Interstellar Ti II in the Milky Way and Magellanic Clouds

We discuss several sets of Ti II absorption-line data, which probe a variety of interstellar environments in our Galaxy and in the Magellanic Clouds. Comparisons of high-resolution (FWHM ~ 1.3-1.5 km/s) Ti II spectra of Galactic targets with corresponding high-resolution spectra of Na I, K I, and Ca II reveal both similarities and differences in the detailed structure of the absorption-line profiles -- reflecting component-to-component differences in the ionization and depletion behaviour of those species. Moderate-resolution (FWHM ~ 3.4-4.5 km/s) spectra of more heavily reddened Galactic stars provide more extensive information on the titanium depletion in colder, denser clouds -- where more than 99.9 per cent of the Ti may be in the dust phase. Moderate-resolution (FWHM ~ 4.5-8.7 km/s) spectra of stars in the Magellanic Clouds suggest that the titanium depletion is generally much less severe in the LMC and SMC than in our Galaxy [for a given N(H_tot), E(B-V), or molecular fraction f(H_2)] -- providing additional evidence for differences in depletion patterns in those two lower-metallicity galaxies. We briefly discuss possible implications of these results for the interpretation of gas-phase abundances in QSO absorption-line systems and of variations in the D/H ratio in the local Galactic ISM.Comment: 56 pages, 26 figures, accepted to MNRA

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

Developmental trends in voice onset time: some evidence for sex differences

This study reports on an investigation into the voice onset time (VOT) patterns of the plosives /p b t d/ in a group of 30 children aged 7 (n = 10), 9 (n = 10) and 11 (n = 10) years. Equal numbers of girls and boys participated in the study. Each child named a series of letter objects to elicit /p b t d/ in a syllable onset position with a fixed vowel context. VOT data were examined for age, sex and plosive differences with the following hypotheses: Firstly, that there would be sex differences in the VOT patterns of preadolescent children. Secondly, that the sex differences in VOT patterns would be linked to age and development, and that these would eventually become marked by the age of 11 years, by which time adult-like VOT values should have been achieved. Finally, that the extent of sex and age differences would be dependent upon the plosive being investigated. Results indicated patterns of decrease with age in the VOT values of /p b/ for the boys, with some evidence of increases in the VOT values of /t/ for the girls. In addition, 'voiced' and 'voiceless' cognates showed a more marked bimodal distribution in the girls' VOT patterns. This bimodal distribution was investigated by examining the degree of difference between the VOT values of voiced and voiceless cognate pairs /p b/ and /t d/, and examining the effects of age, sex and cognate pair. These results indicated that more marked sex differences in the 'voiced'/'voiceless' contrast emerged between the data of the 9- and 11-year-olds, a pattern, which was more marked for the alveolar plosives. These preliminary results confirmed all three hypotheses. The findings are presented and discussed both within a developmental and sociophonetic framework

Multivariate generalised linear mixed-effects models for analysis of clinical trial-based cost-effectiveness data

Economic evaluations conducted alongside randomized controlled trials are a popular vehicle for generating high-quality evidence on the incremental cost-effectiveness of competing health care interventions. Typically, in these studies, resource use (and by extension, economic costs) and clinical (or preference-based health) outcomes data are collected prospectively for trial participants to estimate the joint distribution of incremental costs and incremental benefits associated with the intervention. In this article, we extend the generalized linear mixed-model framework to enable simultaneous modeling of multiple outcomes of mixed data types, such as those typically encountered in trial-based economic evaluations, taking into account correlation of outcomes due to repeated measurements on the same individual and other clustering effects. We provide new wrapper functions to estimate the models in Stata and R by maximum and restricted maximum quasi-likelihood and compare the performance of the new routines with alternative implementations across a range of statistical programming packages. Empirical applications using observed and simulated data from clinical trials suggest that the new methods produce broadly similar results as compared with Stata’s merlin and gsem commands and a Bayesian implementation in WinBUGS. We highlight that, although these empirical applications primarily focus on trial-based economic evaluations, the new methods presented can be generalized to other health economic investigations characterized by multivariate hierarchical data structures

Cln5 represents a new type of cysteine-based S-depalmitoylase linked to neurodegeneration

Genetic CLN5 variants are associated with childhood neurodegeneration and Alzheimer’s disease; however, the molecular function of ceroid lipofuscinosis neuronal protein 5 (Cln5) is unknown. We solved the Cln5 crystal structure and identified a region homologous to the catalytic domain of members of the N1pC/P60 superfamily of papain-like enzymes. However, we observed no protease activity for Cln5; and instead, we discovered that Cln5 and structurally related PPPDE1 and PPPDE2 have efficient cysteine palmitoyl thioesterase (S-depalmitoylation) activity using fluorescent substrates. Mutational analysis revealed that the predicted catalytic residues histidine-166 and cysteine-280 are critical for Cln5 thioesterase activity, uncovering a new cysteine-based catalytic mechanism for S-depalmitoylation enzymes. Last, we found that Cln5-deficient neuronal progenitor cells showed reduced thioesterase activity, confirming live cell function of Cln5 in setting S-depalmitoylation levels. Our results provide new insight into the function of Cln5, emphasize the importance of S-depalmitoylation in neuronal homeostasis, and disclose a new, unexpected enzymatic function for the N1pC/P60 superfamily of proteins

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

The use of artificial media in fungal ecology

Can experiments conducted in agar really help us to understand the complexity of fungal systems? This question has been the focus of persistent and ongoing debate between fungal ecologists that favor reductionist versus holistic approaches. On one hand, artificial media are unrealistic and fail to reflect the heterogeneity and complexity of natural systems. But on the other hand, they offer simplified model systems that allow us to isolate mechanisms that would otherwise be obscured in natural systems. Following various technological advances that enable us to describe various aspects of complex fungal communities in situ, the dial appears to be tipping in favor of observational field studies, and the use of artificial media has declined. However, we argue that the loss of artificial media from experimental studies would impair our capacity to disentangle the complexities of fungal communities. Here, we discuss the pros and cons of artificial media in fungal ecology and outline the types of questions that are best addressed using fungi growing in artificial media. We conclude that renewed emphasis on the value of artificial media could help us to generate the mechanistic understanding that might be critical to explaining the exciting patterns that are emerging from real-world fungal ecology studies

Focused and Deep Brain Magnetic Stimulation Using New Coil Design in Mice

Deep brain transcranial magnetic stimulation (TMS) offers promising treatment for neurological disorders that originate from deeper regions of the brain, such as Parkinson\u27s disease. Coils designed for the human head need significant redesigning to stimulate selective regions of the mouse brain for advanced TMS therapy analysis. We report a focused and deep brain TMS coil for mice that is based on a two coil configuration similar to the \u27Halo coil\u27. A heterogeneous MRI derived head model of mouse was used to obtain an electric field of about 150 V/m in selective deeper regions of the brain. Focality of stimulation was quantified using the ratio of half value volume to half value of depth of electric field. A prototype of the final coil design was fabricated and characterized to compare simulated and physical magnetic field profiles