A CNO Dichotomy among O2 Giant Spectra in the Magellanic Clouds

From a survey of the 3400 Å region in the earliest O-type spectra, we have found that two of the four O2 giants observed in the Large Magellanic Cloud have O IV lines there that are stronger than the N IV lines, while the other two have the opposite. A Small Magellanic Cloud counterpart also has N IV stronger than O IV. Inspection of the blue spectra of these stars shows that the former pair have weaker N lines in all ionization states (III, IV, and V) present as well as lines of C IV λ4658, while the latter three have stronger N lines and greater He/H. Space ultraviolet observations of two of the N-strong stars show N V wind profiles substantially stronger than those of C IV, while in the N-weak stars the C IV features are equal to or stronger than the N V. The N-strong stars are now reclassified as ON2 III(f*), newly defining that category. These characteristics strongly suggest a larger fraction of processed material in the atmospheres of the ON2 stars, which we confirm by modeling the optical spectra. In the context of current models, it is in turn implied that the ON2 stars are in a more advanced evolutionary state than the others, and/or that they had higher initial rotational velocities. The recent formulation of the effects of rotation on massive stellar evolution introduces an additional fundamental parameter, which the CNO abundances are in principle able to constrain. We present some illustrative comparisons with current Geneva evolutionary models for rotating massive stars. It is possible that these very hot, nitrogen-rich objects are products of homogeneous evolution. Our results will provide motivation for further physical modeling of the atmospheres and evolutionary histories of the most massive hot stars.Fil: Walborn, Nolan Revere. Space Telescope Science Institute; Estados UnidosFil: Morrell, Nidia Irene. Las campanas observatory; ChileFil: Howarth, Ian D.. University College London; Estados UnidosFil: Crowther, Paul A.. University of Sheffield; Reino UnidoFil: Lennon, Daniel J.. Isaac Newton Group of Telescopes; EspañaFil: Massey, Philip. Lowell Observatory; Estados UnidosFil: Arias, Julia Ines. Universidad Nacional de la Plata. Facultad de Ciencias Astronómicas y Geofísicas; Argentin

Ablation of the Locus Coeruleus Increases Oxidative Stress in Tg-2576 Transgenic but Not Wild-Type Mice

Mice transgenic for production of excessive or mutant forms of beta-amyloid differ from patients with Alzheimer's disease in the degree of inflammation, oxidative damage, and alteration of intermediary metabolism, as well as the paucity or absence of neuronal atrophy and cognitive impairment. Previous observers have suggested that differences in inflammatory response reflect a discrepancy in the state of the locus coeruleus (LC), loss of which is an early change in Alzheimer's disease but which is preserved in the transgenic mice. In this paper, we extend these observations by examining the effects of the LC on markers of oxidative stress and intermediary metabolism. We compare four groups: wild-type or Tg2576 Aβ transgenic mice injected with DSP4 or vehicle. Of greatest interest were metabolites different between ablated and intact transgenics, but not between ablated and intact wild-type animals. The Tg2576_DSP4 mice were distinguished from the other three groups by oxidative stress and altered energy metabolism. These observations provide further support for the hypothesis that Tg2576 Aβ transgenic mice with this ablation may be a more congruent model of Alzheimer's disease than are transgenics with an intact LC

A CNO dichotomy among O2 giant spectra in the Magellanic Clouds

From a survey of the 3400 Å region in the earliest O-type spectra, we have found that two of the four O2 giants observed in the Large Magellanic Cloud have O IV lines there that are stronger than the N IV lines, while the other two have the opposite. A Small Magellanic Cloud counterpart also has N IV stronger than O IV. Inspection of the blue spectra of these stars shows that the former pair have weaker N lines in all ionization states (III, IV, and V) present as well as lines of C IV λ4658, while the latter three have stronger N lines and greater He/H. Space ultraviolet observations of two of the N-strong stars show N V wind profiles substantially stronger than those of C IV, while in the N-weak stars the C IV features are equal to or stronger than the N V. The N-strong stars are now reclassified as ON2 III(f *), newly defining that category. These characteristics strongly suggest a larger fraction of processed material in the atmospheres of the ON2 stars, which we confirm by modeling the optical spectra. In the context of current models, it is in turn implied that the ON2 stars are in a more advanced evolutionary state than the others, and/or that they had higher initial rotational velocities. The recent formulation of the effects of rotation on massive stellar evolution introduces an additional fundamental parameter, which the CNO abundances are in principle able to constrain. We present some illustrative comparisons with current Geneva evolutionary models for rotating massive stars. It is possible that these very hot, nitrogen-rich objects are products of homogeneous evolution. Our results will provide motivation for further physical modeling of the atmospheres and evolutionary histories of the most massive hot stars.Facultad de Ciencias Astronómicas y Geofísica

Sequence-based prediction for vaccine strain selection and identification of antigenic variability in foot-and-mouth disease virus

Identifying when past exposure to an infectious disease will protect against newly emerging strains is central to understanding the spread and the severity of epidemics, but the prediction of viral cross-protection remains an important unsolved problem. For foot-and-mouth disease virus (FMDV) research in particular, improved methods for predicting this cross-protection are critical for predicting the severity of outbreaks within endemic settings where multiple serotypes and subtypes commonly co-circulate, as well as for deciding whether appropriate vaccine(s) exist and how much they could mitigate the effects of any outbreak. To identify antigenic relationships and their predictors, we used linear mixed effects models to account for variation in pairwise cross-neutralization titres using only viral sequences and structural data. We identified those substitutions in surface-exposed structural proteins that are correlates of loss of cross-reactivity. These allowed prediction of both the best vaccine match for any single virus and the breadth of coverage of new vaccine candidates from their capsid sequences as effectively as or better than serology. Sub-sequences chosen by the model-building process all contained sites that are known epitopes on other serotypes. Furthermore, for the SAT1 serotype, for which epitopes have never previously been identified, we provide strong evidence - by controlling for phylogenetic structure - for the presence of three epitopes across a panel of viruses and quantify the relative significance of some individual residues in determining cross-neutralization. Identifying and quantifying the importance of sites that predict viral strain cross-reactivity not just for single viruses but across entire serotypes can help in the design of vaccines with better targeting and broader coverage. These techniques can be generalized to any infectious agents where cross-reactivity assays have been carried out. As the parameterization uses pre-existing datasets, this approach quickly and cheaply increases both our understanding of antigenic relationships and our power to control disease

Simultaneous non-negative matrix factorization for multiple large scale gene expression datasets in toxicology

Non-negative matrix factorization is a useful tool for reducing the dimension of large datasets. This work considers simultaneous non-negative matrix factorization of multiple sources of data. In particular, we perform the first study that involves more than two datasets. We discuss the algorithmic issues required to convert the approach into a practical computational tool and apply the technique to new gene expression data quantifying the molecular changes in four tissue types due to different dosages of an experimental panPPAR agonist in mouse. This study is of interest in toxicology because, whilst PPARs form potential therapeutic targets for diabetes, it is known that they can induce serious side-effects. Our results show that the practical simultaneous non-negative matrix factorization developed here can add value to the data analysis. In particular, we find that factorizing the data as a single object allows us to distinguish between the four tissue types, but does not correctly reproduce the known dosage level groups. Applying our new approach, which treats the four tissue types as providing distinct, but related, datasets, we find that the dosage level groups are respected. The new algorithm then provides separate gene list orderings that can be studied for each tissue type, and compared with the ordering arising from the single factorization. We find that many of our conclusions can be corroborated with known biological behaviour, and others offer new insights into the toxicological effects. Overall, the algorithm shows promise for early detection of toxicity in the drug discovery process

Illumination in symbiotic binary stars: Non-LTE photoionization models. II. Wind case

We describe a non-LTE photoionization code to calculate the wind structure and emergent spectrum of a red giant wind illuminated by the hot component of a symbiotic binary system. We consider spherically symmetric winds with several different velocity and temperature laws and derive predicted line fluxes as a function of the red giant mass loss rate, \mdot. Our models generally match observations of the symbiotic stars EG And and AG Peg for \mdot about 10^{-8} \msunyr to 10^{-7} \msunyr. The optically thick cross- section of the red giant wind as viewed from the hot component is a crucial parameter in these models. Winds with cross-sections of 2--3 red giant radii reproduce the observed fluxes, because the wind density is then high, about 10^9 cm^{-3}. Our models favor winds with acceleration regions that either lie far from the red giant photosphere or extend for 2--3 red giant radii.Comment: 51 pages, LaTeX including three tables, requires 15 Encapsulated Postscript figures, to appear in Ap

Association of Fidaxomicin with C. difficile spores: Effects of Persistence on Subsequent Spore Recovery, Outgrowth and Toxin Production.

Background: We have previously shown that fidaxomicin instillation prevents spore recovery in an in-vitro gut model, whereas vancomycin does not. The reasons for this are unclear. Here, we have investigated persistence of fidaxomicin and vancomycin on C. difficile spores, and examined post-antibiotic exposure spore recovery, outgrowth and toxin production. Methods: Prevalent UK C. difficile ribotypes (n=10) were incubated with 200mg/L fidaxomicin, vancomycin or a non-antimicrobial containing control for 1 h in faecal filtrate or Phosphate Buffered Saline. Spores were washed three times with faecal filtrate or phosphate buffered saline, and residual spore-associated antimicrobial activity was determined by bioassay. For three ribotypes (027, 078, 015), antimicrobial-exposed, faecal filtrate-washed spores and controls were inoculated into broth. Viable vegetative and spore counts were enumerated on CCEYL agar. Percentage phase bright spores, phase dark spores and vegetative cells were enumerated by phase contrast microscopy at 0, 3, 6, 24 and 48 h post-inoculation. Toxin levels (24 and 48h) were determined by cell cytotoxicity assay. Results: Fidaxomicin, but not vancomycin persisted on spores of all ribotypes following washing in saline (mean=10.1mg/L; range= 4.0-14mg/L) and faecal filtrate (mean =17.4mg/L; 8.4-22.1mg/L). Outgrowth and proliferation rates of vancomycin-exposed spores were similar to controls, whereas fidaxomicin-exposed spores showed no vegetative cell growth after 24 and 48 h. At 48h, toxin levels averaged 3.7 and 3.3 relative units (RU) in control and vancomycin-exposed samples, respectively, but were undetectable in fidaxomicin-exposed samples. Conclusion: Fidaxomicin persists on C. difficile spores, whereas vancomycin does not. This persistence prevents subsequent growth and toxin production in vitro. This may have implications on spore viability, thereby impacting CDI recurrence and transmission rates

A CNO dichotomy among O2 giant spectra in the Magellanic Clouds

From a survey of the 3400 Å region in the earliest O-type spectra, we have found that two of the four O2 giants observed in the Large Magellanic Cloud have O IV lines there that are stronger than the N IV lines, while the other two have the opposite. A Small Magellanic Cloud counterpart also has N IV stronger than O IV. Inspection of the blue spectra of these stars shows that the former pair have weaker N lines in all ionization states (III, IV, and V) present as well as lines of C IV λ4658, while the latter three have stronger N lines and greater He/H. Space ultraviolet observations of two of the N-strong stars show N V wind profiles substantially stronger than those of C IV, while in the N-weak stars the C IV features are equal to or stronger than the N V. The N-strong stars are now reclassified as ON2 III(f *), newly defining that category. These characteristics strongly suggest a larger fraction of processed material in the atmospheres of the ON2 stars, which we confirm by modeling the optical spectra. In the context of current models, it is in turn implied that the ON2 stars are in a more advanced evolutionary state than the others, and/or that they had higher initial rotational velocities. The recent formulation of the effects of rotation on massive stellar evolution introduces an additional fundamental parameter, which the CNO abundances are in principle able to constrain. We present some illustrative comparisons with current Geneva evolutionary models for rotating massive stars. It is possible that these very hot, nitrogen-rich objects are products of homogeneous evolution. Our results will provide motivation for further physical modeling of the atmospheres and evolutionary histories of the most massive hot stars.Facultad de Ciencias Astronómicas y Geofísica

Searching for WR stars in I Zw 18 -- The origin of HeII emission

I Zw 18 is the most metal poor star-forming galaxy known and is an ideal laboratory to probe stellar evolution theory at low metallicities. Using archival HST WFPC2 imaging and FOS spectroscopy we were able to improve previous studies. We constructed a continuum free HeII map, which was used to identify Wolf-Rayet (WR) stars recently found by ground-based spectroscopy and to locate diffuse nebular emission. Most of the HeII emission is associated with the NW stellar cluster, clearly displaced from the surrounding shell-like [OIII] and Halpha emission. We found evidence for HeII sources, compatible with 5--9 WNL stars and/or compact nebular HeII emission, as well as residual diffuse emission. Only one of them is outside the NW cluster. We have calculated evolutionary tracks for massive stars and synthesis models at the appropriate metallicity (Z ~ 0.02 Zsun). These single star models predict a mass limit M_WR ~ 90 Msun for WR stars to become WN and WC/WO. For an instantaneous burst model with a Salpeter IMF extending up to M_up ~ 120-150 Msun our model predictions are in reasonable agreement with the observed equivalent widths. Our model is also able to fully reproduce the observed equivalent widths of nebular HeII emission due to the presence of WC/WO stars. This quantitative agreement and the spatial correlation of nebular HeII with the stellar cluster and the position of WR stars shown from the ground-based spectra further supports the hypothesis that WR stars are responsible for nebular HeII emission in extra-galactic HII regions. (Abridged abstract)Comment: Accepted by ApJ. LaTeX using aas2pp4, psfigs macros. 23 pages including 6 figures. Paper and figures also separately available at http://www.obs-mip.fr/omp/astro/people/schaerer