients, independent of COO subtypes. Given the immunomodulatory activity of avadomide and the need for a patient-selection strategy, we applied the gene expression classifier to pretreatment biopsies from relapsed/refractory DLBCL patients receiving avadomide (NCT01421524). Classifier-positive patients exhibited an enrichment in response rate and progression-free survival of 44% and 6.2 months vs 19% and 1.6 months for classifier-negative patients (hazard ratio, 0.49; 95% confidence interval, 0.280-0.86; P = .0096). The classifier was not prognostic for rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone or salvage immunochemotherapy. The classifier described here discriminates DLBCL tumors based on tumor and nontumor composition and has potential utility to enrich for clinical response to immunomodulatory agents, including avadomide

Electroweak Corrections to the Charged Higgs Boson Decay into Chargino and Neutralino

The electroweak corrections to the partial widths of the $H^+ \to \tilde{\chi}^+_i \tilde{\chi}_j^0 (i=1,j=1,2)$ decays including one-loop diagrams of the third generation quarks and squarks, are investigated within the Supersymmetric Standard Model. The relative corrections can reach the values about 10%, therefore they should be taken into account for the precise experimental measurement at future colliders.Comment: 21 pages, 6 eps figures, 1 Latex fil

Spin-Charge Separation in the t−Jt-J Model: Magnetic and Transport Anomalies

A real spin-charge separation scheme is found based on a saddle-point state of the $t-J$ model. In the one-dimensional (1D) case, such a saddle-point reproduces the correct asymptotic correlations at the strong-coupling fixed-point of the model. In the two-dimensional (2D) case, the transverse gauge field confining spinon and holon is shown to be gapped at {\em finite doping} so that a spin-charge deconfinement is obtained for its first time in 2D. The gap in the gauge fluctuation disappears at half-filling limit, where a long-range antiferromagnetic order is recovered at zero temperature and spinons become confined. The most interesting features of spin dynamics and transport are exhibited at finite doping where exotic {\em residual} couplings between spin and charge degrees of freedom lead to systematic anomalies with regard to a Fermi-liquid system. In spin dynamics, a commensurate antiferromagnetic fluctuation with a small, doping-dependent energy scale is found, which is characterized in momentum space by a Gaussian peak at ($\pi/a$, $\pi/a$) with a doping-dependent width ($\propto \sqrt{\delta}$, $\delta$ is the doping concentration). This commensurate magnetic fluctuation contributes a non-Korringa behavior for the NMR spin-lattice relaxation rate. There also exits a characteristic temperature scale below which a pseudogap behavior appears in the spin dynamics. Furthermore, an incommensurate magnetic fluctuation is also obtained at a {\em finite} energy regime. In transport, a strong short-range phase interference leads to an effective holon Lagrangian which can give rise to a series of interesting phenomena including linear-$T$ resistivity and $T^2$ Hall-angle. We discuss the striking similarities of these theoretical features with those found in the high-$T_c$ cuprates and give aComment: 70 pages, RevTex, hard copies of 7 figures available upon request; minor revisions in the text and references have been made; To be published in July 1 issue of Phys. Rev. B52, (1995

Search for the Rare Decays J/Psi --> Ds- e+ nu_e, J/Psi --> D- e+ nu_e, and J/Psi --> D0bar e+ e-

We report on a search for the decays J/Psi --> Ds- e+ nu_e + c.c., J/Psi --> D- e+ nu_e + c.c., and J/Psi --> D0bar e+ e- + c.c. in a sample of 5.8 * 10^7 J/Psi events collected with the BESII detector at the BEPC. No excess of signal above background is observed, and 90% confidence level upper limits on the branching fractions are set: B(J/Psi --> Ds- e+ nu_e + c.c.)<4.8*10^-5, B(J/Psi --> D- e+ nu_e + c.c.) D0bar e+ e- + c.c.)<1.1*10^-5Comment: 10 pages, 4 figure

Study of J/psi decays to Lambda Lambdabar and Sigma0 Sigma0bar

The branching ratios and Angular distributions for J/psi decays to Lambda Lambdabar and Sigma0 Sigma0bar are measured using BESII 58 million J/psi.Comment: 11 pages, 5 figure

Measurements of J/psi Decays into 2(pi+pi-)eta and 3(pi+pi-)eta

Based on a sample of 5.8X 10^7 J/psi events taken with the BESII detector, the branching fractions of J/psi--> 2(pi+pi-)eta and J/psi-->3(pi+pi-)eta are measured for the first time to be (2.26+-0.08+-0.27)X10^{-3} and (7.24+-0.96+-1.11)X10^{-4}, respectively.Comment: 11 pages, 6 figure

BESII Detector Simulation

A Monte Carlo program based on Geant3 has been developed for BESII detector simulation. The organization of the program is outlined, and the digitization procedure for simulating the response of various sub-detectors is described. Comparisons with data show that the performance of the program is generally satisfactory.Comment: 17 pages, 14 figures, uses elsart.cls, to be submitted to NIM

Study of J/ψ→ωK+K−J/\psi \to \omega K^+K^-

New data are presented on $J/\psi \to \omega K^+K^-$ from a sample of 58M $J/\psi$ events in the upgraded BES II detector at the BEPC. There is a conspicuous signal for $f_0(1710) \to K^+K^-$ and a peak at higher mass which may be fitted with $f_2(2150) \to K\bar K$. From a combined analysis with $\omega \pi ^+ \pi ^-$ data, the branching ratio $BR(f_0(1710)\to\pi\pi)/BR(f_0(1710) \to K\bar K)$ is $< 0.11$ at the 95% confidence level.Comment: 11 pages, 5 figures. Submitted to Phys. Lett.

The σ\sigma pole in J/ψ→ωπ+π−J/\psi \to \omega \pi^+ \pi^-

Using a sample of 58 million $J/\psi$ events recorded in the BESII detector, the decay $J/\psi \to \omega \pi^+ \pi^-$ is studied. There are conspicuous $\omega f_2(1270)$ and $b_1(1235)\pi$ signals. At low $\pi \pi$ mass, a large broad peak due to the $\sigma$ is observed, and its pole position is determined to be $(541 \pm 39)$ - $i$ $(252 \pm 42)$ MeV from the mean of six analyses. The errors are dominated by the systematic errors.Comment: 15 pages, 6 figures, submitted to PL