We present the results of analysis of ``snapshot'' spectra of 253 metal-poor
halo stars -3.8 < Fe/H < -1.5 obtained in the HERES survey. The spectra are
analysed using an automated line profile ...analysis method based on the
Spectroscopy Made Easy codes of Valenti & Piskunov. Elemental abundances of
moderate precision have been obtained for 22 elements, C, Mg, Al, Ca, Sc, Ti,
V, Cr, Mn, Fe, Co, Ni, Zn, Sr, Y, Zr, Ba, La, Ce, Nd, Sm, and Eu, where
detectable. Among the sample of 253 stars, we find 8 r-II stars and 35 r-I
stars. We also find three stars with strong enhancements of Eu which are
s-process rich. A significant number of new very metal-poor stars are
confirmed: 49 stars with Fe/H < -3 and 181 stars with -3 < Fe/H < -2. We
find one star with Fe/H < -3.5. We find the scatter in the abundance ratios
of Mg, Ca, Sc, Ti, Cr, Fe, Co, and Ni, with respect to Fe and Mg, to be similar
to the estimated relative errors and thus the cosmic scatter to be small,
perhaps even non-existent. The elements C, Sr, Y, Ba and Eu, and perhaps Zr,
show scatter at Fe/H < -2.5 significantly larger than can be explained from
the errors in the analysis, implying scatter which is cosmic in origin.
Significant scatter is observed in abundance ratios between light and heavy
neutron-capture elements at low metallicity and low levels of r-process
enrichment. (*** abridged ***)
Aims. This study aims to determine the level and constancy of the Spite
plateau as definitively as possible from homogeneous high-quality VLT-UVES
spectra of 19 of the most metal-poor dwarf stars ...known. Methods. Our
high-resolution (R ~ 43000), high S/N spectra are analysed with OSMARCS 1D LTE
model atmospheres and turbospectrum synthetic spectra to determine effective
temperatures, surface gravities, and metallicities, as well as Li abundances
for our stars. Results. Eliminating a cool subgiant and a spectroscopic binary,
we find 8 stars to have -3.5 < Fe/H < -3.0 and 9 stars with -3.0 < Fe/H <
-2.5. Our best value for the mean level of the plateau is A(Li) =2.10 +- 0.09.
The scatter around the mean is entirely explained by our estimate of the
observational error and does not allow for any intrinsic scatter in the Li
abundances. In addition, we conclude that a systematic error of the order of
200 K in any of the current temperature scales remains possible. The iron
excitation equilibria in our stars support our adopted temperature scale, which
is based on a fit to wings of the Halpha line, and disfavour hotter scales,
which would lead to a higher Li abundance, but fail to achieve excitation
equilibrium for iron. Conclusions. We confirm the previously noted discrepancy
between the Li abundance measured in extremely metal-poor turnoff stars and the
primordial Li abundance predicted by standard Big-Bang nucleosynthesis models
adopting the baryonic density inferred from WMAP. We discuss recent work
explaining the discrepancy in terms of diffusion and find that uncertain
temperature scales remain a major question. (abridged)
Adverse immune responses severely hamper the success of biopharmaceutical therapies. Possible clinical consequences include anaphylaxis, reduced drug half‐life and neutralization of the therapeutic ...protein as well as the endogenous human homologue. Controlling potential triggers of the immune system helps to minimize the immunogenicity of biopharmaceuticals, a crucial consideration in biopharmaceutical manufacturing. This review summarizes the latest advancements that have been made towards insight into the impact of structural characteristics on the immunogenicity of therapeutic proteins. Examples are given to illustrate the role of critical quality attributes, such as protein conformation, glycosylation, chemical modifications and aggregation, in immunogenicity. During the development of biopharmaceutical products, it is important to not just assess the risk for immunogenicity in clinical trials, but to ensure product quality throughout drug design, cell‐line selection, upstream and downstream processing, all the way to to the final product.
A major challenge for bringing biopharmaceuticals to the market is minimizing the formation of anti‐drug antibodies. To improve safety and efficacy of biopharmaceuticals, the critical quality attributes of proteins that affect immunogenicity need to be controlled. This review discusses the impact of protein structure, glycosylation, chemical modification and aggregation on immunogenicity in the current context of quality by design (QbD).
Astron.J. 127 (2004) 1555 We use 2MASS photometry to select blue horizontal branch (BHB) candidates
covering the sky |b|>15 deg. A 12.5<J<15.5 sample of BHB stars traces the thick
disk and inner halo ...to d<9 kpc, with a density comparable to that of M giant
stars. We base our sample selection strategy on the Century Survey Galactic
Halo Project, a survey that provides a complete, spectroscopically-identified
sample of blue stars to a similar depth as the 2MASS catalog. We show that a
-0.20<(J-H)_0<0.10, -0.10<(H-K)_0<0.10 color-selected sample of stars is 65%
complete for BHB stars, and is composed of 47% BHB stars. We apply this
photometric selection to the full 2MASS catalog, and see no spatial
overdensities of BHB candidates at high Galactic latitude |b|>50 deg. We insert
simulated star streams into the data and conclude that the high Galactic
latitude BHB candidates are consistent with having no ~5 deg wide star stream
with density greater than 0.33 objects deg^-2 at the 95% confidence level. The
absence of structure suggests there have been no major accretion events in the
inner halo in the last few Gyr. However, at low Galactic latitudes a two-point
angular correlation analysis reveals structure on angular scales <1 deg. This
structure is apparently associated with stars in the thick disk, and has a
physical scale of 10-100 pc. Interestingly, such structures are expected by
cosmological simulations that predict the majority of the thick disk may arise
from accretion and disruption of satellite mergers.
ABSTRACT We investigate anew the distribution of absolute carbon abundance, A(C) = log ϵ(C), for carbon-enhanced metal-poor (CEMP) stars in the halo of the Milky Way, based on high-resolution ...spectroscopic data for a total sample of 305 CEMP stars. The sample includes 147 CEMP-s (and CEMP-r/s) stars, 127 CEMP-no stars, and 31 CEMP stars that are unclassified, based on the currently employed Ba/Fe criterion. We confirm previous claims that the distribution of A(C) for CEMP stars is (at least) bimodal, with newly determined peaks centered on A(C) = 7.96 (the high-C region) and A(C) = 6.28 (the low-C region). A very high fraction of CEMP-s (and CEMP-r/s) stars belongs to the high-C region, while the great majority of CEMP-no stars resides in the low-C region. However, there exists complexity in the morphology of the A(C)-Fe/H space for the CEMP-no stars, a first indication that more than one class of first-generation stellar progenitors may be required to account for their observed abundances. The two groups of CEMP-no stars we identify exhibit clearly different locations in the A(Na)-A(C) and A(Mg)-A(C) spaces, also suggesting multiple progenitors. The clear distinction in A(C) between the CEMP-s (and CEMP-r/s) stars and the CEMP-no stars appears to be as successful, and likely more astrophysically fundamental, for the separation of these sub-classes as the previously recommended criterion based on Ba/Fe (and Ba/Eu) abundance ratios. This result opens the window for its application to present and future large-scale low- and medium-resolution spectroscopic surveys.
Huntington's disease (HD) is an autosomal-dominant inherited neurodegenerative disorder that is caused by expansion of a CAG-repeat tract in the huntingtin gene and characterized by motor impairment, ...cognitive decline, and neuropsychiatric disturbances. Neuropathological studies show that disease progression follows a characteristic pattern of brain atrophy, beginning in the basal ganglia structures. The HD Regulatory Science Consortium (HD-RSC) brings together diverse stakeholders in the HD community-biopharmaceutical industry, academia, nonprofit, and patient advocacy organizations-to define and address regulatory needs to accelerate HD therapeutic development. Here, the Biomarker Working Group of the HD-RSC summarizes the cross-sectional evidence indicating that regional brain volumes, as measured by volumetric magnetic resonance imaging, are reduced in HD and are correlated with disease characteristics. We also evaluate the relationship between imaging measures and clinical change, their longitudinal change characteristics, and within-individual longitudinal associations of imaging with disease progression. This analysis will be valuable in assessing pharmacodynamics in clinical trials and supporting clinical outcome assessments to evaluate treatment effects on neurodegeneration.
We present a high-resolution spectroscopic analysis of the
extremely-metal-poor star CS 22957-027, which Beers et al (1992) noted to
exhibit a rather strong G-band. For Teff = 4839 K, derived from ...broadband
photometry, our analysis obtains log g = 2.25, and a very low metallicity of
Fe/H=-3.43 +/- 0.12. The carbon-to-iron ratio is found to be enhanced by
about 2 dex relative to the solar value, similar to the handful of other
carbon-rich metal-deficient stars discussed by Norris et al (1997a) and Barbuy
et al (1997). From the 12C13C (1,0) Swan bandhead and 13CH lines the isotope
ratio 12C/13C is about 10, indicating a 13C enrichment. Nitrogen is also found
to be enhanced by about 1 dex. The s-process elements Sr and Ba are,
surprisingly, found to be under-abundant relative to solar, with Sr/Fe=-0.91
and Ba/Fe=-0.93. The star's low luminosity requires that the chemical
enrichment arises from mass transfer from an evolved companion, rather than
self-polluting dredge-up processes. However, the s-process elements Sr and Ba
are unusually low, with a solar ratio to one another, at variance with what
found in the ``classical'' CH stars. Finally we note that a feature due to 13CH
is present in coincidence with the Th II 401.9129 nm resonance line. The blend
is of relevance for the nucleo-chronology use of the Th II line in these
extremely metal poor stars, when significant 13C is present.
We have derived abundances of 33 elements and upper limits for 6 additional elements for the metal-poor (Fe/H = -2.42) turn-off star HE 0338-3945 from high-quality VLT-UVES spectra. The star is ...heavily enriched, by about a factor of 100 relative to iron and the Sun, in the heavy s-elements (Ba, La, ..). It is also heavily enriched in Eu, which is generally considered an r-element, and in other similar elements. It is less enriched, by about a factor of 10, in the lighter s-elements (Sr, Y and Zr). C is also strongly enhanced and, to a somewhat lesser degree, N and O. These abundance estimates are subject to severe uncertainties due to NLTE and thermal inhomogeneities which are not taken into detailed consideration. However, an interesting result, which is most probably robust in spite of these uncertainties, emerges: the abundances derived for this star are very similar to those of other stars with an overall enhancement of all elements beyond the iron peak. We have defined criteria for this class of stars, r+s stars, and discuss nine different scenarios to explain their origin. None of these explanations is found to be entirely convincing. The most plausible hypotheses involve a binary system in which the primary component goes through its giant branch and asymptotic giant branch phases and produces CNO and s-elements which are dumped onto the observed star. Whether the r-element Eu is produced by supernovae before the star was formed (perhaps triggering the formation of a low-mass binary), by a companion as it explodes as a supernova (possibly triggered by mass transfer), or whether it is possibly produced in a high-neutron-density version of the s-process is still unclear. Several suggestions are made on how to clarify this situation.
From high-resolution VLT/UVES spectra (R~43,000), we determine abundances or
upper limits for Li, C, N, O, and other important elements, as well as 12C/13C
isotopic ratio for three Carbon enhanced ...metal poor stars. All three stars have
-3.30 <= Fe/H <= -2.85 and moderate to high CNO abundances. CS 22958-042 is
one of the most carbon-rich CEMP stars known (C/Fe = +3.2), while CS
29528-041 (one of the few N-enhanced metal-poor stars known) is one of the most
nitrogen rich (N/Fe = +3.0). Oxygen is very high in CS 31080-095 (O/Fe =
+2.35) and in CS 22958-042 (O/Fe = +1.35). All three stars exhibit Sr/Fe <
0; Ba is not detected in CS 22958-042 (Ba/Fe < -0.53), but it is moderately
enhanced (Ba/Fe ~ 1) in the other two stars. CS 22958-042 displays one of the
largest sodium overabundances yet found in CEMP stars (Na/Fe = +2.8). CS
22958-042 has 12C/13C = 9, similar to most other CEMP stars without enhanced
neutron-capture elements, while 12C/13C <= 40 in CS 31080-095. CS 31080-095 and
CS 29528-041 have A(Li) ~ 1.7, below the Spite Plateau, while Li is not
detected in CS 22958-042. CS 22958-042 is a CEMP-no star, but the other two
stars are in no known class of CEMP star and thus either constitute a new class
or are a link between the CEMP-no and CEMP-s classes, adding complexity to the
abundance patterns for CEMP stars. We interpret the abundance patterns in our
stars to imply that current models for the presumed AGB binary progenitors lack
an extra-mixing process, similar to those apparently operating in RGB stars.
Mon.Not.Roy.Astron.Soc. 320 (2001) 451 The Edinburgh-Cape Blue Object Survey is an ongoing project to identify and
analyse a large sample of hot stars selected initially on the basis of
photographic ...colours (down to a magnitude limit B~18.0) over the entire
high-Galactic-latitude southern sky, then studied with broadband UBV photometry
and medium-resolution spectroscopy. Due to unavoidable errors in the initial
candidate selection, stars that are likely metal-deficient dwarfs and giants of
the halo and thick-disk populations are inadvertently included, yet are of
interest in their own right. In this paper we discuss a total of 206 candidate
metal-deficient dwarfs, subgiants, giants, and horizontal-branch stars with
photoelectric colours redder than (B-V)o = 0.3, and with available
spectroscopy. Radial velocities, accurate to ~10-15 km/s, are presented for all
of these stars. Spectroscopic metallicity estimates for these stars are
obtained using a recently re-calibrated relation between Ca II K-line strength
and (B-V)o colour. The identification of metal-poor stars from this
colour-selection technique is remarkably efficient, and competitive with
previous survey methods. An additional sample of 186 EC stars with
photoelectric colours in the range -0.4 < (B-V)o < 0.3, comprised primarily of
field horizontal-branch stars and other, higher-gravity, A- and B-type stars,
is also analysed. Estimates of the physical parameters Teff, log g, and Fe/H
are obtained for cooler members of this subsample, and a number of candidate RR
Lyrae variables are identified.
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