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:
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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.
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.
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:
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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.
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.
Neurological hazard assessment of industrial and pesticidal chemicals demands a substantial amount of time and resources.
is an established model organism in developmental biology and neuroscience. ...It presents an ideal test system with relatively fewer neurons (302 in hermaphrodites) versus higher-order species, a transparent body, short lifespan, making it easier to perform neurotoxic assessment in a time and cost-effective manner. Yet, no regulatory testing guidelines have been developed for
in the field of developmental and adult neurotoxicity. Here, we describe a set of morphological and behavioral assessment protocols to examine neurotoxicity in
with relevance to cholinergic and dopaminergic systems. We discuss the homology of human genes and associated proteins in these two signaling pathways and evaluate the morphological and behavioral endpoints of
in the context of published adverse outcome pathways of neurodegenerative diseases. We conclude that
neurotoxicity testing will not only be instrumental to eliminating mammalian testing in neurological hazard assessment but also lead to new knowledge and mechanistic validation in the adverse outcome pathway framework.
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