Clinical manifestations in patients with PI*MMMalton genotypes. A matter still unsolved in alpha-1 antitrypsin deficiency

We report the genetic variants associated with alpha-1 antitrypsin deficiency (AATD) in 117 patients admitted to our outpatient clinic and characterized by a serum concentration of AAT lower than 113 mg/dL. We focused on the M-like heterozygous variant of the SERPINA1 gene called PI*MMMalton, and describe three patients with this variant. While the role of homozygous AATD in liver and pulmonary disease is well established, the association between heterozygous AATD and chronic liver and pulmonary disease is still under investigation. The PI*MMMalton genotype was found in 5.8% of patients with a pathological genotype of AATD and in 14.3% of the subjects when considering only those with intermediate AATD. There were no liver or renal abnormalities in patients with the PI*MMMalton genotype. The PI*MMMalton patients included here showed a normal liver function, and none had renal function abnormalities or abdominal aortic aneurysm. Only a prevalence of lung disease was detected

Concurrent Computing with Shared Replicated Memory

The behavioural theory of concurrent systems states that any concurrent system can be captured by a behaviourally equivalent concurrent Abstract State Machine (cASM). While the theory in general assumes shared locations, it remains valid, if different agents can only interact via messages, i.e. sharing is restricted to mailboxes. There may even be a strict separation between memory managing agents and other agents that can only access the shared memory by sending query and update requests to the memory agents. This article is dedicated to an investigation of replicated data that is maintained by a memory management subsystem, whereas the replication neither appears in the requests nor in the corresponding answers. We show how the behaviour of a concurrent system with such a memory management can be specified using concurrent communicating ASMs. We provide several refinements of a high-level ground model addressing different replication policies and internal messaging between data centres. For all these refinements we analyse their effects on the runs such that decisions concerning the degree of consistency can be consciously made.Comment: 23 page

Dust formation around AGB and SAGB stars: a trend with metallicity?

We calculate the dust formed around AGB and SAGB stars of metallicity Z=0.008 by following the evolution of models with masses in the range 1M<M<8M throughthe thermal pulses phase, and assuming that dust forms via condensation of molecules within a wind expanding isotropically from the stellar surface. We find that, because of the strong Hot Bottom Burning (HBB) experienced, high mass models produce silicates, whereas lower mass objects are predicted to be surrounded by carbonaceous grains; the transition between the two regimes occurs at a threshold mass of 3.5M. These fndings are consistent with the results presented in a previous investigation, for Z=0.001. However, in the present higher metallicity case, the production of silicates in the more massive stars continues for the whole AGB phase, because the HBB experienced is softer at Z=0.008 than at Z=0.001, thus the oxygen in the envelope, essential for the formation of water molecules, is never consumed completely. The total amount of dust formed for a given mass experiencing HBB increases with metallicity, because of the higher abundance of silicon, and the softer HBB, both factors favouring a higher rate of silicates production. This behaviour is not found in low mass stars,because the carbon enrichment of the stellar surface layers, due to repeated Third Drege Up episodes, is almost independent of the metallicity. Regarding cosmic dust enrichment by intermediate mass stars, we find that the cosmic yield at Z=0.008 is a factor 5 larger than at Z=0.001. In the lower metallicity case carbon dust dominates after about 300 Myr, but at Z=0.008 the dust mass is dominated by silicates at all times,with a prompt enrichment occurring after about 40 Myr, associated with the evolution of stars with masses M =7.5 -8M.Comment: 14 pages, 10 figures, 2 Tables, accepted for publication in MNRA

The Importance of N186 in the Alpha-1-Antitrypsin Shutter Region Is Revealed by the Novel Bologna Deficiency Variant

Alpha-1-antitrypsin (AAT) deficiency causes pulmonary disease due to decreased levels of circulating AAT and consequently unbalanced protease activity in the lungs. Deposition of specific AAT variants, such as the common Z AAT, within hepatocytes may also result in liver disease. These deposits are comprised of ordered polymers of AAT formed by an inter-molecular domain swap. The discovery and characterization of rare variants of AAT and other serpins have historically played a crucial role in the dissection of the structural mechanisms leading to AAT polymer formation. Here, we report a severely deficient shutter region variant, Bologna AAT (N186Y), which was identified in five unrelated subjects with different geographical origins. We characterized the new variant by expression in cellular models in comparison with known polymerogenic AAT variants. Bologna AAT showed secretion deficiency and intracellular accumulation as detergent-insoluble polymers. Extracellular polymers were detected in both the culture media of cells expressing Bologna AAT and in the plasma of a patient homozygous for this variant. Structural modelling revealed that the mutation disrupts the hydrogen bonding network in the AAT shutter region. These data support a crucial coordinating role for asparagine 186 and the importance of this network in promoting formation of the native structure

Clinical manifestations of a new alpha-1 antitrypsin genetic variant: Q0parma

Alpha-1 antitrypsin deficiency is an autosomal, codominant disorder caused by mutations of the SERPINA1 gene. Several mutations of SERPINA1 have been described associated with the development of pulmonary emphysema and/or chronic liver disease and cirrhosis. Here, we report a very rare PI*Q0parma variant identified for the first time in an Italian family originally from the city of Parma in Northern Italy

The dust envelope of the pre-planetary nebula IRAS19475+3119

We present the spectral energy distribution (SED) of the pre-planetary nebula, IRAS 19475+3119 (I19475), from the optical to the far-infrared. We identify emission features due to crystalline silicates in the ISO SWS spectra of the star. We have fitted the SED of I19475 using a 1-D radiative transfer code, and find that a shell with inner and outer radii of 8.8X10^{16} and 4.4X10^{17}cm, and dust temperatures ranging from about 94K to 46K provide the best fit. The mass of this shell is greater than/equal to 1[34cm^{2}g^{-1}/kappa(100micron)][delta/200]M_Sun, where kappa(100micron) is the 100micron dust mass absorption coefficient (per unit dust mass), and delta is the gas-to-dust ratio. In agreement with results from optical imaging and millimeter-wave observations of CO emission of I19475, our model fits support an r^{-3} density law for its dust shell, with important implications for the interaction process between the fast collimated post-AGB winds and the dense AGB envelopes which results in the observed shapes of PPNs and PNs. We find that the observed JCMT flux at sub-millimeter wavelengths (850micron) is a factor ~ 2 larger than our model flux, suggesting the presence of large dust grains in the dust shell of I19475 which are not accounted for by our adopted standard MRN grain size distribution.Comment: 38 pages, 8 figures. Accepted for publication in Ap

Dust Emission Features in NGC 7023 between 0.35 and 2.5 micron: Extended Red Emission (0.7 micron) and Two New Emission Features (1.15 and 1.5 micron)

We present 0.35 to 2.5 micron spectra of the south and northwest filaments in the reflection nebula NGC 7023. These spectra were used to test the theory of Seahra & Duley that carbon nanoparticles are responsible for Extended Red Emission (ERE). Our spectra fail to show their predicted second emission band at 1.0 micron even though both filaments exhibit strong emission in the familiar 0.7 micron ERE band. The northwest filament spectrum does show one, and possibly two, new dust emission features in the near-infrared. We clearly detect a strong emission band at 1.5 micron which we tentatively attribute to beta-FeSi_2 grains. We tentatively detect a weaker emission band at 1.15 micron which coincides with the location expected for transitions from the conduction band to mid-gap defect states of silicon nanoparticles. This is added evidence that silicon nanoparticles are responsible for ERE as they already can explain the observed behavior of the main visible ERE band.Comment: 9 pages, color figures, accepted to the ApJ, color and b/w versions available at http://dirty.as.arizona.edu/~kgordon/papers/ere_1um.htm

The mineralogy, geometry and mass-loss history of IRAS 16342-3814

We present the 2-200 um Infrared Space Observatory (ISO) spectrum and 3.8-20 um ISAAC and TIMMI2 images of the extreme OH/IR star IRAS 16342-3814. Amorphous silicate absorption features are seen, together with crystalline silicate absorption features up to almost 45 um. No other OH/IR star is known to have crystalline silicate features in absorption up to these wavelengths. This suggests that IRAS 16342-3814 must have, or recently had, an extremely high mass-loss rate. Preliminary radiative transfer calculations suggest that the mass-loss rate may be as large as 10^{-3} Msun/yr. The 3.8 um ISAAC image shows a bipolar reflection nebula with a dark equatorial waist or torus, similar to that seen in optical Hubble Space Telescope (HST) images. The position angle of the nebula decreases significantly with increasing wavelength, suggesting that the dominant source of emission changes from scattering to thermal emission. Still, even up to 20 um the nebula is oriented approximately along the major axis of the nebula seen in the HST and ISAAC images, suggesting that the torus must be very cold, in agreement with the very red ISO spectrum. The 20 um image shows a roughly spherically symmetric extended halo, approximately 6'' in diameter, which is probably due to a previous phase of mass-loss on the AGB, suggesting a transition from a (more) spherically symmetric to a (more) axial symmetric form of mass-loss at the end of the AGB. We estimate the maximum dust particle sizes in the torus and in the reflection nebula to be 1.3 and 0.09 um respectively. The size of the particles in the torus is large compared to typical ISM values, but in agreement with high mass-loss rate objects like AFGL 4106 and HD161796. We discuss the possible reason for the difference in particle size between the torus and the reflection nebula.Comment: Accepted for publication by A&