Neutron stars are not only of astrophysical interest, but are also of great interest to nuclear physicists because their attributes can be used to determine the properties of the dense matter in ...their cores. One of the most informative approaches for determining the equation of state (EoS) of this dense matter is to measure both a star's equatorial circumferential radius Re and its gravitational mass M. Here we report estimates of the mass and radius of the isolated 205.53 Hz millisecond pulsar PSR J0030+0451 obtained using a Bayesian inference approach to analyze its energy-dependent thermal X-ray waveform, which was observed using the Neutron Star Interior Composition Explorer (NICER). This approach is thought to be less subject to systematic errors than other approaches for estimating neutron star radii. We explored a variety of emission patterns on the stellar surface. Our best-fit model has three oval, uniform-temperature emitting spots and provides an excellent description of the pulse waveform observed using NICER. The radius and mass estimates given by this model are km and (68%). The independent analysis reported in the companion paper by Riley et al. explores different emitting spot models, but finds spot shapes and locations and estimates of Re and M that are consistent with those found in this work. We show that our measurements of Re and M for PSR J0030+0451 improve the astrophysical constraints on the EoS of cold, catalyzed matter above nuclear saturation density.
Recent discoveries on the origins of modern humans from multiple archaic hominin populations and the diversity of human papillomaviruses (HPVs) suggest a complex scenario of virus-host evolution. To ...evaluate the origin of HPV pathogenesis, we estimated the phylogeny, timing, and dispersal of HPV16 variants using a Bayesian Markov Chain Monte Carlo framework. To increase precision, we identified and characterized non-human primate papillomaviruses from New and Old World monkeys to set molecular clock models. We demonstrate specific host niche adaptation of primate papillomaviruses with subsequent coevolution with their primate hosts for at least 40 million years. Analyses of 212 HPV16 complete genomes and 3582 partial sequences estimated ancient divergence of HPV16 variants (between A and BCD lineages) from their most recent common ancestors around half a million years ago, roughly coinciding with the timing of the split between archaic Neanderthals and modern Homo sapiens, and nearly three times longer than divergence times of modern Homo sapiens. HPV16 A lineage variants were significantly underrepresented in present African populations, whereas the A sublineages were highly prevalent in European (A1-3) and Asian (A4) populations, indicative of viral sexual transmission from Neanderthals to modern non-African humans through multiple interbreeding events in the past 80 thousand years. Remarkably, the human leukocyte antigen B*07:02 and C*07:02 alleles associated with increased risk in cervix cancer represent introgressed regions from Neanderthals in present-day Eurasians. The archaic hominin-host-switch model was also supported by other HPV variants. Niche adaptation and virus-host codivergence appear to influence the pathogenesis of papillomaviruses.
ABSTRACT We report the Fermi Large Area Telescope (LAT) detections of high-energy (>100 MeV) γ-ray emission from two recent optically bright classical novae, V1369 Centauri 2013 and V5668 Sagittarii ...2015. At early times, Fermi target-of-opportunity observations prompted by their optical discoveries provided enhanced LAT exposure that enabled the detections of γ-ray onsets beginning ∼2 days after their first optical peaks. Significant γ-ray emission was found extending to 39-55 days after their initial LAT detections, with systematically fainter and longer-duration emission compared to previous γ-ray-detected classical novae. These novae were distinguished by multiple bright optical peaks that encompassed the time spans of the observed γ-rays. The γ-ray light curves and spectra of the two novae are presented along with representative hadronic and leptonic models, and comparisons with other novae detected by the LAT are discussed.
This paper describes the science motivation, measurement objectives, performance requirements, detailed design, approach and implementation, and calibration of the four Hot Plasma Composition ...Analyzers (HPCA) for the Magnetospheric Multiscale mission. The HPCA is based entirely on electrostatic optics combining an electrostatic energy analyzer with a carbon-foil based time-of-flight analyzer. In order to fulfill mission requirements, the HPCA incorporates three unique technologies that give it very wide dynamic range capabilities essential to measuring minor ion species in the presence of extremely high proton fluxes found in the region of magnetopause reconnection. Dynamic range is controlled primarily by a novel radio frequency system analogous to an RF mass spectrometer. The RF, in combination with capabilities for high TOF event processing rates and high current micro-channel plates, ensures the dynamic range and sensitivity needed for accurate measurements of ion fluxes between ∼1 eV and 40 keV that are expected in the region of reconnection events. A third technology enhances mass resolution in the presence of high proton flux.
In order to calibrate the four HPCA instruments we have developed a unique ion calibration system. The system delivers a multi-species beam resolved to
M
/Δ
M
∼100 and current densities between 0.05 and 200 pA/cm
2
with a stability of ±5 %. The entire system is controlled by a dedicated computer synchronized with the HPCA ground support equipment. This approach results not only in accurate calibration but also in a comprehensive set of coordinated instrument and auxiliary data that makes analysis straightforward and ensures archival of all relevant data.
Using the Parkes Radio Telescope, we have carried out deep observations of 11 unassociated gamma-ray sources. Periodicity searches of these data have discovered two millisecond pulsars, PSR ...J1103−5403 (1FGL J1103.9−5355) and PSR J2241−5236 (1FGL J2241.9−5236), and a long-period pulsar, PSR J1604−44 (1FGL J1604.7−4443). In addition, we searched for but did not detect any radio pulsations from six gamma-ray pulsars discovered by the Fermi satellite to a level of ∼0.04 mJy (for pulsars with a 10 per cent duty cycle).
The timing of the millisecond pulsar PSR J1103−5403 has shown that its position is 9 arcmin from the centroid of the gamma-ray source. Since these observations were carried out, independent evidence has shown that 1FGL J1103.9−5355 is associated with the flat spectrum radio source PKS 1101−536. It appears certain that the pulsar is not associated with the gamma-ray source, despite the seemingly low probability of a chance detection of a radio millisecond pulsar. We consider that PSR J1604−44 is a chance discovery of a weak, long-period pulsar and is unlikely to be associated with 1FGL J1604.7−4443. PSR J2241−5236 has a spin period of 2.2 ms and orbits a very low mass companion with a 3.5-h orbital period. The relatively high flux density and low dispersion measure of PSR J2241−5236 make it an excellent candidate for high precision timing experiments. The gamma rays of 1FGL J2241.9−5236 have a spectrum that is well modelled by a power law with an exponential cut-off, and phase binning with the radio ephemeris results in a multipeaked gamma-ray pulse profile. Observations with Chandra have identified a coincident X-ray source within 0.1 arcsec of the position of the pulsar obtained by radio timing.
We report on work to increase the number of well-measured Type Ia supernovae (SNe Ia) at high redshifts. Light curves, including high signal-to-noise Hubble Space Telescope data, and spectra of six ...SNe Ia that were discovered during 2001, are presented. Additionally, for the two SNe with z > 1, we present ground-based J-band photometry from Gemini and the Very Large Telescope. These are among the most distant SNe Ia for which ground-based near-IR observations have been obtained. We add these six SNe Ia together with other data sets that have recently become available in the literature to the Union compilation. We have made a number of refinements to the Union analysis chain, the most important ones being the refitting of all light curves with the SALT2 fitter and an improved handling of systematic errors. We call this new compilation, consisting of 557 SNe, the Union2 compilation. The flat concordance ΛCDM model remains an excellent fit to the Union2 data with the best-fit constant equation-of-state parameter w = -0.997+0.050 -0.054(stat)+0.077 -0.082(stat + sys together) for a flat universe, or w = -1.038+0.056 -0.059(stat)+0.093 -0.097(stat + sys together) with curvature. We also present improved constraints on w(z). While no significant change in w with redshift is detected, there is still considerable room for evolution in w. The strength of the constraints depends strongly on redshift. In particular, at z >~ 1, the existence and nature of dark energy are only weakly constrained by the data. Based in part on observations made with the NASA/ESA Hubble Space Telescope, obtained from the data archive at the Space Telescope Science Institute (STScI). STScI is operated by the Association of Universities for Research in Astronomy (AURA), Inc. under the NASA contract NAS 5-26555. The observations are associated with programs HST-GO-08585 and HST-GO-09075. Based, in part, on observations obtained at the ESO La Silla Paranal Observatory (ESO programs 67.A-0361 and 169.A-0382). Based, in part, on observations obtained at the Cerro-Tololo Inter-American Observatory (CTIO), National Optical Astronomy Observatory (NOAO). Based on observations obtained at the Canada-France-Hawaii Telescope (CFHT). Based, in part, on observations obtained at the Gemini Observatory (Gemini programs GN-2001A-SV-19 and GN-2002A-Q-31). Based, in part on observations obtained at the Subaru Telescope. Based, in part, on data that were obtained at the W. M. Keck Observatory.
Bacteria are associated with the human body and colonize the gut, skin, and mucous membranes. These associations can be either symbiotic or pathogenic. In either case, bacteria derive more benefit ...from their host. The ability of bacteria to enter and survive within the human body can be exploited for human benefit. They can be used as a vehicle for delivering or producing bioactive molecules, such as toxins and lytic enzymes, and eventually for killing tumor cells. Clostridium and Salmonella have been shown to infect and survive within the human body, including in tumors. There is a need to develop genetic circuits, which enable bacterial cells to carry out the following activities: (i) escape the human immune system, (ii) invade tumors, (iii) multiply within the tumorous cells, (iv) produce toxins via quorum sensing at low cell densities, and (v) express suicide genes to undergo cell death or cell lysis after the tumor has been lysed. Thus, bacteria have the potential to be exploited as anticancer agents.
Three periastron passages of the PSR B1259−63/LS 2883 binary system, consisting of a 48 ms rotation-powered pulsar and a Be star, have been observed by the Large Area Telescope (LAT) on board the ...Fermi Gamma-ray Space Telescope, in 2010, 2014, and 2017. During the most recent periastron passage, sustained low-level gamma-ray emission was observed over a ∼3-week-long interval immediately after periastron, which was followed by an interval of no emission. Sporadic flares were detected starting 40 days post-periastron and lasted approximately 50 days, during which the emission displayed significant spectral curvature, variability on timescales as short as 1.5 minutes, and peak flux levels well in excess of the pulsar spin-down power. By contrast, during the 2010 and 2014 periastron passages, significant gamma-ray emission was not observed with the LAT until 30 and 32 days post-periastron, respectively. The previous flares did not exhibit spectral curvature, showed no short term variability, and did not exceed the pulsar spin-down power. The high flux and short timescales observed in 2017 suggest significant beaming of the emission is required and constrain the size of the emission region. The flares occur long enough after periastron that the neutron star should already have passed through the extended disk-like outflow, thus constraining options for target material and seed photon sources for inverse Compton models.
The mechanisms by which some melanoma cells adapt to Serine/threonine-protein kinase B-Raf (BRAF) inhibitor therapy are incompletely understood. In the present study, we used mass spectrometry-based ...phosphoproteomics to determine how BRAF inhibition remodeled the signaling network of melanoma cell lines that were BRAF mutant and PTEN null. Short-term BRAF inhibition was associated with marked changes in fibronectin-based adhesion signaling that were PTEN dependent. These effects were recapitulated through BRAF siRNA knockdown and following treatment with chemotherapeutic drugs. Increased fibronectin expression was also observed in mouse xenograft models as well as specimens from melanoma patients undergoing BRAF inhibitor treatment. Analysis of a melanoma tissue microarray showed loss of PTEN expression to predict for a lower overall survival, with a trend for even lower survival being seen when loss of fibronectin was included in the analysis. Mechanistically, the induction of fibronectin limited the responses of these PTEN-null melanoma cell lines to vemurafenib, with enhanced cytotoxicity observed following the knockdown of either fibronectin or its receptor α5β1 integrin. This in turn abrogated the cytotoxic response to BRAF inhibition via increased AKT signaling, which prevented the induction of cell death by maintaining the expression of the pro-survival protein Mcl-1. The protection conveyed by the induction of FN expression could be overcome through combined treatment with a BRAF and PI3K inhibitor.
Targeted therapies in metastatic renal cell carcinoma (mRCC) have been approved based on registration clinical trials that have strict eligibility criteria. The clinical outcomes of patients treated ...with targeted agents but are ineligible for trials are unknown.
mRCC patients treated with vascular endothelial growth factor-targeted therapy were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria) if they had a Karnofsky performance status (KPS) <70%, nonclear-cell histology, brain metastases, hemoglobin ≤9 g/dl, creatinine >2× the upper limit of normal, corrected calcium ≥12 mg/dl, platelet count of <100 × 103/uL, or neutrophil count <1500/mm3.
Overall, 768 of 2210 (35%) patients in the International Metastatic RCC Database Consortium (IMDC) were deemed ineligible for clinical trials by the above criteria. Between ineligible versus eligible patients, the response rate, median progression-free survival (PFS) and median overall survival of first-line targeted therapy were 22% versus 29% (P = 0.0005), 5.2 versus 8.6 months, and 12.5 versus 28.4 months (both P < 0.0001), respectively. Second-line PFS (if applicable) was 2.8 months in the trial ineligible versus 4.3 months in the trial eligible patients (P = 0.0039). When adjusted by the IMDC prognostic categories, the HR for death between trial ineligible and trial eligible patients was 1.55 (95% confidence interval 1.378–1.751, P < 0.0001).
The number of patients that are ineligible for clinical trials is substantial and their outcomes are inferior. Specific trials addressing the unmet needs of protocol ineligible patients are warranted.
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