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- Rajewsky, N., et al.
(author)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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In: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Journal article (peer-reviewed)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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- Ajello, M., et al.
(author)
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Fermi Large Area Telescope Performance after 10 Years of Operation
- 2021
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In: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 256:1
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Journal article (peer-reviewed)abstract
- The Large Area Telescope (LAT), the primary instrument for the Fermi Gamma-ray Space Telescope (Fermi) mission, is an imaging, wide field-of-view, high-energy gamma-ray telescope, covering the energy range from 30 MeV to more than 300 GeV. We describe the performance of the instrument at the 10 yr milestone. LAT performance remains well within the specifications defined during the planning phase, validating the design choices and supporting the compelling case to extend the duration of the Fermi mission. The details provided here will be useful when designing the next generation of high-energy gamma-ray observatories.
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- Lonardo, F., et al.
(author)
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Influence of the Heat Treatment on the Layer JC of Internal-Sn Nb3Sn Wires With Internally Oxidized Nanoparticles
- 2024
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In: IEEE transactions on applied superconductivity (Print). - : Institute of Electrical and Electronics Engineers (IEEE). - 1051-8223 .- 1558-2515. ; 34:5
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Journal article (peer-reviewed)abstract
- We evaluated various heat treatments (HT) for maximizing the Nb 3 Sn layer thickness while retaining a refined grain microstructure in low filament count internal-Sn Nb 3 Sn Rod-In-Tube wires with internally oxidized nanoparticles. These wires were manufactured in our laboratory using SnO 2 as oxygen source and Nb alloys containing Ta and Zr or Hf. By reacting the wires at 650 °C for 200 hours we obtained relatively thin reaction layers but high layer critical current densities (layer J C ) of ∼3000 A/mm 2 for Hf-containing wires and ∼2700 A/mm 2 for Zr-containing wires, both at 4.2 K and 16 T. Notably, both of these values are over the layer J C threshold of 2500 A/mm 2 , which is estimated to be necessary for attaining the corresponding Future Circular Collider (FCC) target non-Cu J C of 1500 A/mm 2 . Following this heat treatment, the fine-grained Nb 3 Sn area occupies only ∼35% of the filament area for Hf-containing wires and ∼20% for Zr-containing wires. After heat treatments with a reaction step at 700 °C these values increase to 70–80% and ∼60%, respectively, with only a minor increase of the grain size. However, we observed a noticeable decrease in the layer J C for these HT. Magnetic measurements show that the high J C wires exhibit a point defect contribution from precipitates to the pinning force, which is missing in wires with depressed J C values. The higher heat treatment temperatures may have caused excessive coarsening of the oxide precipitates, to sizes unsuitable for flux pinning. Reaction heat treatment temperatures in the range of 650 °C to 700 °C and durations between 50 and 200 hours may provide a better compromise between the Nb 3 Sn layer thickness, its grain size and nanoparticle size.
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- Pierantozzi, E., et al.
(author)
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Impaired Intracellular Ca2+ Dynamics, M-Band and Sarcomere Fragility in Skeletal Muscles of Obscurin KO Mice
- 2022
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In: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 23:3
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Journal article (peer-reviewed)abstract
- Obscurin is a giant sarcomeric protein expressed in striated muscles known to establish several interactions with other proteins of the sarcomere, but also with proteins of the sarcoplasmic reticulum and costameres. Here, we report experiments aiming to better understand the contribution of obscurin to skeletal muscle fibers, starting with a detailed characterization of the diaphragm muscle function, which we previously reported to be the most affected muscle in obscurin (Obscn) KO mice. Twitch and tetanus tension were not significantly different in the diaphragm of WT and Obscn KO mice, while the time to peak (TTP) and half relaxation time (HRT) were prolonged. Differences in force-frequency and force-velocity relationships and an enhanced fatigability are observed in an Obscn KO diaphragm with respect to WT controls. Voltage clamp experiments show that a sarcoplasmic reticulum’s Ca2+ release and SERCA reuptake rates were decreased in muscle fibers from Obscn KO mice, suggesting that an impairment in intracellular Ca2+ dynamics could explain the observed differences in the TTP and HRT in the diaphragm. In partial contrast with previous observations, Obscn KO mice show a normal exercise tolerance, but fiber damage, the altered sarcomere ultrastructure and M-band disarray are still observed after intense exercise. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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- Bagni, T., et al.
(author)
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Modeling Results of the Quench Behavior of a Nb-Ti Canted-Cosine-Theta Corrector Magnet for LHC
- 2024
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In: IEEE transactions on applied superconductivity (Print). - : IEEE. - 1051-8223 .- 1558-2515. ; 34:5
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Journal article (peer-reviewed)abstract
- A newly designed superconducting magnet of the Canted-Cosine-Theta (CCT) type was developed as a result of a collaboration between Swedish universities (Uppsala and Linneaus) and Swedish industries. This magnet was designed to function as a replacement of the present LHC orbit corrector magnets, which are approaching their end of life due to the radiation load. As a result, the new CCT magnet was developed to be more radiation tolerant and to constitute a one-to-one replacement to the currently installed version, which is a 1 m long 70 mm double aperture dipole magnet. The final magnet, which is currently under construction, will be tested at FREIA laboratory at Uppsala University and generate a magnetic field of 3.3 T and an integrated field of 2.8 Tm at about 85 A. To examine the magnet quench behavior and to identify a suitable quench protection system, the 3D electro-magnetic and thermal behavior of the coil was modeled using the RAT-Raccoon software. Based on the simulation results, a Metrosil varistor was selected to protect the magnet during the test. In this article, we report the results of the numerical analysis. The magnet model is equipped with a spot heater to initialize the quench and the temperature and voltages are monitored during the avalanche effect. The simulated current decay and the hot-spot temperature are analyzed with a focus on the impact of quench-back on the magnet protection.
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- Briz, V, et al.
(author)
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The non-coding RNA BC1 regulates experience-dependent structural plasticity and learning
- 2017
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1, s. 293-
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Journal article (peer-reviewed)abstract
- The brain cytoplasmic (BC1) RNA is a non-coding RNA (ncRNA) involved in neuronal translational control. Absence of BC1 is associated with altered glutamatergic transmission and maladaptive behavior. Here, we show that pyramidal neurons in the barrel cortex of BC1 knock out (KO) mice display larger excitatory postsynaptic currents and increased spontaneous activity in vivo. Furthermore, BC1 KO mice have enlarged spine heads and postsynaptic densities and increased synaptic levels of glutamate receptors and PSD-95. Of note, BC1 KO mice show aberrant structural plasticity in response to whisker deprivation, impaired texture novel object recognition and altered social behavior. Thus, our study highlights a role for BC1 RNA in experience-dependent plasticity and learning in the mammalian adult neocortex, and provides insight into the function of brain ncRNAs regulating synaptic transmission, plasticity and behavior, with potential relevance in the context of intellectual disabilities and psychiatric disorders.
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