X-Ray Observations of the supernova remnant G21.5-0.9

We present the analysis of archival X-ray observations of the supernova remnant (SNR) G21.5-0.9. Based on its morphology and spectral properties, G21.5-0.9 has been classified as a Crab-like SNR. In their early analysis of the CHANDRA calibration data, Slane et al. (2000) discovered a low-surface-brightness, extended emission. They interpreted this component as the blast wave formed in the supernova (SN) explosion. In this paper, we present the CHANDRA analysis using a total exposure of ~150 ksec. We also include ROSAT and ASCA observations. Our analysis indicates that the extended emission is non-thermal -- a result in agreement with XMM observations. The entire remnant of radius ~ 2'.5 is best fitted with a power law model with a photon index steepening away from the center. The total unabsorbed flux in the 0.5-10 keV is 1.1E-10 erg/cm2/s with an 85% contribution from the 40" radius inner core. Timing analysis of the High-Resolution Camera (HRC) data failed to detect any pulsations. We put a 16% upper limit on the pulsed fraction. We derive the physical parameters of the putative pulsar and compare them with those of other plerions (such as the Crab and 3C 58). G21.5-0.9 remains the only plerion whose size in X-rays is bigger than in the radio. Deep radio observations will address this puzzle.Comment: 23 pages including 11 figures and 3 tables; accepted by ApJ June 22, 2001; to appear in Oct 20, 2001 issue of Ap

The Third VLBA Calibrator Survey

This paper presents the third extension to the Very Large Baseline Array (VLBA) Calibrator Survey, containing 360 new sources not previously observed with very long baseline interferometry (VLBI). The survey, based on three 24 hour VLBA observing sessions, fills the areas on the sky above declination -45 degrees where the calibrator density is less than one source within a 4 degrees radius disk at any given direction. The positions were derived from astrometric analysis of the group delays determined at 2.3 and 8.6 GHz frequency bands using the Calc/Solve software package. The VCS3 catalogue of source positions, plots of correlated flux density versus the length of projected baseline, contour plots and fits files of naturally weighted CLEAN images as well as calibrated visibility function files are available on the Web at http://gemini.gsfc.nasa.gov/vcs3Comment: 8 pages, 3 figures, 2 tables, accepted for publication in the Astronomical Journal; minor changes to the text are made, table 2 in electronic form is added and can be extracted from the preprint sourc

Filamin C-related myopathies: pathology and mechanisms

The term filaminopathy was introduced after a truncating mutation in the dimerization domain of filamin C (FLNc) was shown to be responsible for a devastating muscle disease. Subsequently, the same mutation was found in patients from diverse ethnical origins, indicating that this specific alteration is a mutational hot spot. Patients initially present with proximal muscle weakness, while distal and respiratory muscles become affected with disease progression. Muscle biopsies of these patients show typical signs of myofibrillar myopathy, including disintegration of myofibrils and aggregation of several proteins into distinct intracellular deposits. Highly similar phenotypes were observed in patients with other mutations in Ig-like domains of FLNc that result in expression of a noxious protein. Biochemical and biophysical studies showed that the mutated domains acquire an abnormal structure causing decreased stability and eventually becoming a seed for abnormal aggregation with other proteins. The disease usually presents only after the fourth decade of life possibly as a result of ageing-related impairments in the machinery that is responsible for disposal of damaged proteins. This is confirmed by mutations in components of this machinery that cause a highly similar phenotype. Transfection studies of cultured muscle cells reflect the events observed in patient muscles and, therefore, may provide a helpful model for testing future dedicated therapeutic strategies. More recently, FLNC mutations were also found in families with a distal myopathy phenotype, caused either by mutations in the actin-binding domain of FLNc that result in increased actin-binding and non-specific myopathic abnormalities without myofibrillar myopathy pathology, or a nonsense mutation in the rod domain that leads to RNA instability, haploinsufficiency with decreased expression levels of FLNc in the muscle fibers and myofibrillar abnormalities, but not to the formation of desmin-positive protein aggregates required for the diagnosis of myofibrillar myopathy

105110^{51} Ergs: The Evolution of Shell Supernova Remnants

This paper reports on a workshop hosted by the University of Minnesota, March 23-26, 1997. It addressed fundamental dynamical issues associated with the evolution of shell supernova remnants and the relationships between supernova remnants and their environments. The workshop considered, in addition to classical shell SNRs, dynamical issues involving X-ray filled composite remnants and pulsar driven shells, such as that in the Crab Nebula. Approximately 75 participants with wide ranging interests attended the workshop. An even larger community helped through extensive on-line debates prior to the meeting. Each of the several sessions, organized mostly around chronological labels, also addressed some underlying, general physical themes: How are SNR dynamics and structures modified by the character of the CSM and the ISM and vice versa? How are magnetic fields generated in SNRs and how do magnetic fields influence SNRs? Where and how are cosmic-rays (electrons and ions) produced in SNRs and how does their presence influence or reveal SNR dynamics? How does SNR blast energy partition into various components over time and what controls conversion between components? In lieu of a proceedings volume, we present here a synopsis of the workshop in the form of brief summaries of the workshop sessions. The sharpest impressions from the workshop were the crucial and under-appreciated roles that environments have on SNR appearance and dynamics and the critical need for broad-based studies to understand these beautiful, but enigmatic objects. \\Comment: 54 pages text, no figures, Latex (aasms4.sty). submitted to the PAS

Radio polarimetric imaging of the interstellar medium: magnetic field and diffuse ionized gas structure near the W3/W4/W5/HB3 complex

We have used polarimetric imaging to study the magneto-ionic medium of the Galaxy, obtaining 1420 MHz images with an angular resolution of 1' over more than 40 square-degrees of sky around the W3/W4/W5/HB3 HII region/SNR complex in the Perseus Arm. Features detected in polarization angle are imposed on the linearly polarized Galactic synchrotron background emission by Faraday rotation arising in foreground ionized gas having an emission measure as low as 1 cm^{-6} pc. Several new remarkable phenomena have been identified, including: mottled polarization arising from random fluctuations in a magneto-ionic screen that we identify with a medium in the Perseus Arm, probably in the vicinity of the HII regions themselves; depolarization arising from very high rotation measures (several times 10^3 rad m^{-2}) and rotation measure gradients due to the dense, turbulent environs of the HII regions; highly ordered features spanning up to several degrees; and an extended influence of the HII regions beyond the boundaries defined by earlier observations. In particular, the effects of an extended, low-density ionized halo around the HII region W4 are evident, probably an example of the extended HII envelopes postulated as the origin of weak recombination-line emission detected from the Galactic ridge. Our polarization observations can be understood if the uniform magnetic field component in this envelope scales with the square-root of electron density and is 20 microG at the edge of the depolarized region around W4, although this is probably an over-estimate since the random field component will have a significant effect.Comment: 18 pages, 8 figures (7 jpeg and 1 postscript), accepted for publication in the Astrophysical Journa

Comparison of drug prescribing before and during the COVID-19 pandemic: A cross-national European study

Purpose: The COVID-19 pandemic had an impact on health care, with disruption to routine clinical care. Our aim was to describe changes in prescription drugs dispensing in the primary and outpatient sectors during the first year of the pandemic across Europe. Methods: We used routine administrative data on dispensed medicines in eight European countries (five whole countries, three represented by one region each) from January 2017 to March 2021 to compare the first year of the COVID-19 pandemic with the preceding 3 years. Results: In the 10 therapeutic subgroups with the highest dispensed volumes across all countries/regions the relative changes between the COVID-19 period and the year before were mostly of a magnitude similar to changes between previous periods. However, for drugs for obstructive airway diseases the changes in the COVID-19 period were stronger in several countries/regions. In all countries/regions a decrease in dispensed DDDs of antibiotics for systemic use (from −39.4% in Romagna to −14.2% in Scotland) and nasal preparations (from −34.4% in Lithuania to −5.7% in Sweden) was observed. We observed a stockpiling effect in the total market in March 2020 in six countries/regions. In Czechia the observed increase was not significant and in Slovenia volumes increased only after the end of the first lockdown. We found an increase in average therapeutic quantity per pack dispensed, which, however, exceeded 5% only in Slovenia, Germany, and Czechia. Conclusions: The findings from this first European cross-national comparison show a substantial decrease in dispensed volumes of antibiotics for systemic use in all countries/regions. The results also indicate that the provision of medicines for common chronic conditions was mostly resilient to challenges faced during the pandemic. However, there were notable differences between the countries/regions for some therapeutic areas

Milestones in the Observations of Cosmic Magnetic Fields

Magnetic fields are observed everywhere in the universe. In this review, we concentrate on the observational aspects of the magnetic fields of Galactic and extragalactic objects. Readers can follow the milestones in the observations of cosmic magnetic fields obtained from the most important tracers of magnetic fields, namely, the star-light polarization, the Zeeman effect, the rotation measures (RMs, hereafter) of extragalactic radio sources, the pulsar RMs, radio polarization observations, as well as the newly implemented sub-mm and mm polarization capabilities. (Another long paragraph is omitted due to the limited space here)Comment: Invited Review (ChJA&A); 32 pages. Sorry if your significant contributions in this area were not mentioned. Published pdf & ps files (with high quality figures) now availble at http://www.chjaa.org/2002_2_4.ht

New insights into the protein aggregation pathology in myotilinopathy by combined proteomic and immunolocalization analyses

Introduction: Myofibrillar myopathies are characterized by progressive muscle weakness and impressive abnormal protein aggregation in muscle fibers. In about 10 % of patients, the disease is caused by mutations in the MYOT gene encoding myotilin. The aim of our study was to decipher the composition of protein deposits in myotilinopathy to get new information about aggregate pathology. Results: Skeletal muscle samples from 15 myotilinopathy patients were included in the study. Aggregate and control samples were collected from muscle sections by laser microdissection and subsequently analyzed by a highly sensitive proteomic approach that enables a relative protein quantification. In total 1002 different proteins were detected. Seventy-six proteins showed a significant over-representation in aggregate samples including 66 newly identified aggregate proteins. Z-disc-associated proteins were the most abundant aggregate components, followed by sarcolemmal and extracellular matrix proteins, proteins involved in protein quality control and degradation, and proteins with a function in actin dynamics or cytoskeletal transport. Forty over-represented proteins were evaluated by immunolocalization studies. These analyses validated our mass spectrometric data and revealed different regions of protein accumulation in abnormal muscle fibers. Comparison of data from our proteomic analysis in myotilinopathy with findings in other myofibrillar myopathy subtypes indicates a characteristic basic pattern of aggregate composition and resulted in identification of a highly sensitive and specific diagnostic marker for myotilinopathy. Conclusions: Our findings i) indicate that main protein components of aggregates belong to a network of interacting proteins, ii) provide new insights into the complex regulation of protein degradation in myotilinopathy that may be relevant for new treatment strategies, iii) imply a combination of a toxic gain-of-function leading to myotilin-positive protein aggregates and a loss-of-function caused by a shift in subcellular distribution with a deficiency of myotilin at Z-discs that impairs the integrity of myofibrils, and iv) demonstrate that proteomic analysis can be helpful in differential diagnosis of protein aggregate myopathies