| 1. |
- Alvarez, Mariano J., et al.
(författare)
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A precision oncology approach to the pharmacological targeting of mechanistic dependencies in neuroendocrine tumors
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:7, s. 979-989
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Tidskriftsartikel (refereegranskat)abstract
- We introduce and validate a new precision oncology framework for the systematic prioritization of drugs targeting mechanistic tumor dependencies in individual patients. Compounds are prioritized on the basis of their ability to invert the concerted activity of master regulator proteins that mechanistically regulate tumor cell state, as assessed from systematic drug perturbation assays. We validated the approach on a cohort of 212 gastroenteropancreatic neuroendocrine tumors (GEP-NETs), a rare malignancy originating in the pancreas and gastrointestinal tract. The analysis identified several master regulator proteins, including key regulators of neuroendocrine lineage progenitor state and immunoevasion, whose role as critical tumor dependencies was experimentally confirmed. Transcriptome analysis of GEP-NET-derived cells, perturbed with a library of 107 compounds, identified the HDAC class I inhibitor entinostat as a potent inhibitor of master regulator activity for 42% of metastatic GEP-NET patients, abrogating tumor growth in vivo. This approach may thus complement current efforts in precision oncology.
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| 2. |
- Balliu, Enkeleda, 1986-, et al.
(författare)
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Pulsed thulium doped fiber laser at 1.94 μm based on a seed diode
- 2013
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Ingår i: <em>Proc. SPIE</em> 8601, Fiber Lasers X: Technology, Systems, and Applications, 860133 (February 26, 2013). - : SPIE - International Society for Optical Engineering.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- A fiber laser operating at 1.94μm in pulsed regime has been developed in a MOPA configuration. The seed consists of a custom-developed board hosting a laser diode, whose current is modulated to achieve the desired pulse shape, duration and repetition rate. The pulses are amplified through a thulium-doped fiber amplifier pumped at 793 nm. The design of the amplifier stage has been performed by dynamic simulation of a rate-equations model and compared to the experimental measurements. Simulations and experimental measurements have exhibited comparable results, devising the realization of an effective pulsed laser system whose parameters can be easily tuned through the seed.
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| 3. |
- Fedele, Vita, et al.
(författare)
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Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression
- 2017
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Ingår i: Molecular Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1541-7786 .- 1557-3125. ; 15:8, s. 998-1011
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma (GBM) comprises distinct subtypes characterized by their molecular profile. Mesenchymal identity in GBM has been associated with a comparatively unfavorable prognosis, primarily due to inherent resistance of these tumors to current therapies. The identification of molecular determinants of mesenchymal transformation could potentially allow for the discovery of new therapeutic targets. Zinc Finger and BTB Domain Containing 18 (ZBTB18/ZNF238/RP58) is a zinc finger transcriptional repressor with a crucial role in brain development and neuronal differentiation. Here, ZBTB18 is primarily silenced in the mesenchymal subtype of GBM through aberrant promoter methylation. Loss of ZBTB18 contributes to the aggressive phenotype of glioblastoma through regulation of poor prognosis-associated signatures. Restitution of ZBTB18 expression reverses the phenotype and impairs tumor-forming ability. These results indicate that ZBTB18 functions as a tumor suppressor in GBM through the regulation of genes associated with phenotypically aggressive properties.
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| 4. |
- Telloni, Daniele, et al.
(författare)
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Observation and Modeling of the Solar Wind Turbulence Evolution in the Sub-Mercury Inner Heliosphere
- 2022
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Ingår i: Astrophysical Journal Letters. - : Institute of Physics Publishing (IOPP). - 2041-8205 .- 2041-8213. ; 938:2
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Tidskriftsartikel (refereegranskat)abstract
- This letter exploits the radial alignment between the Parker Solar Probe and BepiColombo in late 2022 February, when both spacecraft were within Mercury's orbit. This allows the study of the turbulent evolution, namely, the change in spectral and intermittency properties, of the same plasma parcel during its expansion from 0.11 to 0.33 au, a still unexplored region. The observational analysis of the solar wind turbulent features at the two different evolution stages is complemented by a theoretical description based on the turbulence transport model equations for nearly incompressible magnetohydrodynamics. The results provide strong evidence that the solar wind turbulence already undergoes significant evolution at distances less than 0.3 au from the Sun, which can be satisfactorily explained as due to evolving slab fluctuations. This work represents a step forward in understanding the processes that control the transition from weak to strong turbulence in the solar wind and in properly modeling the heliosphere.
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