The New Horizons spacecraft's encounter with the cold classical Kuiper Belt object (486958) Arrokoth (provisional designation 2014 MU
) revealed a contact-binary planetesimal. We investigated how ...Arrokoth formed and found that it is the product of a gentle, low-speed merger in the early Solar System. Its two lenticular lobes suggest low-velocity accumulation of numerous smaller planetesimals within a gravitationally collapsing cloud of solid particles. The geometric alignment of the lobes indicates that they were a co-orbiting binary that experienced angular momentum loss and subsequent merger, possibly because of dynamical friction and collisions within the cloud or later gas drag. Arrokoth's contact-binary shape was preserved by the benign dynamical and collisional environment of the cold classical Kuiper Belt and therefore informs the accretion processes that operated in the early Solar System.
We present experimental results from the first systematic study of performance scaling with drive parameters for a magnetoinertial fusion concept. In magnetized liner inertial fusion experiments, the ...burn-averaged ion temperature doubles to 3.1 keV and the primary deuterium-deuterium neutron yield increases by more than an order of magnitude to 1.1 × 1013 (2 kJ deuterium-tritium equivalent) through a simultaneous increase in the applied magnetic field (from 10.4 to 15.9 T), laser preheat energy (from 0.46 to 1.2 kJ), and current coupling (from 16 to 20 MA). Individual parametric scans of the initial magnetic field and laser preheat energy show the expected trends, demonstrating the importance of magnetic insulation and the impact of the Nernst effect for this concept. A drive-current scan shows that present experiments operate close to the point where implosion stability is a limiting factor in performance, demonstrating the need to raise fuel pressure as drive current is increased. Simulations that capture these experimental trends indicate that another order of magnitude increase in yield on the Z facility is possible with additional increases of input parameters.
Although targeting oncogenic mutations in the BRAF serine/threonine kinase with small molecule inhibitors can lead to significant clinical responses in melanoma, it fails to eradicate tumors in ...nearly all patients. Successful therapy will be aided by identification of intrinsic mechanisms that protect tumor cells from death. Here, we used a bioinformatics approach to identify drug-able, “driver” oncogenes restricted to tumor versus normal tissues. Applying this method to 88 short-term melanoma cell cultures, we show that the antiapoptotic BCL2 family member BCL2A1 is recurrently amplified in ∼30% of melanomas and is necessary for melanoma growth. BCL2A1 overexpression also promotes melanomagenesis of BRAF-immortalized melanocytes. We find that high-level expression of BCL2A1 is restricted to melanoma due to direct transcriptional control by the melanoma oncogene MITF. Although BRAF inhibitors lead to cell cycle arrest and modest apoptosis, we find that apoptosis is significantly enhanced by suppression of BCL2A1 in melanomas with BCL2A1 or MITF amplification. Moreover, we find that BCL2A1 expression is associated with poorer clinical responses to BRAF pathway inhibitors in melanoma patients. Cotreatment of melanomas with BRAF inhibitors and obatoclax, an inhibitor of BCL2A1 and other BCL2 family members, overcomes intrinsic resistance to BRAF inhibitors in BCL2A1-amplified cells in vitro and in vivo. These studies identify MITF-BCL2A1 as a lineage-specific oncogenic pathway in melanoma and underscore its role for improved response to BRAF-directed therapy.
The New Horizons spacecraft flew past the Kuiper Belt object (486958) Arrokoth (also known as 2014 MU69) in January 2019. Because of the great distance to the outer Solar System and limited ...bandwidth, it will take until late 2020 to downlink all the spacecraft's observations back to Earth. Three papers in this issue analyze recently downlinked data, including the highest-resolution images taken during the encounter (see the Perspective by Jewitt). Spencer et al. examined Arrokoth's geology and geophysics using stereo imaging, dated the surface using impact craters, and produced a geomorphological map. Grundy et al. investigated the composition of the surface using color imaging and spectroscopic data and assessed Arrokoth's thermal emission using microwave radiometry. McKinnon et al. used simulations to determine how Arrokoth formed: Two gravitationally bound objects gently spiraled together during the formation of the Solar System. Together, these papers determine the age, composition, and formation process of the most pristine object yet visited by a spacecraft.
A unique feature of Plutos large satellite Charon is its dark red northern polar cap. Similar colours on Plutos surface have been attributed to tholin-like organic macromolecules produced by ...energetic radiation processing of hydrocarbons. The polar location on Charon implicates the temperature extremes that result from Charons high obliquity and long seasons in the production of this material. The escape of Pluto's atmosphere provides a potential feedstock for a complex chemistry. Gas from Pluto that is transiently cold-trapped and processed at Charon's winter pole was proposed as an explanation for the dark coloration on the basis of an image of Charon's northern hemisphere, but not modelled quantitatively. Here we report images of the southern hemisphere illuminated by Pluto-shine and also images taken during the approach phase that show the northern polar cap over a range of longitudes. We model the surface thermal environment on Charon and the supply and temporary cold-trapping of material escaping from Pluto, as well as the photolytic processing of this material into more complex and less volatile molecules while cold-trapped. The model results are consistent with the proposed mechanism for producing the observed colour pattern on Charon.
•Crystal structures of melt spun and well crystallized Sm-Fe-N compared.•Random distribution of Fe-dumbells and Sm ions eliminates iron sites with the largest moments in melt = spun material.•The ...anisotropy constant K1 is much reduced, 2.86 MJ/m3.•The melt spun flakes include traces of free iron, but well-shaped single-phase hysteresis loops are observed nonetheless.•Powder energy product is 162 kJ/m3 due to substantial remanence enhancement (Mr/Ms = 64%).
Following its discovery in the aftermath of Nd2Fe14B, Sm2Fe17N3 seemed to offer intrinsic magnetic properties that were superior or comparable to those of its famous predecessor. But the promise of the new material to challenge Nd2Fe14B was not realized, mainly because the 2:17 nitride powder, prepared by a low-temperature gas-phase interstitial modification process, was unstable at the temperatures needed to process dense sintered magnets. Here we discuss the magnetic properties of Nitroquench, a melt-spun Sm-Fe-N material, which offers superior corrosion resistance and thermal stability compared to melt-spun Nd-Fe-B. The powder, with a crystallite size of approximately 30 nm is in the form of flakes 15–18 µm thick and about 100 µm in diameter. Room-temperature coercivity is 690 kAm−1 after saturation in 14 T, with a remanence of 92 Am2kg−1 and an extrapolated saturation magnetization of 160 Am2kg−1. The remanence enhancement is reflected in a preferred orientation seen in 57Fe Mössbauer spectra of magnetized isotropic powder, which exhibits different relative intensities of the ΔM = 0 absorption lines according to the direction of the field used to saturate the magnetization. When measured in zero internal field, the remanence ratio Mr/Ms is 64%. The remanence enhancement is attributed to a nanocrystallite size that is not very much greater than the exchange length. The maximum energy product for the powder, assuming full density, is 162 kJm−3. Nitroquench powder may be used to produce bonded magnets with an energy product >100 kJm−3.
Abstract Objective Postoperative venous thromboembolism (VTE) creates an 8-fold increase in mortality after lung resection. About one third of postoperative VTEs occur after discharge. The Caprini ...risk assessment model has been used by other specialties to calculate the risk of a VTE. Patients deemed high risk by the model are candidates for prophylactic anticoagulation after discharge, reducing the VTE risk by 60%. Our primary aims were to determine the frequency of VTE events and evaluate whether the Caprini model could risk-stratify patients. Methods Patients undergoing lung cancer resections during 2005 to 2013 were evaluated. Exclusion criteria were preoperative filter and therapeutic anticoagulation. A total of 232 patients were reviewed and Caprini scores calculated. Subjects were risk stratified into groups of low risk (0-4), moderate risk (5-8), and high risk (≥9). Occurrence of VTE events (deep vein thrombosis; pulmonary embolism) were identified by imaging. Results The 60-day VTE incidence was 5.2% (12 of 232); 33.3% occurred postdischarge (n = 4). Half (6 of 12) were pulmonary emboli, 1 of which caused a death, in an inpatient with a score of 16. The VTE incidence increased with Caprini score. Scores in the low, moderate, and high risk groups were associated with a VTE incidence of 0%, 1.7%, and 10.3%, respectively. With a high risk score cutoff of 9, the sensitivity, specificity, and accuracy are 83.3%, 60.5%, and 61.6%, respectively. Conclusions One third of VTE events occurred after discharge. Postoperative VTE incidence was correlated with increasing Caprini scores. Patients in the high risk group had an incidence of 10.3%. Elevated scores may warrant extended chemoprophylaxis for patients after discharge.
Magnetizing the fuel in inertial confinement fusion relaxes ignition requirements by reducing thermal conductivity and changing the physics of burn product confinement. Diagnosing the level of fuel ...magnetization during burn is critical to understanding target performance in magneto-inertial fusion (MIF) implosions. In pure deuterium fusion plasma, 1.01 MeV tritons are emitted during deuterium-deuterium fusion and can undergo secondary deuterium-tritium reactions before exiting the fuel. Increasing the fuel magnetization elongates the path lengths through the fuel of some of the tritons, enhancing their probability of reaction. Based on this feature, a method to diagnose fuel magnetization using the ratio of overall deuterium-tritium to deuterium-deuterium neutron yields is developed. Analysis of anisotropies in the secondary neutron energy spectra further constrain the measurement. Secondary reactions also are shown to provide an upper bound for the volumetric fuel-pusher mix in MIF. The analysis is applied to recent MIF experiments M. R. Gomez et al., Phys. Rev. Lett. 113, 155003 (2014) on the Z Pulsed Power Facility, indicating that significant magnetic confinement of charged burn products was achieved and suggesting a relatively low-mix environment. Both of these are essential features of future ignition-scale MIF designs.
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