Determining electron column density fluctuations in a dominant scattering region using pulsar scintillation

Density fluctuations in the ionised interstellar medium have a profound effect on radio pulsar observations, through angular scattering, intensity scintillations, and small changes in time delays from dispersion. Here we show that it is possible to recover the variations in dispersive delays that originate from a dominant scattering region using measurements of the dynamic spectrum of intensity scintillations, provided that the pulsar velocity and scattering region location are known. We provide a theoretical framework for the technique, which involves estimating the phase gradient from the dynamic spectra and integrating that gradient to obtain phase variations. It can be used to search for "extreme scattering events" (ESEs) in pulsars for which precision dispersion delay measurements are not otherwise possible, or to separate true dispersion variations from apparent variability caused by frequency-dependent pulse shape changes. We demonstrate that it works in practice by recovering an ESE in PSR J1603$-$7202, which is known from precision dispersion delay measurements from pulsar timing. For this pulsar, we find that the phase gradients also track the long-term variations in electron column density observed by pulsar timing, indicating that the column density variations and the scattering are dominated by the same thin scattering screen. We identify a sudden increase in the scintillation strength and magnitude of phase gradients over $\sim$days in 2010, indicating a compact structure. A decrease in the electron density in 2012 was associated with persistent phase gradients and preceded a period of decreased scintillation strength and an absence of scintillation arcs.Comment: 9 pages, 7 figures, Accepted for publication in MNRA

Studies on Age-Related Changes in Equine Cheek Teeth Angulation and Dental Drift

BACKGROUND: Cheek teeth (second through fourth premolars and first through third molars) diastema is a common and painful equine disorder caused by the absence of effective tight interdental contact between these teeth. Limited objective information is available on the angulation of equine cheek teeth that control dental drift or on mesial or distal equine cheek teeth drift that should normally prevent this disorder. OBJECTIVES: To measure the angulation of the mesial and distal cheek teeth in horses of different ages, quantify age-related cheek teeth mesial and distal dental drift, and measure the cheek teeth row length in horses of different ages. STUDY DESIGN: Retrospective review of computed tomographic images of equine heads. METHODS: Case details and CT images from clinical equine cases that had undergone standing CT head examination were collated. Three sets of measurements were acquired from each head. “Head size” calculated as the distance between the caudal aspect of the orbit and the caudal aspect of the naso-incisive notch was used to standardize measurements in different sized heads. The length of the cheek teeth rows measured from the mesial aspect of the Triadan 06 occlusal surface to the distal aspect of the Triadan 11 occlusal surface. The rostro-caudal (antero-posterior) position and angulation of the mandibular and maxillary Triadan 06 and 11 teeth were measured in relation to reference lines drawn on CT images. RESULTS: Significant mesial drift occurred in the maxillary and mandibular Triadan 11s. Despite their distal angulation, the upper and lower Triadan 06s also drifted mesially. The mean angulation of Triadan 06 and 11 mandibular teeth (17.8 and 26.2°, respectively) was almost double that of maxillary teeth (9.2 and 13.3°, respectively) with both Triadan 11s having greater angulation than the 06s. Cheek teeth angulation only significantly decreased in the mandibular 06s. Cheek teeth arcade lengths decreased with age, but these decreases were not significant. MAIN LIMITATIONS: Limitations include the relatively small sample size. CONCLUSIONS: In the population of horses used for this study, age related mesial drift occurred in both Triadan 06 and 11s, and the angulation of these teeth did not decrease with age in most arcades

Pulsar scintillation through thick and thin: Bow shocks, bubbles, and the broader interstellar medium

Observations of pulsar scintillation are among the few astrophysical probes of very small-scale (≲ au) phenomena in the interstellar medium (ISM). In particular, characterization of scintillation arcs, including their curvature and intensity distributions, can be related to interstellar turbulence and potentially overpressurized plasma in local ISM inhomogeneities, such as supernova remnants, H II regions, and bow shocks. Here we present a survey of eight pulsars conducted at the Five-hundred-metre Aperture Spherical Telescope (FAST), revealing a diverse range of scintillation arc characteristics at high sensitivity. These observations reveal more arcs than measured previously for our sample. At least nine arcs are observed toward B1929+10 at screen distances spanning ~90 per cent of the pulsar’s 361 pc path length to the observer. Four arcs are observed toward B0355+54, with one arc yielding a screen distance as close as ∼105 au (<1 pc) from either the pulsar or the observer. Several pulsars show highly truncated, low-curvature arcs that may be attributable to scattering near the pulsar. The scattering screen constraints are synthesized with continuum maps of the local ISM and other well-characterized pulsar scintillation arcs, yielding a three-dimensional view of the scattering media in context

Gravitational-Wave Cosmology across 29 Decades in Frequency

Quantum fluctuations of the gravitational field in the early Universe, amplified by inflation, produce a primordial gravitational-wave background across a broad frequency band. We derive constraints on the spectrum of this gravitational radiation, and hence on theories of the early Universe, by combining experiments that cover 29 orders of magnitude in frequency. These include Planck observations of cosmic microwave background temperature and polarization power spectra and lensing, together with baryon acoustic oscillations and big bang nucleosynthesis measurements, as well as new pulsar timing array and ground-based interferometer limits. While individual experiments constrain the gravitational-wave energy density in specific frequency bands, the combination of experiments allows us to constrain cosmological parameters, including the inflationary spectral index nt and the tensor-to-scalar ratio r. Results from individual experiments include the most stringent nanohertz limit of the primordial background to date from the Parkes Pulsar Timing Array, ΩGW(f)\u3c2.3×10−10. Observations of the cosmic microwave background alone limit the gravitational-wave spectral index at 95% confidence to nt≲5 for a tensor-to-scalar ratio of r=0.11. However, the combination of all the above experiments limits nt\u3c0.36. Future Advanced LIGO observations are expected to further constrain nt\u3c0.34 by 2020. When cosmic microwave background experiments detect a nonzero r, our results will imply even more stringent constraints on nt and, hence, theories of the early Universe

Characterization of an electron conduit between bacteria and the extracellular environment

A number of species of Gram-negative bacteria can use insoluble minerals of Fe(III) and Mn(IV) as extracellular respiratory electron acceptors. In some species of Shewanella, deca-heme electron transfer proteins lie at the extracellular face of the outer membrane (OM), where they can interact with insoluble substrates. To reduce extracellular substrates, these redox proteins must be charged by the inner membrane/periplasmic electron transfer system. Here, we present a spectro-potentiometric characterization of a trans-OM icosa-heme complex, MtrCAB, and demonstrate its capacity to move electrons across a lipid bilayer after incorporation into proteoliposomes. We also show that a stable MtrAB subcomplex can assemble in the absence of MtrC; an MtrBC subcomplex is not assembled in the absence of MtrA; and MtrA is only associated to the membrane in cells when MtrB is present. We propose a model for the modular organization of the MtrCAB complex in which MtrC is an extracellular element that mediates electron transfer to extracellular substrates and MtrB is a trans-OM spanning ß-barrel protein that serves as a sheath, within which MtrA and MtrC exchange electrons. We have identified the MtrAB module in a range of bacterial phyla, suggesting that it is widely used in electron exchange with the extracellular environment

Different Poses for Ligand and Chaperone in Inhibitor Bound Hsp90 and GRP94: Implications for Paralog-specific Drug Design

Hsp90 chaperones contain an N-terminal ATP binding site that has been effectively targeted by competitive inhibitors. Despite the myriad of inhibitors, none to date have been designed to bind specifically to just one of the four mammalian hsp90 paralogs, which are cytoplasmic Hsp90α and β, ER GRP94, and mitochondrial Trap-1. Given that each of the hsp90 paralogs is responsible for chaperoning a distinct set of client proteins, specific targeting of one hsp90 paralog may result in higher efficacy and therapeutic control. Specific inhibitors may also help elucidate the biochemical roles of each hsp90 paralog. Here we present side by side comparisons of the structures of yeast Hsp90 and mammalian GRP94, bound to the pan-hsp90 inhibitors Geldanamycin and Radamide. These structures reveal paralog specific differences in the Hsp90 and GRP94 conformations in response to Geldanamycin binding. We also report significant variation in the pose and disparate binding affinities for the Geldanamycin-Radicicol chimera Radamide when bound to the two paralogs, which may be exploited in the design of paralog-specific inhibitors

Improving pulsar-timing solutions through dynamic pulse fitting

Precision pulsar timing is integral to the detection of the nanohertz stochastic gravitational-wave background as well as understanding the physics of neutron stars. Conventional pulsar timing often uses fixed time and frequency-averaged templates to determine the pulse times of arrival, which can lead to reduced accuracy when the pulse profile evolves over time. We illustrate a dynamic timing method that fits each observing epoch using basis functions. By fitting each epoch separately, we allow for the evolution of the pulse shape epoch to epoch. We apply our method to PSR J1103$-$5403 and demonstrate that it undergoes mode changing, making it the fourth millisecond pulsar to exhibit such behaviour. Our method, which is able to identify and time a single mode, yields a timing solution with a root-mean-square error of 1.343 $\mu \mathrm{s}$, a factor of 1.78 improvement over template fitting on both modes. In addition, the white-noise amplitude is reduced 4.3 times, suggesting that fitting the full data set causes the mode changing to be incorrectly classified as white noise. This reduction in white noise boosts the signal-to-noise ratio of a gravitational-wave background signal for this particular pulsar by 32%. We discuss the possible applications for this method of timing to study pulsar magnetospheres and further improve the sensitivity of searches for nanohertz gravitational waves.Comment: Accepted in MNRAS, 8 pages, 8 figure

Clinical impact of baseline chronic kidney disease in patients undergoing transcatheter or surgical aortic valve replacement

ObjectivesTo assess the treatment effect of TAVR versus SAVR on clinical outcomes to 3 years in patients stratified by chronic kidney disease (CKD) by retrospectively studying patients randomized to TAVR or SAVR.BackgroundThe impact of CKD on mid‐term outcomes of patients undergoing TAVR versus SAVR is unclear.MethodsPatients randomized to TAVR or SAVR in the CoreValve US Pivotal High Risk Trial were retrospectively stratified by eGFR: none/mild or moderate/severe CKD. To evaluate the impact of baseline CKD in TAVR patients only, all patients undergoing an attempted TAVR implant in the US Pivotal Trial and CAS were stratified by baseline eGFR into none/mild, moderate, and severe CKD. The primary endpoint was major adverse cardiovascular and renal events (MACRE), a composite of all‐cause mortality, myocardial infarction, stroke/TIA, and new requirement of dialysis.ResultsModerate/severe CKD was present in 62.7% and 60.7% of high‐risk patients randomized to TAVR or SAVR, respectively. Baseline characteristics were similar between TAVR and SAVR patients in both CKD subgroups, except for higher rates of diabetes and higher serum creatinine in SAVR patients. Among high‐risk patients with moderate/severe CKD, TAVR provided a lower 3‐year MACRE rate compared with SAVR: 42.1% vs. 51.0, P = .04. Of 3,733 extreme‐ and high‐risk TAVR patients, 39.9% had none/mild, 53.8% moderate, and 6.4% severe CKD. Worsening baseline CKD was associated with increased 3‐year MACRE rates [none/mild 51.5%, moderate 54.5%, severe 63.1%, P = .001].ConclusionsTAVR results in lower 3‐year MACRE versus SAVR in high‐risk patients with moderate/severe CKD. In patients undergoing TAVR, worsening CKD increases mid‐term mortality and MACRE. Randomized trials of TAVR vs. SAVR in patients with moderate‐severe CKD would help elucidate the best treatment for these complex patients.Trial RegistrationCoreValve US Pivotal Trial: NCT01240902.CoreValve Continued Access Study: NCT01531374.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148361/1/ccd27928_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148361/2/ccd27928.pd

“What if There's Something Wrong with Her?”‐How Biomedical Technologies Contribute to Epistemic Injustice in Healthcare

While there is a steadily growing literature on epistemic injustice in healthcare, there are few discussions of the role that biomedical technologies play in harming patients in their capacity as knowers. Through an analysis of newborn and pediatric genetic and genomic sequencing technologies (GSTs), I argue that biomedical technologies can lead to epistemic injustice through two primary pathways: epistemic capture and value partitioning. I close by discussing the larger ethical and political context of critical analyses of GSTs and their broader implications for just and equitable healthcare delivery

Precision orbital dynamics from interstellar scintillation arcs for PSR J0437-4715

Intensity scintillations of radio pulsars are known to originate from interference between waves scattered by the electron density irregularities of interstellar plasma, often leading to parabolic arcs in the two-dimensional power spectrum of the recorded dynamic spectrum. The degree of arc curvature depends on the distance to the scattering plasma and its transverse velocity with respect to the line-of-sight. We report the observation of annual and orbital variations in the curvature of scintillation arcs over a period of 16 years for the bright millisecond pulsar, PSR J0437-4715. These variations are the signature of the relative transverse motions of the Earth, pulsar, and scattering medium, which we model to obtain precise measurements of parameters of the pulsar's binary orbit and the scattering medium itself. We observe two clear scintillation arcs in most of our $>$5000 observations and we show that they originate from scattering by thin screens located at distances $D_1 = 89.8 \pm 0.4$ pc and $D_2 = 124 \pm 3$ pc from Earth. The best-fit scattering model we derive for the brightest arc yields the pulsar's orbital inclination angle $i = 137.1 \pm 0.3^\circ$, and longitude of ascending node, $\Omega=206.3\pm0.4^\circ$. Using scintillation arcs for precise astrometry and orbital dynamics can be superior to modelling variations in the diffractive scintillation timescale, because the arc curvature is independent of variations in the level of turbulence of interstellar plasma. This technique can be used in combination with pulsar timing to determine the full three-dimensional orbital geometries of binary pulsars, and provides parameters essential for testing theories of gravity and constraining neutron star masses.Comment: 19 pages, 10 figures. Accepted for publication in Ap