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- 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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- Anchordoqui, Luis A., et al.
(författare)
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The Forward Physics Facility : Sites, experiments, and physics potential
- 2022
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Ingår i: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 968, s. 1-50
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Tidskriftsartikel (refereegranskat)abstract
- The Forward Physics Facility (FPF) is a proposal to create a cavern with the space and infrastructure to support a suite of far-forward experiments at the Large Hadron Collider during the High Luminosity era. Located along the beam collision axis and shielded from the interaction point by at least 100 m of concrete and rock, the FPF will house experiments that will detect particles outside the acceptance of the existing large LHC experiments and will observe rare and exotic processes in an extremely low-background environment. In this work, we summarize the current status of plans for the FPF, including recent progress in civil engineering in identifying promising sites for the FPF and the experiments currently envisioned to realize the FPF's physics potential. We then review the many Standard Model and new physics topics that will be advanced by the FPF, including searches for long-lived particles, probes of dark matter and dark sectors, high-statistics studies of TeV neutrinos of all three flavors, aspects of perturbative and non-perturbative QCD, and high-energy astroparticle physics.
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- Arca Sedda, Manuel, et al.
(författare)
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The missing link in gravitational-wave astronomy A summary of discoveries waiting in the decihertz range
- 2021
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 51, s. 1427-1440
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Tidskriftsartikel (refereegranskat)abstract
- Since 2015 the gravitational-wave observations of LIGO and Virgo have transformed our understanding of compact-object binaries. In the years to come, ground-based gravitational-wave observatories such as LIGO, Virgo, and their successors will increase in sensitivity, discovering thousands of stellar-mass binaries. In the 2030s, the space-based LISA will provide gravitational-wave observations of massive black holes binaries. Between the similar to 10-10(3) Hz band of ground-based observatories and the similar to 10(-4)-10(- 1) Hz band of LISA lies the uncharted decihertz gravitational-wave band. We propose a Decihertz Observatory to study this frequency range, and to complement observations made by other detectors. Decihertz observatories are well suited to observation of intermediate-mass (similar to 10(2)-10(4)M(circle dot)) black holes; they will be able to detect stellar-mass binaries days to years before they merge, providing early warning of nearby binary neutron star mergers and measurements of the eccentricity of binary black holes, and they will enable new tests of general relativity and the Standard Model of particle physics. Here we summarise how a Decihertz Observatory could provide unique insights into how black holes form and evolve across cosmic time, improve prospects for both multimessenger astronomy and multiband gravitational-wave astronomy, and enable new probes of gravity, particle physics and cosmology.
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