Faraday rotation measures of northern-hemisphere pulsars using CHIME/Pulsar

Using commissioning data from the first year of operation of the Canadian Hydrogen Intensity Mapping Experiment's (CHIME) Pulsar backend system, we conduct a systematic analysis of the Faraday Rotation Measure (RM) of the northern hemisphere pulsars detected by CHIME. We present 55 new RMs as well as obtain improved RM uncertainties for 25 further pulsars. CHIME's low observing frequency and wide bandwidth between 400-800 MHz contribute to the precision of our measurements, whereas the high cadence observation provide extremely high signal-to-noise co-added data. Our results represent a significant increase of the pulsar RM census, particularly regarding the northern hemisphere. These new RMs are for sources that are located in the Galactic plane out to 10 kpc, as well as off the plane to a scale height of ~16 kpc. This improved knowledge of the Faraday sky will contribute to future Galactic large-scale magnetic structure and ionosphere modelling.Comment: 13 pages, 7 figures, accepted by MNRA

Covalent Plasmodium falciparum-selective proteasome inhibitors exhibit a low propensity for generating resistance in vitro and synergize with multiple antimalarial agents

Therapeutics with novel modes of action and a low risk of generating resistance are urgently needed to combat drug-resistant Plasmodium falciparum malaria. Here, we report that the peptide vinyl sulfones WLL-vs (WLL) and WLW-vs (WLW), highly selective covalent inhibitors of the P. falciparum proteasome, potently eliminate genetically diverse parasites, including K13-mutant, artemisinin-resistant lines, and are particularly active against ring-stage parasites. Selection studies reveal that parasites do not readily acquire resistance to WLL or WLW and that mutations in the β2, β5 or β6 subunits of the 20S proteasome core particle or in components of the 19S proteasome regulatory particle yield only <five-fold decreases in parasite susceptibility. This result compares favorably against previously published non-covalent inhibitors of the Plasmodium proteasome that can select for resistant parasites with >hundred-fold decreases in susceptibility. We observed no cross-resistance between WLL and WLW. Moreover, most mutations that conferred a modest loss of parasite susceptibility to one inhibitor significantly increased sensitivity to the other. These inhibitors potently synergized multiple chemically diverse classes of antimalarial agents, implicating a shared disruption of proteostasis in their modes of action. These results underscore the potential of targeting the Plasmodium proteasome with covalent small molecule inhibitors as a means of combating multidrug-resistant malaria

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

Local induction of lymphangiogenesis with engineered fibrin-binding VEGF-C promotes wound healing by increasing immune cell trafficking and matrix remodeling

Lymphangiogenesis occurs in inflammation and wound healing, yet its functional roles in these processes are not fully understood. Consequently, clinically relevant strategies for therapeutic lymphangiogenesis remain underdeveloped, particularly using growth factors. To achieve controlled, local capillary lymphangiogenesis with protein engineering and determine its effects on fluid clearance, leukocyte trafficking, and wound healing, we developed a fibrin-binding variant of vascular endothelial growth factor C (FB-VEGF-C) that is slowly released upon demand from infiltrating cells. Using a novel wound healing model, we show that implanted fibrin containing FB-VEGF-C, but not free VEGF-C, could stimulate local lymphangiogenesis in a dose-dependent manner. Importantly, the effects of FB-VEGF-C were restricted to lymphatic capillaries, with no apparent changes to blood vessels and downstream collecting vessels. Leukocyte intravasation and trafficking to lymph nodes were increased in hyperplastic lymphatics, while fluid clearance was maintained at physiological levels. In diabetic wounds, FB-VEGF-C-induced lymphangiogenesis increased extracellular matrix deposition and granulation tissue thickening, indicators of improved wound healing. Together, these results indicate that FB-VEGF-C is a promising strategy for inducing lymphangiogenesis locally, and that such lymphangiogenesis can promote wound healing by enhancing leukocyte trafficking without affecting downstream lymphatic collecting vessels. (C) 2017 The Authors. Published by Elsevier Ltd

The NANOGrav 11-Year Data Set: Limits on Gravitational Waves from Individual Supermassive Black Hole Binaries

Observations indicate that nearly all galaxies contain supermassive black holes (SMBHs) at their centers. When galaxies merge, their component black holes form SMBH binaries (SMBHBs), which emit low-frequency gravitational waves (GWs) that can be detected by pulsar timing arrays (PTAs). We have searched the recently-released North American Nanohertz Observatory for Gravitational Waves (NANOGrav) 11-year data set for GWs from individual SMBHBs in circular orbits. As we did not find strong evidence for GWs in our data, we placed 95\% upper limits on the strength of GWs from such sources as a function of GW frequency and sky location. We placed a sky-averaged upper limit on the GW strain of $h_0 < 7.3(3) \times 10^{-15}$ at $f_\mathrm{gw}= 8$ nHz. We also developed a technique to determine the significance of a particular signal in each pulsar using ``dropout' parameters as a way of identifying spurious signals in measurements from individual pulsars. We used our upper limits on the GW strain to place lower limits on the distances to individual SMBHBs. At the most-sensitive sky location, we ruled out SMBHBs emitting GWs with $f_\mathrm{gw}= 8$ nHz within 120 Mpc for $\mathcal{M} = 10^9 \, M_\odot$, and within 5.5 Gpc for $\mathcal{M} = 10^{10} \, M_\odot$. We also determined that there are no SMBHBs with $\mathcal{M} > 1.6 \times 10^9 \, M_\odot$ emitting GWs in the Virgo Cluster. Finally, we estimated the number of potentially detectable sources given our current strain upper limits based on galaxies in Two Micron All-Sky Survey (2MASS) and merger rates from the Illustris cosmological simulation project. Only 34 out of 75,000 realizations of the local Universe contained a detectable source, from which we concluded it was unsurprising that we did not detect any individual sources given our current sensitivity to GWs.Comment: 10 pages, 11 figures. Accepted by Astrophysical Journal. Please send any comments/questions to S. J. Vigeland ([email protected]

Food color is in the eye of the beholder: the role of human trichromatic vision in food evaluation

Non-human primates evaluate food quality based on brightness of red and green shades of color, with red signaling higher energy or greater protein content in fruits and leafs. Despite the strong association between food and other sensory modalities, humans, too, estimate critical food features, such as calorie content, from vision. Previous research primarily focused on the effects of color on taste/flavor identification and intensity judgments. However, whether evaluation of perceived calorie content and arousal in humans are biased by color has received comparatively less attention. In this study we showed that color content of food images predicts arousal and perceived calorie content reported when viewing food even when confounding variables were controlled for. Specifically, arousal positively co-varied with red-brightness, while green-brightness was negatively associated with arousal and perceived calorie content. This result holds for a large array of food comprising of natural food - where color likely predicts calorie content - and of transformed food where, instead, color is poorly diagnostic of energy content. Importantly, this pattern does not emerged with nonfood items. We conclude that in humans visual inspection of food is central to its evaluation and seems to partially engage the same basic system as non-human primates

Revealing the Dynamic Magneto-ionic Environments of Repeating Fast Radio Burst Sources through Multi-year Polarimetric Monitoring with CHIME/FRB

Fast radio bursts (FRBs) display a confounding variety of burst properties and host galaxy associations. Repeating FRBs offer insight into the FRB population by enabling spectral, temporal and polarimetric properties to be tracked over time. Here, we report on the polarized observations of 12 repeating sources using multi-year monitoring with the Canadian Hydrogen Intensity Mapping Experiment (CHIME) over 400-800 MHz. We observe significant RM variations from many sources in our sample, including RM changes of several hundred $\rm{rad\, m^{-2}}$ over month timescales from FRBs 20181119A, 20190303A and 20190417A, and more modest RM variability ($\rm{\Delta RM \lesssim}$ few tens rad m$^{-2}$) from FRBs 20181030A, 20190208A, 20190213B and 20190117A over equivalent timescales. Several repeaters display a frequency dependent degree of linear polarization that is consistent with depolarization via scattering. Combining our measurements of RM variations with equivalent constraints on DM variability, we estimate the average line-of-sight magnetic field strength in the local environment of each repeater. In general, repeating FRBs display RM variations that are more prevalent/extreme than those seen from radio pulsars in the Milky Way and the Magellanic Clouds, suggesting repeating FRBs and pulsars occupy distinct magneto-ionic environments

Quantum dynamics in strong fluctuating fields

A large number of multifaceted quantum transport processes in molecular systems and physical nanosystems can be treated in terms of quantum relaxation processes which couple to one or several fluctuating environments. A thermal equilibrium environment can conveniently be modelled by a thermal bath of harmonic oscillators. An archetype situation provides a two-state dissipative quantum dynamics, commonly known under the label of a spin-boson dynamics. An interesting and nontrivial physical situation emerges, however, when the quantum dynamics evolves far away from thermal equilibrium. This occurs, for example, when a charge transferring medium possesses nonequilibrium degrees of freedom, or when a strong time-dependent control field is applied externally. Accordingly, certain parameters of underlying quantum subsystem acquire stochastic character. Herein, we review the general theoretical framework which is based on the method of projector operators, yielding the quantum master equations for systems that are exposed to strong external fields. This allows one to investigate on a common basis the influence of nonequilibrium fluctuations and periodic electrical fields on quantum transport processes. Most importantly, such strong fluctuating fields induce a whole variety of nonlinear and nonequilibrium phenomena. A characteristic feature of such dynamics is the absence of thermal (quantum) detailed balance.Comment: review article, Advances in Physics (2005), in pres

Preterm birth: inflammation, fetal injury and treatment strategies

Preterm birth (PTB) is the leading cause of childhood mortality in children under 5 and accounts for approximately 11% of births worldwide. Premature babies are at risk of a number of health complications, notably cerebral palsy, but also respiratory and gastrointestinal disorders. Preterm deliveries can be medically indicated/elective procedures or they can occur spontaneously. Spontaneous PTB is commonly associated with intrauterine infection/inflammation. The presence of inflammatory mediators in utero has been associated with fetal injury, particularly affecting the fetal lungs and brain. This review will outline (i) the role of inflammation in term and PTB, (ii) the effect infection/inflammation has on fetal development and (iii) recent strategies to target PTB. Further research is urgently required to develop effective methods for the prevention and treatment of PTB and above all, to reduce fetal injury