Annihilation Rate of Heavy 0^{++} P-wave Quarkonium in Relativistic Salpeter Method

Two-photon and two-gluon annihilation rates of P-wave scalar charmonium and bottomonium up to third radial excited states are estimated in the relativistic Salpeter method. We solved the full Salpeter equation with a well defined relativistic wave function and calculated the transition amplitude using the Mandelstam formalism. Our model dependent estimates for the decay widths: $\Gamma(\chi_{c0} \to 2\gamma)=3.78$ keV, $\Gamma(\chi'_{c0} \to 2\gamma)=3.51$ keV, $\Gamma(\chi_{b0} \to 2\gamma)=48.8$ eV and $\Gamma(\chi'_{b0} \to 2\gamma)=50.3$ eV. We also give estimates of total widths by the two-gluon decay rates: $\Gamma_{tot}(\chi_{c0})=10.3$ MeV, $\Gamma_{tot}(\chi'_{c0})=9.61$ MeV, $\Gamma_{tot}(\chi_{b0})=0.887$ MeV and $\Gamma_{tot}(\chi'_{b0})=0.914$ MeV.Comment: 8 pages, 1 figure, 4 table

Next-to-Leading-Order QCD Corrections to e^ + e^- -> J/\psi+gg at the B Factories

We calculate the next-to-leading-order (NLO) QCD corrections to $e^+e^-\to J/\psi g g$ via color singlet $J/\psi(^3{-0.8mm}S_1)$ at the B factories. The result shows that the cross section is enhanced to 0.373\pb by a K factor (NLO/LO) of about 1.21. By considering its dependence on the charm quark mass and renormalization scale, the NLO cross section can range from 0.294 to 0.409\pb. Further including the $\psi^\prime$ feed-down, \sigma(e^+e^-\to \jpsi X(\mathrm{non} c\bar{c})) is enhanced by another factor of about 1.29 and reaches 0.482\pb. In addition, the momentum distributions of $J/\psi$ production and polarization are presented. Recent measurements from Belle agree well with our prediction for the cross section and momentum distribution. It is expected that this process can serve as a very good channel to clarify the $J/\psi$ polarization puzzle by performing further experimental measurements.Comment: published version in PRL, 4 pages, 4 figures, references adde

Homogeneous catalysis under ultra-dilute conditions: TAML/NaClO oxidation of persistent metaldehyde

This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in Journal of the American Chemical Society, copyright © American Chemical Society after peer review. To access the final edited and published work see https://doi.org/10.1021/jacs.6b11145TAML activators enable homogenous oxidation catalysis where the catalyst and substrate (S) are ultra-dilute (pM–low μM) and the oxidant is very dilute (high nM–low mM). Water contamination by exceptionally persistent micropollutants (MPs), including metaldehyde (Met), provides an ideal space for determining the characteristics and utilitarian limits of this ultradilute catalysis. The low MP concentrations decrease throughout catalysis with S oxidation (kII) and catalyst inactivation (ki) competing for the active catalyst. The percentage of substrate converted (%Cvn) can be increased by discovering methods to increase kII/ki. Here we show that NaClO extends catalyst lifetime to increase the Met turnover number (TON) threefold compared with H2O2, highlighting the importance of oxidant choice as a design tool in TAML systems. Met oxidation studies (pH 7, D2O, 0.01 M phosphate, 25 °C) monitored by 1H NMR spectroscopy show benign acetic acid as the only significant product. Analysis of TAML/NaClO treated Met solutions employing successive identical catalyst doses revealed that the processes can be modeled by the recently published relationship between the initial and final [S] (S0 and S∞, respectively), the initial [catalyst] (FeTot) and kII/ki. Consequently, this study establishes that S is proportional to S0 and that the %Cvn is conserved across all catalyst doses in multicatalyst-dose processes because the rate of the kII process depends on [S] while that of the ki process does not. A general tool for determining the FeTot required to effect a desired %Cvn is presented. Examination of the dependence of TON on kII/ki and FeTot at a fixed S0 indicates that for any TAML process employing FeTot < 1 10-6 M, small catalyst doses are not more efficient than one large dose.T.J.C thanks the Heinz Endowments for funding. NMR instrumentation at CMU was partially supported by NSF (CHE-0130903 and CHE-1039870)

Spin-Flip Interactions and the Puzzle of psi's Polarization at Tevatron

Nonrelativistic QCD provides a systematic approach for inclusive decays and productions of a quarkonium. By taking color-octet components into account, the approach can explain the $\psi'$-anomaly at Tevatron, where the measured production rate at large transverse momentum $p_\perp$ is in order of magnitude larger than the predicted with color-singlet components only. With the approach one can predict that the produced $J/\psi$ and $\psi'$ at large $p_\perp$ will be transversely polarized. But the prediction fails in confronting with experimental measurements and this generates a puzzle. We examine the role of spin-flip interactions in the spin density matrix of the transition of a color-octet charm quark pair into $J/\psi$ and $\psi'$. These interactions will introduce new nonperturbative parameters in the spin density matrix. Our result shows that the impact of the interactions is always to dilute the polarization and can be very significant. Taking the impact into account, predictions for the polarization are more close to the measured than the previous predicted. The same can also be expected for the polarization of $J/\psi$.Comment: match the published version Phys.Lett.B645:180-184,200

The relevance of neck linker docking in the motility of kinesin

Conventional kinesin is a motor protein, which is able to walk along a microtubule processively. The exact mechanism of the stepping motion and force generation of kinesin is still far from clear. In this paper we argue that neck linker docking is a crucial element of this mechanism, without which the experimentally observed dwell times of the steps could not be explained under a wide range of loading forces. We also show that the experimental data impose very strict constraints on the lengths of both the neck linker and its docking section, which are compatible with the known structure of kinesin.Comment: Accepted for publication in BioSystems as part of the proceedings of BIOCOMP 200

Quarkonium Production at High-Energy Colliders

The theoretical description of heavy quarkonium production at high-energy p-pbar and e-p colliders is reviewed. Predictions based on non-relativistic QCD factorisation are confronted with recent charmonium and bottomonium data from the Tevatron and HERA. Potential shortcomings of the present theoretical analyses are discussed, and the prospects for quarkonium physics at the upgraded Tevatron and HERA colliders and at the LHC are summarised.Comment: 61 pages, 20 figures. To be published in Progress in Particle and Nuclear Physics, Vol. 47, issue

Enhancing astrocytic lysosome biogenesis facilitates Aβ clearance and attenuates amyloid plaque pathogenesis

In sporadic Alzheimer's disease (AD), impaired Aβ removal contributes to elevated extracellular Aβ levels that drive amyloid plaque pathogenesis. Extracellular proteolysis, export across the blood–brain barrier, and cellular uptake facilitate physiologic Aβ clearance. Astrocytes can take up and degrade Aβ, but it remains unclear whether this function is insufficient in AD or can be enhanced to accelerate Aβ removal. Additionally, age-related dysfunction of lysosomes, the major degradative organelles wherein Aβ localizes after uptake, has been implicated in amyloid plaque pathogenesis. We tested the hypothesis that enhancing lysosomal function in astrocytes with transcription factor EB (TFEB), a master regulator of lysosome biogenesis, would promote Aβ uptake and catabolism and attenuate plaque pathogenesis. Exogenous TFEB localized to the nucleus with transcriptional induction of lysosomal biogenesis and function in vitro. This resulted in significantly accelerated uptake of exogenously applied Aβ42, with increased localization to and degradation within lysosomes in C17.2 cells and primary astrocytes, indicating that TFEB is sufficient to coordinately enhance uptake, trafficking, and degradation of Aβ. Stereotactic injection of adeno-associated viral particles carrying TFEB driven by a glial fibrillary acidic protein promoter was used to achieve astrocyte-specific expression in the hippocampus of APP/PS1 transgenic mice. Exogenous TFEB localized to astrocyte nuclei and enhanced lysosome function, resulting in reduced Aβ levels and shortened half-life in the brain interstitial fluid and reduced amyloid plaque load in the hippocampus compared with control virus-injected mice. Therefore, activation of TFEB in astrocytes is an effective strategy to restore adequate Aβ removal and counter amyloid plaque pathogenesis in AD

Annihilation Rate of 2++2^{++} Charmonium and Bottomonium

Two-photon annihilation rates of $2^+$ tensor charmonium and bottomonium up to third radial excited states are estimated in the relativistic Salpeter method. Full Salpeter equation for $2^+$ tensor state is solved with a well defined relativistic wave function and we calculated the annihilation amplitude using the Mandelstam formalism. Our estimates of the decay widths are: $\Gamma(\chi_{c2} \to 2\gamma)=501$ eV, $\Gamma(\chi'_{c2} \to 2\gamma)=534$ eV, $\Gamma(\chi_{b2} \to 2\gamma)=7.4$ eV and $\Gamma(\chi'_{b2} \to 2\gamma)=7.7$ eV. We also give total decay widths of the lowest states estimated by the two-gluon decay rates, and the results are: $\Gamma_{tot}(\chi_{c2})=2.64$ MeV, $\Gamma_{tot}(\chi_{b2})=0.220$ MeV and $\Gamma_{tot}(\chi'_{b2})=0.248$ MeV.Comment: 9 pages,1 figure, 3 table

IRX-2, a Novel Immunotherapeutic, Enhances Functions of Human Dendritic Cells

Background: In a recent phase II clinical trial for HNSCC patients, IRX-2, a cell-derived biologic, promoted T-cell infiltration into the tumor and prolonged overall survival. Mechanisms responsible for these IRX-2-mediated effects are unknown. We hypothesized that IRX-2 enhanced tumor antigen-(TA)-specific immunity by up-regulating functions of dendritic cells (DC). Methodology/Principal Findings: Monocyte-derived DC obtained from 18 HNSCC patients and 12 healthy donors were matured using IRX-2 or a mix of TNF-α, IL-1β and IL-6 ("conv. mix"). Multicolor flow cytometry was used to study the DC phenotype and antigen processing machinery (APM) component expression. ELISPOT and cytotoxicity assays were used to evaluate tumor-reactive cytotoxic T lymphocytes (CTL). IL-12p70 and IL-10 production by DC was measured by Luminex® and DC migration toward CCL21 was tested in transwell migration assays. IRX-2-matured DC functions were compared with those of conv. mix-matured DC. IRX-2-matured DC expressed higher levels (p<0.05) of CD11c, CD40, CCR7 as well as LMP2, TAP1, TAP2 and tapasin than conv. mix-matured DC. IRX-2-matured DC migrated significantly better towards CCL21, produced more IL-12p70 and had a higher IL12p70/IL-10 ratio than conv. mix-matured DC (p<0.05 for all). IRX-2-matured DC carried a higher density of tumor antigen-derived peptides, and CTL primed with these DC mediated higher cytotoxicity against tumor targets (p<0.05) compared to the conv. mix-matured DC. Conclusion: Excellent ability of IRX-2 to induce ex vivo DC maturation in HNSCC patients explains, in part, its clinical benefits and emphasizes its utility in ex vivo maturation of DC generated for therapy. © 2013 Schilling et al

Phase 1 study of capmatinib in MET-positive solid tumor patients: Dose escalation and expansion of selected cohorts

Capmatinib is an oral, ATP-competitive, and highly potent, type 1b MET inhibitor. Herein, we report phase 1 dose-escalation results for capmatinib in advanced METpositive solid tumor patients and dose expansion in advanced non-lung tumors. Capmatinib was well tolerated with a manageable safety profile across all explored doses. Dose-limiting toxicities (DLT) occurred at 200 mg twice daily (bid), 250 mg bid, and 450 mg bid capsules; however, no DLT were reported at 600 mg bid (capsules). Capmatinib tablets at 400 mg bid had comparable tolerability and exposure to that of 600 mg bid capsules. Maximum tolerated dose was not reached; recommended phase 2 dose was 400 mg bid tablets/600 mg bid capsules; at this dose, C-trough >EC90 (90% inhibition of c-MET phosphorylation in animal models) is expected to be achieved and maintained. Among the dose-expansion patients (N = 38), best overall response across all cohorts was stable disease (gastric cancer 22%, hepatocellular carcinoma 46%, other indications 28%); two other indication patients with gene copy number (GCN) >= 6 achieved substantial tumor reduction. Near-complete immunohistochemically determined phospho-MET inhibition (H-score = 2) was shown following capmatinib 450 mg bid capsule in paired biopsies obtained from one advanced colorectal cancer patient. Incidence of high-level MET GCN (GCN >= 6) and MET-overexpressing (immunohistochemistry 3+) tumors in the expansion cohorts was 8% and 13%, respectively; no MET mutations were observed. Thus, the recommended phase 2 dose (RP2D) of capmatinib was 600 mg bid capsule/400 mg bid tablet. Capmatinib was well tolerated and showed antitumor activity and acceptable safety profile at the (ClinicalTrials.gov Identifier: NCT01324479).