@article{11059, abstract = {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.}, author = {Buchwalter, Abigail and Kaneshiro, Jeanae M. and HETZER, Martin W}, issn = {1471-0064}, journal = {Nature Reviews Genetics}, keywords = {Genetics (clinical), Genetics, Molecular Biology}, number = {1}, pages = {39--50}, publisher = {Springer Nature}, title = {{Coaching from the sidelines: The nuclear periphery in genome regulation}}, doi = {10.1038/s41576-018-0063-5}, volume = {20}, year = {2019}, } @article{11060, abstract = {The inner nuclear membrane (INM) is a subdomain of the endoplasmic reticulum (ER) that is gated by the nuclear pore complex. It is unknown whether proteins of the INM and ER are degraded through shared or distinct pathways in mammalian cells. We applied dynamic proteomics to profile protein half-lives and report that INM and ER residents turn over at similar rates, indicating that the INM’s unique topology is not a barrier to turnover. Using a microscopy approach, we observed that the proteasome can degrade INM proteins in situ. However, we also uncovered evidence for selective, vesicular transport-mediated turnover of a single INM protein, emerin, that is potentiated by ER stress. Emerin is rapidly cleared from the INM by a mechanism that requires emerin’s LEM domain to mediate vesicular trafficking to lysosomes. This work demonstrates that the INM can be dynamically remodeled in response to environmental inputs.}, author = {Buchwalter, Abigail and Schulte, Roberta and Tsai, Hsiao and Capitanio, Juliana and HETZER, Martin W}, issn = {2050-084X}, journal = {eLife}, keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience}, publisher = {eLife Sciences Publications}, title = {{Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress}}, doi = {10.7554/elife.49796}, volume = {8}, year = {2019}, } @article{11061, abstract = {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.}, author = {Toyama, Brandon H. and Arrojo e Drigo, Rafael and Lev-Ram, Varda and Ramachandra, Ranjan and Deerinck, Thomas J. and Lechene, Claude and Ellisman, Mark H. and HETZER, Martin W}, issn = {1540-8140}, journal = {Journal of Cell Biology}, keywords = {Cell Biology}, number = {2}, pages = {433--444}, publisher = {Rockefeller University Press}, title = {{Visualization of long-lived proteins reveals age mosaicism within nuclei of postmitotic cells}}, doi = {10.1083/jcb.201809123}, volume = {218}, year = {2019}, } @article{11062, abstract = {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.}, author = {Arrojo e Drigo, Rafael and Lev-Ram, Varda and Tyagi, Swati and Ramachandra, Ranjan and Deerinck, Thomas and Bushong, Eric and Phan, Sebastien and Orphan, Victoria and Lechene, Claude and Ellisman, Mark H. and HETZER, Martin W}, issn = {1550-4131}, journal = {Cell Metabolism}, keywords = {Cell Biology, Molecular Biology, Physiology}, number = {2}, pages = {343--351.e3}, publisher = {Elsevier}, title = {{Age mosaicism across multiple scales in adult tissues}}, doi = {10.1016/j.cmet.2019.05.010}, volume = {30}, year = {2019}, } @article{10354, abstract = {Background ESCRT-III is a membrane remodelling filament with the unique ability to cut membranes from the inside of the membrane neck. It is essential for the final stage of cell division, the formation of vesicles, the release of viruses, and membrane repair. Distinct from other cytoskeletal filaments, ESCRT-III filaments do not consume energy themselves, but work in conjunction with another ATP-consuming complex. Despite rapid progress in describing the cell biology of ESCRT-III, we lack an understanding of the physical mechanisms behind its force production and membrane remodelling. Results Here we present a minimal coarse-grained model that captures all the experimentally reported cases of ESCRT-III driven membrane sculpting, including the formation of downward and upward cones and tubules. This model suggests that a change in the geometry of membrane bound ESCRT-III filaments—from a flat spiral to a 3D helix—drives membrane deformation. We then show that such repetitive filament geometry transitions can induce the fission of cargo-containing vesicles. Conclusions Our model provides a general physical mechanism that explains the full range of ESCRT-III-dependent membrane remodelling and scission events observed in cells. This mechanism for filament force production is distinct from the mechanisms described for other cytoskeletal elements discovered so far. The mechanistic principles revealed here suggest new ways of manipulating ESCRT-III-driven processes in cells and could be used to guide the engineering of synthetic membrane-sculpting systems.}, author = {Harker-Kirschneck, Lena and Baum, Buzz and Šarić, Anđela}, issn = {1741-7007}, journal = {BMC Biology}, keywords = {cell biology}, number = {1}, publisher = {Springer Nature}, title = {{Changes in ESCRT-III filament geometry drive membrane remodelling and fission in silico}}, doi = {10.1186/s12915-019-0700-2}, volume = {17}, year = {2019}, } @article{10355, abstract = {The molecular machinery of life is largely created via self-organisation of individual molecules into functional assemblies. Minimal coarse-grained models, in which a whole macromolecule is represented by a small number of particles, can be of great value in identifying the main driving forces behind self-organisation in cell biology. Such models can incorporate data from both molecular and continuum scales, and their results can be directly compared to experiments. Here we review the state of the art of models for studying the formation and biological function of macromolecular assemblies in living organisms. We outline the key ingredients of each model and their main findings. We illustrate the contribution of this class of simulations to identifying the physical mechanisms behind life and diseases, and discuss their future developments.}, author = {Hafner, Anne E and Krausser, Johannes and Šarić, Anđela}, issn = {0959-440X}, journal = {Current Opinion in Structural Biology}, keywords = {molecular biology, structural biology}, pages = {43--52}, publisher = {Elsevier}, title = {{Minimal coarse-grained models for molecular self-organisation in biology}}, doi = {10.1016/j.sbi.2019.05.018}, volume = {58}, year = {2019}, } @article{105, abstract = {Clinical Utility Gene Card. 1. Name of Disease (Synonyms): Pontocerebellar hypoplasia type 9 (PCH9) and spastic paraplegia-63 (SPG63). 2. OMIM# of the Disease: 615809 and 615686. 3. Name of the Analysed Genes or DNA/Chromosome Segments: AMPD2 at 1p13.3. 4. OMIM# of the Gene(s): 102771.}, author = {Marsh, Ashley and Novarino, Gaia and Lockhart, Paul and Leventer, Richard}, journal = {European Journal of Human Genetics}, pages = {161--166}, publisher = {Springer Nature}, title = {{CUGC for pontocerebellar hypoplasia type 9 and spastic paraplegia-63}}, doi = {10.1038/s41431-018-0231-2}, volume = {27}, year = {2019}, } @article{21095, abstract = {Inspired by DNA mimic proteins, we have introduced aromatic foldamers bearing phosphonate groups as synthetic mimics of the charge surface of B-DNA and competitive inhibitors of some therapeutically relevant DNA-binding enzymes: the human DNA Topoisomerase 1 (Top1) and the human HIV-1 integrase (HIV-1 IN). We now report on variants of these anionic foldamers bearing carboxylates instead of phosphonates. Several new monomers have been synthesized with protecting groups suitable for solid phase synthesis (SPS). Six hexadecaamides have been prepared using SPS. Proof of their resemblance to B-DNA was brought by the first crystal structure of one of these DNA-mimic foldamers in its polyanionic form. While some of the foldamers were found to be as active as, or even more active than, the original phosphonate oligomers, others had no activity at all or could even stimulate enzyme activity in vitro. Some foldamers were found to have differential inhibitory effects on the two enzymes. These results demonstrate a strong dependence of inhibitory activity on foldamer structure and charge distribution. They open broad avenues for the development of new classes of derivatives that could inhibit the interaction of specific proteins with their DNA target thereby influencing the cellular pathways in which they are involved.}, author = {Corvaglia, Valentina and Carbajo, Daniel and Prabhakaran, Panchami and Ziach, Krzysztof and Mandal, Pradeep K and Santos, Victor Dos and Legeay, Carole and Vogel, Rachel and Parissi, Vincent and Pourquier, Philippe and Huc, Ivan}, issn = {1362-4962}, journal = {Nucleic Acids Research}, number = {11}, pages = {5511--5521}, publisher = {Oxford University Press}, title = {{Carboxylate-functionalized foldamer inhibitors of HIV-1 integrase and Topoisomerase 1: Artificial analogues of DNA mimic proteins}}, doi = {10.1093/nar/gkz352}, volume = {47}, year = {2019}, } @article{170, abstract = {Upper and lower bounds, of the expected order of magnitude, are obtained for the number of rational points of bounded height on any quartic del Pezzo surface over ℚ that contains a conic defined over ℚ .}, author = {Browning, Timothy D and Sofos, Efthymios}, journal = {Mathematische Annalen}, number = {3-4}, pages = {977--1016}, publisher = {Springer Nature}, title = {{Counting rational points on quartic del Pezzo surfaces with a rational conic}}, doi = {10.1007/s00208-018-1716-6}, volume = {373}, year = {2019}, } @article{175, abstract = {An upper bound sieve for rational points on suitable varieties isdeveloped, together with applications tocounting rational points in thin sets,to local solubility in families, and to the notion of “friable” rational pointswith respect to divisors. In the special case of quadrics, sharper estimates areobtained by developing a version of the Selberg sieve for rational points.}, author = {Browning, Timothy D and Loughran, Daniel}, issn = {1088-6850}, journal = {Transactions of the American Mathematical Society}, number = {8}, pages = {5757--5785}, publisher = {American Mathematical Society}, title = {{Sieving rational points on varieties}}, doi = {10.1090/tran/7514}, volume = {371}, year = {2019}, } @article{17506, abstract = {Sandboxing is a common technique that allows low-level, untrusted components to safely interact with trusted code. However, previous work has only investigated the low-level memory isolation guarantees of sandboxing, leaving open the question of the end-to-end guarantees that sandboxing affords programmers. In this paper, we fill this gap by showing that sandboxing enables reasoning about the known concept of robust safety, i.e., safety of the trusted code even in the presence of arbitrary untrusted code. To do this, we first present an idealized operational semantics for a language that combines trusted code with untrusted code. Sandboxing is built into our semantics. Then, we prove that safety properties of the trusted code (as enforced through a rich type system) are upheld in the presence of arbitrary untrusted code, so long as all interactions with untrusted code occur at the “any” type (a type inhabited by all values). Finally, to alleviate the burden of having to interact with untrusted code at only the “any” type, we formalize and prove safe several wrappers, which automatically convert values between the “any” type and much richer types. All our results are mechanized in the Coq proof assistant.}, author = {Sammler, Michael Joachim and Garg, Deepak and Dreyer, Derek and Litak, Tadeusz}, issn = {2475-1421}, journal = {Proceedings of the ACM on Programming Languages}, number = {POPL}, pages = {1--32}, publisher = {Association for Computing Machinery}, title = {{The high-level benefits of low-level sandboxing}}, doi = {10.1145/3371100}, volume = {4}, year = {2019}, } @article{17510, abstract = {Weak lensing surveys are reaching sensitivities at which uncertainties in the galaxy redshift distributions n(z) from photo-z errors degrade cosmological constraints. We use ray-tracing simulations and a simple treatment of photo-z errors to assess cosmological parameter biases from uncertainties in n(z) in an LSST-like survey. We use lensing peak counts and the power spectrum to infer cosmological parameters, and find that the latter is somewhat more resilient to photo-z errors. We place conservative lower limits on the survey size at which different types of photo-z errors significantly degrade (${\sim }50{{\ \rm per\ cent}}$) ΛCDM (cold dark matter, wCDM) parameter constraints. A residual constant photo-z bias of |δz| &lt; 0.003(1 + z), the current LSST requirement, does not significantly degrade surveys smaller than ≈1300 (≈490) deg2 using peaks and ≈6500 (≈4900) deg2 using the power spectrum. Surveys smaller than ≈920 (≈450) deg2 and ≈4600 (≈4000) deg2 avoid 25 per cent degradation. Adopting a recent prediction for LSST’s full photo-z probability distribution function (PDF), we find that simply approximating n(z) with the photo-z galaxy distribution computed from this PDF significantly degrades surveys as small as ≈60 (≈65) deg2 using peaks or the power spectrum. If the centroid bias in each tomographic bin is removed from the photo-z galaxy distribution, using peaks or the power spectrum still significantly degrades surveys larger than ≈200 (≈255) or ≈248 (≈315) deg2; 25 per cent degradations occur at survey sizes of ≈140 (≈180) deg2 or ≈165 (≈210) deg2. These results imply that the expected broad photo-z PDF significantly biases parameters, which must be further mitigated using more sophisticated photo-z treatments.}, author = {Abruzzo, Matthew W and Haiman, Zoltán}, issn = {0035-8711}, journal = {Monthly Notices of the Royal Astronomical Society}, number = {2}, pages = {2730--2753}, publisher = {Oxford University Press}, title = {{The impact of photometric redshift errors on lensing statistics in ray-tracing simulations}}, doi = {10.1093/mnras/stz1016}, volume = {486}, year = {2019}, } @article{17511, author = {Marques, Gabriela A. and Liu, Jia and Matilla, José Manuel Zorrilla and Haiman, Zoltán and Bernui, Armando and Novaes, Camila P.}, issn = {1475-7516}, journal = {Journal of Cosmology and Astroparticle Physics}, number = {06}, publisher = {IOP Publishing}, title = {{Constraining neutrino mass with weak lensing Minkowski Functionals}}, doi = {10.1088/1475-7516/2019/06/019}, volume = {2019}, year = {2019}, } @article{17512, abstract = {The localization of stellar-mass binary black hole mergers using gravitational waves is critical in understanding the properties of the binaries’ host galaxies, observing possible electromagnetic emission from the mergers, or using them as a cosmological distance ladder. The precision of this localization can be substantially increased with prior astrophysical information about the binary system. In particular, constraining the inclination of the binary can reduce the distance uncertainty of the source. Here, we present the first realistic set of localizations for binary black hole mergers, including different prior constraints on the binaries’ inclinations. We find that prior information on the inclination can reduce the localization volume by a factor of 3. We discuss two astrophysical scenarios of interest: (i) follow-up searches for beamed electromagnetic/neutrino counterparts and (ii) mergers in the accretion discs of active galactic nuclei.}, author = {Corley, K Rainer and Bartos, Imre and Singer, Leo P and Williamson, Andrew R and Haiman, Zoltán and Kocsis, Bence and Nissanke, Samaya and Márka, Zsuzsa and Márka, Szabolcs}, issn = {0035-8711}, journal = {Monthly Notices of the Royal Astronomical Society}, number = {3}, pages = {4459--4463}, publisher = {Oxford University Press}, title = {{Localization of binary black hole mergers with known inclination}}, doi = {10.1093/mnras/stz2072}, volume = {488}, year = {2019}, } @article{17530, abstract = {Based on the cosmic shear data from the Canada-France-Hawaii Telescope Lensing Survey (CFHTLenS), Kilbinger et al. (2013) obtained a constraint on the amplitude of matter fluctuations of σ8(Ωm/0.27)0.6=0.79±0.03 from the two-point correlation function (2PCF). This is ≈3σ lower than the value 0.89±0.01 derived from Planck data on cosmic microwave background (CMB) anisotropies. On the other hand, based on the same CFHTLenS data, but using the power spectrum, and performing a different analysis, Liu et al. (2015) obtained the higher value of σ8(Ωm/0.27)0.64=0.87+0.05−0.06. We here investigate the origin of this difference, by performing a fair side-by-side comparison of the 2PCF and power spectrum analyses on CFHTLenS data. We find that these two statistics indeed deliver different results, even when applied to the same data in an otherwise identical procedure. We identify excess power in the data on small scales (ℓ>5,000) driving the larger values inferred from the power spectrum. We speculate on the possible origin of this excess small-scale power. More generally, our results highlight the utility of analysing the 2PCF and the power spectrum in tandem, to discover (and to help control) systematic errors.}, author = {Lu, Tianhuan and Haiman, Zoltán}, issn = {0035-8711}, journal = {Monthly Notices of the Royal Astronomical Society}, number = {4}, pages = {5033--5042}, publisher = {Oxford University Press}, title = {{The matter fluctuation amplitude inferred from the weak lensing power spectrum and correlation function in CFHTLenS data}}, doi = {10.1093/mnras/stz2931}, volume = {490}, year = {2019}, } @article{17533, abstract = {The origins of the stellar-mass black hole mergers discovered by LIGO/Virgo are still unknown. Here we show that if migration traps develop in the accretion disks of active galactic nuclei (AGNs) and promote the mergers of their captive black holes, the majority of black holes within disks will undergo hierarchical mergers—with one of the black holes being the remnant of a previous merger. 40% of AGN-assisted mergers detected by LIGO/Virgo will include a black hole with mass ≳50⁢𝑀⊙, the mass limit from stellar core collapse. Hierarchical mergers at traps in AGNs will exhibit black hole spins (anti)aligned with the binary’s orbital axis, a distinct property from other hierarchical channels. Our results suggest, although not definitively (with odds ratio of ∼1), that LIGO’s heaviest merger so far, GW170729, could have originated from this channel.}, author = {Yang, Y. and Bartos, I. and Gayathri, V. and Ford, K. E. S. and Haiman, Zoltán and Klimenko, S. and Kocsis, B. and Márka, S. and Márka, Z. and McKernan, B. and O’Shaughnessy, R.}, issn = {0031-9007}, journal = {Physical Review Letters}, number = {18}, publisher = {American Physical Society}, title = {{Hierarchical black hole mergers in active galactic nuclei}}, doi = {10.1103/physrevlett.123.181101}, volume = {123}, year = {2019}, } @article{17541, abstract = {In recent years, the discovery of massive quasars at z~7 has provided a striking challenge to our understanding of the origin and growth of supermassive black holes in the early Universe. Mounting observational and theoretical evidence indicates the viability of massive seeds, formed by the collapse of supermassive stars, as a progenitor model for such early, massive accreting black holes. Although considerable progress has been made in our theoretical understanding, many questions remain regarding how (and how often) such objects may form, how they live and die, and how next generation observatories may yield new insight into the origin of these primordial titans. This review focusses on our present understanding of this remarkable formation scenario, based on discussions held at the Monash Prato Centre from November 20--24, 2017, during the workshop "Titans of the Early Universe: The Origin of the First Supermassive Black Holes."}, author = {Woods, Tyrone E. and Agarwal, Bhaskar and Bromm, Volker and Bunker, Andrew and Chen, Ke-Jung and Chon, Sunmyon and Ferrara, Andrea and Glover, Simon C. O. and Haemmerlé, Lionel and Haiman, Zoltán and Hartwig, Tilman and Heger, Alexander and Hirano, Shingo and Hosokawa, Takashi and Inayoshi, Kohei and Klessen, Ralf S. and Kobayashi, Chiaki and Koliopanos, Filippos and Latif, Muhammad A. and Li, Yuexing and Mayer, Lucio and Mezcua, Mar and Natarajan, Priyamvada and Pacucci, Fabio and Rees, Martin J. and Regan, John A. and Sakurai, Yuya and Salvadori, Stefania and Schneider, Raffaella and Surace, Marco and Tanaka, Takamitsu L. and Whalen, Daniel J. and Yoshida, Naoki}, issn = {1323-3580}, journal = {Publications of the Astronomical Society of Australia}, publisher = {Cambridge University Press}, title = {{Titans of the early universe: The prato statement on the origin of the first supermassive black holes}}, doi = {10.1017/pasa.2019.14}, volume = {36}, year = {2019}, } @article{17543, abstract = {Massive black-hole (MBH) binaries, which are expected to form following the merger of their parent galaxies, produce gravitational waves which will be detectable by Pulsar Timing Arrays at nanohertz frequencies (year periods). While no confirmed, compact MBH binary systems have been seen in electromagnetic observations, a large number of candidates have recently been identified in optical surveys of AGN variability. Using a combination of cosmological, hydrodynamic simulations; comprehensive, semi-analytic binary merger models; and analytic AGN spectra and variability prescriptions; we calculate the expected electromagnetic detection rates of MBH binaries as periodically variable AGN. In particular, we consider two independent variability models: (i) Doppler boosting due to large orbital velocities, and (ii) hydrodynamic variability in which the fueling of MBH accretion disks is periodically modulated by the companion. Our models predict that numerous MBH binaries should be present and distinguishable in the existing data. In particular, our fiducial models produce an expectation value of 0.2 (Doppler) and 5 (hydrodynamic) binaries to be identifiable in CRTS, while 20 and 100 are expected after five years of LSST observations. The brightness variations in most systems are too small to be distinguishable, but almost 1% of AGN at redshifts z≲0.6 could be in massive binaries. We analyze the predicted binary parameters of observable systems and their selection biases, and include an extensive discussion of our model parameters and uncertainties.}, author = {Kelley, Luke Zoltan and Haiman, Zoltán and Sesana, Alberto and Hernquist, Lars}, issn = {0035-8711}, journal = {Monthly Notices of the Royal Astronomical Society}, number = {2}, pages = {1579--1594}, publisher = {Oxford University Press}, title = {{Massive BH binaries as periodically variable AGN}}, doi = {10.1093/mnras/stz150}, volume = {485}, year = {2019}, } @article{17556, abstract = {The abundance of molecular hydrogen (H2), the primary coolant in primordial gas, is critical for the thermodynamic evolution and star-formation histories in early protogalaxies. Determining the photodissociation rate of H2 by an incident Lyman-Werner (LW) flux is thus crucial, but prohibitively expensive to calculate on the fly in simulations. The rate is sensitive to the H2 rovibrational distribution, which in turn depends on the gas density, temperature, and incident LW radiation field. We use the publicly available cloudy package to model primordial gas clouds and compare exact photodissociation rate calculations to commonly-used fitting formulae. We find the fit from Wolcott-Green et al. (2011) is most accurate for moderate densities n~10^3 cm^{-3} and temperatures, T~10^3K, and we provide a new fit, which captures the increase in the rate at higher densities and temperatures, owing to the increased excited rovibrational populations in this regime. Our new fit has typical errors of a few percent percent up to n =<10^7 cm^{-3}, T =< 8000K, and H2 column density NH2 =<10^{17} cm^{-2}, and can be easily utilized in simulations. We also show that pumping of the excited rovibrational states of H2 by a strong LW flux further modifies the level populations when the gas density is low, and noticeably decreases self-shielding for J_21 > 10^3 and n < 10^2 cm^{-3}. This may lower the "critical flux" at which primordial gas remains H2-poor in some protogalaxies, enabling massive black hole seed formation.}, author = {Wolcott-Green, J and Haiman, Zoltán}, issn = {0035-8711}, journal = {Monthly Notices of the Royal Astronomical Society}, number = {2}, pages = {2467--2473}, publisher = {Oxford University Press}, title = {{H2 self-shielding with non-LTE rovibrational populations: Implications for cooling in protogalaxies}}, doi = {10.1093/mnras/sty3280}, volume = {484}, year = {2019}, } @article{17565, abstract = {The coalescence of a compact object with a 104−107M⊙ supermassive black hole (SMBH) produces mHz gravitational waves (GWs) detectable by the future Laser Interferometer Space Antenna (LISA). If such an inspiral occurs in the accretion disc of an active galactic nucleus (AGN), the gas torques imprint a small deviation in the GW waveform. Here we present two-dimensional hydrodynamical simulations with the moving-mesh code DISCO of a BH inspiraling at the GW rate in a binary system with a mass ratio q=M2/M1=10−3, embedded in an accretion disc. We assume a locally isothermal equation of state for the gas (with Mach number M=20) and implement a standard α-prescription for its viscosity (with α=0.03). We find disc torques on the binary that are weaker than in previous semi-analytic toy models, and are in the opposite direction: the gas disc slows down, rather than speeds up the inspiral. We compute the resulting deviations in the GW waveform, which scale linearly with the mass of the disc. The SNR of these deviations accumulates mostly at high frequencies, and becomes detectable in a 5-year LISA observation if the total phase shift exceeds a few radians. We find that this occurs if the disc surface density exceeds Σ0≳102−3gcm−2, as may be the case in thin discs with near-Eddington accretion rates. Since the characteristic imprint on the GW signal is strongly dependent on disc parameters, a LISA detection of an intermediate mass ratio inspiral would probe the physics of AGN discs and migration.}, author = {Derdzinski, A M and D’Orazio, D and Duffell, P and Haiman, Zoltán and MacFadyen, A}, issn = {0035-8711}, journal = {Monthly Notices of the Royal Astronomical Society}, number = {2}, pages = {2754--2765}, publisher = {Oxford University Press}, title = {{Probing gas disc physics with LISA: simulations of an intermediate mass ratio inspiral in an accretion disc}}, doi = {10.1093/mnras/stz1026}, volume = {486}, year = {2019}, }