| 1. |
- Neumann, A., et al.
(författare)
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Rare variants in IFFO1, DTNB, NLRC3 and SLC22A10 associate with Alzheimer's disease CSF profile of neuronal injury and inflammation
- 2022
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 27, s. 1990-1999
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) biomarkers represent several neurodegenerative processes, such as synaptic dysfunction, neuronal inflammation and injury, as well as amyloid pathology. We performed an exome-wide rare variant analysis of six AD biomarkers (beta-amyloid, total/phosphorylated tau, NfL, YKL-40, and Neurogranin) to discover genes associated with these markers. Genetic and biomarker information was available for 480 participants from two studies: EMIF-AD and ADNI. We applied a principal component (PC) analysis to derive biomarkers combinations, which represent statistically independent biological processes. We then tested whether rare variants in 9576 protein-coding genes associate with these PCs using a Meta-SKAT test. We also tested whether the PCs are intermediary to gene effects on AD symptoms with a SMUT test. One PC loaded on NfL and YKL-40, indicators of neuronal injury and inflammation. Four genes were associated with this PC: IFFO1, DTNB, NLRC3, and SLC22A10. Mediation tests suggest, that these genes also affect dementia symptoms via inflammation/injury. We also observed an association between a PC loading on Neurogranin, a marker for synaptic functioning, with GABBR2 and CASZ1, but no mediation effects. The results suggest that rare variants in IFFO1, DTNB, NLRC3, and SLC22A10 heighten susceptibility to neuronal injury and inflammation, potentially by altering cytoskeleton structure and immune activity disinhibition, resulting in an elevated dementia risk. GABBR2 and CASZ1 were associated with synaptic functioning, but mediation analyses suggest that the effect of these two genes on synaptic functioning is not consequential for AD development.
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| 2. |
- Barrillon, P., et al.
(författare)
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The EUSO@TurLab project in the framework of the JEM-EUSO program
- 2023
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Ingår i: Experimental astronomy. - : Springer Nature. - 0922-6435 .- 1572-9508. ; 55:2, s. 569-602
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Tidskriftsartikel (refereegranskat)abstract
- The EUSO@TurLab project aims at performing experiments to reproduce Earth UV emissions as seen from a low Earth orbit by the planned missions of the JEM-EUSO program. It makes use of the TurLab facility, which is a laboratory, equipped with a 5 m diameter and 1 m depth rotating tank, located at the Physics Department of the University of Turin. All the experiments are designed and performed based on simulations of the expected response of the detectors to be flown in space. In April 2016 the TUS detector and more recently in October 2019 the Mini-EUSO experiment, both part of the JEM-EUSO program, have been placed in orbit to map the UV Earth emissions. It is, therefore, now possible to compare the replicas performed at TurLab with the actual images detected in space to understand the level of fidelity in terms of reproduction of the expected signals. We show that the laboratory tests reproduce at the order of magnitude level the measurements from space in terms of spatial extension and time duration of the emitted UV light, as well as the intensity in terms of expected counts per pixel per unit time when atmospheric transient events, diffuse nightlow background light, and artificial light sources are considered. Therefore, TurLab is found to be a very useful facility for testing the acquisition logic of the detectors of the present and future missions of the JEM-EUSO program and beyond in order to reproduce atmospheric signals in the laboratory.
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| 3. |
- Hong, S. J., et al.
(författare)
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TMEM106B and CPOX are genetic determinants of cerebrospinal fluid Alzheimer's disease biomarker levels
- 2021
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 17:10, s. 1628-1640
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Neurofilament light (NfL), chitinase-3-like protein 1 (YKL-40), and neurogranin (Ng) are biomarkers for Alzheimer's disease (AD) to monitor axonal damage, astroglial activation, and synaptic degeneration, respectively. Methods We performed genome-wide association studies (GWAS) using DNA and cerebrospinal fluid (CSF) samples from the EMIF-AD Multimodal Biomarker Discovery study for discovery, and the Alzheimer's Disease Neuroimaging Initiative study for validation analyses. GWAS were performed for all three CSF biomarkers using linear regression models adjusting for relevant covariates. Results We identify novel genome-wide significant associations between DNA variants in TMEM106B and CSF levels of NfL, and between CPOX and YKL-40. We confirm previous work suggesting that YKL-40 levels are associated with DNA variants in CHI3L1. Discussion Our study provides important new insights into the genetic architecture underlying interindividual variation in three AD-related CSF biomarkers. In particular, our data shed light on the sequence of events regarding the initiation and progression of neuropathological processes relevant in AD.
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| 4. |
- Marcelli, L., et al.
(författare)
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Integration, qualification, and launch of the Mini-EUSO telescope on board the ISS
- 2023
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Ingår i: Rendiconti Lincei SCIENZE FISICHE E NATURALI. - : Springer Nature. - 2037-4631 .- 1720-0776. ; 34:1, s. 23-35
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Tidskriftsartikel (refereegranskat)abstract
- Mini-EUSO is a high-sensitivity imaging telescope that observes the Earth from the ISS in the near ultraviolet band (290÷ 430 nm), through the nadir-facing, UV-transparent window in the Russian Zvezda module. The instrument, launched in 2019, has a field of view of 44∘, a spatial resolution on the Earth’s surface of 6.3 km and a temporal sampling rate of 2.5 microseconds. Thanks to its triggering and on-board processing, the telescope is capable of detecting UV emissions of cosmic, atmospheric, and terrestrial origin on different time scales, from a few microseconds up to tens of milliseconds. The optics is composed of two Fresnel lenses focusing light onto an array of 36 Hamamatsu Multi-Anode PhotoMultiplier Tubes, for a total of 2304 pixels. The telescope also contains two cameras in the near-infrared and visible, an 8-by-8 array of Silicon-PhotoMultipliers and a series of UV sensors to manage night-day transitions. The scientific objectives range from the observation of atmospheric phenomena [lightning, Transient Luminous Events (TLEs), ELVES], the study of meteoroids, the search of interstellar meteoroids and strange quark matter, mapping of the Earth’s nocturnal emissions in the ultraviolet range, and the search of cosmic rays with energy above 1021 eV. The instrument has been integrated and qualified in 2019, with the final tests in Baikonur prior to its launch. Operations involve periodic installation in the Zvezda module of the station with observations during the crew night time, with periodic downlink of data samples, with the full data being sent to the ground via pouches containing the data disks. Mission planning involves the selection of the optimal orbits to maximize the scientific return of the instrument. In this work, we will describe the various phases of construction, testing, and qualification prior to the launch and the in-flight operations of the instrument on board the ISS.
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| 7. |
- Bisconti, F., et al.
(författare)
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Pre-flight qualification tests of the Mini-EUSO telescope engineering model
- 2022
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Ingår i: Experimental astronomy. - : Springer Nature. - 0922-6435 .- 1572-9508. ; 53:1, s. 133-158
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Tidskriftsartikel (refereegranskat)abstract
- Mini-EUSO is part of the JEM-EUSO program and operates on board the International Space Station (ISS). It is a UV-telescope with single-photon counting capability looking at nighttime downwards to the Earth through a nadir-facing UV-transparent window. As part of the pre-flight tests, the Mini-EUSO engineering model, a telescope with 1/9 of the original focal surface and a lens of 2.5 cm diameter, has been built and tested. Tests of the Mini-EUSO engineering model have been made in laboratory and in open-sky conditions. Laboratory tests have been performed at the TurLab facility, located at the Physics Department of the University of Turin, equipped with a rotating tank containing different types of materials and light sources. In this way, the configuration for the observation of the Earth from space was emulated, including the Mini-EUSO trigger schemes. In addition to the qualification and calibration tests, the Mini-EUSO engineering model has also been used to evaluate the possibility of using a JEM-EUSO-type detector for applications such as observation of space debris. Furthermore, observations in open-sky conditions allowed the studies of natural light sources such as stars, meteors, planets, and artificial light sources such as airplanes, satellites reflecting the sunlight, and city lights. Most of these targets could be detected also with Mini-EUSO. In this paper, the tests in laboratory and in open-sky conditions are reported, as well as the obtained results. In addition, the contribution that such tests provided to foresee and improve the performance of Mini-EUSO on board the ISS is discussed.
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