| 1. |
|
|
| 2. |
|
|
| 3. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
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.
|
|
| 4. |
- Sampson, Joshua N., et al.
(författare)
-
Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
|
|
| 5. |
- Abadie, J., et al.
(författare)
-
All-sky search for periodic gravitational waves in the full S5 LIGO data
- 2012
-
Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:2
-
Tidskriftsartikel (refereegranskat)abstract
- We report on an all-sky search for periodic gravitational waves in the frequency band 50-800 Hz and with the frequency time derivative in the range of 0 through -6 x 10(-9) Hz/s. Such a signal could be produced by a nearby spinning and slightly nonaxisymmetric isolated neutron star in our Galaxy. After recent improvements in the search program that yielded a 10x increase in computational efficiency, we have searched in two years of data collected during LIGO's fifth science run and have obtained the most sensitive all-sky upper limits on gravitational-wave strain to date. Near 150 Hz our upper limit on worst-case linearly polarized strain amplitude h(0) is 1 x 10(-24), while at the high end of our frequency range we achieve a worst-case upper limit of 3.8 x 10(-24) for all polarizations and sky locations. These results constitute a factor of 2 improvement upon previously published data. A new detection pipeline utilizing a loosely coherent algorithm was able to follow up weaker outliers, increasing the volume of space where signals can be detected by a factor of 10, but has not revealed any gravitational-wave signals. The pipeline has been tested for robustness with respect to deviations from the model of an isolated neutron star, such as caused by a low-mass or long-period binary companion.
|
|
| 6. |
- Abadie, J., et al.
(författare)
-
Implementation and testing of the first prompt search for gravitational wave transients with electromagnetic counterparts
- 2012
-
Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 539
-
Tidskriftsartikel (refereegranskat)abstract
- Aims. A transient astrophysical event observed in both gravitational wave (GW) and electromagnetic (EM) channels would yield rich scientific rewards. A first program initiating EM follow-ups to possible transient GW events has been developed and exercised by the LIGO and Virgo community in association with several partners. In this paper, we describe and evaluate the methods used to promptly identify and localize GW event candidates and to request images of targeted sky locations. Methods. During two observing periods (Dec. 17, 2009 to Jan. 8, 2010 and Sep. 2 to Oct. 20, 2010), a low-latency analysis pipeline was used to identify GW event candidates and to reconstruct maps of possible sky locations. A catalog of nearby galaxies and Milky Way globular clusters was used to select the most promising sky positions to be imaged, and this directional information was delivered to EM observatories with time lags of about thirty minutes. A Monte Carlo simulation has been used to evaluate the low-latency GW pipeline's ability to reconstruct source positions correctly. Results. For signals near the detection threshold, our low-latency algorithms often localized simulated GW burst signals to tens of square degrees, while neutron star/neutron star inspirals and neutron star/black hole inspirals were localized to a few hundred square degrees. Localization precision improves for moderately stronger signals. The correct sky location of signals well above threshold and originating from nearby galaxies may be observed with similar to 50% or better probability with a few pointings of wide-field telescopes.
|
|
| 7. |
- Abadie, J., et al.
(författare)
-
Search for gravitational waves from low mass compact binary coalescence in LIGO's sixth science run and Virgo's science runs 2 and 3
- 2012
-
Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:8
-
Tidskriftsartikel (refereegranskat)abstract
- We report on a search for gravitational waves from coalescing compact binaries using LIGO and Virgo observations between July 7, 2009, and October 20, 2010. We searched for signals from binaries with total mass between 2 and 25M(circle dot); this includes binary neutron stars, binary black holes, and binaries consisting of a black hole and neutron star. The detectors were sensitive to systems up to 40 Mpc distant for binary neutron stars, and further for higher mass systems. No gravitational-wave signals were detected. We report upper limits on the rate of compact binary coalescence as a function of total mass, including the results from previous LIGO and Virgo observations. The cumulative 90% confidence rate upper limits of the binary coalescence of binary neutron star, neutron star-black hole, and binary black hole systems are 1.3 x 10(-4), 3.1 x 10(-5), and 6.4 x 10(-6) Mpc(-3) yr(-1), respectively. These upper limits are up to a factor 1.4 lower than previously derived limits. We also report on results from a blind injection challenge.
|
|
| 8. |
|
|
| 9. |
- Aprile, E., et al.
(författare)
-
An approximate likelihood for nuclear recoil searches with XENON1T data
- 2022
-
Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 82:11
-
Tidskriftsartikel (refereegranskat)abstract
- The XENON collaboration has published stringent limits on specific dark matter – nucleon recoil spectra from dark matter recoiling on the liquid xenon detector target. In this paper, we present an approximate likelihood for the XENON1T 1 t-year nuclear recoil search applicable to any nuclear recoil spectrum. Alongside this paper, we publish data and code to compute upper limits using the method we present. The approximate likelihood is constructed in bins of reconstructed energy, profiled along the signal expectation in each bin. This approach can be used to compute an approximate likelihood and therefore most statistical results for any nuclear recoil spectrum. Computing approximate results with this method is approximately three orders of magnitude faster than the likelihood used in the original publications of XENON1T, where limits were set for specific families of recoil spectra. Using this same method, we include toy Monte Carlo simulation-derived binwise likelihoods for the upcoming XENONnT experiment that can similarly be used to assess the sensitivity to arbitrary nuclear recoil signatures in its eventual 20 t-year exposure.
|
|
| 10. |
- Aprile, E., et al.
(författare)
-
Application and modeling of an online distillation method to reduce krypton and argon in XENON1T
- 2022
-
Ingår i: Progress of Theoretical and Experimental Physics. - : Oxford University Press (OUP). - 2050-3911. ; 2022:5
-
Tidskriftsartikel (refereegranskat)abstract
- A novel online distillation technique was developed for the XENON1T dark matter experiment to reduce intrinsic background components more volatile than xenon, such as krypton or argon, while the detector was operating. The method is based on a continuous purification of the gaseous volume of the detector system using the XENON1T cryogenic distillation column. A krypton-in-xenon concentration of (360 +/- 60) ppq was achieved. It is the lowest concentration measured in the fiducial volume of an operating dark matter detector to date. A model was developed and fitted to the data to describe the krypton evolution in the liquid and gas volumes of the detector system for several operation modes over the time span of 550 days, including the commissioning and science runs of XENON1T. The online distillation was also successfully applied to remove Ar-37 after its injection for a low-energy calibration in XENON1T. This makes the usage of Ar-37 as a regular calibration source possible in the future. The online distillation can be applied to next-generation liquid xenon time projection chamber experiments to remove krypton prior to, or during, any science run. The model developed here allows further optimization of the distillation strategy for future large-scale detectors.
|
|
