The Local Leo Cold Cloud and New Limits on a Local Hot Bubble

We present a multi-wavelength study of the local Leo cold cloud (LLCC), a very nearby, very cold cloud in the interstellar medium. Through stellar absorption studies we find that the LLCC is between 11.3 pc and 24.3 pc away, making it the closest known cold neutral medium cloud and well within the boundaries of the local cavity. Observations of the cloud in the 21-cm HI line reveal that the LLCC is very cold, with temperatures ranging from 15 K to 30 K, and is best fit with a model composed of two colliding components. The cloud has associated 100 micron thermal dust emission, pointing to a somewhat low dust-to-gas ratio of 48 x 10^-22 MJy sr^-1 cm^2. We find that the LLCC is too far away to be generated by the collision among the nearby complex of local interstellar clouds, but that the small relative velocities indicate that the LLCC is somehow related to these clouds. We use the LLCC to conduct a shadowing experiment in 1/4 keV X-rays, allowing us to differentiate between different possible origins for the observed soft X-ray background. We find that a local hot bubble model alone cannot account for the low-latitude soft X-ray background, but that isotropic emission from solar wind charge exchange does reproduce our data. In a combined local hot bubble and solar wind charge exchange scenario, we rule out emission from a local hot bubble with an 1/4 keV emissivity greater than 1.1 Snowdens / pc at 3 sigma, 4 times lower than previous estimates. This result dramatically changes our perspective on our local interstellar medium.Comment: 13 pages, 12 figures. Accepted for publication in the Astrophysical Journal. Vector figure version available at http://www.astro.columbia.edu/~jpeek

Spatial and temporal characterization of a Bessel beam produced using a conical mirror

We experimentally analyze a Bessel beam produced with a conical mirror, paying particular attention to its superluminal and diffraction-free properties. We spatially characterized the beam in the radial and on-axis dimensions, and verified that the central peak does not spread over a propagation distance of 73 cm. In addition, we measured the superluminal phase and group velocities of the beam in free space. Both spatial and temporal measurements show good agreement with the theoretical predictions.Comment: 5 pages, 6 figure

Crackling Noise, Power Spectra and Disorder Induced Critical Scaling

Crackling noise is observed in many disordered non-equilibrium systems in response to slowly changing external conditions. Examples range from Barkhausen noise in magnets to acoustic emission in martensites to earthquakes. Using the non-equilibrium random field Ising model, we derive universal scaling predictions for the dependence of the associated power spectra on the disorder and field sweep rate, near an underlying disorder-induced non-equilibrium critical point. Our theory applies to certain systems in which the crackling noise results from avalanche-like response to a (slowly) increasing external driving force, and is characterized by a broad power law scaling regime of the power spectra. We compute the critical exponents and discuss the relevance of the results to experiments.Comment: 27 Latex Pages, 14 eps figure

Hysteresis and Avalanches in the Random Anisotropy Ising Model

The behaviour of the Random Anisotropy Ising model at T=0 under local relaxation dynamics is studied. The model includes a dominant ferromagnetic interaction and assumes an infinite anisotropy at each site along local anisotropy axes which are randomly aligned. Two different random distributions of anisotropy axes have been studied. Both are characterized by a parameter that allows control of the degree of disorder in the system. By using numerical simulations we analyze the hysteresis loop properties and characterize the statistical distribution of avalanches occuring during the metastable evolution of the system driven by an external field. A disorder-induced critical point is found in which the hysteresis loop changes from displaying a typical ferromagnetic magnetization jump to a rather smooth loop exhibiting only tiny avalanches. The critical point is characterized by a set of critical exponents, which are consistent with the universal values proposed from the study of other simpler models.Comment: 40 pages, 21 figures, Accepted for publication in Phys. Rev.

Driving Rate Effects on Crackling Noise

Many systems respond to slowly changing external conditions with crackling noise, created by avalanches or pulses of a broad range of sizes. Examples range from Barkhausen Noise in magnets to earthquakes. Here we discuss how the scaling behavior of the avalanche size and duration distribution and the power spectra of this noise depend on the rate at which the external conditionsare changed. We derive an exponent inequality as a criteria for the relevance of adding a small driving rate to the adiabatic model. We use the zero temperature nonequilibrium random field Ising model to test our results, which are expected to be applicable to a large class of systems with crackling noise. They also agree with recent experiments on Barkhausen noise in various materials.Comment: 4 pages, 2 figures, REVTe

Average shape of fluctuations for subdiffusive walks

We study the average shape of fluctuations for subdiffusive processes, i.e., processes with uncorrelated increments but where the waiting time distribution has a broad power-law tail. This shape is obtained analytically by means of a fractional diffusion approach. We find that, in contrast with processes where the waiting time between increments has finite variance, the fluctuation shape is no longer a semicircle: it tends to adopt a table-like form as the subdiffusive character of the process increases. The theoretical predictions are compared with numerical simulation results.Comment: 4 pages, 6 figures. Accepted for publication Phys. Rev. E (Replaced for the latest version, in press.) Section II rewritte

Targeting mitochondrial oxidative phosphorylation eradicates therapy-resistant chronic myeloid leukemia stem cells

Treatment of chronic myeloid leukemia (CML) with imatinib mesylate and other second-and/or third-generation c-Abl-specific tyrosine kinase inhibitors (TKIs) has substantially extended patient survival(1). However, TKIs primarily target differentiated cells and do not eliminate leukemic stem cells (LSCs)(2-4). Therefore, targeting minimal residual disease to prevent acquired resistance and/or disease relapse requires identification of new LSC-selective target(s) that can be exploited therapeutically(5,6). Considering that malignant transformation involves cellular metabolic changes, which may in turn render the transformed cells susceptible to specific assaults in a selective manner(7), we searched for such vulnerabilities in CML LSCs. We performed metabolic analyses on both stem cell-enriched (CD34(+) and CD34(+)CD38(-)) and differentiated (CD34(-)) cells derived from individuals with CML, and we compared the signature of these cells with that of their normal counterparts. Through combination of stable isotope-assisted metabolomics with functional assays, we demonstrate that primitive CML cells rely on upregulated oxidative metabolism for their survival. We also show that combination treatment with imatinib and tigecycline, an antibiotic that inhibits mitochondrial protein translation, selectively eradicates CML LSCs both in vitro and in a xenotransplantation model of human CML. Our findings provide a strong rationale for investigation of the use of TKIs in combination with tigecycline to treat patients with CML with minimal residual disease

Replication, Pathogenesis and Transmission of Pandemic (H1N1) 2009 Virus in Non-Immune Pigs

The declaration of the human influenza A pandemic (H1N1) 2009 (H1N1/09) raised important questions, including origin and host range [1,2]. Two of the three pandemics in the last century resulted in the spread of virus to pigs (H1N1, 1918; H3N2, 1968) with subsequent independent establishment and evolution within swine worldwide [3]. A key public and veterinary health consideration in the context of the evolving pandemic is whether the H1N1/09 virus could become established in pig populations [4]. We performed an infection and transmission study in pigs with A/California/07/09. In combination, clinical, pathological, modified influenza A matrix gene real time RT-PCR and viral genomic analyses have shown that infection results in the induction of clinical signs, viral pathogenesis restricted to the respiratory tract, infection dynamics consistent with endemic strains of influenza A in pigs, virus transmissibility between pigs and virus-host adaptation events. Our results demonstrate that extant H1N1/09 is fully capable of becoming established in global pig populations. We also show the roles of viral receptor specificity in both transmission and tissue tropism. Remarkably, following direct inoculation of pigs with virus quasispecies differing by amino acid substitutions in the haemagglutinin receptor-binding site, only virus with aspartic acid at position 225 (225D) was detected in nasal secretions of contact infected pigs. In contrast, in lower respiratory tract samples from directly inoculated pigs, with clearly demonstrable pulmonary pathology, there was apparent selection of a virus variant with glycine (225G). These findings provide potential clues to the existence and biological significance of viral receptor-binding variants with 225D and 225G during the 1918 pandemic [5]

Incidence of angioedema after initiation of angiotensin-converting enzyme inhibitors in adults with heart failure

Background: Angioedema, a potentially life-threatening adverse event associated with angiotensin-converting enzyme inhibitor (ACEI) use, occurs more often among Black patients than non-Black patients. Specific angioedema incidence rates (IRs) among heart failure (HF) patients initiating an ACEI are limited. Objectives: To provide estimates of angioedema incidence among HF patients initiating an ACEI, particularly among Black patients. Methods: We conducted a retrospective cohort study among adult (≥18 years) patients with HF who initiated ACEI use at 5 health care delivery systems within the Cardiovascular Research Network between July 2015 and May 2019. We required patients to have ≥12 months of continuous medical and prescription drug coverage and no ACEI dispensings in the 1 year before treatment initiation. Our primary outcome was serious angioedema, defined as a primary or secondary diagnosis of ICD-9 code 995.1 (‘Angioneurotic edema not elsewhere classified’) or ICD-10 codes in the T78.3 series (‘Angioneurotic edema’) during hospitalization. Our secondary out-come was ‘any angioedema’, which included serious angioedema and non-serious angioedema that was diagnosed in the outpatient setting. We followed patients from ACEI initiation until first angioedema diagnosis or a censoring event (treatment discontinuation, initiation of another renin-angiotensin-aldosterone system blocking agent, disenrollment, death, or end of 365-day follow-up or study). We calculated crude IRs and exact 95% confidence intervals (CI) for angioedema among HF patients initiating an ACEI. Results: We identified 14 ,241 ACEI users, of which 6,156 (43 .2%)were women and 2,105 (15%) were self-reported Black. Mean age was 70 ± 14 years. We observed 6 serious angioedema events overall (IR: 0.8/1,000 person-years (PYs), 95% CI: 0.3-1.7), with 2 events occurring among Black patients (IR: 1.8/1,000 PYs, 95%CI: 0.2-6.5) and 4 events among non-Black patients (IR: 0.6/1,000PYs, 95% CI: 0.2-1.5). We observed 43 angioedema events overall (IR: 5.4/1,000 PYs, 95% CI: 3.9-7.3), with 21 events occurring among Black patients (IR: 19/1,000 PYs, 95% CI: 11.8-29.1) and 22 events among non-Black patients (IR: 3.2/1,000 PYs, 95%CI: 2.0-4.9). Conclusions: Our estimate of angioedema incidence among HF patients who initiated an ACEI (5.4 events/1,000 PYs) is slightly higher than a previously published estimate (3.3/1,000 PYs) among a similarly-defined population identified through administrative claims data. Similar to prior reports, we found a higher incidence of angioedema, both serious and non-serious, among Black ACEI users than among non-black ACEI users