Biological activities of fusarochromanone: a potent anti-cancer agent

Background Fusarochromanone (FC101) is a small molecule fungal metabolite with a host of interesting biological functions, including very potent anti-angiogenic and direct anti-cancer activity. Results Herein, we report that FC101 exhibits very potent in-vitro growth inhibitory effects (IC50 ranging from 10nM-2.5 μM) against HaCat (pre-malignant skin), P9-WT (malignant skin), MCF-7 (low malignant breast), MDA-231 (malignant breast), SV-HUC (premalignant bladder), UM-UC14 (malignant bladder), and PC3 (malignant prostate) in a time-course and dose-dependent manner, with the UM-UC14 cells being the most sensitive. FC101 induces apoptosis and an increase in proportion of cells in the sub-G1 phase in both HaCat and P9-WT cell lines as evidenced by cell cycle profile analysis. In a mouse xenograft SCC tumor model, FC101 was well tolerated, non-toxic, and achieved a 30% reduction in tumor size at a dose of 8 mg/kg/day. FC101 is also a potent anti-angiogenenic agent. At nanomolar doses, FC101 inhibits the vascular endothelial growth factor-A (VEGF-A)-mediated proliferation of endothelial cells. Conclusions Our data presented here indicates that FC101 is an excellent lead candidate for a small molecule anti-cancer agent that simultaneously affects angiogenesis signaling, cancer signal transduction, and apoptosis. Further understanding of the underlying FC101’s molecular mechanism may lead to the design of novel targeted and selective therapeutics, both of which are pursued targets in cancer drug discovery

Deep Underground Neutrino Experiment (DUNE), Far Detector Technical Design Report, Volume II: DUNE Physics

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay -- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. DUNE is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. Volume II of this TDR, DUNE Physics, describes the array of identified scientific opportunities and key goals. Crucially, we also report our best current understanding of the capability of DUNE to realize these goals, along with the detailed arguments and investigations on which this understanding is based. This TDR volume documents the scientific basis underlying the conception and design of the LBNF/DUNE experimental configurations. As a result, the description of DUNE's experimental capabilities constitutes the bulk of the document. Key linkages between requirements for successful execution of the physics program and primary specifications of the experimental configurations are drawn and summarized. This document also serves a wider purpose as a statement on the scientific potential of DUNE as a central component within a global program of frontier theoretical and experimental particle physics research. Thus, the presentation also aims to serve as a resource for the particle physics community at large

Reconstruction of interactions in the ProtoDUNE-SP detector with Pandora

International audienceThe Pandora Software Development Kit and algorithm libraries provide pattern-recognition logic essential to the reconstruction of particle interactions in liquid argon time projection chamber detectors. Pandora is the primary event reconstruction software used at ProtoDUNE-SP, a prototype for the Deep Underground Neutrino Experiment far detector. ProtoDUNE-SP, located at CERN, is exposed to a charged-particle test beam. This paper gives an overview of the Pandora reconstruction algorithms and how they have been tailored for use at ProtoDUNE-SP. In complex events with numerous cosmic-ray and beam background particles, the simulated reconstruction and identification efficiency for triggered test-beam particles is above 80% for the majority of particle type and beam momentum combinations. Specifically, simulated 1 GeV/$c$ charged pions and protons are correctly reconstructed and identified with efficiencies of 86.1$\pm0.6$% and 84.1$\pm0.6$%, respectively. The efficiencies measured for test-beam data are shown to be within 5% of those predicted by the simulation

Reconstruction of interactions in the ProtoDUNE-SP detector with Pandora

International audienceThe Pandora Software Development Kit and algorithm libraries provide pattern-recognition logic essential to the reconstruction of particle interactions in liquid argon time projection chamber detectors. Pandora is the primary event reconstruction software used at ProtoDUNE-SP, a prototype for the Deep Underground Neutrino Experiment far detector. ProtoDUNE-SP, located at CERN, is exposed to a charged-particle test beam. This paper gives an overview of the Pandora reconstruction algorithms and how they have been tailored for use at ProtoDUNE-SP. In complex events with numerous cosmic-ray and beam background particles, the simulated reconstruction and identification efficiency for triggered test-beam particles is above 80% for the majority of particle type and beam momentum combinations. Specifically, simulated 1 GeV/$c$ charged pions and protons are correctly reconstructed and identified with efficiencies of 86.1$\pm0.6$% and 84.1$\pm0.6$%, respectively. The efficiencies measured for test-beam data are shown to be within 5% of those predicted by the simulation

Reconstruction of interactions in the ProtoDUNE-SP detector with Pandora

International audienceThe Pandora Software Development Kit and algorithm libraries provide pattern-recognition logic essential to the reconstruction of particle interactions in liquid argon time projection chamber detectors. Pandora is the primary event reconstruction software used at ProtoDUNE-SP, a prototype for the Deep Underground Neutrino Experiment far detector. ProtoDUNE-SP, located at CERN, is exposed to a charged-particle test beam. This paper gives an overview of the Pandora reconstruction algorithms and how they have been tailored for use at ProtoDUNE-SP. In complex events with numerous cosmic-ray and beam background particles, the simulated reconstruction and identification efficiency for triggered test-beam particles is above 80% for the majority of particle type and beam momentum combinations. Specifically, simulated 1 GeV/$c$ charged pions and protons are correctly reconstructed and identified with efficiencies of 86.1$\pm0.6$% and 84.1$\pm0.6$%, respectively. The efficiencies measured for test-beam data are shown to be within 5% of those predicted by the simulation

Reconstruction of interactions in the ProtoDUNE-SP detector with Pandora

International audienceThe Pandora Software Development Kit and algorithm libraries provide pattern-recognition logic essential to the reconstruction of particle interactions in liquid argon time projection chamber detectors. Pandora is the primary event reconstruction software used at ProtoDUNE-SP, a prototype for the Deep Underground Neutrino Experiment far detector. ProtoDUNE-SP, located at CERN, is exposed to a charged-particle test beam. This paper gives an overview of the Pandora reconstruction algorithms and how they have been tailored for use at ProtoDUNE-SP. In complex events with numerous cosmic-ray and beam background particles, the simulated reconstruction and identification efficiency for triggered test-beam particles is above 80% for the majority of particle type and beam momentum combinations. Specifically, simulated 1 GeV/$c$ charged pions and protons are correctly reconstructed and identified with efficiencies of 86.1$\pm0.6$% and 84.1$\pm0.6$%, respectively. The efficiencies measured for test-beam data are shown to be within 5% of those predicted by the simulation