Cross-Talk with Myeloid Accessory Cells Regulates Human Natural Killer Cell Interferon-γ Responses to Malaria

Data from a variety of experimental models suggest that natural killer (NK) cells require signals from accessory cells in order to respond optimally to pathogens, but the precise identity of the cells able to provide such signals depends upon the nature of the infectious organism. Here we show that the ability of human NK cells to produce interferon-γ in response to stimulation by Plasmodium falciparum–infected red blood cells (iRBCs) is strictly dependent upon multiple, contact-dependent and cytokine-mediated signals derived from both monocytes and myeloid dendritic cells (mDCs). Contrary to some previous reports, we find that both monocytes and mDCs express an activated phenotype following short-term incubation with iRBCs and secrete pro-inflammatory cytokines. The magnitude of the NK cell response (and of the KIR(−) CD56(bright) NK cell population in particular) is tightly correlated with resting levels of accessory cell maturation, indicating that heterogeneity of the NK response to malaria is a reflection of deep-rooted heterogeneity in the human innate immune system. Moreover, we show that NK cells are required to maintain the maturation status of resting mDCs and monocytes, providing additional evidence for reciprocal regulation of NK cells and accessory cells. However, NK cell–derived signals are not required for activation of accessory cells by either iRBCs or bacterial lipolysaccharide. Together, these data suggest that there may be differences in the sequence of events required for activation of NK cells by non-viral pathogens compared to the classical model of NK activation by virus-infected or major histocompatibility complex–deficient cells. These findings have far-reaching implications for the study of immunity to infection in human populations

Properties of High-Latitude CME-Driven Disturbances During Ulysses Second Northern Polar Passage

Ulysses observed five coronal mass ejections (CMEs) and their associated disturbances while the spacecraft was immersed in the polar coronal hole (CH) flow above 70° N in late 2001. Of these CMEs, two were very fast (\u3e850 km s−1) driving strong shocks in the wind ahead, and two others were over-expanding. The two fast CMEs were observed leaving the Sun by LASCO/SOHO, and were observed in the ecliptic by Genesis and ACE. These were large events, spanning at least from the northern heliospheric pole to the ecliptic. One-dimensional hydrodynamic simulations indicate that these could be described as overpressured CMEs launched from the Sun at speeds initially faster than ambient, but then decelerating to the ambient solar wind speed as they propagated outward. The two over-expanding CMEs mark their first occurrence since Ulysses’ first orbit when such CMEs were only observed in polar CH flow

Effect of Television Programming and Advertising on Alcohol Consumption in Normal Drinkers

The drinking behavior of 96 male normal drinking college students was assessed after they viewed a videotape of a popular prime-time television program complete with advertisements. Different versions of the videotape were used to evaluate the effects of a television program with and without alcohol scenes as crossed with the effects of three different types of advertisements (i.e., beer, nonalcoholic beverages and food). After viewing the videotape, the subjects, who were led to believe that they were participating in two separate and unrelated sets of experimental procedures, were asked to perform a taste rating of light beers, which actually provided an unobtrusive measure of their alcohol consumption. The results provided no support for the widely held assumption that drinking scenes in television programs or televised advertisements for alcoholic beverages precipitate increased drinking by viewers. This finding, however, must be considered in the context of the laboratory setting of the study, and thus may not generalize to real-life television viewing. Further research in this area is clearly needed, including an evaluation of the effects of television program content and advertisements on other populations (e.g., alcohol abusers)

The GALEX View of "Boyajian's Star" (KIC 8462852)

The enigmatic star KIC 8462852, informally known as "Boyajian's Star", has exhibited unexplained variability from both short timescale (days) dimming events, and years-long fading in the Kepler mission. No single physical mechanism has successfully explained these observations to date. Here we investigate the ultraviolet variability of KIC 8462852 on a range of timescales using data from the GALEX mission that occurred contemporaneously with the Kepler mission. The wide wavelength baseline between the Kepler and GALEX data provides a unique constraint on the nature of the variability. Using 1600 seconds of photon-counting data from four GALEX visits spread over 70 days in 2011, we find no coherent NUV variability in the system on 10-100 second or months timescales. Comparing the integrated flux from these 2011 visits to the 2012 NUV flux published in the GALEX-CAUSE Kepler survey, we find a 3% decrease in brightness for KIC 8462852. We find this level of variability is significant, but not necessarily unusual for stars of similar spectral type in the GALEX data. This decrease coincides with the secular optical fading reported by Montet & Simon (2016). We find the multi-wavelength variability is somewhat inconsistent with typical interstellar dust absorption, but instead favors a R$_V$ = 5.0 $\pm$ 0.9 reddening law potentially from circumstellar dust.Comment: 8 pages, 4 figures, ApJ Accepte

Utilising Assured Multi-Agent Reinforcement Learning within safety-critical scenarios

Multi-agent reinforcement learning allows a team of agents to learn how to work together to solve complex decision-making problems in a shared environment. However, this learning process utilises stochastic mechanisms, meaning that its use in safety-critical domains can be problematic. To overcome this issue, we propose an Assured Multi-Agent Reinforcement Learning (AMARL) approach that uses a model checking technique called quantitative verification to provide formal guarantees of agent compliance with safety, performance, and other non-functional requirements during and after the reinforcement learning process. We demonstrate the applicability of our AMARL approach in three different patrolling navigation domains in which multi-agent systems must learn to visit key areas by using different types of reinforcement learning algorithms (temporal difference learning, game theory, and direct policy search). Furthermore, we compare the effectiveness of these algorithms when used in combination with and without our approach. Our extensive experiments with both homogeneous and heterogeneous multi-agent systems of different sizes show that the use of AMARL leads to safety requirements being consistently satisfied and to better overall results than standard reinforcement learning

Synthesis and Evaluation of Small Molecule Inhibitors of the Androgen Receptor N-Terminal Domain

Acknowledgments We thank Craig Irving for his assistance with NMR spectroscopy and Pat Keating, Dr. Jessica Bame, and Dr. Graeme Anderson for their assistance with HRMS.Peer reviewe

Modeling and characterization of the SPIDER half-wave plate

Spider is a balloon-borne array of six telescopes that will observe the Cosmic Microwave Background. The 2624 antenna-coupled bolometers in the instrument will make a polarization map of the CMB with approximately one-half degree resolution at 145 GHz. Polarization modulation is achieved via a cryogenic sapphire half-wave plate (HWP) skyward of the primary optic. We have measured millimeter-wave transmission spectra of the sapphire at room and cryogenic temperatures. The spectra are consistent with our physical optics model, and the data gives excellent measurements of the indices of A-cut sapphire. We have also taken preliminary spectra of the integrated HWP, optical system, and detectors in the prototype Spider receiver. We calculate the variation in response of the HWP between observing the CMB and foreground spectra, and estimate that it should not limit the Spider constraints on inflation

A cryogenic rotation stage with a large clear aperture for the half-wave plates in the Spider instrument

We describe the cryogenic half-wave plate rotation mechanisms built for and used in Spider, a polarization-sensitive balloon-borne telescope array that observed the Cosmic Microwave Background at 95 GHz and 150 GHz during a stratospheric balloon flight from Antarctica in January 2015. The mechanisms operate at liquid helium temperature in flight. A three-point contact design keeps the mechanical bearings relatively small but allows for a large (305 mm) diameter clear aperture. A worm gear driven by a cryogenic stepper motor allows for precise positioning and prevents undesired rotation when the motors are depowered. A custom-built optical encoder system monitors the bearing angle to an absolute accuracy of +/- 0.1 degrees. The system performed well in Spider during its successful 16 day flight.Comment: 11 pages, 7 figures, Published in Review of Scientific Instruments. v2 includes reviewer changes and longer literature revie