The Age of the Milky Way Inner Halo

The Milky Way galaxy is observed to have multiple components with distinct properties, such as the bulge, disk, and halo. Unraveling the assembly history of these populations provides a powerful test to the theory of galaxy formation and evolution, but is often restricted due to difficulties in measuring accurate stellar ages for low mass, hydrogen-burning stars. Unlike these progenitors, the "cinders" of stellar evolution, white dwarf stars, are remarkably simple objects and their fundamental properties can be measured with little ambiguity from spectroscopy. Here I report observations and analysis of newly formed white dwarf stars in the halo of the Milky Way, and a comparison to published analysis of white dwarfs in the well-studied 12.5 billion-year-old globular cluster Messier 4. From this, I measure the mass distribution of the remnants and invert the stellar evolution process to develop a new relation that links this final stellar mass to the mass of their immediate progenitors, and therefore to the age of the parent population. By applying this technique to a small sample of four nearby and kinematically-confirmed halo white dwarfs, I measure the age of local field halo stars to be 11.4 +/- 0.7 billion years. This age is directly tied to the globular cluster age scale, on which the oldest clusters formed 13.5 billion years ago. Future (spectroscopic) observations of newly formed white dwarfs in the Milky Way halo can be used to reduce the present uncertainty, and to probe relative differences between the formation time of the last clusters and the inner halo.Comment: Published in Nature, 2012, 486, 90. Second version corrects a missing reference (#10) in the third paragraph and Figure 1 captio

Automated array-CGH optimized for archival formalin-fixed, paraffin-embedded tumor material

BACKGROUND: Array Comparative Genomic Hybridization (aCGH) is a rapidly evolving technology that still lacks complete standardization. Yet, it is of great importance to obtain robust and reproducible data to enable meaningful multiple hybridization comparisons. Special difficulties arise when aCGH is performed on archival formalin-fixed, paraffin-embedded (FFPE) tissue due to its variable DNA quality. Recently, we have developed an effective DNA quality test that predicts suitability of archival samples for BAC aCGH. METHODS: In this report, we first used DNA from a cancer cell-line (SKBR3) to optimize the aCGH protocol for automated hybridization, and subsequently optimized and validated the procedure for FFPE breast cancer samples. We aimed for highest throughput, accuracy, and reproducibility applicable to FFPE samples, which can also be important in future diagnostic use. RESULTS: Our protocol of automated array-CGH on archival FFPE ULS-labeled DNA showed very similar results compared with published data and our previous manual hybridization method. CONCLUSION: This report combines automated aCGH on unamplified archival FFPE DNA using non-enzymatic ULS labeling, and describes an optimized protocol for this combination resulting in improved quality and reproducibility

Exploring the Universe with Metal-Poor Stars

The early chemical evolution of the Galaxy and the Universe is vital to our understanding of a host of astrophysical phenomena. Since the most metal-poor Galactic stars (with metallicities down to [Fe/H]\sim-5.5) are relics from the high-redshift Universe, they probe the chemical and dynamical conditions of the Milky Way and the origin and evolution of the elements through nucleosynthesis. They also provide constraints on the nature of the first stars, their associated supernovae and initial mass function, and early star and galaxy formation. The Milky Way's dwarf satellites contain a large fraction (~30%) of the known most metal-poor stars that have chemical abundances that closely resemble those of equivalent halo stars. This suggests that chemical evolution may be universal, at least at early times, and that it is driven by massive, energetic SNe. Some of these surviving, ultra-faint systems may show the signature of just one such PopIII star; they may even be surviving first galaxies. Early analogs of the surviving dwarfs may thus have played an important role in the assembly of the old Galactic halo whose formation can now be studied with stellar chemistry. Following the cosmic evolution of small halos in simulations of structure formation enables tracing the cosmological origin of the most metal-poor stars in the halo and dwarf galaxies. Together with future observations and additional modeling, many of these issues, including the reionization history of the Milky Way, may be constrained this way. The chapter concludes with an outlook about upcoming observational challenges and ways forward is to use metal-poor stars to constrain theoretical studies.Comment: 34 pages, 11 figures. Book chapter to appear in "The First Galaxies - Theoretical Predictions and Observational Clues", 2012 by Springer, eds. V. Bromm, B. Mobasher, T. Wiklin

Two Stellar Components in the Halo of the Milky Way

The halo of the Milky Way provides unique elemental abundance and kinematic information on the first objects to form in the Universe, which can be used to tightly constrain models of galaxy formation and evolution. Although the halo was once considered a single component, evidence for its dichotomy has slowly emerged in recent years from inspection of small samples of halo objects. Here we show that the halo is indeed clearly divisible into two broadly overlapping structural components -- an inner and an outer halo -- that exhibit different spatial density profiles, stellar orbits and stellar metallicities (abundances of elements heavier than helium). The inner halo has a modest net prograde rotation, whereas the outer halo exhibits a net retrograde rotation and a peak metallicity one-third that of the inner halo. These properties indicate that the individual halo components probably formed in fundamentally different ways, through successive dissipational (inner) and dissipationless (outer) mergers and tidal disruption of proto-Galactic clumps.Comment: Two stand-alone files in manuscript, concatenated together. The first is for the main paper, the second for supplementary information. The version is consistent with the version published in Natur

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

Saccadic Eye Movements Minimize the Consequences of Motor Noise

The durations and trajectories of our saccadic eye movements are remarkably stereotyped. We have no voluntary control over these properties but they are determined by the movement amplitude and, to a smaller extent, also by the movement direction and initial eye orientation. Here we show that the stereotyped durations and trajectories are optimal for minimizing the variability in saccade endpoints that is caused by motor noise. The optimal duration can be understood from the nature of the motor noise, which is a combination of signal-dependent noise favoring long durations, and constant noise, which prefers short durations. The different durations of horizontal vs. vertical and of centripetal vs. centrifugal saccades, and the somewhat surprising properties of saccades in oblique directions are also accurately predicted by the principle of minimizing movement variability. The simple and sensible principle of minimizing the consequences of motor noise thus explains the full stereotypy of saccadic eye movements. This suggests that saccades are so stereotyped because that is the best strategy to minimize movement errors for an open-loop motor system

Ablation of Proliferating Cells in the CNS Exacerbates Motor Neuron Disease Caused by Mutant Superoxide Dismutase

Proliferation of glia and immune cells is a common pathological feature of many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Here, to investigate the role of proliferating cells in motor neuron disease, SOD1G93A transgenic mice were treated intracerebroventicularly (ICV) with the anti-mitotic drug cytosine arabinoside (Ara-C). ICV delivery of Ara-C accelerated disease progression in SOD1G93A mouse model of ALS. Ara-C treatment caused substantial decreases in the number of microglia, NG2+ progenitors, Olig2+ cells and CD3+ T cells in the lumbar spinal cord of symptomatic SOD1G93A transgenic mice. Exacerbation of disease was also associated with significant alterations in the expression inflammatory molecules IL-1β, IL-6, TGF-β and the growth factor IGF-1

Using Strategic Movement to Calibrate a Neural Compass: A Spiking Network for Tracking Head Direction in Rats and Robots

The head direction (HD) system in mammals contains neurons that fire to represent the direction the animal is facing in its environment. The ability of these cells to reliably track head direction even after the removal of external sensory cues implies that the HD system is calibrated to function effectively using just internal (proprioceptive and vestibular) inputs. Rat pups and other infant mammals display stereotypical warm-up movements prior to locomotion in novel environments, and similar warm-up movements are seen in adult mammals with certain brain lesion-induced motor impairments. In this study we propose that synaptic learning mechanisms, in conjunction with appropriate movement strategies based on warm-up movements, can calibrate the HD system so that it functions effectively even in darkness. To examine the link between physical embodiment and neural control, and to determine that the system is robust to real-world phenomena, we implemented the synaptic mechanisms in a spiking neural network and tested it on a mobile robot platform. Results show that the combination of the synaptic learning mechanisms and warm-up movements are able to reliably calibrate the HD system so that it accurately tracks real-world head direction, and that calibration breaks down in systematic ways if certain movements are omitted. This work confirms that targeted, embodied behaviour can be used to calibrate neural systems, demonstrates that ‘grounding’ of modelled biological processes in the real world can reveal underlying functional principles (supporting the importance of robotics to biology), and proposes a functional role for stereotypical behaviours seen in infant mammals and those animals with certain motor deficits. We conjecture that these calibration principles may extend to the calibration of other neural systems involved in motion tracking and the representation of space, such as grid cells in entorhinal cortex

Detection and characterization of subvisible aggregates of monoclonal lgG in serum

To detect and characterize the aggregation of therapeutic monoclonal antibodies in undiluted biological fluids. Fluorescently labeled subvisible IgG aggregates formed by applying either heat stress or by pH-shift were investigated immediately after addition to human serum, and after 24 h. Unstressed and stressed IgG formulations were analyzed by fluorescence single particle tracking, confocal laser scanning microscopy and flow cytometry. Unstressed formulations remained free from subvisible aggregates in serum, whereas heat-stressed and pH-shift stressed formulations showed dissimilar aggregation behaviors. The aggregation profile of the heat-stressed formulation diluted in serum remained practically the same as the one diluted in buffer, even after the 24 h incubation period. The pH-shift stressed formulation had strikingly smaller and more numerous subvisible aggregates immediately after dilution in serum compared to buffer. These aggregates became noticeably larger in both diluents after 24 h, but in serum they appeared to be formed by other types of constituents than the labeled protein itself. These results show that subvisible therapeutic protein aggregates may undergo changes in number, type and size distribution upon contact with human serum. This emphasizes the importance of analytical strategies for monitoring aggregation in undiluted biological fluids

Homogeneous analysis of globular clusters from the APOGEE survey with the BACCHUS code – II. The Southern clusters and overview

We investigate the Fe, C, N, O, Mg, Al, Si, K, Ca, Ce, and Nd abundances of 2283 red giant stars in 31 globular clusters from high-resolution spectra observed in both the Northern and Southern hemisphere by the SDSS-IV APOGEE-2 survey. This unprecedented homogeneous data set, largest to date, allows us to discuss the intrinsic Fe spread, the shape, and statistics of Al-Mg and N-C anti-correlations as a function of cluster mass, luminosity, age, and metallicity for all 31 clusters. We find that the Fe spread does not depend on these parameters within our uncertainties including cluster metallicity, contradicting earlier observations. We do not confirm the metallicity variations previously observed in M22 and NGC 1851. Some clusters show a bimodal Al distribution, while others exhibit a continuous distribution as has been previously reported in the literature. We confirm more than two populations in ω Cen and NGC 6752, and find new ones in M79. We discuss the scatter of Al by implementing a correction to the standard chemical evolution of Al in the Milky Way. After correction, its dependence on cluster mass is increased suggesting that the extent of Al enrichment as a function of mass was suppressed before the correction. We observe a turnover in the Mg-Al anticorrelation at very low Mg in ω Cen, similar to the pattern previously reported in M15 and M92. ω Cen may also have a weak K-Mg anticorrelation, and if confirmed, it would be only the third cluster known to show such a pattern