Dual blockage of STAT3 and ERK1/2 eliminates radioresistant GBM cells.

Radiotherapy (RT) is the major modality for control of glioblastoma multiforme (GBM), the most aggressive brain tumor in adults with poor prognosis and low patient survival rate. To improve the RT efficacy on GBM, the mechanism causing tumor adaptive radioresistance which leads to the failure of tumor control and lethal progression needs to be further elucidated. Here, we conducted a comparative analysis of RT-treated recurrent tumors versus primary counterparts in GBM patients, RT-treated orthotopic GBM tumors xenografts versus untreated tumors and radioresistant GBM cells versus wild type cells. The results reveal that activation of STAT3, a well-defined redox-sensitive transcriptional factor, is causally linked with GBM adaptive radioresistance. Database analysis also agrees with the worse prognosis in GBM patients due to the STAT3 expression-associated low RT responsiveness. However, although the radioresistant GBM cells can be resensitized by inhibition of STAT3, a fraction of radioresistant cells can still survive the RT combined with STAT3 inhibition or CRISPR/Cas9-mediated STAT3 knockout. A complementally enhanced activation of ERK1/2 by STAT3 inhibition is identified responsible for the survival of the remaining resistant tumor cells. Dual inhibition of ERK1/2 and STAT3 remarkably eliminates resistant GBM cells and inhibits tumor regrowth. These findings demonstrate a previously unknown feature ofSTAT3-mediated ERK1/2 regulation and an effective combination of two targets in resensitizing GBM to RT

Recurrence and Polya number of general one-dimensional random walks

The recurrence properties of random walks can be characterized by P\'{o}lya number, i.e., the probability that the walker has returned to the origin at least once. In this paper, we consider recurrence properties for a general 1D random walk on a line, in which at each time step the walker can move to the left or right with probabilities $l$ and $r$, or remain at the same position with probability $o$ ($l+r+o=1$). We calculate P\'{o}lya number $P$ of this model and find a simple expression for $P$ as, $P=1-\Delta$, where $\Delta$ is the absolute difference of $l$ and $r$ ($\Delta=|l-r|$). We prove this rigorous expression by the method of creative telescoping, and our result suggests that the walk is recurrent if and only if the left-moving probability $l$ equals to the right-moving probability $r$.Comment: 3 page short pape

Quantum Dense Coding Exploiting Bright EPR Beam

Highly efficient quantum dense coding for continuous variables has been experimentally accomplished by means of exploiting bright EPR beam with anticorrelation of amplitude quadratures and correlation of phase quadratures, which is generated from a nondegenerate optical parametric amplifier operating in the state of deamplification. Two bits of classical information are encoded on two quadratures of a half of bright EPR beam at the sender Alice and transmitted to the receiver Bob via one qubit of the shared quantum state after encoding. The amplitude and phase signals are simultaneously decoded with the other half of EPR beam by the direct measurement of the Bell-state at Bob. The signal to noise ratios of the simultaneously measured amplitude and phase signals are improved 5.4dB and 4.8dB with respect to that of the shot noise limit respectively. A high degree of immunity to unauthorized eavesdropping of the presented quantum communication scheme is experimentally demonstrated.Comment: 11 pages, 5 figure

A targeted gene panel that covers coding, non-coding and short tandem repeat regions improves the diagnosis of patients with neurodegenerative diseases

Genetic testing for neurodegenerative diseases (NDs) is highly challenging because of genetic heterogeneity and overlapping manifestations. Targeted-gene panels (TGPs), coupled with next-generation sequencing (NGS), can facilitate the profiling of a large repertoire of ND-related genes. Due to the technical limitations inherent in NGS and TGPs, short tandem repeat (STR) variations are often ignored. However, STR expansions are known to cause such NDs as Huntington\u27s disease and spinocerebellar ataxias type 3 (SCA3). Here, we studied the clinical utility of a custom-made TGP that targets 199 NDs and 311 ND-associated genes on 118 undiagnosed patients. At least one known or likely pathogenic variation was found in 54 patients; 27 patients demonstrated clinical profiles that matched the variants; and 16 patients whose original diagnosis were refined. A high concordance of variant calling were observed when comparing the results from TGP and whole-exome sequencing of four patients. Our in-house STR detection algorithm has reached a specificity of 0.88 and a sensitivity of 0.82 in our SCA3 cohort. This study also uncovered a trove of novel and recurrent variants that may enrich the repertoire of ND-related genetic markers. We propose that a combined comprehensive TGPs-bioinformatics pipeline can improve the clinical diagnosis of NDs

A π-Extended Donor-Acceptor-Donor Triphenylene Twin linked via a Pyrazine-bridge

Beta-amino triphenylenes can be accessed via palladium catalyzed amination of the corresponding triflate using benzophe-none imine. Transformation of amine 6 to benzoyl amide 18 is also straightforward and its wide mesophase range demon-strates that the new linkage supports columnar liquid crystal formation. Amine 6 also undergoes clean aerobic oxidation to give a new twinned structure linked through an electron-poor pyrazine ring. The new discotic liquid crystal motif contains donor and acceptor fragments, and is more oval in shape rather than disk-like. It forms a wide range columnar mesophase. Absorption spectra are strong and broad; emission is also broad and occurs with a Stokes shift of ca. 0.7 eV, indicative of charge-transfer characte

Quantum Theory Approach for Neutron Single and Double-Slit Diffraction

We provide a quantum approach description of neutron single and double-slit diffraction, with specific attention to the cold neutron diffraction ($\lambda \approx 20$\AA) carried out by Zeilinger et al. in 1988. We find the theoretical results are good agreement with experimental data.Comment: 10 page

Isostructural Phase Transition of TiN Under High Pressure

In situ high-pressure energy dispersive x-ray diffraction experiments on polycrystalline powder TiN with NaCl-type structure have been conducted with the pressure up to 30.1 GPa by using the diamond anvil cell instrument with synchrotron radiation at room tempearture. The experimental results suggested that an isostructural phase transition might exist at about 7 GPa as revealed by the discontinuity of V/V0 with pressure.Comment: submitte

Fermions tunnelling from the charged dilatonic black holes

Kerner and Mann's recent work shows that, for an uncharged and non-rotating black hole, its Hawking temperature can be exactly derived by fermions tunnelling from its horizons. In this paper, our main work is to improve the analysis to deal with charged fermion tunnelling from the general dilatonic black holes, specifically including the charged, spherically symmetric dilatonic black hole, the rotating Einstein-Maxwell-Dilaton-Axion (EMDA) black hole and the rotating Kaluza-Klein (KK) black hole. As a result, the correct Hawking temperatures are well recovered by charged fermions tunnelling from these black holes.Comment: 16 pages, revised version to appear in Class. Quant. Gra