Evidence for a Binary Companion to the Central Compact Object 1E 1207.4-5209

Unique among neutron stars, 1E 1207.4-5209 is an X-ray pulsar with a spin period of 424 ms that contains at least two strong absorption features in its energy spectrum. This neutron star has been identified as a member of the radio-quiet compact central objects in supernova remnants. It has been found that 1E 1207.4-5209 is not spinning down monotonically suggesting that this neutron star undergoes strong, frequent glitches, contains a fall-back disk, or possess a binary companion. Here, we report on a sequence of seven XMM-Newton observations of 1E 1207.4-5209 performed during a 40 day window in June/July 2005. Due to unanticipated variance in the phase measurements beyond the statistical uncertainties, we could not identify a unique phase-coherent timing solution. The three most probable timing solutions give frequency time derivatives of +0.9, -2.6, and +1.6 X 10^(-12) Hz/s (listed in descending order of significance). We conclude that the local frequency derivative during our XMM-Newton observing campaign differs from the long-term spin-down rate by more than an order of magnitude, effectively ruling out glitch models for 1E 1207.4-5209. If the long-term spin frequency variations are caused by timing noise, the strength of the timing noise in 1E 1207.4-5209 is much stronger than in other pulsars with similar period derivatives. Therefore, it is highly unlikely that the spin variations are caused by the same physical process that causes timing noise in other isolated pulsars. The most plausible scenario for the observed spin irregularities is the presence of a binary companion to 1E 1207.4-5209. We identified a family of orbital solutions that are consistent with our phase-connected timing solution, archival frequency measurements, and constraints on the companions mass imposed by deep IR and optical observations.Comment: 8 pages, 4 figures. To be published in the proceedings of "Isolated Neutron Stars: from the Interior to the Surface" (April 24-28, 2006) - eds. D. Page, R. Turolla & S. Zan

Modulation of the high-order chromatin structure by Polycomb complexes

The multi-subunit Polycomb Repressive Complex (PRC) 1 and 2 act, either independently or synergistically, to maintain and enforce a repressive state of the target chromatin, thereby regulating the processes of cell lineage specification and organismal development. In recent years, deep sequencing-based and imaging-based technologies, especially those tailored for mapping three-dimensional (3D) chromatin organization and structure, have allowed a better understanding of the PRC complex-mediated long-range chromatin contacts and DNA looping. In this review, we review current advances as for how Polycomb complexes function to modulate and help define the high-order chromatin structure and topology, highlighting the multi-faceted roles of Polycomb proteins in gene and genome regulation

Astrophysical Axion Bounds

Axion emission by hot and dense plasmas is a new energy-loss channel for stars. Observational consequences include a modification of the solar sound-speed profile, an increase of the solar neutrino flux, a reduction of the helium-burning lifetime of globular-cluster stars, accelerated white-dwarf cooling, and a reduction of the supernova SN 1987A neutrino burst duration. We review and update these arguments and summarize the resulting axion constraints.Comment: Contribution to Axion volume of Lecture Notes in Physics, 20 pages, 3 figure

Interaction between androgen receptor and coregulator SLIRP is regulated by Ack1 tyrosine kinase and androgen

Aberrant activation of the androgen receptor (AR) may play a critical role in castration resistant prostate cancer. After ligand binding, AR is recruited to the androgen responsive element (ARE) sequences on the DNA where AR interaction with coactivators and corepressors modulates transcription. We demonstrated that phosphorylation of AR at Tyr-267 by Ack1/TNK2 tyrosine kinase results in nuclear translocation, DNA binding, and androgen-dependent gene transcription in a low androgen environment. In order to dissect downstream mechanisms, we searched for proteins whose interaction with AR was regulated by Ack1. SLIRP (SRA stem-loop interacting RNA binding protein) was identified as a candidate protein. Interaction between AR and SLIRP was disrupted by Ack1 kinase activity as well as androgen or heregulin treatment. The noncoding RNA, SRA, was required for AR-SLIRP interaction. SLIRP was bound to ARE’s of AR target genes in the absence of androgen. Treatment with androgen or heregulin led to dissociation of SLIRP from the ARE. Whole transcriptome analysis of SLIRP knockdown in androgen responsive LNCaP cells showed that SLIRP affects a significant subset of androgen-regulated genes. Our data suggest that Ack1 kinase and androgen regulate interaction between AR and SLIRP and that SLIRP functions as a coregulator of AR with properties of a corepressor in a context-dependent manner

Characterizing top gated bilayer graphene interaction with its environment by Raman spectroscopy

In this work we study the behavior of the optical phonon modes in bilayer graphene devices by applying top gate voltage, using Raman scattering. We observe the splitting of the Raman G band as we tune the Fermi level of the sample, which is explained in terms of mixing of the Raman (Eg) and infrared (Eu) phonon modes, due to different doping in the two layers. We theoretically analyze our data in terms of the bilayer graphene phonon self-energy which includes non-homogeneous charge carrier doping between the graphene layers. We show that the comparison between the experiment and theoretical model not only gives information about the total charge concentration in the bilayer graphene device, but also allows to separately quantify the amount of unintentional charge coming from the top and the bottom of the system, and therefore to characterize the interaction of bilayer graphene with its surrounding environment

A randomised, double-blind, phase 3 study comparing the efficacy and safety of ceftazidime/avibactam plus metronidazole versus meropenem for complicated intra-abdominal infections in hospitalised adults in Asia

Ceftazidime/avibactam comprises the broad-spectrum cephalosporin ceftazidime and the non-β-lactam β-lactamase inhibitor avibactam. This phase 3, randomised, double-blind study (NCT01726023) assessed the efficacy and safety of ceftazidime/avibactam plus metronidazole compared with meropenem in patients with complicated intra-abdominal infection (cIAI) in Asian countries. Subjects aged 18–90 years and hospitalised with cIAI requiring surgical intervention were randomised 1:1 to receive every 8 h either: ceftazidime/avibactam (2000/500 mg, 2-h infusion) followed by metronidazole (500 mg, 60-min infusion); or meropenem (1000 mg, 30-min infusion). Non-inferiority of ceftazidime/avibactam plus metronidazole to meropenem was concluded if the lower limit of the 95% confidence interval (CI) for the between-group difference in clinical cure rate was greater than −12.5% at the test-of-cure (TOC) visit (28–35 days after randomisation) in the clinically evaluable (CE) population. Safety was also evaluated. Of 441 subjects randomised, 432 received at least one dose of study medication (ceftazidime/avibactam plus metronidazole, n = 215; meropenem, n = 217). In the CE population at the TOC visit, non-inferiority of ceftazidime/avibactam plus metronidazole to meropenem was demonstrated, with clinical cure reported for 93.8% (166/177) and 94.0% (173/184) of subjects, respectively (between-group difference, −0.2, 95% CI −5.53 to 4.97). The clinical cure rate with ceftazidime/avibactam plus metronidazole was comparable in subjects with ceftazidime-non-susceptible and ceftazidime-susceptible isolates (95.7% vs. 92.1%, respectively). Adverse events were similar between the study groups. Ceftazidime/avibactam plus metronidazole was non-inferior to meropenem in the treatment of cIAIs in Asian populations and was effective against ceftazidime-non-susceptible pathogens. No new safety concerns were identified

ZFX Mediates Non-canonical Oncogenic Functions of the Androgen Receptor Splice Variant 7 in Castrate-Resistant Prostate Cancer

Androgen receptor splice variant 7 (AR-V7) is crucial for prostate cancer progression and therapeutic resistance. We show that, independent of ligand, AR-V7 binds both androgen-responsive elements (AREs) and non-canonical sites distinct from full-length AR (AR-FL) targets. Consequently, AR-V7 not only recapitulates AR-FL's partial functions but also regulates an additional gene expression program uniquely via binding to gene promoters rather than ARE enhancers. AR-V7 binding and AR-V7-mediated activation at these unique targets do not require FOXA1 but rely on ZFX and BRD4. Knockdown of ZFX or select unique targets of AR-V7/ZFX, or BRD4 inhibition, suppresses growth of castration-resistant prostate cancer cells. We also define an AR-V7 direct target gene signature that correlates with AR-V7 expression in primary tumors, differentiates metastatic prostate cancer from normal, and predicts poor prognosis. Thus, AR-V7 has both ARE/FOXA1 canonical and ZFX-directed non-canonical regulatory functions in the evolution of anti-androgen therapeutic resistance, providing information to guide effective therapeutic strategies. By cistrome profiling of endogenous androgen receptor (AR) versus an AR splice variant, AR-V7, Cai et al. uncovered non-canonical pathways uniquely targeted by AR-V7 and ZFX, a previously unknown AR-V7 partner. Targeting cofactors (ZFX or BRD4) or non-canonical downstream pathways of AR-V7 provides potential therapeutic ways for treating prostate cancer

The Chromatin Remodeler BPTF Activates a Stemness Gene-Expression Program Essential for the Maintenance of Adult Hematopoietic Stem Cells

Self-renewal and differentiation of adult stem cells are tightly regulated partly through configuration of chromatin structure by chromatin remodelers. Using knockout mice, we here demonstrate that bromodomain PHD finger transcription factor (BPTF), a component of the nucleosome remodeling factor (NURF) chromatin-remodeling complex, is essential for maintaining the population size of hematopoietic stem/progenitor cells (HSPCs), including long-term hematopoietic stem cells (HSCs). Bptf-deficient HSCs are defective in reconstituted hematopoiesis, and hematopoietic-specific knockout of Bptf caused profound defects including bone marrow failure and anemia. Genome-wide transcriptome profiling revealed that BPTF loss caused downregulation of HSC-specific gene-expression programs, which contain several master transcription factors (Meis1, Pbx1, Mn1, and Lmo2) required for HSC maintenance and self-renewal. Furthermore, we show that BPTF potentiates the chromatin accessibility of key HSC “stemness” genes. These results demonstrate an essential requirement of the chromatin remodeler BPTF and NURF for activation of “stemness” gene-expression programs and proper function of adult HSCs. Wang and colleagues show that a chromatin remodeler, BPTF, sustains appropriate functions of hematopoietic stem/progenitor cells (HSPCs). BPTF loss causes bone marrow failure and anemia. The authors further define a BPTF-dependent gene-expression program in HSPCs, which contains key HSC stemness factors. These results demonstrate an essential requirement of the BPTF-associated chromatin remodelers for HSC functionality and adult hematopoiesis

Dynamic study on fusion reactions for 40,48^{40,48}Ca+90,96^{90,96}Zr around Coulomb barrier

By using the updated improved Quantum Molecular Dynamics model in which a surface-symmetry potential term has been introduced for the first time, the excitation functions for fusion reactions of $^{40,48}$Ca+$^{90,96}$Zr at energies around the Coulomb barrier have been studied. The experimental data of the fusion cross sections for $^{40}$Ca+$^{90,96}$Zr have been reproduced remarkably well without introducing any new parameters. The fusion cross sections for the neutron-rich fusion reactions of $^{48}$Ca+$^{90,96}$Zr around the Coulomb barrier are predicted to be enhanced compared with a non-neutron-rich fusion reaction. In order to clarify the mechanism of the enhancement of the fusion cross sections for neutron-rich nuclear fusions, we pay a great attention to study the dynamic lowering of the Coulomb barrier during a neck formation. The isospin effect on the barrier lowering is investigated. It is interesting that the effect of the projectile and target nuclear structure on fusion dynamics can be revealed to a certain extent in our approach. The time evolution of the N/Z ratio at the neck region has been firstly illustrated. A large enhancement of the N/Z ratio at neck region for neutron-rich nuclear fusion reactions is found.Comment: 21 pages, 7 figures,3 table

High-p_T pion and kaon production in relativistic nuclear collisions

High-p_T pion and kaon production is studied in relativistic proton-proton, proton-nucleus, and nucleus-nucleus collisions in a wide energy range. Cross sections are calculated based on perturbative QCD, augmented by a phenomenological transverse momentum distribution of partons (``intrinsic k_T''). An energy dependent width of the transverse momentum distribution is extracted from pion and charged hadron production data in proton-proton/proton-antiproton collisions. Effects of multiscattering and shadowing in the strongly interacting medium are taken into account. Enhancement of the transverse momentum width is introduced and parameterized to explain the Cronin effect. In collisions between heavy nuclei, the model over-predicts central pion production cross sections (more significantly at higher energies), hinting at the presence of jet quenching. Predictions are made for proton-nucleus and nucleus-nucleus collisions at RHIC energies.Comment: 26 pages in Latex, 19 EPS figure