Probing anomalous top quark interactions at the Fermilab Tevatron Collider

We study the effects of dimension-six operators contributing to the $gt\bar t$ vertex in top quark pair production at the Tevatron collider. We derive both the limits from Run 1 data and the potential bounds from future runs (Run 2 and 3). Although the current constraints are not very strong, the future runs are quite effective in probing these operators. We investigate the possibility of disentangling different operators with the $t\bar t$ invariant mass distribution and the top quark polarization asymmetry. We also study the effects of a different set of operators contributing to single top production via the $Wt\bar b$ coupling. We derive the current and potential future bounds on these anomalous operators and find that the upgraded Tevatron can improve the existing constraints from $R_b$ for one of the operators.Comment: 20 pages, 2 figures, REVTEX, some clarifying remarks adde

C-Terminal Binding Protein 2 Is a Novel Tumor Suppressor Targeting the Myc-Irf4 axis in Multiple Myeloma

Multiple myeloma (MM) cells are addicted to MYC and its direct transactivation targets IRF4 for proliferation and survival. MYC and IRF4 are still considered undruggable, as most small-molecule inhibitors suffer from low potency, suboptimal pharmacokinetic properties, and undesirable off-target effects. Indirect inhibition of MYC/IRF4 emerges as a therapeutic vulnerability in MM. Here, we uncovered an unappreciated tumor-suppressive role of C-terminal binding protein 2 (CTBP2) in MM via strong inhibition of the MYC-IRF4 axis. In contrast to epithelial cancers, CTBP2 is frequently downregulated in MM, in association with shortened survival, hyperproliferative features, and adverse clinical outcomes. Restoration of CTBP2 exhibited potent antitumor effects against MM in vitro and in vivo, with marked repression of the MYC-IRF4 network genes. Mechanistically, CTBP2 impeded the transcription of MYC and IRF4 by histone H3 lysine 27 deacetylation (H3K27ac) and indirectly via activation of the MYC repressor IFIT3. In addition, activation of the interferon gene signature by CTBP2 suggested its concomitant immunomodulatory role in MM. Epigenetic studies have revealed the contribution of polycomb-mediated silencing and DNA methylation to CTBP2 inactivation in MM. Notably, inhibitors of Enhance of zeste homolog 2, histone deacetylase, and DNA methyltransferase, currently under evaluation in clinical trials, were effective in restoring CTBP2 expression in MM. Our findings indicated that the loss of CTBP2 plays an essential role in myelomagenesis and deciphers an additional mechanistic link to MYC-IRF4 dysregulation in MM. We envision that the identification of novel critical regulators will facilitate the development of selective and effective approaches for treating this MYC/IRF4-addicted malignancy

Probing anomalous top quark couplings at e\gamma colliders

We study in the effective Lagrangian approach the possibility of probing anomalous top quark charged current couplings in the single top production at a high energy e\gamma collider. We analyzed all possible dimension-six CP-conserving operators which can give rise to an anomalous Wtb coupling which represent new physics effect generated at a higher energy scale. For those operators which also give rise to anomalous Zbb_bar or right-handed Wtb couplings, we find that they are strongly constrained by the existing R_b and b->s\gamma data. As a result, a collider with a luminosity of the order of 100 fb^{-1} is required to observe the anomalous effects. For other operators which currently subject to no strong constraints, the high energy e\gamma collider can probe their couplings effectively because of the clean environment of such a collider.Comment: version in PRD, refs adde

CD9 shapes glucocorticoid sensitivity in pediatric B-cell precursor acute lymphoblastic leukemia

Resistance to glucocorticoids (GCs), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patients with a CD9- phenotype, especially for those with adverse presenting features including older age, higher white cell count and BCR-ABL1. Furthermore, gain- and loss-of-function experiments dictated a definitive functional linkage between CD9 expression and GC susceptibility, as demonstrated by the reversal and acquisition of relative GC resistance in CD9low and CD9high BCP-ALL cells, respectively. Despite physical binding to the GC receptor NR3C1, CD9 did not alter its expression, phosphorylation or nuclear translocation but potentiated the induction of GC-responsive genes in GCresistant cells. Importantly, the MEK inhibitor trametinib exhibited higher synergy with GCs against CD9- than CD9+ lymphoblasts to reverse drug resistance in vitro and in vivo. Collectively, our results elucidate a previously unrecognized regulatory function of CD9 in GC sensitivity, and inform new strategies for management of children with resistant BCP-ALL

Simulation of Adaptive Array Algorithms for OFDM and Adaptive Vector OFDM Systems

The increasing demand for high data rate services necessitates the adoption of very wideband waveforms. In this case, the channel is frequency-selective, that is, a large number of resolvable multipaths are present in this environment and fading is not highly correlated across the band. Orthogonal frequency division multiplexing (OFDM) is well-known to be effective against multipath distortion. It is a multicarrier communication scheme, in which the bandwidth of the channel is divided into subcarriers and data symbols are modulated and transmitted on each subcarrier simultaneously. By inserting guard time that is longer than the delay spread of the channel, an OFDM system is able to mitigate intersymbol interference (ISI). Deploying an adaptive antenna array at the receiver can help separate the desired signal from interfering signals which originate from different spatial locations. This enhancement of signal integrity increases system capacity. In this research, we apply adaptive array algorithms to OFDM systems and study their performance in a multipath environment with the presence of interference. A novel adaptive beamforming algorithm based on the minimum mean-squared error (MMSE) criterion, which is referred to as frequency-domain beamforming, is proposed that exploits the characteristics of OFDM signals. The computational complexity of frequency-domain beamforming is also studied. Simulation results show employing an adaptive antenna array with an OFDM system significantly improves system performance when interference is present. Simulations also show that the computational complexity of the algorithm can be reduced by half without significant performance degradation. Adaptive array algorithms based on the maximum signal-to-noise ratio (MSNR) and the maximum signal-to-interference-plus-noise ratio (MSINR) criteria are also applied to adaptive vector OFDM systems (AV-OFDM). Simulation results show that the adaptive algorithm based on the MSNR criterion has superior performance in the multipath environment but performs worse than the one based on the MSINR criterion under the flat fading channel.Master of Scienc