| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Patil, Ajinkya H., et al.
(författare)
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Constraining the epoch of reionization with the variance statistic : simulations of the LOFAR case
- 2014
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 443:2, s. 1113-1124
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Tidskriftsartikel (refereegranskat)abstract
- Several experiments are underway to detect the cosmic-redshifted 21-cm signal from neutral hydrogen from the Epoch of Reionization (EoR). Due to their very low signal-to-noise ratio, these observations aim for a statistical detection of the signal by measuring its power spectrum. We investigate the extraction of the variance of the signal as a first step towards detecting and constraining the global history of the EoR. Signal variance is the integral of the signal's power spectrum, and it is expected to be measured with a high significance. We demonstrate this through results from a simulation and parameter estimation pipeline developed for the Low-Frequency Array (LOFAR)-EoR experiment. We show that LOFAR should be able to detect the EoR in 600 h of integration using the variance statistic. Additionally, the redshift (z(r)) and duration (Delta z) of reionization can be constrained assuming a parametrization. We use an EoR simulation of z(r) = 7.68 and Delta(z) = 0.43 to test the pipeline. We are able to detect the simulated signal with a significance of four standard deviations and extract the EoR parameters as z(r) = 7.72(-0.18)(+0.37) and Delta z = 0.53(-0.23)(+0.12) in 600 h, assuming that systematic errors can be adequately controlled. We further show that the significance of detection and constraints on EoR parameters can be improved by measuring the cross-variance of the signal by cross-correlating consecutive redshift bins.
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| 3. |
- Harker, Geraint, et al.
(författare)
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Power spectrum extraction for redshifted 21-cm Epoch of Reionization experiments : the LOFAR case
- 2010
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 405:4, s. 2492-2504
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Tidskriftsartikel (refereegranskat)abstract
- One of the aims of the Low Frequency Array (LOFAR) Epoch of Reionization (EoR) project is to measure the power spectrum of variations in the intensity of redshifted 21-cm radiation from the EoR. The sensitivity with which this power spectrum can be estimated depends on the level of thermal noise and sample variance, and also on the systematic errors arising from the extraction process, in particular from the subtraction of foreground contamination. We model the extraction process using realistic simulations of the cosmological signal, the foregrounds and noise, and so estimate the sensitivity of the LOFAR EoR experiment to the redshifted 21-cm power spectrum. Detection of emission from the EoR should be possible within 360 h of observation with a single station beam. Integrating for longer, and synthesizing multiple station beams within the primary (tile) beam, then enables us to extract progressively more accurate estimates of the power at a greater range of scales and redshifts. We discuss different observational strategies which compromise between depth of observation, sky coverage and frequency coverage. A plan in which lower frequencies receive a larger fraction of the time appears to be promising. We also study the nature of the bias which foreground fitting errors induce on the inferred power spectrum and discuss how to reduce and correct for this bias. The angular and line-of-sight power spectra have different merits in this respect, and we suggest considering them separately in the analysis of LOFAR data.
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| 4. |
- Jelic, Vibor, et al.
(författare)
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A cross-correlation study between the cosmological 21 cm signal and the kinetic Sunyaev-Zel'dovich effect
- 2010
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 402:4, s. 2279-2290
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Tidskriftsartikel (refereegranskat)abstract
- The Universe's Epoch of Reionization can be studied using a number of observational probes that provide complementary or corroborating information. Each of these probes suffers from its own systematic and statistical uncertainties. It is therefore useful to consider the mutual information that these data sets contain. In this paper, we present a cross-correlation study between the kinetic Sunyaev-Zel'dovich effect - produced by the scattering of cosmic microwave background (CMB) photons off free electrons produced during the reionization process - and the cosmological 21 cm signal - which reflects the neutral hydrogen content of the Universe, as a function of redshift. The study is carried out using a simulated reionization history in 100 h(-1) Mpc scale N-body simulations with radiative transfer. In essence, we find that the two probes anticorrelate. The significance of the anticorrelation signal depends on the extent of the reionization process, wherein extended histories result in a much stronger signal compared to instantaneous cases. Unfortunately, however, once the primary CMB fluctuations are included into our simulation they serve as a source of large correlated noise that renders the cross-correlation signal insignificant, regardless of the reionization scenario.
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