TY - GEN
AB - Acquired mutations are sufficiently frequent such that the genome of a single cell offers a record of its history of cell divisions. Among more common somatic genomic alterations are loss of heterozygosity (LOH). Large LOH events are potentially detectable in single cell RNA sequencing (scRNA-seq) datasets as tracts of monoallelic expression for constitutionally heterozygous single nucleotide variants (SNVs) located among contiguous genes. We identified runs of monoallelic expression, consistent with LOH, uniquely distributed throughout the genome in single cell brain cortex transcriptomes of F1 hybrids involving different inbred mouse strains. We then phylogenetically reconstructed single cell lineages and simultaneously identified cell types by corresponding gene expression patterns. Our results are consistent with progenitor cells giving rise to multiple cortical cell types through stereotyped expansion and distinct waves of neurogenesis. Compared to engineered recording systems, LOH events accumulate throughout the genome and across the lifetime of an organism, affording tremendous capacity for encoding lineage information and increasing resolution for later cell divisions. This approach can conceivably be computationally incorporated into scRNA-seq analysis and may be useful for organisms where genetic engineering is prohibitive, such as humans.
AU - Anderson, Donovan J.
AU - Pauler, Florian
AU - McKenna, Aaron
AU - Shendure, Jay
AU - Hippenmeyer, Simon
AU - Horwitz, Marshall S.
ID - 9082
T2 - bioRxiv
TI - Simultaneous identification of brain cell type and lineage via single cell RNA sequencing
ER -
TY - JOUR
AB - We employ the Gross-Pitaevskii equation to study acoustic emission generated in a uniform Bose gas by a static impurity. The impurity excites a sound-wave packet, which propagates through the gas. We calculate the shape of this wave packet in the limit of long wave lengths, and argue that it is possible to extract properties of the impurity by observing this shape. We illustrate here this possibility for a Bose gas with a trapped impurity atom -- an example of a relevant experimental setup. Presented results are general for all one-dimensional systems described by the nonlinear Schrödinger equation and can also be used in nonatomic systems, e.g., to analyze light propagation in nonlinear optical media. Finally, we calculate the shape of the sound-wave packet for a three-dimensional Bose gas assuming a spherically symmetric perturbation.
AU - Marchukov, Oleksandr
AU - Volosniev, Artem
ID - 9093
IS - 2
JF - SciPost Physics
SN - 2542-4653
TI - Shape of a sound wave in a weakly-perturbed Bose gas
VL - 10
ER -
TY - JOUR
AB - Psoriasis is a chronic inflammatory skin disease clinically characterized by the appearance of red colored, well-demarcated plaques with thickened skin and with silvery scales. Recent studies have established the involvement of a complex signalling network of interactions between cytokines, immune cells and skin cells called keratinocytes. Keratinocytes form the cells of the outermost layer of the skin (epidermis). Visible plaques in psoriasis are developed due to the fast proliferation and unusual differentiation of keratinocyte cells. Despite that, the exact mechanism of the appearance of these plaques in the cytokine-immune cell network is not clear. A mathematical model embodying interactions between key immune cells believed to be involved in psoriasis, keratinocytes and relevant cytokines has been developed. The complex network formed of these interactions poses several challenges. Here, we choose to study subnetworks of this complex network and initially focus on interactions involving TNFα, IL-23/IL-17, and IL-15. These are chosen based on known evidence of their therapeutic efficacy. In addition, we explore the role of IL-15 in the pathogenesis of psoriasis and its potential as a future drug target for a novel treatment option. We perform steady state analyses for these subnetworks and demonstrate that the interactions between cells, driven by cytokines could cause the emergence of a psoriasis state (hyper-proliferation of keratinocytes) when levels of TNFα, IL-23/IL-17 or IL-15 are increased. The model results explain and support the clinical potentiality of anti-cytokine treatments. Interestingly, our results suggest different dynamic scenarios underpin the pathogenesis of psoriasis, depending upon the dominant cytokines of subnetworks. We observed that the increase in the level of IL-23/IL-17 and IL-15 could lead to psoriasis via a bistable route, whereas an increase in the level of TNFα would lead to a monotonic and gradual disease progression. Further, we demonstrate how this insight, bistability, could be exploited to improve the current therapies and develop novel treatment strategies for psoriasis.
AU - Pandey, Rakesh
AU - Al-Nuaimi, Yusur
AU - Mishra, Rajiv Kumar
AU - Spurgeon, Sarah K.
AU - Goodfellow, Marc
ID - 9097
JF - Scientific Reports
TI - Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis
VL - 11
ER -
TY - JOUR
AB - Marine environments are inhabited by a broad representation of the tree of life, yet our understanding of speciation in marine ecosystems is extremely limited compared with terrestrial and freshwater environments. Developing a more comprehensive picture of speciation in marine environments requires that we 'dive under the surface' by studying a wider range of taxa and ecosystems is necessary for a more comprehensive picture of speciation. Although studying marine evolutionary processes is often challenging, recent technological advances in different fields, from maritime engineering to genomics, are making it increasingly possible to study speciation of marine life forms across diverse ecosystems and taxa. Motivated by recent research in the field, including the 14 contributions in this issue, we highlight and discuss six axes of research that we think will deepen our understanding of speciation in the marine realm: (a) study a broader range of marine environments and organisms; (b) identify the reproductive barriers driving speciation between marine taxa; (c) understand the role of different genomic architectures underlying reproductive isolation; (d) infer the evolutionary history of divergence using model‐based approaches; (e) study patterns of hybridization and introgression between marine taxa; and (f) implement highly interdisciplinary, collaborative research programmes. In outlining these goals, we hope to inspire researchers to continue filling this critical knowledge gap surrounding the origins of marine biodiversity.
AU - Faria, Rui
AU - Johannesson, Kerstin
AU - Stankowski, Sean
ID - 9100
IS - 1
JF - Journal of Evolutionary Biology
SN - 1010061X
TI - Speciation in marine environments: Diving under the surface
VL - 34
ER -
TY - JOUR
AB - We present DILS, a deployable statistical analysis platform for conducting demographic inferences with linked selection from population genomic data using an Approximate Bayesian Computation framework. DILS takes as input single‐population or two‐population data sets (multilocus fasta sequences) and performs three types of analyses in a hierarchical manner, identifying: (a) the best demographic model to study the importance of gene flow and population size change on the genetic patterns of polymorphism and divergence, (b) the best genomic model to determine whether the effective size Ne and migration rate N, m are heterogeneously distributed along the genome (implying linked selection) and (c) loci in genomic regions most associated with barriers to gene flow. Also available via a Web interface, an objective of DILS is to facilitate collaborative research in speciation genomics. Here, we show the performance and limitations of DILS by using simulations and finally apply the method to published data on a divergence continuum composed by 28 pairs of Mytilus mussel populations/species.
AU - Fraisse, Christelle
AU - Popovic, Iva
AU - Mazoyer, Clément
AU - Spataro, Bruno
AU - Delmotte, Stéphane
AU - Romiguier, Jonathan
AU - Loire, Étienne
AU - Simon, Alexis
AU - Galtier, Nicolas
AU - Duret, Laurent
AU - Bierne, Nicolas
AU - Vekemans, Xavier
AU - Roux, Camille
ID - 9119
JF - Molecular Ecology Resources
SN - 1755098X
TI - DILS: Demographic inferences with linked selection by using ABC
ER -
TY - JOUR
AB - We show that the energy gap for the BCS gap equation is
Ξ=μ(8e−2+o(1))exp(π2μ−−√a)
in the low density limit μ→0. Together with the similar result for the critical temperature by Hainzl and Seiringer (Lett Math Phys 84: 99–107, 2008), this shows that, in the low density limit, the ratio of the energy gap and critical temperature is a universal constant independent of the interaction potential V. The results hold for a class of potentials with negative scattering length a and no bound states.
AU - Lauritsen, Asbjørn Bækgaard
ID - 9121
JF - Letters in Mathematical Physics
KW - Mathematical Physics
KW - Statistical and Nonlinear Physics
SN - 0377-9017
TI - The BCS energy gap at low density
VL - 111
ER -
TY - JOUR
AB - While several tools have been developed to study the ground state of many-body quantum spin systems, the limitations of existing techniques call for the exploration of new approaches. In this manuscript we develop an alternative analytical and numerical framework for many-body quantum spin ground states, based on the disentanglement formalism. In this approach, observables are exactly expressed as Gaussian-weighted functional integrals over scalar fields. We identify the leading contribution to these integrals, given by the saddle point of a suitable effective action. Analytically, we develop a field-theoretical expansion of the functional integrals, performed by means of appropriate Feynman rules. The expansion can be truncated to a desired order to obtain analytical approximations to observables. Numerically, we show that the disentanglement approach can be used to compute ground state expectation values from classical stochastic processes. While the associated fluctuations grow exponentially with imaginary time and the system size, this growth can be mitigated by means of an importance sampling scheme based on knowledge of the saddle point configuration. We illustrate the advantages and limitations of our methods by considering the quantum Ising model in 1, 2 and 3 spatial dimensions. Our analytical and numerical approaches are applicable to a broad class of systems, bridging concepts from quantum lattice models, continuum field theory, and classical stochastic processes.
AU - De Nicola, Stefano
ID - 9158
IS - 1
JF - Journal of Statistical Mechanics: Theory and Experiment
KW - Statistics
KW - Probability and Uncertainty
KW - Statistics and Probability
KW - Statistical and Nonlinear Physics
SN - 1742-5468
TI - Disentanglement approach to quantum spin ground states: Field theory and stochastic simulation
VL - 2021
ER -
TY - JOUR
AB - We show that Hilbert schemes of points on supersingular Enriques surface in characteristic 2, Hilbn(X), for n ≥ 2 are simply connected, symplectic varieties but are not irreducible symplectic as the hodge number h2,0 > 1, even though a supersingular Enriques surface is an irreducible symplectic variety. These are the classes of varieties which appear only in characteristic 2 and they show that the hodge number formula for G¨ottsche-Soergel does not hold over haracteristic 2. It also gives examples of varieties with trivial canonical class which are neither irreducible symplectic nor Calabi-Yau, thereby showing that there are strictly more classes of simply connected varieties with trivial canonical class in characteristic 2 than over C as given by Beauville-Bogolomov decomposition theorem.
AU - Srivastava, Tanya K
ID - 9173
IS - 03
JF - Bulletin des Sciences Mathematiques
SN - 0007-4497
TI - Pathologies of the Hilbert scheme of points of a supersingular Enriques surface
VL - 167
ER -
TY - GEN
AB - We associate a certain tensor product lattice to any primitive integer lattice and ask about its typical shape. These lattices are related to the tangent bundle of Grassmannians and their study is motivated by Peyre's programme on "freeness" for rational points of bounded height on Fano
varieties.
AU - Browning, Timothy D
AU - Horesh, Tal
AU - Wilsch, Florian Alexander
ID - 9199
T2 - arXiv
TI - Equidistribution and freeness on Grassmannians
ER -
TY - JOUR
AB - Cryo-EM grid preparation is an important bottleneck in protein structure determination, especially for membrane proteins, typically requiring screening of a large number of conditions. We systematically investigated the effects of buffer components, blotting conditions and grid types on the outcome of grid preparation of five different membrane protein samples. Aggregation was the most common type of problem which was addressed by changing detergents, salt concentration or reconstitution of proteins into nanodiscs or amphipols. We show that the optimal concentration of detergent is between 0.05 and 0.4% and that the presence of a low concentration of detergent with a high critical micellar concentration protects the proteins from denaturation at the air-water interface. Furthermore, we discuss the strategies for achieving an adequate ice thickness, particle coverage and orientation distribution on free ice and on support films. Our findings provide a clear roadmap for comprehensive screening of conditions for cryo-EM grid preparation of membrane proteins.
AU - Kampjut, Domen
AU - Steiner, Julia
AU - Sazanov, Leonid A
ID - 9205
IS - 3
JF - iScience
TI - Cryo-EM grid optimization for membrane proteins
VL - 24
ER -
TY - JOUR
AB - The precise engineering of thermoelectric materials using nanocrystals as their building blocks has proven to be an excellent strategy to increase energy conversion efficiency. Here we present a synthetic route to produce Sb-doped PbS colloidal nanoparticles. These nanoparticles are then consolidated into nanocrystalline PbS:Sb using spark plasma sintering. We demonstrate that the introduction of Sb significantly influences the size, geometry, crystal lattice and especially the carrier concentration of PbS. The increase of charge carrier concentration achieved with the introduction of Sb translates into an increase of the electrical and thermal conductivities and a decrease of the Seebeck coefficient. Overall, PbS:Sb nanomaterial were characterized by two-fold higher thermoelectric figures of merit than undoped PbS.
AU - Cadavid, Doris
AU - Wei, Kaya
AU - Liu, Yu
AU - Zhang, Yu
AU - Li, Mengyao
AU - Genç, Aziz
AU - Berestok, Taisiia
AU - Ibáñez, Maria
AU - Shavel, Alexey
AU - Nolas, George S.
AU - Cabot, Andreu
ID - 9206
IS - 4
JF - Materials
TI - Synthesis, bottom up assembly and thermoelectric properties of Sb-doped PbS nanocrystal building blocks
VL - 14
ER -
TY - CONF
AB - We propose a novel hybridization method for stability analysis that over-approximates nonlinear dynamical systems by switched systems with linear inclusion dynamics. We observe that existing hybridization techniques for safety analysis that over-approximate nonlinear dynamical systems by switched affine inclusion dynamics and provide fixed approximation error, do not suffice for stability analysis. Hence, we propose a hybridization method that provides a state-dependent error which converges to zero as the state tends to the equilibrium point. The crux of our hybridization computation is an elegant recursive algorithm that uses partial derivatives of a given function to obtain upper and lower bound matrices for the over-approximating linear inclusion. We illustrate our method on some examples to demonstrate the application of the theory for stability analysis. In particular, our method is able to establish stability of a nonlinear system which does not admit a polynomial Lyapunov function.
AU - Garcia Soto, Miriam
AU - Prabhakar, Pavithra
ID - 9202
T2 - 2020 IEEE Real-Time Systems Symposium
TI - Hybridization for stability verification of nonlinear switched systems
ER -
TY - CONF
AB - In the multiway cut problem we are given a weighted undirected graph G=(V,E) and a set T⊆V of k terminals. The goal is to find a minimum weight set of edges E′⊆E with the property that by removing E′ from G all the terminals become disconnected. In this paper we present a simple local search approximation algorithm for the multiway cut problem with approximation ratio 2−2k . We present an experimental evaluation of the performance of our local search algorithm and show that it greatly outperforms the isolation heuristic of Dalhaus et al. and it has similar performance as the much more complex algorithms of Calinescu et al., Sharma and Vondrak, and Buchbinder et al. which have the currently best known approximation ratios for this problem.
AU - Bloch-Hansen, Andrew
AU - Samei, Nasim
AU - Solis-Oba, Roberto
ID - 9227
SN - 0302-9743
T2 - Conference on Algorithms and Discrete Applied Mathematics
TI - Experimental evaluation of a local search approximation algorithm for the multiway cut problem
VL - 12601
ER -
TY - JOUR
AB - Half a century after Lewis Wolpert's seminal conceptual advance on how cellular fates distribute in space, we provide a brief historical perspective on how the concept of positional information emerged and influenced the field of developmental biology and beyond. We focus on a modern interpretation of this concept in terms of information theory, largely centered on its application to cell specification in the early Drosophila embryo. We argue that a true physical variable (position) is encoded in local concentrations of patterning molecules, that this mapping is stochastic, and that the processes by which positions and corresponding cell fates are determined based on these concentrations need to take such stochasticity into account. With this approach, we shift the focus from biological mechanisms, molecules, genes and pathways to quantitative systems-level questions: where does positional information reside, how it is transformed and accessed during development, and what fundamental limits it is subject to?
AU - Tkačik, Gašper
AU - Gregor, Thomas
ID - 9226
IS - 2
JF - Development
TI - The many bits of positional information
VL - 148
ER -
TY - GEN
AB - We consider a model of the Riemann zeta function on the critical axis and study its maximum over intervals of length (log T)θ, where θ is either fixed or tends to zero at a suitable rate.
It is shown that the deterministic level of the maximum interpolates smoothly between the ones
of log-correlated variables and of i.i.d. random variables, exhibiting a smooth transition ‘from
3/4 to 1/4’ in the second order. This provides a natural context where extreme value statistics of
log-correlated variables with time-dependent variance and rate occur. A key ingredient of the
proof is a precise upper tail tightness estimate for the maximum of the model on intervals of
size one, that includes a Gaussian correction. This correction is expected to be present for the
Riemann zeta function and pertains to the question of the correct order of the maximum of
the zeta function in large intervals.
AU - Arguin, Louis-Pierre
AU - Dubach, Guillaume
AU - Hartung, Lisa
ID - 9230
T2 - arXiv
TI - Maxima of a random model of the Riemann zeta function over intervals of varying length
ER -
TY - JOUR
AB - Cesium lead halides have intrinsically unstable crystal lattices and easily transform within perovskite and nonperovskite structures. In this work, we explore the conversion of the perovskite CsPbBr3 into Cs4PbBr6 in the presence of PbS at 450 °C to produce doped nanocrystal-based composites with embedded Cs4PbBr6 nanoprecipitates. We show that PbBr2 is extracted from CsPbBr3 and diffuses into the PbS lattice with a consequent increase in the concentration of free charge carriers. This new doping strategy enables the adjustment of the density of charge carriers between 1019 and 1020 cm–3, and it may serve as a general strategy for doping other nanocrystal-based semiconductors.
AU - Calcabrini, Mariano
AU - Genc, Aziz
AU - Liu, Yu
AU - Kleinhanns, Tobias
AU - Lee, Seungho
AU - Dirin, Dmitry N.
AU - Akkerman, Quinten A.
AU - Kovalenko, Maksym V.
AU - Arbiol, Jordi
AU - Ibáñez, Maria
ID - 9118
IS - 2
JF - ACS Energy Letters
TI - Exploiting the lability of metal halide perovskites for doping semiconductor nanocomposites
VL - 6
ER -
TY - JOUR
AB - We consider the Fröhlich polaron model in the strong coupling limit. It is well‐known that to leading order the ground state energy is given by the (classical) Pekar energy. In this work, we establish the subleading correction, describing quantum fluctuation about the classical limit. Our proof applies to a model of a confined polaron, where both the electron and the polarization field are restricted to a set of finite volume, with linear size determined by the natural length scale of the Pekar problem.
AU - Frank, Rupert
AU - Seiringer, Robert
ID - 8603
IS - 3
JF - Communications on Pure and Applied Mathematics
SN - 00103640
TI - Quantum corrections to the Pekar asymptotics of a strongly coupled polaron
VL - 74
ER -
TY - JOUR
AB - This paper is concerned with a non-isothermal Cahn-Hilliard model based on a microforce balance. The model was derived by A. Miranville and G. Schimperna starting from the two fundamental laws of Thermodynamics, following M. Gurtin's two-scale approach. The main working assumptions are made on the behaviour of the heat flux as the absolute temperature tends to zero and to infinity. A suitable Ginzburg-Landau free energy is considered. Global-in-time existence for the initial-boundary value problem associated to the entropy formulation and, in a subcase, also to the weak formulation of the model is proved by deriving suitable a priori estimates and by showing weak sequential stability of families of approximating solutions. At last, some highlights are given regarding a possible approximation scheme compatible with the a-priori estimates available for the system.
AU - Marveggio, Alice
AU - Schimperna, Giulio
ID - 8792
IS - 2
JF - Journal of Differential Equations
SN - 00220396
TI - On a non-isothermal Cahn-Hilliard model based on a microforce balance
VL - 274
ER -
TY - CHAP
AB - Expansion microscopy is a recently developed super-resolution imaging technique, which provides an alternative to optics-based methods such as deterministic approaches (e.g. STED) or stochastic approaches (e.g. PALM/STORM). The idea behind expansion microscopy is to embed the biological sample in a swellable gel, and then to expand it isotropically, thereby increasing the distance between the fluorophores. This approach breaks the diffraction barrier by simply separating the emission point-spread-functions of the fluorophores. The resolution attainable in expansion microscopy is thus directly dependent on the separation that can be achieved, i.e. on the expansion factor. The original implementation of the technique achieved an expansion factor of fourfold, for a resolution of 70–80 nm. The subsequently developed X10 method achieves an expansion factor of 10-fold, for a resolution of 25–30 nm. This technique can be implemented with minimal technical requirements on any standard fluorescence microscope, and is more easily applied for multi-color imaging than either deterministic or stochastic super-resolution approaches. This renders X10 expansion microscopy a highly promising tool for new biological discoveries, as discussed here, and as demonstrated by several recent applications.
AU - Truckenbrodt, Sven M
AU - Rizzoli, Silvio O.
ID - 7941
SN - 0091-679X
T2 - Methods in Cell Biology
TI - Simple multi-color super-resolution by X10 microscopy
VL - 161
ER -
TY - JOUR
AB - Interspecific crossing experiments have shown that sex chromosomes play a major role in reproductive isolation between many pairs of species. However, their ability to act as reproductive barriers, which hamper interspecific genetic exchange, has rarely been evaluated quantitatively compared to Autosomes. This genome-wide limitation of gene flow is essential for understanding the complete separation of species, and thus speciation. Here, we develop a mainland-island model of secondary contact between hybridizing species of an XY (or ZW) sexual system. We obtain theoretical predictions for the frequency of introgressed alleles, and the strength of the barrier to neutral gene flow for the two types of chromosomes carrying multiple interspecific barrier loci. Theoretical predictions are obtained for scenarios where introgressed alleles are rare. We show that the same analytical expressions apply for sex chromosomes and autosomes, but with different sex-averaged effective parameters. The specific features of sex chromosomes (hemizygosity and absence of recombination in the heterogametic sex) lead to reduced levels of introgression on the X (or Z) compared to autosomes. This effect can be enhanced by certain types of sex-biased forces, but it remains overall small (except when alleles causing incompatibilities are recessive). We discuss these predictions in the light of empirical data comprising model-based tests of introgression and cline surveys in various biological systems.
AU - Fraisse, Christelle
AU - Sachdeva, Himani
ID - 9168
IS - 2
JF - Genetics
SN - 1943-2631
TI - The rates of introgression and barriers to genetic exchange between hybridizing species: Sex chromosomes vs autosomes
VL - 217
ER -