TY - CONF AB - This report presents the results of a friendly competition for formal verification of continuous and hybrid systems with piecewise constant dynamics. The friendly competition took place as part of the workshop Applied Verification for Continuous and Hybrid Systems (ARCH) in 2019. In this third edition, six tools have been applied to solve five different benchmark problems in the category for piecewise constant dynamics: BACH, Lyse, Hy- COMP, PHAVer/SX, PHAVerLite, and VeriSiMPL. Compared to last year, a new tool has participated (HyCOMP) and PHAVerLite has replaced PHAVer-lite. The result is a snap- shot of the current landscape of tools and the types of benchmarks they are particularly suited for. Due to the diversity of problems, we are not ranking tools, yet the presented results probably provide the most complete assessment of tools for the safety verification of continuous and hybrid systems with piecewise constant dynamics up to this date. AU - Frehse, Goran AU - Abate, Alessandro AU - Adzkiya, Dieky AU - Becchi, Anna AU - Bu, Lei AU - Cimatti, Alessandro AU - Giacobbe, Mirco AU - Griggio, Alberto AU - Mover, Sergio AU - Mufid, Muhammad Syifa'ul AU - Riouak, Idriss AU - Tonetta, Stefano AU - Zaffanella, Enea ED - Frehse, Goran ED - Althoff, Matthias ID - 10877 SN - 2398-7340 T2 - ARCH19. 6th International Workshop on Applied Verification of Continuous and Hybrid Systems TI - ARCH-COMP19 Category Report: Hybrid systems with piecewise constant dynamics VL - 61 ER - TY - JOUR AB - Many adult tissues contain postmitotic cells as old as the host organism. The only organelle that does not turn over in these cells is the nucleus, and its maintenance represents a formidable challenge, as it harbors regulatory proteins that persist throughout adulthood. Here we developed strategies to visualize two classes of such long-lived proteins, histones and nucleoporins, to understand the function of protein longevity in nuclear maintenance. Genome-wide mapping of histones revealed specific enrichment of long-lived variants at silent gene loci. Interestingly, nuclear pores are maintained by piecemeal replacement of subunits, resulting in mosaic complexes composed of polypeptides with vastly different ages. In contrast, nondividing quiescent cells remove old nuclear pores in an ESCRT-dependent manner. Our findings reveal distinct molecular strategies of nuclear maintenance, linking lifelong protein persistence to gene regulation and nuclear integrity. AU - Toyama, Brandon H. AU - Arrojo e Drigo, Rafael AU - Lev-Ram, Varda AU - Ramachandra, Ranjan AU - Deerinck, Thomas J. AU - Lechene, Claude AU - Ellisman, Mark H. AU - HETZER, Martin W ID - 11061 IS - 2 JF - Journal of Cell Biology KW - Cell Biology SN - 0021-9525 TI - Visualization of long-lived proteins reveals age mosaicism within nuclei of postmitotic cells VL - 218 ER - TY - JOUR AB - Most neurons are not replaced during an animal’s lifetime. This nondividing state is characterized by extreme longevity and age-dependent decline of key regulatory proteins. To study the lifespans of cells and proteins in adult tissues, we combined isotope labeling of mice with a hybrid imaging method (MIMS-EM). Using 15N mapping, we show that liver and pancreas are composed of cells with vastly different ages, many as old as the animal. Strikingly, we also found that a subset of fibroblasts and endothelial cells, both known for their replicative potential, are characterized by the absence of cell division during adulthood. In addition, we show that the primary cilia of beta cells and neurons contains different structural regions with vastly different lifespans. Based on these results, we propose that age mosaicism across multiple scales is a fundamental principle of adult tissue, cell, and protein complex organization. AU - Arrojo e Drigo, Rafael AU - Lev-Ram, Varda AU - Tyagi, Swati AU - Ramachandra, Ranjan AU - Deerinck, Thomas AU - Bushong, Eric AU - Phan, Sebastien AU - Orphan, Victoria AU - Lechene, Claude AU - Ellisman, Mark H. AU - HETZER, Martin W ID - 11062 IS - 2 JF - Cell Metabolism KW - Cell Biology KW - Molecular Biology KW - Physiology SN - 1550-4131 TI - Age mosaicism across multiple scales in adult tissues VL - 30 ER - TY - JOUR AB - The genome is packaged and organized nonrandomly within the 3D space of the nucleus to promote efficient gene expression and to faithfully maintain silencing of heterochromatin. The genome is enclosed within the nucleus by the nuclear envelope membrane, which contains a set of proteins that actively participate in chromatin organization and gene regulation. Technological advances are providing views of genome organization at unprecedented resolution and are beginning to reveal the ways that cells co-opt the structures of the nuclear periphery for nuclear organization and gene regulation. These genome regulatory roles of proteins of the nuclear periphery have important influences on development, disease and ageing. AU - Buchwalter, Abigail AU - Kaneshiro, Jeanae M. AU - HETZER, Martin W ID - 11059 IS - 1 JF - Nature Reviews Genetics KW - Genetics (clinical) KW - Genetics KW - Molecular Biology SN - 1471-0056 TI - Coaching from the sidelines: The nuclear periphery in genome regulation VL - 20 ER - TY - JOUR AB - Deep optical spectroscopic surveys of galaxies provide a unique opportunity to investigate rest-frame ultra-violet (UV) emission line properties of galaxies at z ∼ 2 − 4.5. Here we combine VLT/MUSE Guaranteed Time Observations of the Hubble Deep Field South, Ultra Deep Field, COSMOS, and several quasar fields with other publicly available data from VLT/VIMOS and VLT/FORS2 to construct a catalogue of He II λ1640 emitters at z ≳ 2. The deepest areas of our MUSE pointings reach a 3σ line flux limit of 3.1 × 10−19 erg s−1 cm−2. After discarding broad-line active galactic nuclei, we find 13 He II λ1640 detections from MUSE with a median MUV = −20.1 and 21 tentative He II λ1640 detections from other public surveys. Excluding Lyα, all except two galaxies in our sample show at least one other rest-UV emission line, with C III] λ1907, λ1909 being the most prominent. We use multi-wavelength data available in the Hubble legacy fields to derive basic galaxy properties of our sample through spectral energy distribution fitting techniques. Taking advantage of the high-quality spectra obtained by MUSE (∼10 − 30 h of exposure time per pointing), we use photo-ionisation models to study the rest-UV emission line diagnostics of the He II λ1640 emitters. Line ratios of our sample can be reproduced by moderately sub-solar photo-ionisation models, however, we find that including effects of binary stars lead to degeneracies in most free parameters. Even after considering extra ionising photons produced by extreme sub-solar metallicity binary stellar models, photo-ionisation models are unable to reproduce rest-frame He II λ1640 equivalent widths (∼0.2 − 10 Å), thus additional mechanisms are necessary in models to match the observed He II λ1640 properties. AU - Nanayakkara, Themiya AU - Brinchmann, Jarle AU - Boogaard, Leindert AU - Bouwens, Rychard AU - Cantalupo, Sebastiano AU - Feltre, Anna AU - Kollatschny, Wolfram AU - Marino, Raffaella Anna AU - Maseda, Michael AU - Matthee, Jorryt J AU - Paalvast, Mieke AU - Richard, Johan AU - Verhamme, Anne ID - 11499 JF - Astronomy & Astrophysics KW - Space and Planetary Science KW - Astronomy and Astrophysics KW - galaxies: ISM / galaxies: star formation / galaxies: evolution / galaxies: high-redshift SN - 0004-6361 TI - Exploring He II λ1640 emission line properties at z ∼2−4 VL - 648 ER -