@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}, } @article{17567, abstract = {The growing number of stellar-mass binary black hole mergers discovered by Advanced LIGO and Advanced Virgo are starting to constrain the binaries' origin and environment. However, we still lack sufficiently accurate modeling of binary formation channels to obtain strong constraints, or to identify sub-populations. One promising formation mechanism that could result in different black hole properties is binaries merging within the accretion disks of Active Galactic Nuclei (AGN). Here we show that the black holes' orbital alignment with the AGN disks preferentially selects heavier black holes. We carry out Monte Carlo simulations of orbital alignment with AGN disks, and find that AGNs harden the initial black hole mass function. Assuming an initial power law mass distribution M−βbh, we find that the power law index changes by Δβ∼1.3, resulting in a more top-heavy population of merging black holes. This change is independent of the mass of, and accretion rate onto, the supermassive black hole in the center of the AGN. Our simulations predict an AGN-assisted merger rate of ∼4Gpc−3yr−1. With its hardened mass spectra, the AGN channel could be responsible for 10−50% of gravitational-wave detections.}, author = {Yang, Y. and Bartos, I. and Haiman, Zoltán and Kocsis, B. and Márka, Z. and Stone, N. C. and Márka, S.}, issn = {0004-637X}, journal = {The Astrophysical Journal}, number = {2}, publisher = {American Astronomical Society}, title = {{AGN disks harden the mass distribution of stellar-mass binary black hole mergers}}, doi = {10.3847/1538-4357/ab16e3}, volume = {876}, year = {2019}, } @article{17603, abstract = {Weak gravitational lensing is one of the most promising cosmological probes of the late universe. Several large ongoing (DES, KiDS, HSC) and planned (LSST, Euclid, WFIRST) astronomical surveys attempt to collect even deeper and larger scale data on weak lensing. Due to gravitational collapse, the distribution of dark matter is non-Gaussian on small scales. However, observations are typically evaluated through the two-point correlation function of galaxy shear, which does not capture non-Gaussian features of the lensing maps. Previous studies attempted to extract non-Gaussian information from weak lensing observations through several higher order statistics such as the three-point correlation function, peak counts, or Minkowski functionals. Deep convolutional neural networks (CNN) emerged in the field of computer vision with tremendous success, and they offer a new and very promising framework to extract information from 2D or 3D astronomical data sets, confirmed by recent studies on weak lensing. We show that a CNN is able to yield significantly stricter constraints of (σ8, Ωm) cosmological parameters than the power spectrum using convergence maps generated by full N-body simulations and ray-tracing, at angular scales and shape noise levels relevant for future observations. In a scenario mimicking LSST or Euclid, the CNN yields 2.4–2.8 times smaller credible contours than the power spectrum, and 3.5–4.2 times smaller at noise levels corresponding to a deep space survey such as WFIRST. We also show that at shape noise levels achievable in future space surveys the CNN yields 1.4–2.1 times smaller contours than peak counts, a higher order statistic capable of extracting non-Gaussian information from weak lensing maps.}, author = {Ribli, Dezső and Pataki, Bálint Ármin and Zorrilla Matilla, José Manuel and Hsu, Daniel and Haiman, Zoltán and Csabai, István}, issn = {0035-8711}, journal = {Monthly Notices of the Royal Astronomical Society}, number = {2}, pages = {1843--1860}, publisher = {Oxford University Press}, title = {{Weak lensing cosmology with convolutional neural networks on noisy data}}, doi = {10.1093/mnras/stz2610}, volume = {490}, year = {2019}, } @article{7710, abstract = {The number of human genomes being genotyped or sequenced increases exponentially and efficient haplotype estimation methods able to handle this amount of data are now required. Here we present a method, SHAPEIT4, which substantially improves upon other methods to process large genotype and high coverage sequencing datasets. It notably exhibits sub-linear running times with sample size, provides highly accurate haplotypes and allows integrating external phasing information such as large reference panels of haplotypes, collections of pre-phased variants and long sequencing reads. We provide SHAPEIT4 in an open source format and demonstrate its performance in terms of accuracy and running times on two gold standard datasets: the UK Biobank data and the Genome In A Bottle.}, author = {Delaneau, Olivier and Zagury, Jean-François and Robinson, Matthew Richard and Marchini, Jonathan L. and Dermitzakis, Emmanouil T.}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Accurate, scalable and integrative haplotype estimation}}, doi = {10.1038/s41467-019-13225-y}, volume = {10}, year = {2019}, } @article{7711, abstract = {The nature and extent of mitochondrial DNA variation in a population and how it affects traits is poorly understood. Here we resequence the mitochondrial genomes of 169 Drosophila Genetic Reference Panel lines, identifying 231 variants that stratify along 12 mitochondrial haplotypes. We identify 1,845 cases of mitonuclear allelic imbalances, thus implying that mitochondrial haplotypes are reflected in the nuclear genome. However, no major fitness effects are associated with mitonuclear imbalance, suggesting that such imbalances reflect population structure at the mitochondrial level rather than genomic incompatibilities. Although mitochondrial haplotypes have no direct impact on mitochondrial respiration, some haplotypes are associated with stress- and metabolism-related phenotypes, including food intake in males. Finally, through reciprocal swapping of mitochondrial genomes, we demonstrate that a mitochondrial haplotype associated with high food intake can rescue a low food intake phenotype. Together, our findings provide new insight into population structure at the mitochondrial level and point to the importance of incorporating mitochondrial haplotypes in genotype–phenotype relationship studies.}, author = {Bevers, Roel P. J. and Litovchenko, Maria and Kapopoulou, Adamandia and Braman, Virginie S. and Robinson, Matthew Richard and Auwerx, Johan and Hollis, Brian and Deplancke, Bart}, issn = {2522-5812}, journal = {Nature Metabolism}, number = {12}, pages = {1226--1242}, publisher = {Springer Nature}, title = {{Mitochondrial haplotypes affect metabolic phenotypes in the Drosophila Genetic Reference Panel}}, doi = {10.1038/s42255-019-0147-3}, volume = {1}, year = {2019}, } @unpublished{7782, abstract = {As genome-wide association studies (GWAS) increased in size, numerous gene-environment interactions (GxE) have been discovered, many of which however explore only one environment at a time and may suffer from statistical artefacts leading to biased interaction estimates. Here we propose a maximum likelihood method to estimate the contribution of GxE to complex traits taking into account all interacting environmental variables at the same time, without the need to measure any. This is possible because GxE induces fluctuations in the conditional trait variance, the extent of which depends on the strength of GxE. The approach can be applied to continuous outcomes and for single SNPs or genetic risk scores (GRS). Extensive simulations demonstrated that our method yields unbiased interaction estimates and excellent confidence interval coverage. We also offer a strategy to distinguish specific GxE from general heteroscedasticity (scale effects). Applying our method to 32 complex traits in the UK Biobank reveals that for body mass index (BMI) the GRSxE explains an additional 1.9% variance on top of the 5.2% GRS contribution. However, this interaction is not specific to the GRS and holds for any variable similarly correlated with BMI. On the contrary, the GRSxE interaction effect for leg impedance Embedded Image is significantly (P < 10−56) larger than it would be expected for a similarly correlated variable Embedded Image. We showed that our method could robustly detect the global contribution of GxE to complex traits, which turned out to be substantial for certain obesity measures.}, author = {Sulc, Jonathan and Mounier, Ninon and Günther, Felix and Winkler, Thomas and Wood, Andrew R. and Frayling, Timothy M. and Heid, Iris M. and Robinson, Matthew Richard and Kutalik, Zoltán}, booktitle = {bioRxiv}, pages = {20}, publisher = {Cold Spring Harbor Laboratory}, title = {{Maximum likelihood method quantifies the overall contribution of gene-environment interaction to continuous traits: An application to complex traits in the UK Biobank}}, year = {2019}, } @article{8, abstract = {Despite their different origins, Drosophila glia and hemocytes are related cell populations that provide an immune function. Drosophila hemocytes patrol the body cavity and act as macrophages outside the nervous system whereas glia originate from the neuroepithelium and provide the scavenger population of the nervous system. Drosophila glia are hence the functional orthologs of vertebrate microglia, even though the latter are cells of immune origin that subsequently move into the brain during development. Interestingly, the Drosophila immune cells within (glia) and outside the nervous system (hemocytes) require the same transcription factor Glide/Gcm for their development. This raises the issue of how do glia specifically differentiate in the nervous system and hemocytes in the procephalic mesoderm. The Repo homeodomain transcription factor and pan-glial direct target of Glide/Gcm is known to ensure glial terminal differentiation. Here we show that Repo also takes center stage in the process that discriminates between glia and hemocytes. First, Repo expression is repressed in the hemocyte anlagen by mesoderm-specific factors. Second, Repo ectopic activation in the procephalic mesoderm is sufficient to repress the expression of hemocyte-specific genes. Third, the lack of Repo triggers the expression of hemocyte markers in glia. Thus, a complex network of tissue-specific cues biases the potential of Glide/Gcm. These data allow us to revise the concept of fate determinants and help us understand the bases of cell specification. Both sexes were analyzed.SIGNIFICANCE STATEMENTDistinct cell types often require the same pioneer transcription factor, raising the issue of how does one factor trigger different fates. In Drosophila, glia and hemocytes provide a scavenger activity within and outside the nervous system, respectively. While they both require the Glide/Gcm transcription factor, glia originate from the ectoderm, hemocytes from the mesoderm. Here we show that tissue-specific factors inhibit the gliogenic potential of Glide/Gcm in the mesoderm by repressing the expression of the homeodomain protein Repo, a major glial-specific target of Glide/Gcm. Repo expression in turn inhibits the expression of hemocyte-specific genes in the nervous system. These cell-specific networks secure the establishment of the glial fate only in the nervous system and allow cell diversification.}, author = {Trébuchet, Guillaume and Cattenoz, Pierre B and Zsámboki, János and Mazaud, David and Siekhaus, Daria E and Fanto, Manolis and Giangrande, Angela}, journal = {Journal of Neuroscience}, number = {2}, pages = {238--255}, publisher = {Society for Neuroscience}, title = {{The Repo homeodomain transcription factor suppresses hematopoiesis in Drosophila and preserves the glial fate}}, doi = {10.1523/JNEUROSCI.1059-18.2018}, volume = {39}, year = {2019}, } @article{80, abstract = {We consider an interacting, dilute Bose gas trapped in a harmonic potential at a positive temperature. The system is analyzed in a combination of a thermodynamic and a Gross–Pitaevskii (GP) limit where the trap frequency ω, the temperature T, and the particle number N are related by N∼ (T/ ω) 3→ ∞ while the scattering length is so small that the interaction energy per particle around the center of the trap is of the same order of magnitude as the spectral gap in the trap. We prove that the difference between the canonical free energy of the interacting gas and the one of the noninteracting system can be obtained by minimizing the GP energy functional. We also prove Bose–Einstein condensation in the following sense: The one-particle density matrix of any approximate minimizer of the canonical free energy functional is to leading order given by that of the noninteracting gas but with the free condensate wavefunction replaced by the GP minimizer.}, author = {Deuchert, Andreas and Seiringer, Robert and Yngvason, Jakob}, journal = {Communications in Mathematical Physics}, number = {2}, pages = {723--776}, publisher = {Springer}, title = {{Bose–Einstein condensation in a dilute, trapped gas at positive temperature}}, doi = {10.1007/s00220-018-3239-0}, volume = {368}, year = {2019}, } @article{8013, author = {Currin, Christopher B. and Khoza, Phumlani N. and Antrobus, Alexander D. and Latham, Peter E. and Vogels, Tim P and Raimondo, Joseph V.}, issn = {1553-7358}, journal = {PLOS Computational Biology}, number = {7}, publisher = {Public Library of Science}, title = {{Think: Theory for Africa}}, doi = {10.1371/journal.pcbi.1007049}, volume = {15}, year = {2019}, } @article{8014, abstract = {Working memory, the ability to keep recently accessed information available for immediate manipulation, has been proposed to rely on two mechanisms that appear difficult to reconcile: self-sustained neural firing, or the opposite—activity-silent synaptic traces. Here we review and contrast models of these two mechanisms, and then show that both phenomena can co-exist within a unified system in which neurons hold information in both activity and synapses. Rapid plasticity in flexibly-coding neurons allows features to be bound together into objects, with an important emergent property being the focus of attention. One memory item is held by persistent activity in an attended or “focused” state, and is thus remembered better than other items. Other, previously attended items can remain in memory but in the background, encoded in activity-silent synaptic traces. This dual functional architecture provides a unified common mechanism accounting for a diversity of perplexing attention and memory effects that have been hitherto difficult to explain in a single theoretical framework.}, author = {Manohar, Sanjay G. and Zokaei, Nahid and Fallon, Sean J. and Vogels, Tim P and Husain, Masud}, issn = {0149-7634}, journal = {Neuroscience and Biobehavioral Reviews}, pages = {1--12}, publisher = {Elsevier }, title = {{Neural mechanisms of attending to items in working memory}}, doi = {10.1016/j.neubiorev.2019.03.017}, volume = {101}, year = {2019}, } @inproceedings{8175, abstract = {We study edge asymptotics of poissonized Plancherel-type measures on skew Young diagrams (integer partitions). These measures can be seen as generalizations of those studied by Baik--Deift--Johansson and Baik--Rains in resolving Ulam's problem on longest increasing subsequences of random permutations and the last passage percolation (corner growth) discrete versions thereof. Moreover they interpolate between said measures and the uniform measure on partitions. In the new KPZ-like 1/3 exponent edge scaling limit with logarithmic corrections, we find new probability distributions generalizing the classical Tracy--Widom GUE, GOE and GSE distributions from the theory of random matrices.}, author = {Betea, Dan and Bouttier, Jérémie and Nejjar, Peter and Vuletíc, Mirjana}, booktitle = {Proceedings on the 31st International Conference on Formal Power Series and Algebraic Combinatorics}, location = {Ljubljana, Slovenia}, publisher = {Formal Power Series and Algebraic Combinatorics}, title = {{New edge asymptotics of skew Young diagrams via free boundaries}}, year = {2019}, } @article{8227, author = {Ilieva, Kristina M. and Fazekas-Singer, Judit and Bax, Heather J. and Crescioli, Silvia and Montero‐Morales, Laura and Mele, Silvia and Sow, Heng Sheng and Stavraka, Chara and Josephs, Debra H. and Spicer, James F. and Steinkellner, Herta and Jensen‐Jarolim, Erika and Tutt, Andrew N. J. and Karagiannis, Sophia N.}, issn = {0105-4538}, journal = {Allergy}, number = {10}, pages = {1985--1989}, publisher = {Wiley}, title = {{AllergoOncology: Expression platform development and functional profiling of an anti‐HER2 IgE antibody}}, doi = {10.1111/all.13818}, volume = {74}, year = {2019}, } @article{8228, abstract = {Background: Atopics have a lower risk for malignancies, and IgE targeted to tumors is superior to IgG in fighting cancer. Whether IgE-mediated innate or adaptive immune surveillance can confer protection against tumors remains unclear. Objective: We aimed to investigate the effects of active and passive immunotherapy to the tumor-associated antigen HER-2 in three murine models differing in Epsilon-B-cell-receptor expression affecting the levels of expressed IgE. Methods: We compared the levels of several serum specific anti-HER-2 antibodies (IgE, IgG1, IgG2a, IgG2b, IgA) and the survival rates in low-IgE ΔM1M2 mice lacking the transmembrane/cytoplasmic domain of Epsilon-B-cell-receptors expressing reduced IgE levels, high-IgE KN1 mice expressing chimeric Epsilon-Gamma1-B-cell receptors with 4-6-fold elevated serum IgE levels, and wild type (WT) BALB/c. Prior engrafting mice with D2F2/E2 mammary tumors overexpressing HER-2, mice were vaccinated with HER-2 or vehicle control PBS using the Th2-adjuvant Al(OH)3 (active immunotherapy), or treated with the murine anti-HER-2 IgG1 antibody 4D5 (passive immunotherapy). Results: Overall, among the three strains of mice, HER-2 vaccination induced significantly higher levels of HER-2 specific IgE and IgG1 in high-IgE KN1, while low-IgE ΔM1M2 mice had higher IgG2a levels. HER-2 vaccination and passive immunotherapy prolonged the survival in tumor-grafted WT and low-IgE ΔM1M2 strains compared with treatment controls; active vaccination provided the highest benefit. Notably, untreated high-IgE KN1 mice displayed the longest survival of all strains, which could not be further extended by active or passive immunotherapy. Conclusion: Active and passive immunotherapies prolong survival in wild type and low-IgE ΔM1M2 mice engrafted with mammary tumors. High-IgE KN1 mice have an innate survival benefit following tumor challenge.}, author = {Singer, Josef and Achatz-Straussberger, Gertrude and Bentley-Lukschal, Anna and Fazekas-Singer, Judit and Achatz, Gernot and Karagiannis, Sophia N. and Jensen-Jarolim, Erika}, issn = {1939-4551}, journal = {World Allergy Organization Journal}, number = {7}, publisher = {Elsevier}, title = {{AllergoOncology: High innate IgE levels are decisive for the survival of cancer-bearing mice}}, doi = {10.1016/j.waojou.2019.100044}, volume = {12}, year = {2019}, } @article{8229, abstract = {Food proteins may get nitrated by various exogenous or endogenous mechanisms. As individuals might get recurrently exposed to nitrated proteins via daily diet, we aimed to investigate the effect of repeatedly ingested nitrated food proteins on the subsequent immune response in non-allergic and allergic mice using the milk allergen beta-lactoglobulin (BLG) as model food protein in a mouse model. Evaluating the presence of nitrated proteins in food, we could detect 3-nitrotyrosine (3-NT) in extracts of different foods and in stomach content extracts of non-allergic mice under physiological conditions. Chemically nitrated BLG (BLGn) exhibited enhanced susceptibility to degradation in simulated gastric fluid experiments compared to untreated BLG (BLGu). Gavage of BLGn to non-allergic animals increased interferon-γ and interleukin-10 release of stimulated spleen cells and led to the formation of BLG-specific serum IgA. Allergic mice receiving three oral gavages of BLGn had higher levels of mouse mast cell protease-1 (mMCP-1) compared to allergic mice receiving BLGu. Regardless of the preceding immune status, non-allergic or allergic, repeatedly ingested nitrated food proteins seem to considerably influence the subsequent immune response.}, author = {Ondracek, Anna S. and Heiden, Denise and Oostingh, Gertie J. and Fuerst, Elisabeth and Fazekas-Singer, Judit and Bergmayr, Cornelia and Rohrhofer, Johanna and Jensen-Jarolim, Erika and Duschl, Albert and Untersmayr, Eva}, issn = {2072-6643}, journal = {Nutrients}, number = {10}, publisher = {MDPI}, title = {{Immune effects of the nitrated food allergen beta-lactoglobulin in an experimental food allergy model}}, doi = {10.3390/nu11102463}, volume = {11}, year = {2019}, } @article{8263, abstract = {Background: The genus Streptococcus comprises pathogens that strongly influence the health of humans and animals. Genome sequencing of multiple Streptococcus strains demonstrated high variability in gene content and order even in closely related strains of the same species and created a newly emerged object for genomic analysis, the pan-genome. Here we analysed the genome evolution of 25 strains of Streptococcus suis, 50 strains of Streptococcus pyogenes and 28 strains of Streptococcus pneumoniae. Results: Fractions of the pan-genome, unique, periphery, and universal genes differ in size, functional composition, the level of nucleotide substitutions, and predisposition to horizontal gene transfer and genomic rearrangements. The density of substitutions in intergenic regions appears to be correlated with selection acting on adjacent genes, implying that more conserved genes tend to have more conserved regulatory regions. The total pan-genome of the genus is open, but only due to strain-specific genes, whereas other pan-genome fractions reach saturation. We have identified the set of genes with phylogenies inconsistent with species and non-conserved location in the chromosome; these genes are rare in at least one species and have likely experienced recent horizontal transfer between species. The strain-specific fraction is enriched with mobile elements and hypothetical proteins, but also contains a number of candidate virulence-related genes, so it may have a strong impact on adaptability and pathogenicity. Mapping the rearrangements to the phylogenetic tree revealed large parallel inversions in all species. A parallel inversion of length 15 kB with breakpoints formed by genes encoding surface antigen proteins PhtD and PhtB in S. pneumoniae leads to replacement of gene fragments that likely indicates the action of an antigen variation mechanism. Conclusions: Members of genus Streptococcus have a highly dynamic, open pan-genome, that potentially confers them with the ability to adapt to changing environmental conditions, i.e. antibiotic resistance or transmission between different hosts. Hence, integrated analysis of all aspects of genome evolution is important for the identification of potential pathogens and design of drugs and vaccines.}, author = {Shelyakin, Pavel V. and Bochkareva, Olga and Karan, Anna A. and Gelfand, Mikhail S.}, issn = {1471-2148}, journal = {BMC Evolutionary Biology}, publisher = {Springer Nature}, title = {{Micro-evolution of three Streptococcus species: Selection, antigenic variation, and horizontal gene inflow}}, doi = {10.1186/s12862-019-1403-6}, volume = {19}, year = {2019}, } @inbook{8281, abstract = {We review the history of population genetics, starting with its origins a century ago from the synthesis between Mendel and Darwin's ideas, through to the recent development of sophisticated schemes of inference from sequence data, based on the coalescent. We explain the close relation between the coalescent and a diffusion process, which we illustrate by their application to understand spatial structure. We summarise the powerful methods available for analysis of multiple loci, when linkage equilibrium can be assumed, and then discuss approaches to the more challenging case, where associations between alleles require that we follow genotype, rather than allele, frequencies. Though we can hardly cover the whole of population genetics, we give an overview of the current state of the subject, and future challenges to it.}, author = {Barton, Nicholas H and Etheridge, Alison}, booktitle = {Handbook of statistical genomics}, editor = {Balding, David and Moltke, Ida and Marioni, John}, isbn = {9781119429142}, pages = {115--144}, publisher = {Wiley}, title = {{Mathematical models in population genetics}}, doi = {10.1002/9781119487845.ch4}, year = {2019}, } @inproceedings{8296, abstract = {While showing great promise, smart contracts are difficult to program correctly, as they need a deep understanding of cryptography and distributed algorithms, and offer limited functionality, as they have to be deterministic and cannot operate on secret data. In this paper we present Protean, a general-purpose decentralized computing platform that addresses these limitations by moving from a monolithic execution model, where all participating nodes store all the state and execute every computation, to a modular execution-model. Protean employs secure specialized modules, called functional units, for building decentralized applications that are currently insecure or impossible to implement with smart contracts. Each functional unit is a distributed system that provides a special-purpose functionality by exposing atomic transactions to the smart-contract developer. Combining these transactions into arbitrarily-defined workflows, developers can build a larger class of decentralized applications, such as provably-secure and fair lotteries or e-voting.}, author = {Alp, Enis Ceyhun and Kokoris Kogias, Eleftherios and Fragkouli, Georgia and Ford, Bryan}, booktitle = {Proceedings of the Workshop on Hot Topics in Operating Systems}, isbn = {9781450367271}, location = {Bertinoro, Italy}, pages = {105--112}, publisher = {ACM}, title = {{Rethinking general-purpose decentralized computing}}, doi = {10.1145/3317550.3321448}, year = {2019}, } @unpublished{8303, abstract = {ByzCoin, a promising alternative of Bitcoin, is a scalable consensus protocol used as a building block of many research and enterprise-level decentralized systems. In this paper, we show that ByzCoin is unsuitable for deployment in an anopen, adversarial network and instead introduceMOTOR. MOTORis designed as a secure, robust, and scalable consensus suitable for permissionless sharded blockchains. MOTORachieves these properties by making four key design choices: (a) it prioritizes robustness in adversarial environments while maintaining adequate scalability, (b) it employees provably correct cryptography that resists DoS attacks from individual nodes, (c) it deploys unpredictable rotating leaders to defend against mildly-adaptive adversaries and prevents censorship, and (d) it creates an incentive compatible reward mechanism. These choices are materialized as (a) a “rotating subleader” communication pattern that balances the scalability needs with the robustness requirements under failures, (b) deployment of provable secure BLS multi-signatures, (c) use of deterministic thresh-old signatures as a source of randomness and (d) careful design of the reward allocation mechanism. We have implemented MOTORand compare it withByzCoin. We show that MOTORcan scale similar to ByzCoin with an at most2xoverhead whereas it maintains good performance even under high-percentage of faults, unlike ByzCoin.}, author = {Kokoris Kogias, Eleftherios}, booktitle = {Cryptology ePrint Archive}, title = {{Robust and scalable consensus for sharded distributed ledgers}}, year = {2019}, } @unpublished{8304, abstract = {Enabling secure communication across distributed systems is usually studied under the assumption of trust between the different systems and an external adversary trying to compromise the messages. With the appearance of distributed ledgers or blockchains, numerous protocols have emerged, which attempt to achieve trustless communication between distrusting ledgers and participants. Cross-chain communication (CCC) thereby plays a fundamental role in cryptocurrency exchanges, sharding, bootstrapping of new and feature-extension of existing distributed ledgers. Unfortunately, existing proposals are designed ad-hoc for specific use-cases, making it hard to gain confidence on their correctness and composability. We provide the first systematic exposition of protocols for CCC. First, we formalize the underlying research problem and show that CCC is impossible without a trusted third party, contrary to common beliefs in the blockchain community. We then develop a framework to evaluate existing and to design new cross-chain protocols. The framework is based on the use case, the trust model, and the security assumptions of interlinked blockchains. Finally, we identify security and privacy challenges faced by protocols in the cross-chain setting. This Systematization of Knowledge (SoK) offers a comprehensive guide for designing protocols bridging the numerous distributed ledgers available today. It aims to facilitate clearer communication between academia and industry in the field.}, author = {Zamyatin, Alexei and Al-Bassam, Mustafa and Zindros, Dionysis and Kokoris Kogias, Eleftherios and Moreno-Sanchez, Pedro and Kiayias, Aggelos and Knottenbelt, William J.}, booktitle = {Cryptology ePrint Archive}, title = {{SoK: Communication across distributed ledgers}}, year = {2019}, }