Probing the Interstellar Medium on AU Size Scales Using Pulsar Scintillation

We have used pulsar scintillation observations to probe the ionized component of the interstellar medium on AU size scales. Previous work had shown that the presence of scintillation arcs in pulsar secondary spectra requires that the scattering along the line of sight to the pulsar is dominated by a thin screen of scattering material. An isotropic image gives rise to a sharply delineated arc, while an anisotropic image with refractive hot spots elongated along the pulsar velocity vector gives rise to detailed substructure and arclets in the secondary spectrum. Twenty-five years of archival scintillation data from the Arecibo Observatory show that arclets are present in ~ 25% of low radio frequency observations of PSR B0834+06 and PSR B1133+16 and that the decorrelation time scale of substructure is ~ 6 months. Observations of the pulsar PSR B0834+06 at Arecibo identified four isolated arclets at high delays. These arclets were present throughout a month of observations, and their angular separation from the pulsar changed over the course of the month in a linear fashion. This transverse motion is dominated by the velocity of the pulsar and implies an approximate upper limit to the screen velocity of 7 km s-1. We applied a plasma lens model to these observations assuming that the high delay arclets are caused by refracting plasma lenses in the scattering screen. We place an upper bound of a ~ 0.1 AU on the lens size and estimate an electron density within the lens of ne ~ 200 cm-3. The ionized component of the lens thus has a mass of Ml ~ 10-18 Msun. These parameters are very similar to the predicted parameters for the plasma lenses thought to cause Extreme Scattering Events in quasars

The range of axial rotation of the glenohumeral joint.

Accepted versio

Harnessing autophagy to overcome mitogen‐activated protein kinase kinase inhibitor‐induced resistance in metastatic melanoma

Background Patients with malignant melanoma often relapse after treatment with BRAF and/or mitogen‐activated protein kinase kinase (MEK) inhibitors (MEKi) owing to development of drug resistance. Objectives To establish the temporal pattern of CD271 regulation during development of resistance by melanoma to trametinib, and determine the association between development of resistance to trametinib and induction of prosurvival autophagy. Methods Immunohistochemistry for CD271 and p62 was performed on human naevi and primary malignant melanoma tumours. Western blotting was used to analyse expression of CD271, p62 and LC3 in melanoma subpopulations. Flow cytometry and immunofluorescence microscopy was used to evaluate trametinib‐induced cell death and CD271 expression. MTS viability assays and zebrafish xenografts were used to evaluate the effect of CD271 and autophagy modulation on trametinib‐resistant melanoma cell survival and invasion, respectively. Results CD271 and autophagic signalling are increased in stage III primary melanomas vs. benign naevi. In vitro studies demonstrate MEKi of BRAF‐mutant melanoma induced cytotoxic autophagy, followed by the emergence of CD271‐expressing subpopulations. Trametinib‐induced CD271 reduced autophagic flux, leading to activation of prosurvival autophagy and development of MEKi resistance. Treatment of CD271‐expressing melanoma subpopulations with RNA interference and small‐molecule inhibitors to CD271 reduced the development of MEKi resistance, while clinically applicable autophagy modulatory agents – including Δ9‐tetrahydrocannabinol and Vps34 – reduced survival of MEKi‐resistant melanoma cells. Combined MEK/autophagy inhibition also reduced the invasive and metastatic potential of MEKi‐resistant cells in an in vivo zebrafish xenograft. Conclusions These results highlight a novel mechanism of MEKi‐induced drug resistance and suggest that targeting autophagy may be a translatable approach to resensitize drug‐resistant melanoma cells to the cytotoxic effects of MEKi

Accurate <i>ab initio</i> ro-vibronic spectroscopy of the X²&#8719; CCN radical using explicitly correlated methods

Explicitly correlated CCSD(T)-F12b calculations have been carried out with systematic sequences of correlation consistent basis sets to determine accurate near-equilibrium potential energy surfaces for the X&lt;sup&gt;2&lt;/sup&gt;&#8719; and a&lt;sup&gt;4&lt;/sup&gt;&#931;&lt;sup&gt;−&lt;/sup&gt; electronic states of the CCN radical. After including contributions due to core correlation, scalar relativity, and higher order electron correlation effects, the latter utilizing large-scale multireference configuration interaction calculations, the resulting surfaces were employed in variational calculations of the ro-vibronic spectra. These calculations also included the use of accurate spin-orbit and dipole moment matrix elements. The resulting ro-vibronic transition energies, including the Renner-Teller sub-bands involving the bending mode, agree with the available experimental data to within 3 cm&lt;sup&gt;−1&lt;/sup&gt; in all cases. Full sets of spectroscopic constants are reported using the usual second-order perturbation theory expressions. Integrated absorption intensities are given for a number of selected vibronic band origins. A computational procedure similar to that used in the determination of the potential energy functions was also utilized to predict the formation enthalpy of CCN, &#916;H&lt;sub&gt;f&lt;/sub&gt;(0K) = 161.7 &#177; 0.5 kcal/mol

Probing a Set of Trajectories to Maximize Captured Information

We study a trajectory analysis problem we call the Trajectory Capture Problem (TCP), in which, for a given input set T of trajectories in the plane, and an integer k? 2, we seek to compute a set of k points ("portals") to maximize the total weight of all subtrajectories of T between pairs of portals. This problem naturally arises in trajectory analysis and summarization. We show that the TCP is NP-hard (even in very special cases) and give some first approximation results. Our main focus is on attacking the TCP with practical algorithm-engineering approaches, including integer linear programming (to solve instances to provable optimality) and local search methods. We study the integrality gap arising from such approaches. We analyze our methods on different classes of data, including benchmark instances that we generate. Our goal is to understand the best performing heuristics, based on both solution time and solution quality. We demonstrate that we are able to compute provably optimal solutions for real-world instances

Quantum tunneling of superconducting string currents

We investigate the decay of current on a superconducting cosmic string through quantum tunneling. We construct the instanton describing tunneling in a simple bosonic string model, and estimate the decay rate. The tunneling rate vanishes in the limit of a chiral current. This conclusion, which is supported by a symmetry argument, is expected to apply in general. It has important implications for the stability of chiral vortons.Comment: 16 pages, 2 figure

High Energy Particles from Monopoles Connected by Strings

Monopole-antimonopole pairs connected by strings and monopole-string networks with $N>2$ strings attached to each monopole can be formed at phase transitions in the early universe. In such hybrid defects, monopoles accelerate under the string tension and can reach ultrarelativistic Lorentz factors, $\gamma\gg 1$. We study the radiation of gauge quanta by accelerating monopoles. For monopoles with a chromomagnetic charge, we also discuss the high-energy hadron production through emission of virtual gluons and their subsequent fragmentation into hadrons. The relevant parameter for gauge boson radiation is $M/a$, where $M$ is the boson mass and $a$ is the proper acceleration of the monopole. For $M\ll a$, the gauge bosons can be considered as massless and the typical energy of the emitted quanta is $E\sim\gamma a$. In the opposite limit, $M\gg a$, the radiation power is exponentially suppressed and gauge quanta are emitted with a typical energy $E\sim\gamma M$ in a narrow range $\Delta E/E\sim (a/M)^{1/2}$. Cosmological monopole-string networks can produce photons and hadrons of extremely high energies. For a wide range of parameters these energies can be much greater than the Planck scale.Comment: 28 pages, ReVTex, 5 postscript figures. Minor changes, some references added. Submitted to Phys. Rev.

Association of the 2011 ACGME Resident Duty Hour Reforms with Mortality and Readmissions among Hospitalized Medicare Patients

Importance Patient outcomes associated with the 2011 Accreditation Council for Graduate Medical Education (ACGME) duty hour reforms have not been evaluated at a national level. Objective To evaluate the association of the 2011 ACGME duty hour reforms with mortality and readmissions. Design, Setting, and Participants Observational study of Medicare patient admissions (6 384 273 admissions from 2 790 356 patients) to short-term, acute care, nonfederal hospitals (n = 3104) with principal medical diagnoses of acute myocardial infarction, stroke, gastrointestinal bleeding, or congestive heart failure or a Diagnosis Related Group classification of general, orthopedic, or vascular surgery. Of the hospitals, 96 (3.1%) were very major teaching, 138 (4.4%) major teaching, 442 (14.2%) minor teaching, 443 (14.3%) very minor teaching, and 1985 (64.0%) nonteaching. Exposure Resident-to-bed ratio as a continuous measure of hospital teaching intensity. Main Outcomes and Measures Change in 30-day all-location mortality and 30-day all-cause readmission, comparing patients in more intensive relative to less intensive teaching hospitals before (July 1, 2009–June 30, 2011) and after (July 1, 2011–June 30, 2012) duty hour reforms, adjusting for patient comorbidities, time trends, and hospital site. Results In the 2 years before duty hour reforms, there were 4 325 854 admissions with 288 422 deaths and 602 380 readmissions. In the first year after the reforms, accounting for teaching hospital intensity, there were 2 058 419 admissions with 133 547 deaths and 272 938 readmissions. There were no significant postreform differences in mortality accounting for teaching hospital intensity for combined medical conditions (odds ratio [OR], 1.00; 95% CI, 0.96-1.03), combined surgical categories (OR, 0.99; 95% CI, 0.94-1.04), or any of the individual medical conditions or surgical categories. There were no significant postreform differences in readmissions for combined medical conditions (OR, 1.00; 95% CI, 0.97-1.02) or combined surgical categories (OR, 1.00; 95% CI, 0.98-1.03). For the medical condition of stroke, there were higher odds of readmissions in the postreform period (OR, 1.06; 95% CI, 1.001-1.13). However, this finding was not supported by sensitivity analyses and there were no significant postreform differences for readmissions for any other individual medical condition or surgical category. Conclusions and Relevance Among Medicare beneficiaries, there were no significant differences in the change in 30-day mortality rates or 30-day all-cause readmission rates for those hospitalized in more intensive relative to less intensive teaching hospitals in the year after implementation of the 2011 ACGME duty hour reforms compared with those hospitalized in the 2 years before implementation

Cosmic Necklaces and Ultrahigh Energy Cosmic Rays

Cosmic necklaces are hybrid topological defects consisting of monopoles and strings, with two strings attached to each monopole. We argue that the cosmological evolution of necklaces may significantly differ from that of cosmic strings. The typical velocity of necklaces can be much smaller than the speed of light, and the characteristic scale of the network much smaller than the horizon. We estimate the flux of high-energy protons produced by monopole annihilation in the decaying closed loops. For some reasonable values of the parameters it is comparable to the observed flux of ultrahigh-energy cosmic rays.Comment: 10 pages, Revtex, 1 figur