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| 2. |
- 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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| 3. |
- Ahumada, Tomas, et al.
(författare)
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In Search of Short Gamma-Ray Burst Optical Counterparts with the Zwicky Transient Facility
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 932:1
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Tidskriftsartikel (refereegranskat)abstract
- The Fermi Gamma-ray Burst Monitor (GBM) triggers on-board in response to ∼40 short gamma-ray bursts (SGRBs) per year; however, their large localization regions have made the search for optical counterparts a challenging endeavour. We have developed and executed an extensive program with the wide field of view of the Zwicky Transient Facility (ZTF) camera, mounted on the Palomar 48 inch Oschin telescope (P48), to perform target-of-opportunity (ToO) observations on 10 Fermi-GBM SGRBs during 2018 and 2020–2021. Bridging the large sky areas with small field-of-view optical telescopes in order to track the evolution of potential candidates, we look for the elusive SGRB afterglows and kilonovae (KNe) associated with these high-energy events. No counterpart has yet been found, even though more than 10 ground-based telescopes, part of the Global Relay of Observatories Watching Transients Happen (GROWTH) network, have taken part in these efforts. The candidate selection procedure and the follow-up strategy have shown that ZTF is an efficient instrument for searching for poorly localized SGRBs, retrieving a reasonable number of candidates to follow up and showing promising capabilities as the community approaches the multi-messenger era. Based on the median limiting magnitude of ZTF, our searches would have been able to retrieve a GW170817-like event up to ∼200 Mpc and SGRB afterglows to z = 0.16 or 0.4, depending on the assumed underlying energy model. Future ToOs will expand the horizon to z = 0.2 and 0.7, respectively.
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| 4. |
- Bolin, Bryce T., et al.
(författare)
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Characterization of the Nucleus, Morphology, and Activity of Interstellar Comet 2I/Borisov by Optical and Near-infrared GROWTH, Apache Point, IRTF, ZTF, and Keck Observations
- 2020
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 160:1
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Tidskriftsartikel (refereegranskat)abstract
- We present visible and near-infrared (NIR) photometric and spectroscopic observations of interstellar object (ISO) 2I/Borisov taken from 2019 September 10 to 2019 December 20 using the GROWTH, the Apache Point Observatory Astrophysical Research Consortium 3.5 m, and the NASA Infrared Telescope Facility 3.0 m combined with pre- and postdiscovery observations of 2I obtained by the Zwicky Transient Facility from 2019 March 17 to 2019 May 5. Comparison with imaging of distant solar system comets shows an object very similar to mildly active solar system comets with an outgassing rate of similar to 10(27)mol s(-1). The photometry, taken in filters spanning the visible and NIR range, shows a gradual brightening trend of similar to 0.03 mag day(-1)since 2019 September 10 UTC for a reddish object becoming neutral in the NIR. The light curve from recent and prediscovery data reveals a brightness trend suggesting the recent onset of significant H2O sublimation with the comet being active with super volatiles such as CO at heliocentric distances >6 au consistent with its extended morphology. Using the advanced capability to significantly reduce the scattered light from the coma enabled by high-resolution NIR images from Keck adaptive optics taken on 2019 October 4, we estimate a diameter for 2I's nucleus of less than or similar to 1.4 km. We use the size estimates of 1I/'Oumuamua and 2I/Borisov to roughly estimate the slope of the ISO size distribution, resulting in a slope of similar to 3.4 1.2, similar to solar system comets and bodies produced from collisional equilibrium.
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| 5. |
- Coughlin, Michael W., et al.
(författare)
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2900 Square Degree Search for the Optical Counterpart of Short Gamma-Ray Burst GRB 180523B with the Zwicky Transient Facility
- 2019
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 131:998
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Tidskriftsartikel (refereegranskat)abstract
- There is significant interest in the models for production of short gamma-ray bursts (GRBs). Until now, the number of known short GRBs with multi-wavelength afterglows has been small. While the Fermi GRB Monitor detects many GRBs relative to the Neil Gehrels Swift Observatory, the large localization regions makes the search for counterparts difficult. With the Zwicky Transient Facility (ZTF) recently achieving first light, it is now fruitful to use its combination of depth (m(AB) similar to 20.6), field of view (approximate to 47 square degrees), and survey cadence (every similar to 3 days) to perform Target of Opportunity observations. We demonstrate this capability on GRB 180523B, which was recently announced by the Fermi GRB Monitor as a short GRB. ZTF imaged approximate to 2900 square degrees of the localization region, resulting in the coverage of 61.6% of the enclosed probability over two nights to a depth of m(AB) similar to 20.5. We characterized 14 previously unidentified transients, and none were found to be consistent with a short GRB counterpart. This search with the ZTF shows it is an efficient camera for searching for coarsely localized short GRB and gravitational-wave counterparts, allowing for a sensitive search with minimal interruption to its nominal cadence.
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| 6. |
- Ho, Anna Y. Q., et al.
(författare)
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Cosmological Fast Optical Transients with the Zwicky Transient Facility : A Search for Dirty Fireballs
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 938:1
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Tidskriftsartikel (refereegranskat)abstract
- Dirty fireballs are a hypothesized class of relativistic massive-star explosions with an initial Lorentz factor Γinit below the Γinit ∼ 100 required to produce a long-duration gamma-ray burst (LGRB), but which could still produce optical emission resembling LGRB afterglows. Here we present the results of a search for on-axis optical afterglows using the Zwicky Transient Facility (ZTF). Our search yielded seven optical transients that resemble on-axis LGRB afterglows in terms of their red colors (g − r > 0 mag), faint host galaxies (r > 23 mag), rapid fading (dr/dt > 1 mag day−1), and in some cases X-ray and radio emission. Spectroscopy of the transient emission within a few days of discovery established cosmological distances (redshift z = 0.876 to 2.9) for six of the seven events, tripling the number of afterglows with redshift measurements discovered by optical surveys without a γ-ray trigger. A likely associated LGRB (GRB 200524A, GRB 210204A, GRB 210212B, and GRB 210610B) was identified for four events (ZTF 20abbiixp/AT 2020kym, ZTF 21aagwbjr/AT 2021buv, ZTF 21aakruew/AT 2021cwd, and ZTF 21abfmpwn/AT 2021qbd) post facto, while three (ZTF 20aajnksq/AT 2020blt, ZTF 21aaeyldq/AT 2021any, and ZTF 21aayokph/AT 2021lfa) had no detected LGRB counterpart. The simplest explanation for the three "orphan" events is that they were regular LGRBs missed by high-energy satellites owing to detector sensitivity and duty cycle, although it is possible that they were intrinsically subluminous in γ-rays or viewed slightly off-axis. We rule out a scenario in which dirty fireballs have a similar energy per solid angle to LGRBs and are an order of magnitude more common. In addition, we set the first direct constraint on the ratio of the opening angles of the material producing γ-rays and the material producing early optical afterglow emission, finding that they must be comparable.
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| 7. |
- Strosberg, Jonathan, et al.
(författare)
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Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with Lu-177-Dotatate : an analysis of the NETTER-1 study
- 2020
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : SPRINGER. - 1619-7070 .- 1619-7089. ; 47:10, s. 2372-2382
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with Lu-177-Dotatate. Methods In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results Significantly prolonged median PFS occurred with Lu-177-Dotatate versus octreotide LAR 60 mg in patients with low (< 25%), moderate (25-50%), and high (> 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the Lu-177-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions Lu-177-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. : NCT01578239, EudraCT: 2011-005049-11
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| 8. |
- Alfredsson, Joakim, et al.
(författare)
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Sex differences in management and outcomes of patients with type 2 diabetes and cardiovascular disease: A report from TECOS
- 2018
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Ingår i: Diabetes, obesity and metabolism. - : WILEY. - 1462-8902 .- 1463-1326. ; 20:10, s. 2379-2388
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine sex differences in baseline characteristics and outcomes in patients with type 2 diabetes and atherosclerotic vascular disease. Materials and methods: Cox models were used to analyse the association between sex and outcomes in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), a randomized, placebo-controlled trial assessing the impact of sitagliptin on cardiovascular (CV) outcomes in patients with type 2 diabetes and atherosclerotic vascular disease. Results: A total of 4297 women and 10 374 men were followed for a median of 3.0 years. Women were slightly older and more often had cerebrovascular disease and peripheral arterial disease but less often coronary heart disease than men. At baseline, women were less likely to use aspirin or statins. The primary composite outcome of CV death, myocardial infarction, stroke, or hospitalization for unstable angina occurred in 418 women (9.7%) and 1272 men (12.3%; 3.48 vs 4.38 events/100 participant-years, crude hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.71-0.89, adjusted HR 0.64, 95% CI 0.55-0.74; P amp;lt; .0001). Women also had a significantly lower risk of secondary CV outcomes and all-cause death. Conclusions: In this large prospective study of people with type 2 diabetes and CV disease, women had different CV disease burden, worse CV risk factor profiles, and less use of indicated medications than men. Despite this, women had significantly lower risk of CV events, suggesting that the cardioprotective effects of female sex extend to populations with type 2 diabetes.
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| 9. |
- Bellm, Eric C., et al.
(författare)
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The Zwicky Transient Facility : Surveys and Scheduler
- 2019
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 131:1000
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Tidskriftsartikel (refereegranskat)abstract
- We present a novel algorithm for scheduling the observations of time-domain imaging surveys. Our integer linear programming approach optimizes an observing plan for an entire night by assigning targets to temporal blocks, enabling strict control of the number of exposures obtained per field and minimizing filter changes. A subsequent optimization step minimizes slew times between each observation. Our optimization metric self-consistently weights contributions from time-varying airmass, seeing, and sky brightness to maximize the transient discovery rate. We describe the implementation of this algorithm on the surveys of the Zwicky Transient Facility and present its on-sky performance.
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| 10. |
- Bellm, Eric C., et al.
(författare)
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The Zwicky Transient Facility : System Overview, Performance, and First Results
- 2019
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 131:995
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Tidskriftsartikel (refereegranskat)abstract
- The Zwicky Transient Facility (ZTF) is a new optical time-domain survey that uses the Palomar 48 inch Schmidt telescope. A custom-built wide-field camera provides a 47 deg(2) field of view and 8 s readout time, yielding more than an order of magnitude improvement in survey speed relative to its predecessor survey, the Palomar Transient Factory. We describe the design and implementation of the camera and observing system. The ZTF data system at the Infrared Processing and Analysis Center provides near-real-time reduction to identify moving and varying objects. We outline the analysis pipelines, data products, and associated archive. Finally, we present on-sky performance analysis and first scientific results from commissioning and the early survey. ZTF's public alert stream will serve as a useful precursor for that of the Large Synoptic Survey Telescope.
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