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.
SB1518 is an innovative pyrimidine-based macrocycle that shows a unique kinase profile with selective inhibition of Janus Kinase-2 (JAK2; IC50=23 and 19 nM for JAK2(WT) and JAK2(V617F), respectively) ...within the JAK family (IC50=1280, 520 and 50 nM for JAK1, JK3 and TYK2, respectively) and fms-like tyrosine kinase-3 (FLT3; IC50=22 nM). SB1518 shows potent effects on cellular JAK/STAT pathways, inhibiting tyrosine phosphorylation on JAK2 (Y221) and downstream STATs. As a consequence SB1518 has potent anti-proliferative effects on myeloid and lymphoid cell lines driven by mutant or wild-type JAK2 or FLT3, resulting from cell cycle arrest and induction of apoptosis. SB1518 has favorable pharmacokinetic properties after oral dosing in mice, is well tolerated and significantly reduces splenomegaly and hepatomegaly in a JAK2(V617F)-driven disease model. SB1518 dose-dependently inhibits intra-tumor JAK2/STAT5 signaling, leading to tumor growth inhibition in a subcutaneous model generated with SET-2 cells derived from a JAK2(V617F) patient with megakaryoblastic leukemia. Moreover, SB1518 is active against primary erythroid progenitor cells sampled from patients with myeloproliferative disease. In summary, SB1518 has a unique profile and is efficacious and well tolerated in JAK2-dependent models. These favorable properties are now being confirmed in clinical studies in patients with myelofibrosis and lymphoma.
We present optical light curves, redshifts, and classifications for spectroscopically confirmed Type Ia supernovae (SNe Ia) discovered by the Pan-STARRS1 (PS1) Medium Deep Survey. We detail ...improvements to the PS1 SN photometry, astrometry, and calibration that reduce the systematic uncertainties in the PS1 SN Ia distances. We combine the subset of PS1 SNe Ia (0.03 < z < 0.68) with useful distance estimates of SNe Ia from the Sloan Digital Sky Survey (SDSS), SNLS, and various low-z and Hubble Space Telescope samples to form the largest combined sample of SNe Ia, consisting of a total of SNe Ia in the range of 0.01 < z < 2.3, which we call the "Pantheon Sample." When combining Planck 2015 cosmic microwave background (CMB) measurements with the Pantheon SN sample, we find and for the wCDM model. When the SN and CMB constraints are combined with constraints from BAO and local H0 measurements, the analysis yields the most precise measurement of dark energy to date: and for the CDM model. Tension with a cosmological constant previously seen in an analysis of PS1 and low-z SNe has diminished after an increase of 2× in the statistics of the PS1 sample, improved calibration and photometry, and stricter light-curve quality cuts. We find that the systematic uncertainties in our measurements of dark energy are almost as large as the statistical uncertainties, primarily due to limitations of modeling the low-redshift sample. This must be addressed for future progress in using SNe Ia to measure dark energy.
The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ ...systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.
How and where in the brain audio-visual signals are bound to create multimodal objects remains unknown. One hypothesis is that temporal coherence between dynamic multisensory signals provides a ...mechanism for binding stimulus features across sensory modalities. Here, we report that when the luminance of a visual stimulus is temporally coherent with the amplitude fluctuations of one sound in a mixture, the representation of that sound is enhanced in auditory cortex. Critically, this enhancement extends to include both binding and non-binding features of the sound. We demonstrate that visual information conveyed from visual cortex via the phase of the local field potential is combined with auditory information within auditory cortex. These data provide evidence that early cross-sensory binding provides a bottom-up mechanism for the formation of cross-sensory objects and that one role for multisensory binding in auditory cortex is to support auditory scene analysis.
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•Visual stimuli can shape how auditory cortical neurons respond to sound mixtures•Temporal coherence between senses enhances sound features of a bound multisensory object•Visual stimuli elicit changes in the phase of the local field potential in auditory cortex•Vision-induced phase effects are lost when visual cortex is reversibly silenced
Atilgan et al. demonstrate that temporal coherence between auditory and visual stimuli shapes the representation of a sound scene in auditory cortex. Auditory cortex is identified as a site of multisensory binding, with inputs from visual cortex underpinning these effects.
We herein present an overview of the upcoming 5
edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms ...will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4
edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5
edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.
Abstract
The Pan-STARRS1 (PS1) Science Consortium has carried out a set of imaging surveys using the 1.4 gigapixel GPC1 camera on the PS1 telescope. As this camera is composed of many individual ...electronic readouts and covers a very large field of view, great care was taken to ensure that the many instrumental effects were corrected to produce the most uniform detector response possible. We present the image-detrending steps used as part of the processing of the data contained within the public release of Pan-STARRS1 Data Release 1 (DR1). In addition to the single image processing, the methods used to transform the 375,573 individual exposures into a common sky-oriented grid are discussed, as well as those used to produce both the image stack and difference combination products.
The flare of radiation from the tidal disruption and accretion of a star can be used as a marker for supermassive black holes that otherwise lie dormant and undetected in the centres of distant ...galaxies. Previous candidate flares have had declining light curves in good agreement with expectations, but with poor constraints on the time of disruption and the type of star disrupted, because the rising emission was not observed. Recently, two 'relativistic' candidate tidal disruption events were discovered, each of whose extreme X-ray luminosity and synchrotron radio emission were interpreted as the onset of emission from a relativistic jet. Here we report a luminous ultraviolet-optical flare from the nuclear region of an inactive galaxy at a redshift of 0.1696. The observed continuum is cooler than expected for a simple accreting debris disk, but the well-sampled rise and decay of the light curve follow the predicted mass accretion rate and can be modelled to determine the time of disruption to an accuracy of two days. The black hole has a mass of about two million solar masses, modulo a factor dependent on the mass and radius of the star disrupted. On the basis of the spectroscopic signature of ionized helium from the unbound debris, we determine that the disrupted star was a helium-rich stellar core.
Pedigrees from 269 patients with frontotemporal lobar degeneration (FTLD), including frontotemporal dementia (FTD), FTD with ALS (FTD/ALS), progressive nonfluent aphasia, semantic dementia (SD), ...corticobasal degeneration, and progressive supranuclear palsy were analyzed to determine the degree of heritability of these disorders. FTD/ALS was the most and SD the least heritable subtype. FTLD syndromes appear to have different etiologies and recurrence risks.
TG02 is a novel pyrimidine-based multi-kinase inhibitor that inhibits CDKs 1, 2, 7 and 9 together with JAK2 and FLT3. It dose-dependently inhibits signaling pathways downstream of CDKs, JAK2 and FLT3 ...in cancer cells with the main targets being CDKs. TG02 is anti-proliferative in a broad range of tumor cell lines, inducing G1 cell cycle arrest and apoptosis. Primary cultures of progenitor cells derived from acute myeloid leukemia (AML) and polycythemia vera patients are very sensitive to TG02. Comparison with reference inhibitors that block only one of the main targets of TG02 demonstrate the benefit of combined CDK and JAK2/FLT3 inhibition in cell lines as well as primary cells. In vivo, TG02 exhibits favorable pharmacokinetics after oral dosing in xenograft models and accumulates in tumor tissues, inducing an effective blockade of both CDK and STAT signaling. TG02 induces tumor regression after oral dosing on both daily and intermittent schedules in a murine model of mutant-FLT3 leukemia (MV4-11) and prolongs survival in a disseminated AML model with wild-type FLT3 and JAK2 (HL-60). These data demonstrate that TG02 is active in various models of leukemia and provide a rationale for the ongoing clinical evaluation of TG02 in patients with advanced leukemias.
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