199 research outputs found
Three new Alpha1-Antitrypsin deficiency variants help to define a C-Terminal region regulating conformational change and polymerization
Alpha1-antitrypsin (AAT) deficiency is a hereditary disorder associated with reduced AAT plasma levels, predisposing adults to pulmonary emphysema. The most common genetic AAT variants found in patients are the mildly deficient S and the severely deficient Z alleles, but several other pathogenic rare alleles have been reported. While the plasma AAT deficiency is a common trait of the disease, only a few AAT variants, including the prototypic Z AAT and some rare variants, form cytotoxic polymers in the endoplasmic reticulum of hepatocytes and predispose to liver disease. Here we report the identification of three new rare AAT variants associated to reduced plasma levels and characterize their molecular behaviour in cellular models. The variants, called Mpisa (Lys259Ile), Etaurisano (Lys368Glu) and Yorzinuovi (Pro391His), showed reduced secretion compared to control M AAT, and accumulated to different extents in the cells as ordered polymeric structures resembling those formed by the Z variant. Structural analysis of the mutations showed that they may facilitate polymerization both by loosening ‘latch’ interactions constraining the AAT reactive loop and through effects on core packing. In conclusion, the new AAT deficiency variants, besides increasing the risk of lung disease, may predispose to liver disease, particularly if associated with the common Z variant. The new mutations cluster structurally, thus defining a region of the AAT molecule critical for regulating its conformational state
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 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&
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
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