The GALAH survey: scientific motivation De Silva, G. M; Freeman, K. C; Bland-Hawthorn, J ...
Monthly Notices of the Royal Astronomical Society,
05/2015, Letnik:
449, Številka:
3
Journal Article
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The Galactic Archaeology with HERMES (GALAH) survey is a large high-resolution spectroscopic survey using the newly commissioned High Efficiency and Resolution Multi-Element Spectrograph (HERMES) on ...the Anglo-Australian Telescope. The HERMES spectrograph provides high-resolution (R ∼ 28 000) spectra in four passbands for 392 stars simultaneously over a 2 deg field of view. The goal of the survey is to unravel the formation and evolutionary history of the Milky Way, using fossil remnants of ancient star formation events which have been disrupted and are now dispersed throughout the Galaxy. Chemical tagging seeks to identify such dispersed remnants solely from their common and unique chemical signatures; these groups are unidentifiable from their spatial, photometric or kinematic properties. To carry out chemical tagging, the GALAH survey will acquire spectra for a million stars down to V ∼ 14. The HERMES spectra of FGK stars contain absorption lines from 29 elements including light proton-capture elements, α-elements, odd-Z elements, iron-peak elements and n-capture elements from the light and heavy s-process and the r-process. This paper describes the motivation and planned execution of the GALAH survey, and presents some results on the first-light performance of HERMES.
The Anglo-Australian Observatory 2dF facility Lewis, I. J.; Cannon, R. D.; Taylor, K. ...
Monthly Notices of the Royal Astronomical Society,
06/2002, Letnik:
333, Številka:
2
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The 2dF (Two-degree Field) facility at the prime focus of the Anglo-Australian Telescope provides multiple-object spectroscopy over a 2° field of view. Up to 400 target fibres can be independently ...positioned by a complex robot. Two spectrographs provide spectra with resolutions of between 500 and 2000, over wavelength ranges of 440 and 110 nm respectively. The 2dF facility began routine observations in 1997. 2dF was designed primarily for galaxy redshift surveys and has a number of innovative features. The large corrector lens incorporates an atmospheric dispersion compensator, essential for wide wavelength coverage with small-diameter fibres. The instrument has two full sets of fibres on separate field plates, so that re-configuring can be done in parallel with observing. The robot positioner places one fibre every 6 s, to a precision of 0.3 arcsec (20 μm) over the full field. All components of 2dF, including the spectrographs, are mounted on a 5-m diameter telescope top end ring for ease of handling and to keep the optical fibres short in order to maximize UV throughput. There is a pipeline data reduction system which allows each data set to be fully analysed while the next field is being observed. 2dF has achieved its initial astronomical goals. The redshift surveys obtain spectra at the rate of 2500 galaxies per night, yielding a total of about 200 000 objects in the first four years. Typically a B=19 galaxy gives a spectrum with a signal-to-noise ratio of better than 10 per pixel in less than an hour; redshifts are derived for about 95 per cent of all galaxies, with 99 per cent reliability or better. Total system throughput is about 5 per cent. The failure rate of the positioner and fibre system is about 1:10 000 moves or once every few nights, and recovery time is usually short. In this paper we provide the historical background to the 2dF facility, the design philosophy, a full technical description and a summary of the performance of the instrument. We also briefly review its scientific applications and possible future developments.
Programmable nucleases, such as Cas9, are used for precise genome editing by homology-dependent repair (HDR). However, HDR efficiency is constrained by competition from other double-strand break ...(DSB) repair pathways, including non-homologous end-joining (NHEJ). We report the discovery of a genetically encoded inhibitor of 53BP1 that increases the efficiency of HDR-dependent genome editing in human and mouse cells. 53BP1 is a key regulator of DSB repair pathway choice in eukaryotic cells and functions to favor NHEJ over HDR by suppressing end resection, which is the rate-limiting step in the initiation of HDR. We screened an existing combinatorial library of engineered ubiquitin variants for inhibitors of 53BP1. Expression of one variant, named i53 (inhibitor of 53BP1), in human and mouse cells, blocked accumulation of 53BP1 at sites of DNA damage and improved gene targeting and chromosomal gene conversion with either double-stranded DNA or single-stranded oligonucleotide donors by up to 5.6-fold. Inhibition of 53BP1 is a robust method to increase efficiency of HDR-based precise genome editing.
Organophosphate (OP) pesticides are widely used in agriculture. While acute cholinergic toxicity has been extensively studied, chronic effects on other neurons are less understood. Here, we ...demonstrated that the OP pesticide chlorpyrifos (CPF) and its oxon metabolite are dopaminergic neurotoxicants in Caenorhabditis elegans. CPF treatment led to inhibition of mitochondrial complex II, II + III, and V in rat liver mitochondria, while CPF-oxon did not (complex II + III and IV inhibition observed only at high doses). While the effect on C. elegans cholinergic behavior was mostly reversible with toxicant washout, dopamine-associated deficits persisted, suggesting dopaminergic neurotoxicity was irreversible. CPF reduced the mitochondrial content in a dose-dependent manner and the fat modulatory genes cyp-35A2 and cyp-35A3 were found to have a key role in CPF neurotoxicity. These findings were consistent with in vitro effects of CPF and CPF-oxon on nuclear receptor signaling and fatty acid/steroid metabolism observed in ToxCast assays. Two-way hierarchical analysis revealed in vitro effects on estrogen receptor, pregnane X receptor, and peroxisome proliferator-activated receptor gamma pathways as well as neurotoxicity of CPF, malathion, and diazinon, whereas these effects were not detected in malaoxon and diazoxon. Taken together, our study suggests that mitochondrial toxicity and metabolic effects of CPF, but not CPF-oxon, have a key role of CPF neurotoxicity in the low-dose, chronic exposure. Further mechanistic studies are needed to examine mitochondria as a common target for all OP pesticide parent compounds, because this has important implications on cumulative pesticide risk assessment.
The aims of this study were to investigate the clinical effectiveness and patient acceptability of a modified glass ionomer cement placed using the atraumatic restorative treatment (ART) technique to ...treat root caries, and to carry out microbiological analysis of the restored sites. Two clinically visible root surface carious lesions per participant were restored using ART. One was restored with commercial glass ionomer cement (GIC) (ChemFil® Superior, DENTSPLY, Konstonz, Germany) which acted as the control. The other carious root lesion was restored with the same GIC modified with 5% chlorhexidine digluconate (GIC-CHX; test). Patient acceptability and restoration survival rate were evaluated at baseline and after 6 months. Plaque and saliva samples around the test and control restorations were collected, and microbiological analysis for selected bacterial and fungal viability were completed at baseline, and after 1, 3, and 6 months. In total, 52 restorations were placed using GIC and GIC-CHX in 26 participants; 1 patient was lost to follow-up. After reviewing the restorations during their baseline appointments, participants indicated that they were satisfied with the appearance of the restorations (n = 25, 96%) and did not feel anxious during the procedure (n = 24, 92%). Forty-eight percent (n = 12) of the GIC-CHX restorations were continuous with the existing anatomic form as opposed to six for the GIC restorations (24%), a difference which was statistically significant (p = 0.036). There was no statistically significant reduction in the mean count of the tested microorganisms in plaque samples for either type of restorations after 1, 3, or 6 months. Restoration of carious root surfaces with GIC-CHX resulted in higher survival rates than the control GIC. ART using GIC-CHX may therefore be a viable approach for use in outreach dental services to restore root surface carious lesions where dental services are not readily available, and for older people and special needs groups.
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•Reliable calculation of relative binding free energy changes for most protein mutations to within ∼1 kcal/mol.•Automated Protein FEP+ Groups treatment of alternate protonation states ...for titratable residues.•Application of FEP+ methodology to “real-world” protein design projects.
Computational free energy-based methods have the potential to significantly improve throughput and decrease costs of protein design efforts. Such methods must reach a high level of reliability, accuracy, and automation to be effectively deployed in practical industrial settings in a way that impacts protein design projects. Here, we present a benchmark study for the calculation of relative changes in protein–protein binding affinity for single point mutations across a variety of systems from the literature, using free energy perturbation (FEP+) calculations. We describe a method for robust treatment of alternate protonation states for titratable amino acids, which yields improved correlation with and reduced error compared to experimental binding free energies. Following careful analysis of the largest outlier cases in our dataset, we assess limitations of the default FEP+ protocols and introduce an automated script which identifies probable outlier cases that may require additional scrutiny and calculates an empirical correction for a subset of charge-related outliers. Through a series of three additional case study systems, we discuss how Protein FEP+ can be applied to real-world protein design projects, and suggest areas of further study.
On April 1st, 2019, the Advanced Laser Interferometer Gravitational-Wave Observatory (aLIGO), joined by the Advanced Virgo detector, began the third observing run, a year-long dedicated search for ...gravitational radiation. The LIGO detectors have achieved a higher duty cycle and greater sensitivity to gravitational waves than ever before, with LIGO Hanford achieving angle-averaged sensitivity to binary neutron star coalescences to a distance of 111 Mpc, and LIGO Livingston to 134 Mpc with duty factors of 74.6% and 77.0% respectively. The improvement in sensitivity and stability is a result of several upgrades to the detectors, including doubled intracavity power, the addition of an in-vacuum optical parametric oscillator for squeezed-light injection, replacement of core optics and end reaction masses, and installation of acoustic mode dampers. This paper explores the purposes behind these upgrades, and explains to the best of our knowledge the noise currently limiting the sensitivity of each detector.
The Laser Interferometer Gravitational Wave Observatory (LIGO) has been directly detecting gravitational waves from compact binary mergers since 2015. We report on the first use of squeezed vacuum ...states in the direct measurement of gravitational waves with the Advanced LIGO H1 and L1 detectors. This achievement is the culmination of decades of research to implement squeezed states in gravitational-wave detectors. During the ongoing O3 observation run, squeezed states are improving the sensitivity of the LIGO interferometers to signals above 50 Hz by up to 3 dB, thereby increasing the expected detection rate by 40% (H1) and 50% (L1).
Abstract
The characterization of the Advanced LIGO detectors in the second and third observing runs has increased the sensitivity of the instruments, allowing for a higher number of detectable ...gravitational-wave signals, and provided confirmation of all observed gravitational-wave events. In this work, we present the methods used to characterize the LIGO detectors and curate the publicly available datasets, including the LIGO strain data and data quality products. We describe the essential role of these datasets in LIGO–Virgo Collaboration analyses of gravitational-waves from both transient and persistent sources and include details on the provenance of these datasets in order to support analyses of LIGO data by the broader community. Finally, we explain anticipated changes in the role of detector characterization and current efforts to prepare for the high rate of gravitational-wave alerts and events in future observing runs.