Structural Simplification of Bedaquiline: the Discovery of 3-(4-(N,N-dimethylaminomethyl)phenyl)quinoline Derived Antitubercular Lead Compounds

Bedaquiline (BDQ) is a novel and highly potent last-line antituberculosis drug that was approved by the US FDA in 2013. Owing to its stereo-structural complexity, chemical synthesis and compound optimization are rather difficult and expensive. This study describes the structural simplification of bedaquiline while preserving antitubercular activity. The compound's structure was split into fragments and reassembled in various combinations while replacing the two chiral carbon atoms with an achiral linkage instead. Four series of analogues were designed; these candidates retained their potent antitubercular activity at sub-microgram per mL concentrations against both sensitive and multidrug-resistant (MDR) Mycobacterium tuberculosis strains. Six out of the top nine MIC-ranked candidates were found to inhibit mycobacterial ATP synthesis activity with IC50 values between 20 and 40 μm, one had IC50>66 μm, and two showed no inhibition, despite their antitubercular activity. These results provide a basis for the development of chemically less complex, lower-cost bedaquiline derivatives and describe the identification of two derivatives with antitubercular activity against non-ATP synthase related targets

First observation of psi(2S)-->K_S K_L

The decay psi(2S)-->K_S K_L is observed for the first time using psi(2S) data collected with the Beijing Spectrometer (BESII) at the Beijing Electron Positron Collider (BEPC); the branching ratio is determined to be B(psi(2S)-->K_S K_L) = (5.24\pm 0.47 \pm 0.48)\times 10^{-5}. Compared with J/psi-->K_S K_L, the psi(2S) branching ratio is enhanced relative to the prediction of the perturbative QCD ``12%'' rule. The result, together with the branching ratios of psi(2S) decays to other pseudoscalar meson pairs (\pi^+\pi^- and K^+K^-), is used to investigate the relative phase between the three-gluon and the one-photon annihilation amplitudes of psi(2S) decays.Comment: 5 pages, 4 figures, 2 tables, submitted to Phys. Rev. Let

Study of psi(2S) decays to X J/psi

Using J/psi -> mu^+ mu^- decays from a sample of approximately 4 million psi(2S) events collected with the BESI detector, the branching fractions of psi(2S) -> eta J/psi, pi^0 pi^0 J/psi, and anything J/psi normalized to that of psi(2S) -> pi^+ pi^- J/psi are measured. The results are B(psi(2S) -> eta J/psi)/B(psi(2S) -> pi^+ pi^- J/psi) = 0.098 \pm 0.005 \pm 0.010, B(psi(2S) -> pi^0 pi^0 J/psi)/B(psi(2S) -> pi^+ pi^- J/psi) = 0.570 \pm 0.009 \pm 0.026, and B(psi(2S) -> anything J/psi)/B(psi(2S) -> pi^+ pi^- J/psi) = 1.867 \pm 0.026 \pm 0.055.Comment: 13 pages, 8 figure

Measurement of the Branching Fraction of J/psi --> pi+ pi- pi0

Using 58 million J/psi and 14 million psi' decays obtained by the BESII experiment, the branching fraction of J/psi --> pi+ pi- pi0 is determined. The result is (2.10+/-0.12)X10^{-2}, which is significantly higher than previous measurements.Comment: 9 pages, 8 figures, RevTex

Creation and annihilation of topological meron pairs in in-plane magnetized films

Merons which are topologically equivalent to one-half of skyrmions can exist only in pairs or groups in two-dimensional (2D) ferromagnetic (FM) systems. The recent discovery of meron lattice in chiral magnet Co8Zn9Mn3 raises the immediate challenging question that whether a single meron pair, which is the most fundamental topological structure in any 2D meron systems, can be created and stabilized in a continuous FM film? Utilizing winding number conservation, we develop a new method to create and stabilize a single pair of merons in a continuous Py film by local vortex imprinting from a Co disk. By observing the created meron pair directly within a magnetic field, we determine its topological structure unambiguously and explore the topological effect in its creation and annihilation processes. Our work opens a pathway towards developing and controlling topological structures in general magnetic systems without the restriction of perpendicular anisotropy and Dzyaloshinskii-Moriya interaction

Resonances in J/ψ→ϕπ+π−J/\psi \to \phi \pi ^+\pi ^- and ϕK+K−\phi K^+K^-

A partial wave analysis is presented of $J/\psi \to \phi \pi ^+\pi ^-$ and $\phi K^+K^-$ from a sample of 58M $J/\psi$ events in the BES II detector. The $f_0(980)$ is observed clearly in both sets of data, and parameters of the Flatt\' e formula are determined accurately: $M = 965 \pm 8$ (stat) $\pm 6$ (syst) MeV/c$^2$, $g_1 = 165 \pm 10 \pm 15$ MeV/c$^2$, $g_2/g_1 = 4.21 \pm 0.25 \pm 0.21$. The $\phi \pi \pi$ data also exhibit a strong $\pi \pi$ peak centred at $M = 1335$ MeV/c$^2$. It may be fitted with $f_2(1270)$ and a dominant $0^+$ signal made from $f_0(1370)$ interfering with a smaller $f_0(1500)$ component. There is evidence that the $f_0(1370)$ signal is resonant, from interference with $f_2(1270)$. There is also a state in $\pi \pi$ with $M = 1790 ^{+40}_{-30}$ MeV/c$^2$ and $\Gamma = 270 ^{+60}_{-30}$ MeV/c$^2$; spin 0 is preferred over spin 2. This state, $f_0(1790)$, is distinct from $f_0(1710)$. The $\phi K\bar K$ data contain a strong peak due to $f_2'(1525)$. A shoulder on its upper side may be fitted by interference between $f_0(1500)$ and $f_0(1710)$.Comment: 17 pages, 6 figures, 1 table. Submitted to Phys. Lett.

Search for K_S K_L in psi'' decays

K_S K_L from psi'' decays is searched for using the psi'' data collected by BESII at BEPC, the upper limit of the branching fraction is determined to be B(psi''--> K_S K_L) < 2.1\times 10^{-4} at 90% C. L. The measurement is compared with the prediction of the S- and D-wave mixing model of the charmonia, based on the measurements of the branching fractions of J/psi-->K_S K_L and psi'-->K_S K_L.Comment: 5 pages, 1 figur

First Measurements of eta_c Decaying into K^+K^-2(pi^+pi^-) and 3(pi^+pi^-)

The decays of eta_c to K^+K^-2(pi^+pi^-) and 3(pi^+pi^-) are observed for the first time using a sample of 5.8X10^7 J/\psi events collected by the BESII detector. The product branching fractions are determined to be B(J/\psi-->gamma eta_c)*B(eta_c-->K^+K^-pi^+pi^-pi^+pi^-)=(1.21+-0.32+- 0.23)X10^{-4}$,B(J/\psi-->gamma eta_c)*B(eta_c-->K^{*0}\bar{K}^{*0}pi^+pi^-)= (1.29+-0.43+-0.32)X10^{-4}$, and (J/\psi-->gamma eta_c)* B(eta_c-->pi^+pi^-pi^+pi^-pi^+pi^-)= (2.59+-0.32+-0.48)X10^{-4}. The upper limit for eta_c-->phi pi^+pi^-pi^+pi^- is also obtained as B(J/\psi-->gamma eta_c)*B(eta_c--> phi pi^+pi^-pi^+pi^-)< 6.03 X10^{-5} at the 90% confidence level.Comment: 11 pages, 4 figure

Rapidity and Centrality Dependence of Proton and Anti-proton Production from Au+Au Collisions at sqrt(sNN) = 130GeV

We report on the rapidity and centrality dependence of proton and anti-proton transverse mass distributions from Au+Au collisions at sqrt(sNN) = 130GeV as measured by the STAR experiment at RHIC. Our results are from the rapidity and transverse momentum range of |y|<0.5 and 0.35 <p_t<1.00GeV/c. For both protons and anti-protons, transverse mass distributions become more convex from peripheral to central collisions demonstrating characteristics of collective expansion. The measured rapidity distributions and the mean transverse momenta versus rapidity are flat within |y|<0.5. Comparisons of our data with results from model calculations indicate that in order to obtain a consistent picture of the proton(anti-proton) yields and transverse mass distributions the possibility of pre-hadronic collective expansion may have to be taken into account.Comment: 4 pages, 3 figures, 1 table, submitted to PR

Overall Survival of Primary Single Intracranial Atypical Meningioma with Different Surgical and Postoperative Treatment Options: Evidence from the SEER Database

Jia-Jun Qin,&ast; Chao Li,&ast; Jin Fu, Xian-Zhen Chen Department of Neurosurgery, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xian-Zhen Chen; Jin Fu, Department of Neurosurgery, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, No. 301, Yanchang Middle Road, Jing’an District, Shanghai, 200072, People’s Republic of China, Tel +8613901793331 ; +86 13262727292, Email [email protected]; [email protected]: The aim of this study is to evaluate the impact of different surgical and postoperative treatment options on the long-term overall survival (OS) in patients with primary single intracranial atypical meningioma.Methods: In this retrospective study, participants were drawn from the Surveillance, Epidemiology, and End Results (SEER) database. Inclusion criteria comprised patients who underwent either gross total resection (GTR) or subtotal resection (STR). The inverse probability weighting (IPW) method using generalized boosted models was used to achieve balance in variables across various treatment groups. Subsequent to IPW, multivariate Cox analysis and Kaplan–Meier analysis were conducted, with OS as the endpoint.Results: GTR was conducted on 1650 patients, while STR was conducted on 1109 patients. Among these, 432 patients who underwent GTR and 401 patients who underwent STR received postoperative radiotherapy (PORT). In the case of patients who were under 60 years old, PORT emerged as a significant protective factor for OS in those who underwent STR (HR 0.44; 95% CI 0.23– 0.84; p = 0.013). Survival curves demonstrated that patients who underwent STR with PORT exhibited comparable OS to those who underwent GTR without PORT (p = 0.546). Conversely, for patients aged 60 years or older, PORT emerged as an independent risk factor for both GTR (HR 1.42; 95% CI 1.00– 2.00; p = 0.048) and STR (HR 1.81; 95% CI 1.26– 2.60; p = 0.001).Conclusion: PORT may contribute to improving OS in primary single atypical meningioma patients under 60 years old who receive STR. However, in older patients who underwent either GTR or STR, the administration of PORT may be associated with a potential risk of OS. Therefore, age should be taken into account in applying PORT therapy, and the optimal treatment strategy for PORT in patients with atypical meningiomas needs to be further explored and validated.Keywords: age, atypical meningioma, gross total resection, postoperative radiotherapy, subtotal resectio