@article{10378, abstract = {The ability of biological molecules to replicate themselves is the foundation of life, requiring a complex cellular machinery. However, a range of aberrant processes involve the self-replication of pathological protein structures without any additional assistance. One example is the autocatalytic generation of pathological protein aggregates, including amyloid fibrils, involved in neurodegenerative disorders. Here, we use computer simulations to identify the necessary requirements for the self-replication of fibrillar assemblies of proteins. We establish that a key physical determinant for this process is the affinity of proteins for the surfaces of fibrils. We find that self-replication can take place only in a very narrow regime of inter-protein interactions, implying a high level of sensitivity to system parameters and experimental conditions. We then compare our theoretical predictions with kinetic and biosensor measurements of fibrils formed from the Aβ peptide associated with Alzheimer’s disease. Our results show a quantitative connection between the kinetics of self-replication and the surface coverage of fibrils by monomeric proteins. These findings reveal the fundamental physical requirements for the formation of supra-molecular structures able to replicate themselves, and shed light on mechanisms in play in the proliferation of protein aggregates in nature.}, author = {Šarić, Anđela and Buell, Alexander K. and Meisl, Georg and Michaels, Thomas C. T. and Dobson, Christopher M. and Linse, Sara and Knowles, Tuomas P. J. and Frenkel, Daan}, issn = {1745-2481}, journal = {Nature Physics}, keywords = {general physics and astronomy}, number = {9}, pages = {874--880}, publisher = {Springer Nature}, title = {{Physical determinants of the self-replication of protein fibrils}}, doi = {10.1038/nphys3828}, volume = {12}, year = {2016}, } @article{10380, abstract = {Using non-equilibrium molecular dynamics simulations, it has been recently demonstrated that water molecules align in response to an imposed temperature gradient, resulting in an effective electric field. Here, we investigate how thermally induced fields depend on the underlying treatment of long-ranged interactions. For the short-ranged Wolf method and Ewald summation, we find the peak strength of the field to range between 2 × 107 and 5 × 107 V/m for a temperature gradient of 5.2 K/Å. Our value for the Wolf method is therefore an order of magnitude lower than the literature value [J. A. Armstrong and F. Bresme, J. Chem. Phys. 139, 014504 (2013); J. Armstrong et al., J. Chem. Phys. 143, 036101 (2015)]. We show that this discrepancy can be traced back to the use of an incorrect kernel in the calculation of the electrostatic field. More seriously, we find that the Wolf method fails to predict correct molecular orientations, resulting in dipole densities with opposite sign to those computed using Ewald summation. By considering two different multipole expansions, we show that, for inhomogeneous polarisations, the quadrupole contribution can be significant and even outweigh the dipole contribution to the field. Finally, we propose a more accurate way of calculating the electrostatic potential and the field. In particular, we show that averaging the microscopic field analytically to obtain the macroscopic Maxwell field reduces the error bars by up to an order of magnitude. As a consequence, the simulation times required to reach a given statistical accuracy decrease by up to two orders of magnitude.}, author = {Wirnsberger, P. and Fijan, D. and Šarić, Anđela and Neumann, M. and Dellago, C. and Frenkel, D.}, issn = {1089-7690}, journal = {The Journal of Chemical Physics}, keywords = {physical and theoretical chemistry, general physics and astronomy}, number = {22}, publisher = {American Institute of Physics}, title = {{Non-equilibrium simulations of thermally induced electric fields in water}}, doi = {10.1063/1.4953036}, volume = {144}, year = {2016}, } @article{10381, abstract = {We study phase behaviour of lipid-bilayer vesicles functionalised by ligand–receptor complexes made of synthetic DNA by introducing a modelling framework and a dedicated experimental platform. In particular, we perform Monte Carlo simulations that combine a coarse grained description of the lipid bilayer with state of art analytical models for multivalent ligand–receptor interactions. Using density of state calculations, we derive the partition function in pairs of vesicles and compute the number of ligand–receptor bonds as a function of temperature. Numerical results are compared to microscopy and fluorimetry experiments on large unilamellar vesicles decorated by DNA linkers carrying complementary overhangs. We find that vesicle aggregation is suppressed when the total number of linkers falls below a threshold value. Within the model proposed here, this is due to the higher configurational costs required to form inter-vesicle bridges as compared to intra-vesicle loops, which are in turn related to membrane deformability. Our findings and our numerical/experimental methodologies are applicable to the rational design of liposomes used as functional materials and drug delivery applications, as well as to study inter-membrane interactions in living systems, such as cell adhesion.}, author = {Bachmann, Stephan Jan and Kotar, Jurij and Parolini, Lucia and Šarić, Anđela and Cicuta, Pietro and Di Michele, Lorenzo and Mognetti, Bortolo Matteo}, issn = {1744-6848}, journal = {Soft Matter}, keywords = {condensed matter physics, general chemistry}, number = {37}, pages = {7804--7817}, publisher = {Royal Society of Chemistry}, title = {{Melting transition in lipid vesicles functionalised by mobile DNA linkers}}, doi = {10.1039/c6sm01515h}, volume = {12}, year = {2016}, } @article{21101, abstract = {It has previously been shown that the use of racemic mixtures of naturally chiral macromolecules such as protein and DNA can significantly aid the crystallogenesis process, thereby addressing one of the major bottlenecks to structure determination by X-ray crystallographic methods—that of crystal growth. Although previous studies have provided convincing evidence of the applicability of the racemic crystallization technique to DNA through the study of well-characterized DNA structures, we sought to apply this method to a historically challenging DNA sequence. For this purpose we chose a non-self-complementary DNA duplex containing the biologically-relevant Pribnow box consensus sequence ‘TATAAT’. Four racemic crystal structures of this previously un-crystallizable DNA target are reported (with resolutions in the range of 1.65–2.3 Å), with further crystallographic studies and structural analysis providing insight into the racemic crystallization process as well as structural details of this highly pertinent DNA sequence.}, author = {Mandal, Pradeep K and Collie, Gavin W. and Srivastava, Suresh C. and Kauffmann, Brice and Huc, Ivan}, issn = {1362-4962}, journal = {Nucleic Acids Research}, number = {12}, pages = {5936--5943}, publisher = {Oxford University Press}, title = {{Structure elucidation of the Pribnow box consensus promoter sequence by racemic DNA crystallography}}, doi = {10.1093/nar/gkw367}, volume = {44}, year = {2016}, } @article{1552, abstract = {Antibiotic resistance carries a fitness cost that must be overcome in order for resistance to persist over the long term. Compensatory mutations that recover the functional defects associated with resistance mutations have been argued to play a key role in overcoming the cost of resistance, but compensatory mutations are expected to be rare relative to generally beneficial mutations that increase fitness, irrespective of antibiotic resistance. Given this asymmetry, population genetics theory predicts that populations should adapt by compensatory mutations when the cost of resistance is large, whereas generally beneficial mutations should drive adaptation when the cost of resistance is small. We tested this prediction by determining the genomic mechanisms underpinning adaptation to antibiotic-free conditions in populations of the pathogenic bacterium Pseudomonas aeruginosa that carry costly antibiotic resistance mutations. Whole-genome sequencing revealed that populations founded by high-cost rifampicin-resistant mutants adapted via compensatory mutations in three genes of the RNA polymerase core enzyme, whereas populations founded by low-cost mutants adapted by generally beneficial mutations, predominantly in the quorum-sensing transcriptional regulator gene lasR. Even though the importance of compensatory evolution in maintaining resistance has been widely recognized, our study shows that the roles of general adaptation in maintaining resistance should not be underestimated and highlights the need to understand how selection at other sites in the genome influences the dynamics of resistance alleles in clinical settings.}, author = {Qi, Qin and Toll Riera, Macarena and Heilbron, Karl and Preston, Gail and Maclean, R Craig}, journal = {Proceedings of the Royal Society of London Series B Biological Sciences}, number = {1822}, publisher = {Royal Society, The}, title = {{The genomic basis of adaptation to the fitness cost of rifampicin resistance in Pseudomonas aeruginosa}}, doi = {10.1098/rspb.2015.2452}, volume = {283}, year = {2016}, } @article{1599, abstract = {The addition of polysialic acid to N- and/or O-linked glycans, referred to as polysialylation, is a rare posttranslational modification that is mainly known to control the developmental plasticity of the nervous system. Here we show that CCR7, the central chemokine receptor controlling immune cell trafficking to secondary lymphatic organs, carries polysialic acid. This modification is essential for the recognition of the CCR7 ligand CCL21. As a consequence, dendritic cell trafficking is abrogated in polysialyltransferase-deficient mice, manifesting as disturbed lymph node homeostasis and unresponsiveness to inflammatory stimuli. Structure-function analysis of chemokine-receptor interactions reveals that CCL21 adopts an autoinhibited conformation, which is released upon interaction with polysialic acid. Thus, we describe a glycosylation-mediated immune cell trafficking disorder and its mechanistic basis. }, author = {Kiermaier, Eva and Moussion, Christine and Veldkamp, Christopher and Gerardy Schahn, Rita and De Vries, Ingrid and Williams, Larry and Chaffee, Gary and Phillips, Andrew and Freiberger, Friedrich and Imre, Richard and Taleski, Deni and Payne, Richard and Braun, Asolina and Förster, Reinhold and Mechtler, Karl and Mühlenhoff, Martina and Volkman, Brian and Sixt, Michael K}, journal = {Science}, number = {6269}, pages = {186 -- 190}, publisher = {American Association for the Advancement of Science}, title = {{Polysialylation controls dendritic cell trafficking by regulating chemokine recognition}}, doi = {10.1126/science.aad0512}, volume = {351}, year = {2016}, } @article{1608, abstract = {We show that the Anderson model has a transition from localization to delocalization at exactly 2 dimensional growth rate on antitrees with normalized edge weights which are certain discrete graphs. The kinetic part has a one-dimensional structure allowing a description through transfer matrices which involve some Schur complement. For such operators we introduce the notion of having one propagating channel and extend theorems from the theory of one-dimensional Jacobi operators that relate the behavior of transfer matrices with the spectrum. These theorems are then applied to the considered model. In essence, in a certain energy region the kinetic part averages the random potentials along shells and the transfer matrices behave similar as for a one-dimensional operator with random potential of decaying variance. At d dimensional growth for d>2 this effective decay is strong enough to obtain absolutely continuous spectrum, whereas for some uniform d dimensional growth with d<2 one has pure point spectrum in this energy region. At exactly uniform 2 dimensional growth also some singular continuous spectrum appears, at least at small disorder. As a corollary we also obtain a change from singular spectrum (d≤2) to absolutely continuous spectrum (d≥3) for random operators of the type rΔdr+λ on ℤd, where r is an orthogonal radial projection, Δd the discrete adjacency operator (Laplacian) on ℤd and λ a random potential. }, author = {Sadel, Christian}, journal = {Annales Henri Poincare}, number = {7}, pages = {1631 -- 1675}, publisher = {Birkhäuser}, title = {{Anderson transition at 2 dimensional growth rate on antitrees and spectral theory for operators with one propagating channel}}, doi = {10.1007/s00023-015-0456-3}, volume = {17}, year = {2016}, } @article{1612, abstract = {We prove that whenever A is a 3-conservative relational structure with only binary and unary relations,then the algebra of polymorphisms of A either has no Taylor operation (i.e.,CSP(A)is NP-complete),or it generates an SD(∧) variety (i.e.,CSP(A)has bounded width).}, author = {Kazda, Alexandr}, journal = {Algebra Universalis}, number = {1}, pages = {75 -- 84}, publisher = {Springer}, title = {{CSP for binary conservative relational structures}}, doi = {10.1007/s00012-015-0358-8}, volume = {75}, year = {2016}, } @article{1613, abstract = {In the last decade, induced pluripotent stem (iPS) cells have revolutionized the utility of human in vitro models of neurological disease. The iPS-derived and differentiated cells allow researchers to study the impact of a distinct cell type in health and disease as well as performing therapeutic drug screens on a human genetic background. In particular, clinical trials for Alzheimer's disease (AD) have been often failing. Two of the potential reasons are first, the species gap involved in proceeding from initial discoveries in rodent models to human studies, and second, an unsatisfying patient stratification, meaning subgrouping patients based on the disease severity due to the lack of phenotypic and genetic markers. iPS cells overcome this obstacles and will improve our understanding of disease subtypes in AD. They allow researchers conducting in depth characterization of neural cells from both familial and sporadic AD patients as well as preclinical screens on human cells. In this review, we briefly outline the status quo of iPS cell research in neurological diseases along with the general advantages and pitfalls of these models. We summarize how genome-editing techniques such as CRISPR/Cas will allow researchers to reduce the problem of genomic variability inherent to human studies, followed by recent iPS cell studies relevant to AD. We then focus on current techniques for the differentiation of iPS cells into neural cell types that are relevant to AD research. Finally, we discuss how the generation of three-dimensional cell culture systems will be important for understanding AD phenotypes in a complex cellular milieu, and how both two- and three-dimensional iPS cell models can provide platforms for drug discovery and translational studies into the treatment of AD.}, author = {Mungenast, Alison and Siegert, Sandra and Tsai, Li}, journal = {Molecular and Cellular Neuroscience}, pages = {13 -- 31}, publisher = {Academic Press}, title = {{Modeling Alzheimer's disease with human induced pluripotent stem (iPS) cells}}, doi = {doi:10.1016/j.mcn.2015.11.010}, volume = {73}, year = {2016}, } @article{1616, abstract = {The hippocampus plays a key role in learning and memory. Previous studies suggested that the main types of principal neurons, dentate gyrus granule cells (GCs), CA3 pyramidal neurons, and CA1 pyramidal neurons, differ in their activity pattern, with sparse firing in GCs and more frequent firing in CA3 and CA1 pyramidal neurons. It has been assumed but never shown that such different activity may be caused by differential synaptic excitation. To test this hypothesis, we performed high-resolution whole-cell patch-clamp recordings in anesthetized rats in vivo. In contrast to previous in vitro data, both CA3 and CA1 pyramidal neurons fired action potentials spontaneously, with a frequency of ∼3–6 Hz, whereas GCs were silent. Furthermore, both CA3 and CA1 cells primarily fired in bursts. To determine the underlying mechanisms, we quantitatively assessed the frequency of spontaneous excitatory synaptic input, the passive membrane properties, and the active membrane characteristics. Surprisingly, GCs showed comparable synaptic excitation to CA3 and CA1 cells and the highest ratio of excitation versus hyperpolarizing inhibition. Thus, differential synaptic excitation is not responsible for differences in firing. Moreover, the three types of hippocampal neurons markedly differed in their passive properties. While GCs showed the most negative membrane potential, CA3 pyramidal neurons had the highest input resistance and the slowest membrane time constant. The three types of neurons also differed in the active membrane characteristics. GCs showed the highest action potential threshold, but displayed the largest gain of the input-output curves. In conclusion, our results reveal that differential firing of the three main types of hippocampal principal neurons in vivo is not primarily caused by differences in the characteristics of the synaptic input, but by the distinct properties of synaptic integration and input-output transformation.}, author = {Kowalski, Janina and Gan, Jian and Jonas, Peter M and Pernia-Andrade, Alejandro}, issn = {1098-1063}, journal = {Hippocampus}, number = {5}, pages = {668 -- 682}, publisher = {Wiley}, title = {{Intrinsic membrane properties determine hippocampal differential firing pattern in vivo in anesthetized rats}}, doi = {10.1002/hipo.22550}, volume = {26}, year = {2016}, } @article{1617, abstract = {We study the discrepancy of jittered sampling sets: such a set P⊂ [0,1]d is generated for fixed m∈ℕ by partitioning [0,1]d into md axis aligned cubes of equal measure and placing a random point inside each of the N=md cubes. We prove that, for N sufficiently large, 1/10 d/N1/2+1/2d ≤EDN∗(P)≤ √d(log N) 1/2/N1/2+1/2d, where the upper bound with an unspecified constant Cd was proven earlier by Beck. Our proof makes crucial use of the sharp Dvoretzky-Kiefer-Wolfowitz inequality and a suitably taylored Bernstein inequality; we have reasons to believe that the upper bound has the sharp scaling in N. Additional heuristics suggest that jittered sampling should be able to improve known bounds on the inverse of the star-discrepancy in the regime N≳dd. We also prove a partition principle showing that every partition of [0,1]d combined with a jittered sampling construction gives rise to a set whose expected squared L2-discrepancy is smaller than that of purely random points.}, author = {Pausinger, Florian and Steinerberger, Stefan}, journal = {Journal of Complexity}, pages = {199 -- 216}, publisher = {Academic Press}, title = {{On the discrepancy of jittered sampling}}, doi = {10.1016/j.jco.2015.11.003}, volume = {33}, year = {2016}, } @article{1620, abstract = {We consider the Bardeen–Cooper–Schrieffer free energy functional for particles interacting via a two-body potential on a microscopic scale and in the presence of weak external fields varying on a macroscopic scale. We study the influence of the external fields on the critical temperature. We show that in the limit where the ratio between the microscopic and macroscopic scale tends to zero, the next to leading order of the critical temperature is determined by the lowest eigenvalue of the linearization of the Ginzburg–Landau equation.}, author = {Frank, Rupert and Hainzl, Christian and Seiringer, Robert and Solovej, Jan}, journal = {Communications in Mathematical Physics}, number = {1}, pages = {189 -- 216}, publisher = {Springer}, title = {{The external field dependence of the BCS critical temperature}}, doi = {10.1007/s00220-015-2526-2}, volume = {342}, year = {2016}, } @article{1622, abstract = {We prove analogues of the Lieb–Thirring and Hardy–Lieb–Thirring inequalities for many-body quantum systems with fractional kinetic operators and homogeneous interaction potentials, where no anti-symmetry on the wave functions is assumed. These many-body inequalities imply interesting one-body interpolation inequalities, and we show that the corresponding one- and many-body inequalities are actually equivalent in certain cases.}, author = {Lundholm, Douglas and Nam, Phan and Portmann, Fabian}, journal = {Archive for Rational Mechanics and Analysis}, number = {3}, pages = {1343 -- 1382}, publisher = {Springer}, title = {{Fractional Hardy–Lieb–Thirring and related Inequalities for interacting systems}}, doi = {10.1007/s00205-015-0923-5}, volume = {219}, year = {2016}, } @article{1631, abstract = {Ancestral processes are fundamental to modern population genetics and spatial structure has been the subject of intense interest for many years. Despite this interest, almost nothing is known about the distribution of the locations of pedigree or genetic ancestors. Using both spatially continuous and stepping-stone models, we show that the distribution of pedigree ancestors approaches a travelling wave, for which we develop two alternative approximations. The speed and width of the wave are sensitive to the local details of the model. After a short time, genetic ancestors spread far more slowly than pedigree ancestors, ultimately diffusing out with radius ## rather than spreading at constant speed. In contrast to the wave of pedigree ancestors, the spread of genetic ancestry is insensitive to the local details of the models.}, author = {Kelleher, Jerome and Etheridge, Alison and Véber, Amandine and Barton, Nicholas H}, journal = {Theoretical Population Biology}, pages = {1 -- 12}, publisher = {Academic Press}, title = {{Spread of pedigree versus genetic ancestry in spatially distributed populations}}, doi = {10.1016/j.tpb.2015.10.008}, volume = {108}, year = {2016}, } @article{1641, abstract = {The plant hormone auxin (indole-3-acetic acid) is a major regulator of plant growth and development including embryo and root patterning, lateral organ formation and growth responses to environmental stimuli. Auxin is directionally transported from cell to cell by the action of specific auxin influx [AUXIN-RESISTANT1 (AUX1)] and efflux [PIN-FORMED (PIN)] transport regulators, whose polar, subcellular localizations are aligned with the direction of the auxin flow. Auxin itself regulates its own transport by modulation of the expression and subcellular localization of the auxin transporters. Increased auxin levels promote the transcription of PIN2 and AUX1 genes as well as stabilize PIN proteins at the plasma membrane, whereas prolonged auxin exposure increases the turnover of PIN proteins and their degradation in the vacuole. In this study, we applied a forward genetic approach, to identify molecular components playing a role in the auxin-mediated degradation. We generated EMS-mutagenized Arabidopsis PIN2::PIN2:GFP, AUX1::AUX1:YFP eir1aux1 populations and designed a screen for mutants with persistently strong fluorescent signals of the tagged PIN2 and AUX1 after prolonged treatment with the synthetic auxin 2,4-dichlorophenoxyacetic acid (2,4-D). This approach yielded novel auxin degradation mutants defective in trafficking and degradation of PIN2 and AUX1 proteins and established a role for auxin-mediated degradation in plant development.}, author = {Zemová, Radka and Zwiewka, Marta and Bielach, Agnieszka and Robert, Hélène and Friml, Jirí}, journal = {Journal of Plant Growth Regulation}, number = {2}, pages = {465 -- 476}, publisher = {Springer}, title = {{A forward genetic screen for new regulators of auxin mediated degradation of auxin transport proteins in Arabidopsis thaliana}}, doi = {10.1007/s00344-015-9553-2}, volume = {35}, year = {2016}, } @inproceedings{1653, abstract = {A somewhere statistically binding (SSB) hash, introduced by Hubáček and Wichs (ITCS ’15), can be used to hash a long string x to a short digest y = H hk (x) using a public hashing-key hk. Furthermore, there is a way to set up the hash key hk to make it statistically binding on some arbitrary hidden position i, meaning that: (1) the digest y completely determines the i’th bit (or symbol) of x so that all pre-images of y have the same value in the i’th position, (2) it is computationally infeasible to distinguish the position i on which hk is statistically binding from any other position i’. Lastly, the hash should have a local opening property analogous to Merkle-Tree hashing, meaning that given x and y = H hk (x) it should be possible to create a short proof π that certifies the value of the i’th bit (or symbol) of x without having to provide the entire input x. A similar primitive called a positional accumulator, introduced by Koppula, Lewko and Waters (STOC ’15) further supports dynamic updates of the hashed value. These tools, which are interesting in their own right, also serve as one of the main technical components in several recent works building advanced applications from indistinguishability obfuscation (iO). The prior constructions of SSB hashing and positional accumulators required fully homomorphic encryption (FHE) and iO respectively. In this work, we give new constructions of these tools based on well studied number-theoretic assumptions such as DDH, Phi-Hiding and DCR, as well as a general construction from lossy/injective functions.}, author = {Okamoto, Tatsuaki and Pietrzak, Krzysztof Z and Waters, Brent and Wichs, Daniel}, location = {Auckland, New Zealand}, pages = {121 -- 145}, publisher = {Springer}, title = {{New realizations of somewhere statistically binding hashing and positional accumulators}}, doi = {10.1007/978-3-662-48797-6_6}, volume = {9452}, year = {2016}, } @article{1705, abstract = {Hybrid systems represent an important and powerful formalism for modeling real-world applications such as embedded systems. A verification tool like SpaceEx is based on the exploration of a symbolic search space (the region space). As a verification tool, it is typically optimized towards proving the absence of errors. In some settings, e.g., when the verification tool is employed in a feedback-directed design cycle, one would like to have the option to call a version that is optimized towards finding an error trajectory in the region space. A recent approach in this direction is based on guided search. Guided search relies on a cost function that indicates which states are promising to be explored, and preferably explores more promising states first. In this paper, we propose an abstraction-based cost function based on coarse-grained space abstractions for guiding the reachability analysis. For this purpose, a suitable abstraction technique that exploits the flexible granularity of modern reachability analysis algorithms is introduced. The new cost function is an effective extension of pattern database approaches that have been successfully applied in other areas. The approach has been implemented in the SpaceEx model checker. The evaluation shows its practical potential.}, author = {Bogomolov, Sergiy and Donzé, Alexandre and Frehse, Goran and Grosu, Radu and Johnson, Taylor and Ladan, Hamed and Podelski, Andreas and Wehrle, Martin}, journal = {International Journal on Software Tools for Technology Transfer}, number = {4}, pages = {449 -- 467}, publisher = {Springer}, title = {{Guided search for hybrid systems based on coarse-grained space abstractions}}, doi = {10.1007/s10009-015-0393-y}, volume = {18}, year = {2016}, } @article{173, abstract = {We calculate admissible values of r such that a square-free polynomial with integer coefficients, no fixed prime divisor and irreducible factors of degree at most 3 takes infinitely many values that are a product of at most r distinct primes.}, author = {Browning, Timothy D and Booker, Andrew}, journal = {Discrete Analysis}, pages = {1 -- 18}, title = {{Square-free values of reducible polynomials}}, doi = {10.19086/da.732}, volume = {8}, year = {2016}, } @article{17618, abstract = {The largest observed supermassive black holes (SMBHs) have a mass of M_BH ~ 10^{10} M_sun, nearly independent of redshift, from the local (z~0) to the early (z>6) Universe. We suggest that the growth of SMBHs above a few 10^{10} M_sun is prevented by small-scale accretion physics, independent of the properties of their host galaxies or of cosmology. Growing more massive BHs requires a gas supply rate from galactic scales onto a nuclear region as high as >10^3 M_sun/yr. At such a high accretion rate, most of the gas converts to stars at large radii (~10-100 pc), well before reaching the BH. We adopt a simple model (Thompson et al. 2005) for a star-forming accretion disk, and find that the accretion rate in the sub-pc nuclear region is reduced to the smaller value of at most a few M_sun/yr. This prevents SMBHs from growing above ~10^{11} M_sun in the age of the Universe. Furthermore, once a SMBH reaches a sufficiently high mass, this rate falls below the critical value at which the accretion flow becomes advection dominated. Once this transition occurs, BH feeding can be suppressed by strong outflows and jets from hot gas near the BH. We find that the maximum SMBH mass, given by this transition, is between M_{BH,max} ~ (1-6) * 10^{10} M_sun, depending primarily on the efficiency of angular momentum transfer inside the galactic disk, and not on other properties of the host galaxy.}, author = {Inayoshi, Kohei and Haiman, Zoltán}, issn = {0004-637X}, journal = {The Astrophysical Journal}, number = {2}, publisher = {American Astronomical Society}, title = {{Is there a maximum mass for black holes in galactic nuclei?}}, doi = {10.3847/0004-637x/828/2/110}, volume = {828}, year = {2016}, } @article{17621, abstract = {We introduce an intrinsic Lyα emission-line profile reconstruction method for high-z quasars (QSOs). This approach utilises a covariance matrix of emission-line properties obtained from a large, moderate-z (2 ≤ z ≤ 2.5), high signal to noise (S/N > 15) sample of BOSS QSOs. For each QSO, we complete a Monte Carlo Markov Chain fitting of the continuum and emission-line properties and perform a visual quality assessment to construct a large data base of robustly fit spectra. With this data set, we construct a covariance matrix to describe the correlations between the high-ionization emission lines Lyα, C iv, Si iv +O iv] and C iii], and find it to be well approximated by an N-dimensional Gaussian distribution. This covariance matrix characterizes the correlations between the linewidth, peak height and velocity offset from systemic while also allowing for the existence of broad- and narrow-line components for Lyα and C iv. We illustrate how this covariance matrix allows us to statistically characterize the intrinsic Lyα line solely from the observed spectrum redward of 1275 Å. This procedure can be used to reconstruct the intrinsic Lyα line emission profile in cases where Lyα may otherwise be obscured. Applying this reconstruction method to our sample of QSOs, we recovered the Lyα line flux to within 15 per cent of the measured flux at 1205 Å (1220 Å) ∼85 (90) per cent of the time.}, author = {Greig, Bradley and Mesinger, Andrei and McGreer, Ian D. and Gallerani, Simona and Haiman, Zoltán}, issn = {0035-8711}, journal = {Monthly Notices of the Royal Astronomical Society}, number = {2}, pages = {1814--1838}, publisher = {Oxford University Press}, title = {{Lyα emission-line reconstruction for high-z QSOs}}, doi = {10.1093/mnras/stw3210}, volume = {466}, year = {2016}, }