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- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)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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- Takahashi, H., et al.
(author)
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A thermal-neutron detector with a phoswich system of LiCaAlF6 and BGO crystal scintillators onboard PoGOLite
- 2010
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In: 2010 IEEE Nuclear Science Symposium, Medical Imaging Conference, NSS/MIC 2010 and 17th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors, RTSD 2010. ; , s. 32-37
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Conference paper (peer-reviewed)abstract
- To measure the flux of atmospheric neutrons and study the neutron contribution to the background of the main detector of the PoGOLite (Polarized Gamma-ray Observer) balloon-borne experiment, a thermal-neutron detector with a phoswich system of LiCaAlF6 (Eu) and BGO crystal scintillators is developed. The performance to separate thermal-neutron events from those of gamma-rays and charged particles is validated with 252Cf on ground. The detector is attached to the PoGOLite instrument and is launched in 2011 from the Esrange facility in the North of Sweden. Although the emission wavelength of the LiCaAlF6 (Ce) is 300 nm and overlaps with the absorption wavelength of the BGO, the phoswich capability of the LiCaAlF6 (Ce) with the BGO is also confirmed with installing a waveform shifter.
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- Kole, Merlin, et al.
(author)
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Neutron background detection for a hard X-ray balloon-borne polarimeter
- 2014
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In: Proceedings of Science. - : Proceedings of Science (PoS).
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Conference paper (peer-reviewed)abstract
- PoGOLite is a balloon-borne hard X-ray polarimeter. It determines polarisation by measuring the azimuthal angular distribution of Compton scattered photons in a plastic scintillator array. The use of an all-plastic target yields a relatively large, low-mass detection area. The dominant source of background for these measurements has been shown, through Geant4 simulations, to originate from high energy (MeV range) atmospheric neutrons. Neutrons can pass the instrument's Bismuth Germanium Oxide (BGO) anti-coincidence shield undetected and subsequently scatter between plastic scintillator elements to produce a polarisation signature. A passive 15 cm thick polyethylene shield surrounding the polarimeter reduces the neutron induced background by an order of magnitude. The background level remains however significant, prompting the need for active monitoring of the continuously changing neutron flux. For this purpose PoGOLite makes use of a phoswich scintillator cell. The phoswich cell consists of a 5 mm thick Lithium Calcium Aluminium Fluoride (LiCAF) scintillator, used for neutron detection. The LiCAF is surrounded by a BGO anti-coincidence system. This small light weight detector can therefore be used to measure the neutron flux even in high radiation environments. This type of neutron detector was tested on a separate dedicated stratospheric balloon mission in March 2013, called PoGOLino, prior to the PoGOLite flight which took place in July 2013. Results from the test flight and implications for the measurements performed on the PoGOLite flight will be discussed.
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- Evans, Jason L., et al.
(author)
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Hermitian Flavor Violation
- 2011
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In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 703:5, s. 599-605
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Journal article (peer-reviewed)abstract
- The fundamental constraint on two Higgs doublet models comes from the requirement of sufficiently suppressing flavor-changing neutral currents. There are various standard approaches for dealing with this problem, but they all tend to share a common feature; all of the Higgs doublets couple very weakly to the first generation quarks. Here we consider a simple two Higgs doublet model which is able to have large couplings to the first generation, while also being safe from flavor constraints. We assume only that there is an SUf(3)SU(3)f flavor symmetry which is respected by the couplings of one of the Higgs doublets, and which is broken by Hermitian Yukawa couplings of the second doublet. As a result of the large permitted couplings to the first generation quarks, this scenario may be used to address the excess in W+dijetW+dijet events recently observed by CDF at the Tevatron. Moreover, Hermitian Yukawa coupling matrices arise naturally in a broad class of solutions to the strong CP problem, providing a compelling context for the model.
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