An activation domain of plasmid R1 TraI protein delineates stages of gene transfer initiation

Bacterial conjugation is a form of type IV secretion that transports protein and DNA to recipient cells. Specific bacteriophage exploit the conjugative pili and cell envelope spanning protein machinery of these systems to invade bacterial cells. Infection by phage R17 requires F-like pili and coupling protein TraD, which gates the cytoplasmic entrance of the secretion channel. Here we investigate the role of TraD in R17 nucleoprotein uptake and find parallels to secretion mechanisms. The relaxosome of IncFII plasmid R1 is required. A ternary complex of plasmid oriT, TraD and a novel activation domain within the N-terminal 992 residues of TraI contributes a key mechanism involving relaxase-associated properties of TraI, protein interaction and the TraD ATPase. Helicase-associated activities of TraI are dispensable. These findings distinguish for the first time specific protein domains and complexes that process extracellular signals into distinct activation stages in the type IV initiation pathway. The study also provided insights into the evolutionary interplay of phage and the plasmids they exploit. Related plasmid F adapted to R17 independently of TraI. It follows that selection for phage resistance drives not only variation in TraA pilins but diversifies TraD and its binding partners in a plasmid-specific manner

New SPB stars in the field of the young open cluster NGC 2244 discovered by the MOST photometric satellite

During two weeks of nearly continuous optical photometry of the young open cluster NGC 2244 obtained by the MOST satellite, we discovered two new SPB stars, GSC 00154-00785 and GSC 00154-01871. We present frequency analyses of the MOST light curves of these stars, which reveal two oscillation frequencies (0.61 and 0.71 c/d) in GSC 00154-00785 and two (0.40 and 0.51 c/d) in GSC 00154-01871. These frequency ranges are consistent with g-modes of $\ell \leq 2$ excited in models of main-sequence or pre-main-sequence (PMS) stars of masses 4.5 - 5 $M_{\odot}$ and solar composition $(X, Z)= (0.7, 0.02)$. Published proper motion measurements and radial velocities are insufficient to establish unambiguously cluster membership for these two stars. However, the PMS models which fit best their eigenspectra have ages consistent with NGC 2244. If cluster membership can be confirmed, these would be the first known PMS SPB stars, and would open a new window on testing asteroseismically the interior structures of PMS stars.Comment: accepted for publication in MNRA

International comparison of cosmetic outcomes of breast conserving surgery and radiation therapy for women with ductal carcinoma in situ of the breast

Purpose: To assess the cosmetic impact of breast conserving surgery (BCS), whole breast irradiation (WBI) fractionation and tumour bed boost (TBB) use in a phase III trial for women with ductal carcinoma in situ (DCIS) of the breast. Materials and methods: Baseline and 3-year cosmesis were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Cosmetic Rating System and digital images in a randomised trial of non-low risk DCIS treated with postoperative WBI +/- TBB. Baseline cosmesis was assessed for four geographic clusters of treating centres. Cosmetic failure was a global score of fair or poor. Cosmetic deterioration was a score change from excellent or good at baseline to fair or poor at three years. Odds ratios for cosmetic deterioration by WBI dose-fractionation and TBB use were calculated for both scoring systems. Results: 1608 women were enrolled from 11 countries between 2007 and 2014. 85-90% had excellent or good baseline cosmesis independent of geography or assessment method. TBB (16 Gy in 8 fractions) was associated with a >2-fold risk of cosmetic deterioration (p

The Drosophila 7SK snRNP and the essential role of dHEXIM in development

Regulation of the positive transcription elongation factor, P-TEFb, plays a major role in controlling mammalian transcription and this is accomplished in part by controlled release of P-TEFb from the 7SK snRNP that sequesters the kinase in an inactive state. We demonstrate here that a similar P-TEFb control system exists in Drosophila. We show that an RNA previously suggested to be a 7SK homolog is, in fact, associated with P-TEFb, through the action of a homolog of the human HEXIM1/2 proteins (dHEXIM). In addition, a Drosophila La related protein (now called dLARP7) is shown to be the functional homolog of human LARP7. The Drosophila 7SK snRNP (d7SK snRNP) responded to treatment of cells with P-TEFb inhibitors and to nuclease treatment of cell lysates by releasing P-TEFb. Supporting a critical role for the d7SK snRNP in Drosophila development, dLARP7 and dHEXIM were found to be ubiquitously expressed throughout embryos and tissues at all stages. Importantly, knockdown of dHEXIM was embryonic lethal, and reduction of dHEXIM in specific tissues led to serious developmental defects. Our results suggest that regulation of P-TEFb by the d7SK snRNP is essential for the growth and differentiation of tissues required during Drosophila development

Real-time compression feedback for patients with in-hospital cardiac arrest: a multi-center randomized controlled clinical trial

Objective: To determine if real-time compression feedback using a non-automated hand-held device improves patient outcomes from in-hospital cardiac arrest (IHCA). Methods: We conducted a prospective, randomized, controlled, parallel study (no crossover) of patients with IHCA in the mixed medical–surgical intensive care units (ICUs) of eight academic hospitals. Patients received either standard manual chest compressions or compressions performed with real-time feedback using the Cardio First Angel™ (CFA) device. The primary outcome was sustained return of spontaneous circulation (ROSC), and secondary outcomes were survival to ICU and hospital discharge. Results: One thousand four hundred fifty-four subjects were randomized; 900 were included. Sustained ROSC was significantly improved in the CFA group (66.7% vs. 42.4%, P < 0.001), as was survival to ICU discharge (59.8% vs. 33.6%) and survival to hospital discharge (54% vs. 28.4%, P < 0.001). Outcomes were not affected by intra-group comparisons based on intubation status. ROSC, survival to ICU, and hospital discharge were noted to be improved in inter-group comparisons of non-intubated patients, but not intubated ones. Conclusion: Use of the CFA compression feedback device improved event survival and survival to ICU and hospital discharge

Oncoplastic breast consortium recommendations for mastectomy and whole breast reconstruction in the setting of post-mastectomy radiation therapy

Aim: Demand for nipple-and skin-sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. Methods: A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. Results: The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recom-mendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. Conclusions: The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BRPeer reviewe

Measurement of ϒ production in pp collisions at s = 13 TeV

Abstract: The production cross-sections of ϒ(1S), ϒ(2S) and ϒ(3S) mesons in proton-proton collisions at s=13 TeV are measured with a data sample corresponding to an integrated luminosity of 277 ± 11 pb−1 recorded by the LHCb experiment in 2015. The ϒ mesons are reconstructed in the decay mode ϒ → μ+μ−. The differential production cross-sections times the dimuon branching fractions are measured as a function of the ϒ transverse momentum, pT, and rapidity, y, over the range 0 < pT< 30 GeV/c and 2.0 < y < 4.5. The ratios of the cross-sections with respect to the LHCb measurement at s=8 TeV are also determined. The measurements are compared with theoretical predictions based on NRQCD

Precision measurement of the Lambda(+)(c) baryon mass

A precision measurement of the $B_{c}^{+}$ meson mass is performed using proton-proton collision data collected with the LHCb experiment at centre-of-mass energies of $7, 8$ and $13$ TeV, corresponding to a total integrated luminosity of $9.0 \,{\rm fb}^{-1}$. The $B_{c}^{+}$ mesons are reconstructed via the decays $B_{c}^{+} \rightarrow J\mskip -3mu/\mskip -2mu\psi\mskip 2mu \pi^+$, $B_{c}^{+} \rightarrow J\mskip -3mu/\mskip -2mu\psi\mskip 2mu \pi^+ \pi^- \pi^+$, $B_{c}^{+} \rightarrow J\mskip -3mu/\mskip -2mu\psi\mskip 2mu p \bar{p} \pi^+$, $B_{c}^{+} \rightarrow J\mskip -3mu/\mskip -2mu\psi\mskip 2mu D_{s}^{+}$, $B_{c}^{+} \rightarrow J\mskip -3mu/\mskip -2mu\psi\mskip 2mu D^{0} K^{+}$ and $B_{c}^{+} \rightarrow B_{s}^{0} \pi^{+}$. Combining the results of the individual decay channels, the $B_{c}^{+}$ mass is measured to be $6274.47 \pm 0.27 \,({\rm stat}) \pm 0.17 \,({\rm syst}) \mathrm{\,Me\kern -0.1em V}/c^{2}$. This is the most precise measurement of the $B_{c}^{+}$ mass to date. The difference between the $B_{c}^{+}$ and $B_{s}^{0}$ meson masses is measured to be $907.75 \pm 0.37 \,({\rm stat}) \pm 0.27 \,({\rm syst}) \mathrm{\,Me\kern -0.1em V}/c^{2}$