TY - JOUR AB - Because of the intrinsic randomness of the evolutionary process, a mutant with a fitness advantage has some chance to be selected but no certainty. Any experiment that searches for advantageous mutants will lose many of them due to random drift. It is therefore of great interest to find population structures that improve the odds of advantageous mutants. Such structures are called amplifiers of natural selection: they increase the probability that advantageous mutants are selected. Arbitrarily strong amplifiers guarantee the selection of advantageous mutants, even for very small fitness advantage. Despite intensive research over the past decade, arbitrarily strong amplifiers have remained rare. Here we show how to construct a large variety of them. Our amplifiers are so simple that they could be useful in biotechnology, when optimizing biological molecules, or as a diagnostic tool, when searching for faster dividing cells or viruses. They could also occur in natural population structures. AU - Pavlogiannis, Andreas AU - Tkadlec, Josef AU - Chatterjee, Krishnendu AU - Nowak, Martin A. ID - 5751 IS - 1 JF - Communications Biology SN - 2399-3642 TI - Construction of arbitrarily strong amplifiers of natural selection using evolutionary graph theory VL - 1 ER - TY - DATA AB - File S1. Variant Calling Format file of the ingroup: 197 haploid sequences of D. melanogaster from Zambia (Africa) aligned to the D. melanogaster 5.57 reference genome. File S2. Variant Calling Format file of the outgroup: 1 haploid sequence of D. simulans aligned to the D. melanogaster 5.57 reference genome. File S3. Annotations of each transcript in coding regions with SNPeff: Ps (# of synonymous polymorphic sites); Pn (# of non-synonymous polymorphic sites); Ds (# of synonymous divergent sites); Dn (# of non-synonymous divergent sites); DoS; ⍺ MK . All variants were included. File S4. Annotations of each transcript in non-coding regions with SNPeff: Ps (# of synonymous polymorphic sites); Pu (# of UTR polymorphic sites); Ds (# of synonymous divergent sites); Du (# of UTR divergent sites); DoS; ⍺ MK . All variants were included. File S5. Annotations of each transcript in coding regions with SNPGenie: Ps (# of synonymous polymorphic sites); πs (synonymous diversity); Ss_p (total # of synonymous sites in the polymorphism data); Pn (# of non-synonymous polymorphic sites); πn (non-synonymous diversity); Sn_p (total # of non-synonymous sites in the polymorphism data); Ds (# of synonymous divergent sites); ks (synonymous evolutionary rate); Ss_d (total # of synonymous sites in the divergence data); Dn (# of non-synonymous divergent sites); kn (non-synonymous evolutionary rate); Sn_d (total # of non- synonymous sites in the divergence data); DoS; ⍺ MK . All variants were included. File S6. Gene expression values (RPKM summed over all transcripts) for each sample. Values were quantile-normalized across all samples. File S7. Final dataset with all covariates, ⍺ MK , ωA MK and DoS for coding sites, excluding variants below 5% frequency. File S8. Final dataset with all covariates, ⍺ MK , ωA MK and DoS for non-coding sites, excluding variants below 5% frequency. File S9. Final dataset with all covariates, ⍺ EWK , ωA EWK and deleterious SFS for coding sites obtained with the Eyre-Walker and Keightley method on binned data and using all variants. AU - Fraisse, Christelle ID - 5757 KW - (mal)adaptation KW - pleiotropy KW - selective constraint KW - evo-devo KW - gene expression KW - Drosophila melanogaster TI - Supplementary Files for "Pleiotropy modulates the efficacy of selection in Drosophila melanogaster" ER - TY - THES AB - The eigenvalue density of many large random matrices is well approximated by a deterministic measure, the self-consistent density of states. In the present work, we show this behaviour for several classes of random matrices. In fact, we establish that, in each of these classes, the self-consistent density of states approximates the eigenvalue density of the random matrix on all scales slightly above the typical eigenvalue spacing. For large classes of random matrices, the self-consistent density of states exhibits several universal features. We prove that, under suitable assumptions, random Gram matrices and Hermitian random matrices with decaying correlations have a 1/3-Hölder continuous self-consistent density of states ρ on R, which is analytic, where it is positive, and has either a square root edge or a cubic root cusp, where it vanishes. We, thus, extend the validity of the corresponding result for Wigner-type matrices from [4, 5, 7]. We show that ρ is determined as the inverse Stieltjes transform of the normalized trace of the unique solution m(z) to the Dyson equation −m(z) −1 = z − a + S[m(z)] on C N×N with the constraint Im m(z) ≥ 0. Here, z lies in the complex upper half-plane, a is a self-adjoint element of C N×N and S is a positivity-preserving operator on C N×N encoding the first two moments of the random matrix. In order to analyze a possible limit of ρ for N → ∞ and address some applications in free probability theory, we also consider the Dyson equation on infinite dimensional von Neumann algebras. We present two applications to random matrices. We first establish that, under certain assumptions, large random matrices with independent entries have a rotationally symmetric self-consistent density of states which is supported on a centered disk in C. Moreover, it is infinitely often differentiable apart from a jump on the boundary of this disk. Second, we show edge universality at all regular (not necessarily extreme) spectral edges for Hermitian random matrices with decaying correlations. AU - Alt, Johannes ID - 149 SN - 2663-337X TI - Dyson equation and eigenvalue statistics of random matrices ER - TY - JOUR AB - Recently it was shown that a molecule rotating in a quantum solvent can be described in terms of the “angulon” quasiparticle [M. Lemeshko, Phys. Rev. Lett. 118, 095301 (2017)]. Here we extend the angulon theory to the case of molecules possessing an additional spin-1/2 degree of freedom and study the behavior of the system in the presence of a static magnetic field. We show that exchange of angular momentum between the molecule and the solvent can be altered by the field, even though the solvent itself is non-magnetic. In particular, we demonstrate a possibility to control resonant emission of phonons with a given angular momentum using a magnetic field. AU - Rzadkowski, Wojciech AU - Lemeshko, Mikhail ID - 415 IS - 10 JF - The Journal of Chemical Physics TI - Effect of a magnetic field on molecule–solvent angular momentum transfer VL - 148 ER - TY - JOUR AB - The current state of the art in real-time two-dimensional water wave simulation requires developers to choose between efficient Fourier-based methods, which lack interactions with moving obstacles, and finite-difference or finite element methods, which handle environmental interactions but are significantly more expensive. This paper attempts to bridge this long-standing gap between complexity and performance, by proposing a new wave simulation method that can faithfully simulate wave interactions with moving obstacles in real time while simultaneously preserving minute details and accommodating very large simulation domains. Previous methods for simulating 2D water waves directly compute the change in height of the water surface, a strategy which imposes limitations based on the CFL condition (fast moving waves require small time steps) and Nyquist's limit (small wave details require closely-spaced simulation variables). This paper proposes a novel wavelet transformation that discretizes the liquid motion in terms of amplitude-like functions that vary over space, frequency, and direction, effectively generalizing Fourier-based methods to handle local interactions. Because these new variables change much more slowly over space than the original water height function, our change of variables drastically reduces the limitations of the CFL condition and Nyquist limit, allowing us to simulate highly detailed water waves at very large visual resolutions. Our discretization is amenable to fast summation and easy to parallelize. We also present basic extensions like pre-computed wave paths and two-way solid fluid coupling. Finally, we argue that our discretization provides a convenient set of variables for artistic manipulation, which we illustrate with a novel wave-painting interface. AU - Jeschke, Stefan AU - Skrivan, Tomas AU - Mueller Fischer, Matthias AU - Chentanez, Nuttapong AU - Macklin, Miles AU - Wojtan, Christopher J ID - 134 IS - 4 JF - ACM Transactions on Graphics TI - Water surface wavelets VL - 37 ER - TY - JOUR AB - We introduce a diagrammatic Monte Carlo approach to angular momentum properties of quantum many-particle systems possessing a macroscopic number of degrees of freedom. The treatment is based on a diagrammatic expansion that merges the usual Feynman diagrams with the angular momentum diagrams known from atomic and nuclear structure theory, thereby incorporating the non-Abelian algebra inherent to quantum rotations. Our approach is applicable at arbitrary coupling, is free of systematic errors and of finite-size effects, and naturally provides access to the impurity Green function. We exemplify the technique by obtaining an all-coupling solution of the angulon model; however, the method is quite general and can be applied to a broad variety of systems in which particles exchange quantum angular momentum with their many-body environment. AU - Bighin, Giacomo AU - Tscherbul, Timur AU - Lemeshko, Mikhail ID - 6339 IS - 16 JF - Physical Review Letters TI - Diagrammatic Monte Carlo approach to angular momentum in quantum many-particle systems VL - 121 ER - TY - JOUR AB - We introduce a Diagrammatic Monte Carlo (DiagMC) approach to complex molecular impurities with rotational degrees of freedom interacting with a many-particle environment. The treatment is based on the diagrammatic expansion that merges the usual Feynman diagrams with the angular momentum diagrams known from atomic and nuclear structure theory, thereby incorporating the non-Abelian algebra inherent to quantum rotations. Our approach works at arbitrary coupling, is free of systematic errors and of finite size effects, and naturally provides access to the impurity Green function. We exemplify the technique by obtaining an all-coupling solution of the angulon model, however, the method is quite general and can be applied to a broad variety of quantum impurities possessing angular momentum degrees of freedom. AU - Bighin, Giacomo AU - Tscherbul, Timur AU - Lemeshko, Mikhail ID - 417 IS - 16 JF - Physical Review Letters TI - Diagrammatic Monte Carlo approach to rotating molecular impurities VL - 121 ER - TY - JOUR AB - Clathrin-mediated endocytosis (CME) is a cellular trafficking process in which cargoes and lipids are internalized from the plasma membrane into vesicles coated with clathrin and adaptor proteins. CME is essential for many developmental and physiological processes in plants, but its underlying mechanism is not well characterised compared to that in yeast and animal systems. Here, we searched for new factors involved in CME in Arabidopsis thaliana by performing Tandem Affinity Purification of proteins that interact with clathrin light chain, a principal component of the clathrin coat. Among the confirmed interactors, we found two putative homologues of the clathrin-coat uncoating factor auxilin previously described in non-plant systems. Overexpression of AUXILIN-LIKE1 and AUXILIN-LIKE2 in A. thaliana caused an arrest of seedling growth and development. This was concomitant with inhibited endocytosis due to blocking of clathrin recruitment after the initial step of adaptor protein binding to the plasma membrane. By contrast, auxilin-like(1/2) loss-of-function lines did not present endocytosis-related developmental or cellular phenotypes under normal growth conditions. This work contributes to the on-going characterization of the endocytotic machinery in plants and provides a robust tool for conditionally and specifically interfering with CME in A. thaliana. AU - Adamowski, Maciek AU - Narasimhan, Madhumitha AU - Kania, Urszula AU - Glanc, Matous AU - De Jaeger, Geert AU - Friml, Jirí ID - 412 IS - 3 JF - The Plant Cell SN - 1040-4651 TI - A functional study of AUXILIN LIKE1 and 2 two putative clathrin uncoating factors in Arabidopsis VL - 30 ER - TY - JOUR AB - With the advent of optogenetics, it became possible to change the activity of a targeted population of neurons in a temporally controlled manner. To combine the advantages of 60-channel in vivo tetrode recording and laser-based optogenetics, we have developed a closed-loop recording system that allows for the actual electrophysiological signal to be used as a trigger for the laser light mediating the optogenetic intervention. We have optimized the weight, size, and shape of the corresponding implant to make it compatible with the size, force, and movements of a behaving mouse, and we have shown that the system can efficiently block sharp wave ripple (SWR) events using those events themselves as a trigger. To demonstrate the full potential of the optogenetic recording system we present a pilot study addressing the contribution of SWR events to learning in a complex behavioral task. AU - Rangel Guerrero, Dámaris K AU - Donnett, James G. AU - Csicsvari, Jozsef L AU - Kovács, Krisztián ID - 5914 IS - 4 JF - eNeuro TI - Tetrode recording from the hippocampus of behaving mice coupled with four-point-irradiation closed-loop optogenetics: A technique to study the contribution of Hippocampal SWR events to learning VL - 5 ER - TY - JOUR AB - During metastasis, malignant cells escape the primary tumor, intravasate lymphatic vessels, and reach draining sentinel lymph nodes before they colonize distant organs via the blood circulation. Although lymph node metastasis in cancer patients correlates with poor prognosis, evidence is lacking as to whether and how tumor cells enter the bloodstream via lymph nodes. To investigate this question, we delivered carcinoma cells into the lymph nodes of mice by microinfusing the cells into afferent lymphatic vessels. We found that tumor cells rapidly infiltrated the lymph node parenchyma, invaded blood vessels, and seeded lung metastases without involvement of the thoracic duct. These results suggest that the lymph node blood vessels can serve as an exit route for systemic dissemination of cancer cells in experimental mouse models. Whether this form of tumor cell spreading occurs in cancer patients remains to be determined. AU - Brown, Markus AU - Assen, Frank P AU - Leithner, Alexander F AU - Abe, Jun AU - Schachner, Helga AU - Asfour, Gabriele AU - Bagó Horváth, Zsuzsanna AU - Stein, Jens AU - Uhrin, Pavel AU - Sixt, Michael K AU - Kerjaschki, Dontscho ID - 402 IS - 6382 JF - Science TI - Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice VL - 359 ER -