Magnetar-like Emission from the Young Pulsar in Kes 75

We report detection of magnetar-like X-ray bursts from the young pulsar PSR J1846-0258, at the center of the supernova remnant Kes 75. This pulsar, long thought to be rotation-powered, has an inferred surface dipolar magnetic field of 4.9x10^13 G, higher than those of the vast majority of rotation-powered pulsars, but lower than those of the ~12 previously identified magnetars. The bursts were accompanied by a sudden flux increase and an unprecedented change in timing behavior. These phenomena lower the magnetic and rotational thresholds associated with magnetar-like behavior, and suggest that in neutron stars there exists a continuum of magnetic activity that increases with inferred magnetic field strength.Comment: 17 pages, 2 figures, accepted for publication in Science. Note: The content of this paper is embargoed until February 21, 200

Long-term X-ray changes in the emission from the anomalous X-ray pulsar 4U 0142+61

We present results obtained from X-ray observations of the anomalous X-ray pulsar (AXP) 4U 0142+61 taken between 2000-2007 using XMM-Newton, Chandra and Swift. In observations taken before 2006, the pulse profile is observed to become more sinusoidal and the pulsed fraction increased with time. These results confirm those derived using the Rossi X-ray Timing Explorer and expand the observed evolution to energies below 2 keV. The XMM-Newton total flux in the 0.5-10 keV band is observed to be nearly constant in observations taken before 2006, while an increase of ~10% is seen afterwards and coincides with the burst activity detected from the source in 2006-2007. After these bursts, the evolution towards more sinusoidal pulse profiles ceased while the pulsed fraction showed a further increase. No evidence for large-scale, long-term changes in the emission as a result of the bursts is seen. The data also suggest a correlation between the flux and hardness of the spectrum, with brighter observations on average having a harder spectrum. As pointed out by other authors, we find that the standard blackbody plus power-law model does not provide the best spectral fit to the emission from 4U 0142+61. We also report on observations taken with the Gemini telescope after two bursts. These observations show source magnitudes consistent with previous measurements. Our results demonstrate the wide range of X-ray variability characteristics seen in AXPs and we discuss them in light of current emission models for these sources.Comment: 10 pages, 9 figures, in emulateapj style. Submitted to Ap

A Burst and Simultaneous Short-Term Pulsed Flux Enhancement from the Magnetar Candidate 1E 1048.1-5937

We report on the 2004 June 29 burst detected from the direction of the Anomalous X-ray Pulsar (AXP) 1E 1048.1-5937 using the Rossi X-ray Timing Explorer (RXTE). We find a simultaneous increase of ~3.5 times the quiescent value in the 2-10 keV pulsed flux of 1E 1048.1-5937 during the tail of the burst which identifies the AXP as the burst's origin. The burst was overall very similar to the two others reported from the direction of this source in 2001. The unambiguous identification of 1E 1048.1-5937 as the burster here confirms it was the origin of the 2001 bursts as well. The epoch of the burst peak was very close to the arrival time of 1E 1048.1-5937's pulse peak. The burst exhibited significant spectral evolution with the trend going from hard to soft. During the 11 days following the burst, the AXP was observed further with RXTE, XMM-Newton and Chandra. Pre- and post-burst observations revealed no change in the total flux or spectrum of the quiescent emission. Comparing all three bursts detected thus far from this source we find that this event was the most fluent (>3.3x10^-8 erg/cm^2 in the 2-20 keV band), had the highest peak flux (59+/-9x10^-10 erg/s/cm^2 in the 2-20 keV band), and the longest duration (>699 s). The long duration of the burst differentiates it from Soft Gamma Repeater (SGR) bursts which have typical durations of ~0.1 s. Bursts that occur preferentially at pulse maximum, have fast-rises and long X-tails containing the majority of the total burst energy have been seen uniquely from AXPs. The marked differences between AXP and SGRs bursts may provide new clues to help understand the physical differences between these objects.Comment: 24 pages, 4 figures, submitted to the Astrophysical Journa

X-ray and Near-IR Variability of the Anomalous X-ray Pulsar 1E 1048.1-5937: From Quiescence Back to Activity

(Abridged) We report on new and archival X-ray and near-infrared observations of the anomalous X-ray pulsar 1E 1048.1-5937 performed between 2001-2007 with RXTE, CXO, Swift, HST, and VLT. During its ~2001-2004 active period, 1E 1048.-5937 exhibited two large, long-term X-ray pulsed-flux flares as well as short bursts, and large (>10x) torque changes. Monitoring with RXTE revealed that the source entered a phase of timing stability in 2004; at the same time, a series of four simultaneous observations with CXO and HST in 2006 showed that its X-ray flux and spectrum and near-IR flux, all variable prior to 2005, stabilized. The near-IR flux, when detected by HST (H~22.7 mag) and VLT (K_S~21.0 mag), was considerably fainter than previously measured. Recently, in 2007 March, this newfound quiescence was interrupted by a sudden flux enhancement, X-ray spectral changes and a pulse morphology change, simultaneous with a large spin-up glitch and near-IR enhancement. Our RXTE observations revealed a sudden pulsed flux increase by a factor of ~3 in the 2-10 keV band. In observations with CXO and Swift, we found that the total X-ray flux increased much more than the pulsed flux, reaching a peak value of >7 times the quiescent value (2-10 keV). With these recent data, we find a strong anti-correlation between X-ray flux and pulsed fraction, and a correlation between X-ray spectral hardness and flux. Simultaneously with the radiative and timing changes, we observed a significant X-ray pulse morphology change such that the profile went from nearly sinusoidal to having multiple peaks. We compare these remarkable events with other AXP outbursts and discuss implications in the context of the magnetar model and other models of AXP emission.Comment: 13 pages (6 figures) in emulateapj style. Accepted for publication in ApJ. New version includes referee's corrections; split Figure 1 into 2 figures; modified Figs. 4b and 6b; rearranged and renumbered of some figures and sections; added an X-ray dataset; improved analysis of pulse morphology and pulsed fraction; added paragraph to sec. 3.2.

Engineering Solutions for Mitigation of Chimeric Antigen Receptor T-Cell Dysfunction

The clinical successes of chimeric antigen receptor (CAR)-T-cell therapy targeting cell surface antigens in B cell leukaemias and lymphomas has demonstrated the proof of concept that appropriately engineered T-cells have the capacity to destroy advanced cancer with long term remissions ensuing. Nevertheless, it has been significantly more problematic to effect long term clinical benefit in a solid tumour context. A major contributing factor to the clinical failure of CAR-T-cells in solid tumours has been named, almost interchangeably, as T-cell "dysfunction" or "exhaustion". While unhelpful ambiguity surrounds the term "dysfunction", "exhaustion" is canonically regarded as a pejorative term for T-cells. Recent understanding of T-cell developmental biology now identifies exhausted cells as vital for effective immune responses in the context of ongoing antigenic challenge. The purpose of this review is to explore the critical stages in the CAR-T-cell life-cycle and their various contributions to T-cell exhaustion. Through an appreciation of the predominant mechanisms of CAR-T-cell exhaustion and resultant dysfunction, we describe a range of engineering approaches to improve CAR-T-cell function