@misc{9789, author = {Pokusaeva, Victoria and Usmanova, Dinara R. and Putintseva, Ekaterina V. and Espinar, Lorena and Sarkisyan, Karen and Mishin, Alexander S. and Bogatyreva, Natalya S. and Ivankov, Dmitry and Akopyan, Arseniy and Avvakumov, Sergey and Povolotskaya, Inna S. and Filion, Guillaume J. and Carey, Lucas B. and Kondrashov, Fyodor}, publisher = {Public Library of Science}, title = {{Multiple alignment of His3 orthologues}}, doi = {10.1371/journal.pgen.1008079.s010}, year = {2019}, } @inproceedings{6462, abstract = {A controller is a device that interacts with a plant. At each time point,it reads the plant’s state and issues commands with the goal that the plant oper-ates optimally. Constructing optimal controllers is a fundamental and challengingproblem. Machine learning techniques have recently been successfully applied totrain controllers, yet they have limitations. Learned controllers are monolithic andhard to reason about. In particular, it is difficult to add features without retraining,to guarantee any level of performance, and to achieve acceptable performancewhen encountering untrained scenarios. These limitations can be addressed bydeploying quantitative run-timeshieldsthat serve as a proxy for the controller.At each time point, the shield reads the command issued by the controller andmay choose to alter it before passing it on to the plant. We show how optimalshields that interfere as little as possible while guaranteeing a desired level ofcontroller performance, can be generated systematically and automatically usingreactive synthesis. First, we abstract the plant by building a stochastic model.Second, we consider the learned controller to be a black box. Third, we mea-surecontroller performanceandshield interferenceby two quantitative run-timemeasures that are formally defined using weighted automata. Then, the problemof constructing a shield that guarantees maximal performance with minimal inter-ference is the problem of finding an optimal strategy in a stochastic2-player game“controller versus shield” played on the abstract state space of the plant with aquantitative objective obtained from combining the performance and interferencemeasures. We illustrate the effectiveness of our approach by automatically con-structing lightweight shields for learned traffic-light controllers in various roadnetworks. The shields we generate avoid liveness bugs, improve controller per-formance in untrained and changing traffic situations, and add features to learnedcontrollers, such as giving priority to emergency vehicles.}, author = {Avni, Guy and Bloem, Roderick and Chatterjee, Krishnendu and Henzinger, Thomas A and Konighofer, Bettina and Pranger, Stefan}, booktitle = {31st International Conference on Computer-Aided Verification}, isbn = {9783030255398}, issn = {0302-9743}, location = {New York, NY, United States}, pages = {630--649}, publisher = {Springer}, title = {{Run-time optimization for learned controllers through quantitative games}}, doi = {10.1007/978-3-030-25540-4_36}, volume = {11561}, year = {2019}, } @article{6477, abstract = {Thermalizing quantum systems are conventionallydescribed by statistical mechanics at equilib-rium. However, not all systems fall into this category, with many-body localization providinga generic mechanism for thermalization to fail in strongly disordered systems. Many-bodylocalized (MBL) systems remain perfect insulators at nonzero temperature, which do notthermalize and therefore cannot be describedusing statistical mechanics. This Colloquiumreviews recent theoretical and experimental advances in studies of MBL systems, focusing onthe new perspective provided by entanglement and nonequilibrium experimental probes suchas quantum quenches. Theoretically, MBL systems exhibit a new kind of robust integrability: anextensive set of quasilocal integrals of motion emerges, which provides an intuitive explanationof the breakdown of thermalization. A description based on quasilocal integrals of motion isused to predict dynamical properties of MBL systems, such as the spreading of quantumentanglement, the behavior of local observables, and the response to external dissipativeprocesses. Furthermore, MBL systems can exhibit eigenstate transitions and quantum ordersforbidden in thermodynamic equilibrium. An outline isgiven of the current theoretical under-standing of the quantum-to-classical transitionbetween many-body localized and ergodic phasesand anomalous transport in the vicinity of that transition. Experimentally, synthetic quantumsystems, which are well isolated from an external thermal reservoir, provide natural platforms forrealizing the MBL phase. Recent experiments with ultracold atoms, trapped ions, superconductingqubits, and quantum materials, in which different signatures of many-body localization have beenobserved, are reviewed. This Colloquium concludes by listing outstanding challenges andpromising future research directions.}, author = {Abanin, Dmitry A. and Altman, Ehud and Bloch, Immanuel and Serbyn, Maksym}, issn = {0034-6861}, journal = {Reviews of Modern Physics}, number = {2}, publisher = {American Physical Society}, title = {{Colloquium: Many-body localization, thermalization, and entanglement}}, doi = {10.1103/revmodphys.91.021001}, volume = {91}, year = {2019}, } @article{6466, abstract = {One of the most striking and consistent results in speciation genomics is the heterogeneous divergence observed across the genomes of closely related species. This pattern was initially attributed to different levels of gene exchange—with divergence preserved at loci generating a barrier to gene flow but homogenized at unlinked neutral loci. Although there is evidence to support this model, it is now recognized that interpreting patterns of divergence across genomes is not so straightforward. One problem is that heterogenous divergence between populations can also be generated by other processes (e.g. recurrent selective sweeps or background selection) without any involvement of differential gene flow. Thus, integrated studies that identify which loci are likely subject to divergent selection are required to shed light on the interplay between selection and gene flow during the early phases of speciation. In this issue of Molecular Ecology, Rifkin et al. (2019) confront this challenge using a pair of sister morning glory species. They wisely design their sampling to take the geographic context of individuals into account, including geographically isolated (allopatric) and co‐occurring (sympatric) populations. This enabled them to show that individuals are phenotypically less differentiated in sympatry. They also found that the loci that resist introgression are enriched for those most differentiated in allopatry and loci that exhibit signals of divergent selection. One great strength of the study is the combination of methods from population genetics and molecular evolution, including the development of a model to simultaneously infer admixture proportions and selfing rates.}, author = {Field, David and Fraisse, Christelle}, issn = {1365294X}, journal = {Molecular ecology}, number = {7}, pages = {1579--1581}, publisher = {Wiley}, title = {{Breaking down barriers in morning glories}}, doi = {10.1111/mec.15048}, volume = {28}, year = {2019}, } @article{6465, abstract = {Tight control over protein degradation is a fundamental requirement for cells to respond rapidly to various stimuli and adapt to a fluctuating environment. Here we develop a versatile, easy-to-handle library of destabilizing tags (degrons) for the precise regulation of protein expression profiles in mammalian cells by modulating target protein half-lives in a predictable manner. Using the well-established tetracycline gene-regulation system as a model, we show that the dynamics of protein expression can be tuned by fusing appropriate degron tags to gene regulators. Next, we apply this degron library to tune a synthetic pulse-generating circuit in mammalian cells. With this toolbox we establish a set of pulse generators with tailored pulse lengths and magnitudes of protein expression. This methodology will prove useful in the functional roles of essential proteins, fine-tuning of gene-expression systems, and enabling a higher complexity in the design of synthetic biological systems in mammalian cells.}, author = {Chassin, Hélène and Müller, Marius and Tigges, Marcel and Scheller, Leo and Lang, Moritz and Fussenegger, Martin}, issn = {20411723}, journal = {Nature Communications}, number = {1}, publisher = {Springer Nature}, title = {{A modular degron library for synthetic circuits in mammalian cells}}, doi = {10.1038/s41467-019-09974-5}, volume = {10}, year = {2019}, } @article{6467, abstract = {Fitness interactions between mutations can influence a population’s evolution in many different ways. While epistatic effects are difficult to measure precisely, important information is captured by the mean and variance of log fitnesses for individuals carrying different numbers of mutations. We derive predictions for these quantities from a class of simple fitness landscapes, based on models of optimizing selection on quantitative traits. We also explore extensions to the models, including modular pleiotropy, variable effect sizes, mutational bias and maladaptation of the wild type. We illustrate our approach by reanalysing a large dataset of mutant effects in a yeast snoRNA (small nucleolar RNA). Though characterized by some large epistatic effects, these data give a good overall fit to the non-epistatic null model, suggesting that epistasis might have limited influence on the evolutionary dynamics in this system. We also show how the amount of epistasis depends on both the underlying fitness landscape and the distribution of mutations, and so is expected to vary in consistent ways between new mutations, standing variation and fixed mutations.}, author = {Fraisse, Christelle and Welch, John J.}, issn = {1744957X}, journal = {Biology Letters}, number = {4}, publisher = {Royal Society of London}, title = {{The distribution of epistasis on simple fitness landscapes}}, doi = {10.1098/rsbl.2018.0881}, volume = {15}, year = {2019}, } @article{6470, abstract = {Investigating neuronal activity using genetically encoded Ca2+ indicators in behaving animals is hampered by inaccuracies in spike inference from fluorescent tracers. Here we combine two‐photon [Ca2+] imaging with cell‐attached recordings, followed by post hoc determination of the expression level of GCaMP6f, to explore how it affects the amplitude, kinetics and temporal summation of somatic [Ca2+] transients in mouse hippocampal pyramidal cells (PCs). The amplitude of unitary [Ca2+] transients (evoked by a single action potential) negatively correlates with GCaMP6f expression, but displays large variability even among PCs with similarly low expression levels. The summation of fluorescence signals is frequency‐dependent, supralinear and also shows remarkable cell‐to‐cell variability. We performed experimental data‐based simulations and found that spike inference error rates using MLspike depend strongly on unitary peak amplitudes and GCaMP6f expression levels. We provide simple methods for estimating the unitary [Ca2+] transients in individual weakly GCaMP6f‐expressing PCs, with which we achieve spike inference error rates of ∼5%. }, author = {Éltes, Tímea and Szoboszlay, Miklos and Szigeti, Margit Katalin and Nusser, Zoltan}, issn = {14697793}, journal = {Journal of Physiology}, number = {11}, pages = {2925–2947}, publisher = {Wiley}, title = {{Improved spike inference accuracy by estimating the peak amplitude of unitary [Ca2+] transients in weakly GCaMP6f-expressing hippocampal pyramidal cells}}, doi = {10.1113/JP277681}, volume = {597}, year = {2019}, } @inproceedings{6493, abstract = {We present two algorithmic approaches for synthesizing linear hybrid automata from experimental data. Unlike previous approaches, our algorithms work without a template and generate an automaton with nondeterministic guards and invariants, and with an arbitrary number and topology of modes. They thus construct a succinct model from the data and provide formal guarantees. In particular, (1) the generated automaton can reproduce the data up to a specified tolerance and (2) the automaton is tight, given the first guarantee. Our first approach encodes the synthesis problem as a logical formula in the theory of linear arithmetic, which can then be solved by an SMT solver. This approach minimizes the number of modes in the resulting model but is only feasible for limited data sets. To address scalability, we propose a second approach that does not enforce to find a minimal model. The algorithm constructs an initial automaton and then iteratively extends the automaton based on processing new data. Therefore the algorithm is well-suited for online and synthesis-in-the-loop applications. The core of the algorithm is a membership query that checks whether, within the specified tolerance, a given data set can result from the execution of a given automaton. We solve this membership problem for linear hybrid automata by repeated reachability computations. We demonstrate the effectiveness of the algorithm on synthetic data sets and on cardiac-cell measurements.}, author = {Garcia Soto, Miriam and Henzinger, Thomas A and Schilling, Christian and Zeleznik, Luka}, booktitle = {31st International Conference on Computer-Aided Verification}, isbn = {9783030255398}, issn = {0302-9743}, keywords = {Synthesis, Linear hybrid automaton, Membership}, location = {New York City, NY, USA}, pages = {297--314}, publisher = {Springer}, title = {{Membership-based synthesis of linear hybrid automata}}, doi = {10.1007/978-3-030-25540-4_16}, volume = {11561}, year = {2019}, } @misc{6485, abstract = {Traditional concurrent programming involves manipulating shared mutable state. Alternatives to this programming style are communicating sequential processes (CSP) [1] and actor [2] models, which share data via explicit communication. Rendezvous channelis the common abstraction for communication between several processes, where senders and receivers perform a rendezvous handshake as a part of their protocol (senders wait for receivers and vice versa). Additionally to this, channels support the select expression. In this work, we present the first efficient lock-free channel algorithm, and compare it against Go [3] and Kotlin [4] baseline implementations.}, author = {Koval, Nikita and Alistarh, Dan-Adrian and Elizarov, Roman}, booktitle = {Proceedings of the 24th Symposium on Principles and Practice of Parallel Programming}, isbn = {9781450362252}, location = {Washington, NY, United States}, pages = {417--418}, publisher = {ACM Press}, title = {{Lock-free channels for programming via communicating sequential processes}}, doi = {10.1145/3293883.3297000}, year = {2019}, } @article{6504, abstract = {Root gravitropism is one of the most important processes allowing plant adaptation to the land environment. Auxin plays a central role in mediating root gravitropism, but how auxin contributes to gravitational perception and the subsequent response is still unclear. Here, we showed that the local auxin maximum/gradient within the root apex, which is generated by the PIN directional auxin transporters, regulates the expression of three key starch granule synthesis genes, SS4, PGM and ADG1, which in turn influence the accumulation of starch granules that serve as a statolith perceiving gravity. Moreover, using the cvxIAA‐ccvTIR1 system, we also showed that TIR1‐mediated auxin signaling is required for starch granule formation and gravitropic response within root tips. In addition, axr3 mutants showed reduced auxin‐mediated starch granule accumulation and disruption of gravitropism within the root apex. Our results indicate that auxin‐mediated statolith production relies on the TIR1/AFB‐AXR3‐mediated auxin signaling pathway. In summary, we propose a dual role for auxin in gravitropism: the regulation of both gravity perception and response.}, author = {Zhang, Yuzhou and He, P and Ma, X and Yang, Z and Pang, C and Yu, J and Wang, G and Friml, Jiří and Xiao, G}, issn = {1469-8137}, journal = {New Phytologist}, number = {2}, pages = {761--774}, publisher = {Wiley}, title = {{Auxin-mediated statolith production for root gravitropism}}, doi = {10.1111/nph.15932}, volume = {224}, year = {2019}, } @article{6506, abstract = {How does environmental complexity affect the evolution of single genes? Here, we measured the effects of a set of Bacillus subtilis glutamate dehydrogenase mutants across 19 different environments—from phenotypically homogeneous single-cell populations in liquid media to heterogeneous biofilms, plant roots and soil populations. The effects of individual gene mutations on organismal fitness were highly reproducible in liquid cultures. However, 84% of the tested alleles showed opposing fitness effects under different growth conditions (sign environmental pleiotropy). In colony biofilms and soil samples, different alleles dominated in parallel replica experiments. Accordingly, we found that in these heterogeneous cell populations the fate of mutations was dictated by a combination of selection and drift. The latter relates to programmed prophage excisions that occurred during biofilm development. Overall, for each condition, a wide range of glutamate dehydrogenase mutations persisted and sometimes fixated as a result of the combined action of selection, pleiotropy and chance. However, over longer periods and in multiple environments, nearly all of this diversity would be lost—across all the environments and conditions that we tested, the wild type was the fittest allele.}, author = {Noda-García, Lianet and Davidi, Dan and Korenblum, Elisa and Elazar, Assaf and Putintseva, Ekaterina and Aharoni, Asaph and Tawfik, Dan S.}, issn = {2058-5276}, journal = {Nature Microbiology}, number = {7}, pages = {1221–1230}, publisher = {Springer Nature}, title = {{Chance and pleiotropy dominate genetic diversity in complex bacterial environments}}, doi = {10.1038/s41564-019-0412-y}, volume = {4}, year = {2019}, } @article{6521, abstract = {Microglia have emerged as a critical component of neurodegenerative diseases. Genetic manipulation of microglia can elucidate their functional impact in disease. In neuroscience, recombinant viruses such as lentiviruses and adeno-associated viruses (AAVs) have been successfully used to target various cell types in the brain, although effective transduction of microglia is rare. In this review, we provide a short background of lentiviruses and AAVs, and strategies for designing recombinant viral vectors. Then, we will summarize recent literature on successful microglial transductions in vitro and in vivo, and discuss the current challenges. Finally, we provide guidelines for reporting the efficiency and specificity of viral targeting in microglia, which will enable the microglial research community to assess and improve methodologies for future studies.}, author = {Maes, Margaret E and Colombo, Gloria and Schulz, Rouven and Siegert, Sandra}, issn = {0304-3940}, journal = {Neuroscience Letters}, publisher = {Elsevier}, title = {{Targeting microglia with lentivirus and AAV: Recent advances and remaining challenges}}, doi = {10.1016/j.neulet.2019.134310}, volume = {707}, year = {2019}, } @article{6513, abstract = {Adult intestinal stem cells are located at the bottom of crypts of Lieberkühn, where they express markers such as LGR5 1,2 and fuel the constant replenishment of the intestinal epithelium1. Although fetal LGR5-expressing cells can give rise to adult intestinal stem cells3,4, it remains unclear whether this population in the patterned epithelium represents unique intestinal stem-cell precursors. Here we show, using unbiased quantitative lineage-tracing approaches, biophysical modelling and intestinal transplantation, that all cells of the mouse intestinal epithelium—irrespective of their location and pattern of LGR5 expression in the fetal gut tube—contribute actively to the adult intestinal stem cell pool. Using 3D imaging, we find that during fetal development the villus undergoes gross remodelling and fission. This brings epithelial cells from the non-proliferative villus into the proliferative intervillus region, which enables them to contribute to the adult stem-cell niche. Our results demonstrate that large-scale remodelling of the intestinal wall and cell-fate specification are closely linked. Moreover, these findings provide a direct link between the observed plasticity and cellular reprogramming of differentiating cells in adult tissues following damage5,6,7,8,9, revealing that stem-cell identity is an induced rather than a hardwired property.}, author = {Guiu, Jordi and Hannezo, Edouard B and Yui, Shiro and Demharter, Samuel and Ulyanchenko, Svetlana and Maimets, Martti and Jørgensen, Anne and Perlman, Signe and Lundvall, Lene and Mamsen, Linn Salto and Larsen, Agnete and Olesen, Rasmus H. and Andersen, Claus Yding and Thuesen, Lea Langhoff and Hare, Kristine Juul and Pers, Tune H. and Khodosevich, Konstantin and Simons, Benjamin D. and Jensen, Kim B.}, issn = {14764687}, journal = {Nature}, pages = {107--111}, publisher = {Springer Nature}, title = {{Tracing the origin of adult intestinal stem cells}}, doi = {10.1038/s41586-019-1212-5}, volume = {570}, year = {2019}, } @article{6564, abstract = {Optogenetics enables the spatio-temporally precise control of cell and animal behavior. Many optogenetic tools are driven by light-controlled protein–protein interactions (PPIs) that are repurposed from natural light-sensitive domains (LSDs). Applying light-controlled PPIs to new target proteins is challenging because it is difficult to predict which of the many available LSDs, if any, will yield robust light regulation. As a consequence, fusion protein libraries need to be prepared and tested, but methods and platforms to facilitate this process are currently not available. Here, we developed a genetic engineering strategy and vector library for the rapid generation of light-controlled PPIs. The strategy permits fusing a target protein to multiple LSDs efficiently and in two orientations. The public and expandable library contains 29 vectors with blue, green or red light-responsive LSDs, many of which have been previously applied ex vivo and in vivo. We demonstrate the versatility of the approach and the necessity for sampling LSDs by generating light-activated caspase-9 (casp9) enzymes. Collectively, this work provides a new resource for optical regulation of a broad range of target proteins in cell and developmental biology.}, author = {Tichy, Alexandra-Madelaine and Gerrard, Elliot J. and Legrand, Julien M.D. and Hobbs, Robin M. and Janovjak, Harald L}, issn = {10898638}, journal = {Journal of Molecular Biology}, number = {17}, pages = {3046--3055}, publisher = {Elsevier}, title = {{Engineering strategy and vector library for the rapid generation of modular light-controlled protein–protein interactions}}, doi = {10.1016/j.jmb.2019.05.033}, volume = {431}, year = {2019}, } @article{6552, abstract = {When animals become sick, infected cells and an armada of activated immune cells attempt to eliminate the pathogen from the body. Once infectious particles have breached the body's physical barriers of the skin or gut lining, an initially local response quickly escalates into a systemic response, attracting mobile immune cells to the site of infection. These cells complement the initial, unspecific defense with a more specialized, targeted response. This can also provide long-term immune memory and protection against future infection. The cell-autonomous defenses of the infected cells are thus aided by the actions of recruited immune cells. These specialized cells are the most mobile cells in the body, constantly patrolling through the otherwise static tissue to detect incoming pathogens. Such constant immune surveillance means infections are noticed immediately and can be rapidly cleared from the body. Some immune cells also remove infected cells that have succumbed to infection. All this prevents pathogen replication and spread to healthy tissues. Although this may involve the sacrifice of some somatic tissue, this is typically replaced quickly. Particular care is, however, given to the reproductive organs, which should always remain disease free (immune privilege). }, author = {Cremer, Sylvia}, issn = {09609822}, journal = {Current Biology}, number = {11}, pages = {R458--R463}, publisher = {Elsevier}, title = {{Social immunity in insects}}, doi = {10.1016/j.cub.2019.03.035}, volume = {29}, year = {2019}, } @article{6511, abstract = {Let U and V be two independent N by N random matrices that are distributed according to Haar measure on U(N). Let Σ be a nonnegative deterministic N by N matrix. The single ring theorem [Ann. of Math. (2) 174 (2011) 1189–1217] asserts that the empirical eigenvalue distribution of the matrix X:=UΣV∗ converges weakly, in the limit of large N, to a deterministic measure which is supported on a single ring centered at the origin in ℂ. Within the bulk regime, that is, in the interior of the single ring, we establish the convergence of the empirical eigenvalue distribution on the optimal local scale of order N−1/2+ε and establish the optimal convergence rate. The same results hold true when U and V are Haar distributed on O(N).}, author = {Bao, Zhigang and Erdös, László and Schnelli, Kevin}, issn = {00911798}, journal = {Annals of Probability}, number = {3}, pages = {1270--1334}, publisher = {Institute of Mathematical Statistics}, title = {{Local single ring theorem on optimal scale}}, doi = {10.1214/18-AOP1284}, volume = {47}, year = {2019}, } @article{6559, abstract = {Branching morphogenesis is a prototypical example of complex three-dimensional organ sculpting, required in multiple developmental settings to maximize the area of exchange surfaces. It requires, in particular, the coordinated growth of different cell types together with complex patterning to lead to robust macroscopic outputs. In recent years, novel multiscale quantitative biology approaches, together with biophysical modelling, have begun to shed new light of this topic. Here, we wish to review some of these recent developments, highlighting the generic design principles that can be abstracted across different branched organs, as well as the implications for the broader fields of stem cell, developmental and systems biology.}, author = {Hannezo, Edouard B and Simons, Benjamin D.}, issn = {18790410}, journal = {Current Opinion in Cell Biology}, pages = {99--105}, publisher = {Elsevier}, title = {{Multiscale dynamics of branching morphogenesis}}, doi = {10.1016/j.ceb.2019.04.008}, volume = {60}, year = {2019}, } @article{6566, abstract = {Methodologies that involve the use of nanoparticles as “artificial atoms” to rationally build materials in a bottom-up fashion are particularly well-suited to control the matter at the nanoscale. Colloidal synthetic routes allow for an exquisite control over such “artificial atoms” in terms of size, shape, and crystal phase as well as core and surface compositions. We present here a bottom-up approach to produce Pb–Ag–K–S–Te nanocomposites, which is a highly promising system for thermoelectric energy conversion. First, we developed a high-yield and scalable colloidal synthesis route to uniform lead sulfide (PbS) nanorods, whose tips are made of silver sulfide (Ag2S). We then took advantage of the large surface-to-volume ratio to introduce a p-type dopant (K) by replacing native organic ligands with K2Te. Upon thermal consolidation, K2Te-surface modified PbS–Ag2S nanorods yield p-type doped nanocomposites with PbTe and PbS as major phases and Ag2S and Ag2Te as embedded nanoinclusions. Thermoelectric characterization of such consolidated nanosolids showed a high thermoelectric figure-of-merit of 1 at 620 K.}, author = {Ibáñez, Maria and Genç, Aziz and Hasler, Roger and Liu, Yu and Dobrozhan, Oleksandr and Nazarenko, Olga and Mata, María de la and Arbiol, Jordi and Cabot, Andreu and Kovalenko, Maksym V.}, issn = {1936-086X}, journal = {ACS Nano}, keywords = {colloidal nanoparticles, asymmetric nanoparticles, inorganic ligands, heterostructures, catalyst assisted growth, nanocomposites, thermoelectrics}, number = {6}, pages = {6572--6580}, publisher = {American Chemical Society}, title = {{Tuning transport properties in thermoelectric nanocomposites through inorganic ligands and heterostructured building blocks}}, doi = {10.1021/acsnano.9b00346}, volume = {13}, year = {2019}, } @article{6607, abstract = {Acute myeloid leukemia (AML) is a heterogeneous disease with respect to its genetic and molecular basis and to patients´ outcome. Clinical, cytogenetic, and mutational data are used to classify patients into risk groups with different survival, however, within-group heterogeneity is still an issue. Here, we used a robust likelihood-based survival modeling approach and publicly available gene expression data to identify a minimal number of genes whose combined expression values were prognostic of overall survival. The resulting gene expression signature (4-GES) consisted of 4 genes (SOCS2, IL2RA, NPDC1, PHGDH), predicted patient survival as an independent prognostic parameter in several cohorts of AML patients (total, 1272 patients), and further refined prognostication based on the European Leukemia Net classification. An oncogenic role of the top scoring gene in this signature, SOCS2, was investigated using MLL-AF9 and Flt3-ITD/NPM1c driven mouse models of AML. SOCS2 promoted leukemogenesis as well as the abundance, quiescence, and activity of AML stem cells. Overall, the 4-GES represents a highly discriminating prognostic parameter in AML, whose clinical applicability is greatly enhanced by its small number of genes. The newly established role of SOCS2 in leukemia aggressiveness and stemness raises the possibility that the signature might even be exploitable therapeutically.}, author = {Nguyen, Chi Huu and Glüxam, Tobias and Schlerka, Angela and Bauer, Katharina and Grandits, Alexander M. and Hackl, Hubert and Dovey, Oliver and Zöchbauer-Müller, Sabine and Cooper, Jonathan L. and Vassiliou, George S. and Stoiber, Dagmar and Wieser, Rotraud and Heller, Gerwin}, journal = {Scientific Reports}, number = {1}, publisher = {Nature Publishing Group}, title = {{SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness}}, doi = {10.1038/s41598-019-45579-0}, volume = {9}, year = {2019}, } @article{6609, abstract = {Mechanical systems facilitate the development of a hybrid quantum technology comprising electrical, optical, atomic and acoustic degrees of freedom1, and entanglement is essential to realize quantum-enabled devices. Continuous-variable entangled fields—known as Einstein–Podolsky–Rosen (EPR) states—are spatially separated two-mode squeezed states that can be used for quantum teleportation and quantum communication2. In the optical domain, EPR states are typically generated using nondegenerate optical amplifiers3, and at microwave frequencies Josephson circuits can serve as a nonlinear medium4,5,6. An outstanding goal is to deterministically generate and distribute entangled states with a mechanical oscillator, which requires a carefully arranged balance between excitation, cooling and dissipation in an ultralow noise environment. Here we observe stationary emission of path-entangled microwave radiation from a parametrically driven 30-micrometre-long silicon nanostring oscillator, squeezing the joint field operators of two thermal modes by 3.40 decibels below the vacuum level. The motion of this micromechanical system correlates up to 50 photons per second per hertz, giving rise to a quantum discord that is robust with respect to microwave noise7. Such generalized quantum correlations of separable states are important for quantum-enhanced detection8 and provide direct evidence of the non-classical nature of the mechanical oscillator without directly measuring its state9. This noninvasive measurement scheme allows to infer information about otherwise inaccessible objects, with potential implications for sensing, open-system dynamics and fundamental tests of quantum gravity. In the future, similar on-chip devices could be used to entangle subsystems on very different energy scales, such as microwave and optical photons.}, author = {Barzanjeh, Shabir and Redchenko, Elena and Peruzzo, Matilda and Wulf, Matthias and Lewis, Dylan and Arnold, Georg M and Fink, Johannes M}, journal = {Nature}, pages = {480--483}, publisher = {Nature Publishing Group}, title = {{Stationary entangled radiation from micromechanical motion}}, doi = {10.1038/s41586-019-1320-2}, volume = {570}, year = {2019}, } @article{6596, abstract = {It is well known that many problems in image recovery, signal processing, and machine learning can be modeled as finding zeros of the sum of maximal monotone and Lipschitz continuous monotone operators. Many papers have studied forward-backward splitting methods for finding zeros of the sum of two monotone operators in Hilbert spaces. Most of the proposed splitting methods in the literature have been proposed for the sum of maximal monotone and inverse-strongly monotone operators in Hilbert spaces. In this paper, we consider splitting methods for finding zeros of the sum of maximal monotone operators and Lipschitz continuous monotone operators in Banach spaces. We obtain weak and strong convergence results for the zeros of the sum of maximal monotone and Lipschitz continuous monotone operators in Banach spaces. Many already studied problems in the literature can be considered as special cases of this paper.}, author = {Shehu, Yekini}, issn = {1420-9012}, journal = {Results in Mathematics}, number = {4}, publisher = {Springer}, title = {{Convergence results of forward-backward algorithms for sum of monotone operators in Banach spaces}}, doi = {10.1007/s00025-019-1061-4}, volume = {74}, year = {2019}, } @article{6601, abstract = {There is increasing evidence that both mechanical and biochemical signals play important roles in development and disease. The development of complex organisms, in particular, has been proposed to rely on the feedback between mechanical and biochemical patterning events. This feedback occurs at the molecular level via mechanosensation but can also arise as an emergent property of the system at the cellular and tissue level. In recent years, dynamic changes in tissue geometry, flow, rheology, and cell fate specification have emerged as key platforms of mechanochemical feedback loops in multiple processes. Here, we review recent experimental and theoretical advances in understanding how these feedbacks function in development and disease.}, author = {Hannezo, Edouard B and Heisenberg, Carl-Philipp J}, issn = {00928674}, journal = {Cell}, number = {1}, pages = {12--25}, publisher = {Elsevier}, title = {{Mechanochemical feedback loops in development and disease}}, doi = {10.1016/j.cell.2019.05.052}, volume = {178}, year = {2019}, } @article{6617, abstract = {The effective large-scale properties of materials with random heterogeneities on a small scale are typically determined by the method of representative volumes: a sample of the random material is chosen—the representative volume—and its effective properties are computed by the cell formula. Intuitively, for a fixed sample size it should be possible to increase the accuracy of the method by choosing a material sample which captures the statistical properties of the material particularly well; for example, for a composite material consisting of two constituents, one would select a representative volume in which the volume fraction of the constituents matches closely with their volume fraction in the overall material. Inspired by similar attempts in materials science, Le Bris, Legoll and Minvielle have designed a selection approach for representative volumes which performs remarkably well in numerical examples of linear materials with moderate contrast. In the present work, we provide a rigorous analysis of this selection approach for representative volumes in the context of stochastic homogenization of linear elliptic equations. In particular, we prove that the method essentially never performs worse than a random selection of the material sample and may perform much better if the selection criterion for the material samples is chosen suitably.}, author = {Fischer, Julian L}, issn = {1432-0673}, journal = {Archive for Rational Mechanics and Analysis}, number = {2}, pages = {635–726}, publisher = {Springer}, title = {{The choice of representative volumes in the approximation of effective properties of random materials}}, doi = {10.1007/s00205-019-01400-w}, volume = {234}, year = {2019}, } @article{6611, abstract = {Cell polarity is crucial for the coordinated development of all multicellular organisms. In plants, this is exemplified by the PIN-FORMED (PIN) efflux carriers of the phytohormone auxin: The polar subcellular localization of the PINs is instructive to the directional intercellular auxin transport, and thus to a plethora of auxin-regulated growth and developmental processes. Despite its importance, the regulation of PIN polar subcellular localization remains poorly understood. Here, we have employed advanced live-cell imaging techniques to study the roles of microtubules and actin microfilaments in the establishment of apical polar localization of PIN2 in the epidermis of the Arabidopsis root meristem. We report that apical PIN2 polarity requires neither intact actin microfilaments nor microtubules, suggesting that the primary spatial cue for polar PIN distribution is likely independent of cytoskeleton-guided endomembrane trafficking.}, author = {Glanc, Matous and Fendrych, Matyas and Friml, Jiří}, journal = {Biomolecules}, number = {6}, publisher = {MDPI}, title = {{PIN2 polarity establishment in arabidopsis in the absence of an intact cytoskeleton}}, doi = {10.3390/biom9060222}, volume = {9}, year = {2019}, } @article{6620, abstract = {This paper establishes an asymptotic formula with a power-saving error term for the number of rational points of bounded height on the singular cubic surface of ℙ3ℚ given by the following equation 𝑥0(𝑥21+𝑥22)−𝑥33=0 in agreement with the Manin-Peyre conjectures. }, author = {De La Bretèche, Régis and Destagnol, Kevin N and Liu, Jianya and Wu, Jie and Zhao, Yongqiang}, issn = {16747283}, journal = {Science China Mathematics}, number = {12}, pages = {2435–2446}, publisher = {Springer}, title = {{On a certain non-split cubic surface}}, doi = {10.1007/s11425-018-9543-8}, volume = {62}, year = {2019}, } @article{6637, abstract = {The environment changes constantly at various time scales and, in order to survive, species need to keep adapting. Whether these species succeed in avoiding extinction is a major evolutionary question. Using a multilocus evolutionary model of a mutation‐limited population adapting under strong selection, we investigate the effects of the frequency of environmental fluctuations on adaptation. Our results rely on an “adaptive‐walk” approximation and use mathematical methods from evolutionary computation theory to investigate the interplay between fluctuation frequency, the similarity of environments, and the number of loci contributing to adaptation. First, we assume a linear additive fitness function, but later generalize our results to include several types of epistasis. We show that frequent environmental changes prevent populations from reaching a fitness peak, but they may also prevent the large fitness loss that occurs after a single environmental change. Thus, the population can survive, although not thrive, in a wide range of conditions. Furthermore, we show that in a frequently changing environment, the similarity of threats that a population faces affects the level of adaptation that it is able to achieve. We check and supplement our analytical results with simulations.}, author = {Trubenova, Barbora and Krejca, Martin and Lehre, Per Kristian and Kötzing, Timo}, journal = {Evolution}, number = {7}, pages = {1356--1374}, publisher = {Wiley}, title = {{Surfing on the seascape: Adaptation in a changing environment}}, doi = {10.1111/evo.13784}, volume = {73}, year = {2019}, } @article{6634, abstract = {In this paper we prove several new results around Gromov's waist theorem. We give a simple proof of Vaaler's theorem on sections of the unit cube using the Borsuk-Ulam-Crofton technique, consider waists of real and complex projective spaces, flat tori, convex bodies in Euclidean space; and establish waist-type results in terms of the Hausdorff measure.}, author = {Akopyan, Arseniy and Hubard, Alfredo and Karasev, Roman}, journal = {Topological Methods in Nonlinear Analysis}, number = {2}, pages = {457--490}, publisher = {Akademicka Platforma Czasopism}, title = {{Lower and upper bounds for the waists of different spaces}}, doi = {10.12775/TMNA.2019.008}, volume = {53}, year = {2019}, } @article{6638, abstract = {The crossing number of a graph G is the least number of crossings over all possible drawings of G. We present a structural characterization of graphs with crossing number one.}, author = {Silva, André and Arroyo Guevara, Alan M and Richter, Bruce and Lee, Orlando}, issn = {0012-365X}, journal = {Discrete Mathematics}, number = {11}, pages = {3201--3207}, publisher = {Elsevier}, title = {{Graphs with at most one crossing}}, doi = {10.1016/j.disc.2019.06.031}, volume = {342}, year = {2019}, } @article{6631, abstract = {The spatiotemporal organization of cell divisions constitutes an integral part in the development of multicellular organisms, and mis-regulation of cell divisions can lead to severe developmental defects. Cell divisions have an important morphogenetic function in development by regulating growth and shape acquisition of developing tissues, and, conversely, tissue morphogenesis is known to affect both the rate and orientation of cell divisions. Moreover, cell divisions are associated with an extensive reorganization of the cytoskeleton and adhesion apparatus in the dividing cells that in turn can affect large-scale tissue rheological properties. Thus, the interplay between cell divisions and tissue morphogenesis plays a key role in embryo and tissue morphogenesis.}, author = {Godard, Benoit G and Heisenberg, Carl-Philipp J}, issn = {0955-0674}, journal = {Current Opinion in Cell Biology}, pages = {114--120}, publisher = {Elsevier}, title = {{Cell division and tissue mechanics}}, doi = {10.1016/j.ceb.2019.05.007}, volume = {60}, year = {2019}, } @article{6660, abstract = {Commercially available full-color 3D printing allows for detailed control of material deposition in a volume, but an exact reproduction of a target surface appearance is hampered by the strong subsurface scattering that causes nontrivial volumetric cross-talk at the print surface. Previous work showed how an iterative optimization scheme based on accumulating absorptive materials at the surface can be used to find a volumetric distribution of print materials that closely approximates a given target appearance. In this work, we first revisit the assumption that pushing the absorptive materials to the surface results in minimal volumetric cross-talk. We design a full-fledged optimization on a small domain for this task and confirm this previously reported heuristic. Then, we extend the above approach that is critically limited to color reproduction on planar surfaces, to arbitrary 3D shapes. Our method enables high-fidelity color texture reproduction on 3D prints by effectively compensating for internal light scattering within arbitrarily shaped objects. In addition, we propose a content-aware gamut mapping that significantly improves color reproduction for the pathological case of thin geometric features. Using a wide range of sample objects with complex textures and geometries, we demonstrate color reproduction whose fidelity is superior to state-of-the-art drivers for color 3D printers.}, author = {Sumin, Denis and Weyrich, Tim and Rittig, Tobias and Babaei, Vahid and Nindel, Thomas and Wilkie, Alexander and Didyk, Piotr and Bickel, Bernd and Křivánek, Jaroslav and Myszkowski, Karol}, issn = {0730-0301}, journal = {ACM Transactions on Graphics}, number = {4}, publisher = {ACM}, title = {{Geometry-aware scattering compensation for 3D printing}}, doi = {10.1145/3306346.3322992}, volume = {38}, year = {2019}, } @article{6658, abstract = {New genes are a major source of novelties, and a disproportionate amount of them are known to show testis expression in later phases of male gametogenesis in different groups such as mammals and plants. Here, we propose that this enhanced expression is a consequence of haploid selection during the latter stages of male gametogenesis. Because emerging adaptive mutations will be fixed faster if their phenotypes are expressed by haploid rather than diploid genotypes, new genes with advantageous functions arising during this unique stage of development have a better chance to become fixed. To test this hypothesis, expression levels of genes of differing evolutionary age were examined at various stages of Drosophila spermatogenesis. We found, consistent with a model based on haploid selection, that new Drosophila genes are both expressed in later haploid phases of spermatogenesis and harbor a significant enrichment of adaptive mutations. Additionally, the observed overexpression of new genes in the latter phases of spermatogenesis was limited to the autosomes. Because all male cells exhibit hemizygous expression for X-linked genes (and therefore effectively haploid), there is no expectation that selection acting on late spermatogenesis will have a different effect on X-linked genes in comparison to initial diploid phases. Together, our proposed hypothesis and the analyzed data suggest that natural selection in haploid cells elucidates several aspects of the origin of new genes by explaining the general prevalence of their testis expression, and a parsimonious solution for new alleles to avoid being lost by genetic drift or pseudogenization. }, author = {Raices, Julia and Otto, Paulo and Vibranovski, Maria}, journal = {Genome Research}, number = {7}, pages = {1115--1122}, publisher = {CSH Press}, title = {{Haploid selection drives new gene male germline expression}}, doi = {10.1101/gr.238824.118}, volume = {29}, year = {2019}, } @article{6650, abstract = {We propose a novel technique for the automatic design of molds to cast highly complex shapes. The technique generates composite, two-piece molds. Each mold piece is made up of a hard plastic shell and a flexible silicone part. Thanks to the thin, soft, and smartly shaped silicone part, which is kept in place by a hard plastic shell, we can cast objects of unprecedented complexity. An innovative algorithm based on a volumetric analysis defines the layout of the internal cuts in the silicone mold part. Our approach can robustly handle thin protruding features and intertwined topologies that have caused previous methods to fail. We compare our results with state of the art techniques, and we demonstrate the casting of shapes with extremely complex geometry.}, author = {Alderighi, Thomas and Malomo, Luigi and Giorgi, Daniela and Bickel, Bernd and Cignoni, Paolo and Pietroni, Nico}, issn = {0730-0301}, journal = {ACM Transactions on Graphics}, number = {4}, publisher = {ACM}, title = {{Volume-aware design of composite molds}}, doi = {10.1145/3306346.3322981}, volume = {38}, year = {2019}, } @article{6717, abstract = {With the recent publication by Silpe and Bassler (2019), considering phage detection of a bacterial quorum-sensing (QS) autoinducer, we now have as many as five examples of phage-associated intercellular communication (Table 1). Each potentially involves ecological inferences by phages as to concentrations of surrounding phage-infected or uninfected bacteria. While the utility of phage detection of bacterial QS molecules may at first glance appear to be straightforward, we suggest in this commentary that the underlying ecological explanation is unlikely to be simple.}, author = {Igler, Claudia and Abedon, Stephen T.}, journal = {Frontiers in Microbiology}, publisher = {Frontiers}, title = {{Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision}}, doi = {10.3389/fmicb.2019.01171}, volume = {10}, year = {2019}, } @article{6680, abstract = {This paper analyzes how partial selfing in a large source population influences its ability to colonize a new habitat via the introduction of a few founder individuals. Founders experience inbreeding depression due to partially recessive deleterious alleles as well as maladaptation to the new environment due to selection on a large number of additive loci. I first introduce a simplified version of the Inbreeding History Model (Kelly, 2007) in order to characterize mutation‐selection balance in a large, partially selfing source population under selection involving multiple non‐identical loci. I then use individual‐based simulations to study the eco‐evolutionary dynamics of founders establishing in the new habitat under a model of hard selection. The study explores how selfing rate shapes establishment probabilities of founders via effects on both inbreeding depression and adaptability to the new environment, and also distinguishes the effects of selfing on the initial fitness of founders from its effects on the long‐term adaptive response of the populations they found. A high rate of (but not complete) selfing is found to aid establishment over a wide range of parameters, even in the absence of mate limitation. The sensitivity of the results to assumptions about the nature of polygenic selection are discussed.}, author = {Sachdeva, Himani}, issn = {1558-5646}, journal = {Evolution}, number = {9}, pages = {1729--1745}, publisher = {Wiley}, title = {{Effect of partial selfing and polygenic selection on establishment in a new habitat}}, doi = {10.1111/evo.13812}, volume = {73}, year = {2019}, } @article{6710, abstract = {Sexual dimorphism in morphology, physiology or life history traits is common in dioecious plants at reproductive maturity, but it is typically inconspicuous or absent in juveniles. Although plants of different sexes probably begin to diverge in gene expression both before their reproduction commences and before dimorphism becomes readily apparent, to our knowledge transcriptome-wide differential gene expression has yet to be demonstrated for any angiosperm species.}, author = {Cossard, Guillaume and Toups, Melissa A and Pannell, John }, issn = {1095-8290}, journal = {Annals of botany}, number = {7}, pages = {1119--1131}, publisher = {Oxford University Press}, title = {{Sexual dimorphism and rapid turnover in gene expression in pre-reproductive seedlings of a dioecious herb}}, doi = {10.1093/aob/mcy183}, volume = {123}, year = {2019}, } @misc{9804, abstract = {Evolutionary studies are often limited by missing data that are critical to understanding the history of selection. Selection experiments, which reproduce rapid evolution under controlled conditions, are excellent tools to study how genomes evolve under selection. Here we present a genomic dissection of the Longshanks selection experiment, in which mice were selectively bred over 20 generations for longer tibiae relative to body mass, resulting in 13% longer tibiae in two replicates. We synthesized evolutionary theory, genome sequences and molecular genetics to understand the selection response and found that it involved both polygenic adaptation and discrete loci of major effect, with the strongest loci tending to be selected in parallel between replicates. We show that selection may favor de-repression of bone growth through inactivating two limb enhancers of an inhibitor, Nkx3-2. Our integrative genomic analyses thus show that it is possible to connect individual base-pair changes to the overall selection response.}, author = {Castro, João Pl and Yancoskie, Michelle N. and Marchini, Marta and Belohlavy, Stefanie and Hiramatsu, Layla and Kučka, Marek and Beluch, William H. and Naumann, Ronald and Skuplik, Isabella and Cobb, John and Barton, Nicholas H and Rolian, Campbell and Chan, Yingguang Frank}, publisher = {Dryad}, title = {{Data from: An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice}}, doi = {10.5061/dryad.0q2h6tk}, year = {2019}, } @misc{9802, abstract = {This paper analyzes how partial selfing in a large source population influences its ability to colonize a new habitat via the introduction of a few founder individuals. Founders experience inbreeding depression due to partially recessive deleterious alleles as well as maladaptation to the new environment due to selection on a large number of additive loci. I first introduce a simplified version of the Inbreeding History Model (Kelly, 2007) in order to characterize mutation-selection balance in a large, partially selfing source population under selection involving multiple non-identical loci. I then use individual-based simulations to study the eco-evolutionary dynamics of founders establishing in the new habitat under a model of hard selection. The study explores how selfing rate shapes establishment probabilities of founders via effects on both inbreeding depression and adaptability to the new environment, and also distinguishes the effects of selfing on the initial fitness of founders from its effects on the long-term adaptive response of the populations they found. A high rate of (but not complete) selfing is found to aid establishment over a wide range of parameters, even in the absence of mate limitation. The sensitivity of the results to assumptions about the nature of polygenic selection are discussed.}, author = {Sachdeva, Himani}, publisher = {Dryad}, title = {{Data from: Effect of partial selfing and polygenic selection on establishment in a new habitat}}, doi = {10.5061/dryad.8tp0900}, year = {2019}, } @article{6756, abstract = {We study the topology generated by the temperature fluctuations of the cosmic microwave background (CMB) radiation, as quantified by the number of components and holes, formally given by the Betti numbers, in the growing excursion sets. We compare CMB maps observed by the Planck satellite with a thousand simulated maps generated according to the ΛCDM paradigm with Gaussian distributed fluctuations. The comparison is multi-scale, being performed on a sequence of degraded maps with mean pixel separation ranging from 0.05 to 7.33°. The survey of the CMB over 𝕊2 is incomplete due to obfuscation effects by bright point sources and other extended foreground objects like our own galaxy. To deal with such situations, where analysis in the presence of “masks” is of importance, we introduce the concept of relative homology. The parametric χ2-test shows differences between observations and simulations, yielding p-values at percent to less than permil levels roughly between 2 and 7°, with the difference in the number of components and holes peaking at more than 3σ sporadically at these scales. The highest observed deviation between the observations and simulations for b0 and b1 is approximately between 3σ and 4σ at scales of 3–7°. There are reports of mildly unusual behaviour of the Euler characteristic at 3.66° in the literature, computed from independent measurements of the CMB temperature fluctuations by Planck’s predecessor, the Wilkinson Microwave Anisotropy Probe (WMAP) satellite. The mildly anomalous behaviour of the Euler characteristic is phenomenologically related to the strongly anomalous behaviour of components and holes, or the zeroth and first Betti numbers, respectively. Further, since these topological descriptors show consistent anomalous behaviour over independent measurements of Planck and WMAP, instrumental and systematic errors may be an unlikely source. These are also the scales at which the observed maps exhibit low variance compared to the simulations, and approximately the range of scales at which the power spectrum exhibits a dip with respect to the theoretical model. Non-parametric tests show even stronger differences at almost all scales. Crucially, Gaussian simulations based on power-spectrum matching the characteristics of the observed dipped power spectrum are not able to resolve the anomaly. Understanding the origin of the anomalies in the CMB, whether cosmological in nature or arising due to late-time effects, is an extremely challenging task. Regardless, beyond the trivial possibility that this may still be a manifestation of an extreme Gaussian case, these observations, along with the super-horizon scales involved, may motivate the study of primordial non-Gaussianity. Alternative scenarios worth exploring may be models with non-trivial topology, including topological defect models.}, author = {Pranav, Pratyush and Adler, Robert J. and Buchert, Thomas and Edelsbrunner, Herbert and Jones, Bernard J.T. and Schwartzman, Armin and Wagner, Hubert and Van De Weygaert, Rien}, issn = {14320746}, journal = {Astronomy and Astrophysics}, publisher = {EDP Sciences}, title = {{Unexpected topology of the temperature fluctuations in the cosmic microwave background}}, doi = {10.1051/0004-6361/201834916}, volume = {627}, year = {2019}, } @article{6755, abstract = {Differentiated sex chromosomes are accompanied by a difference in gene dose between X/Z-specific and autosomal genes. At the transcriptomic level, these sex-linked genes can lead to expression imbalance, or gene dosage can be compensated by epigenetic mechanisms and results into expression level equalization. Schistosoma mansoni has been previously described as a ZW species (i.e., female heterogamety, in opposition to XY male heterogametic species) with a partial dosage compensation, but underlying mechanisms are still unexplored. Here, we combine transcriptomic (RNA-Seq) and epigenetic data (ChIP-Seq against H3K4me3, H3K27me3,andH4K20me1histonemarks) in free larval cercariae and intravertebrate parasitic stages. For the first time, we describe differences in dosage compensation status in ZW females, depending on the parasitic status: free cercariae display global dosage compensation, whereas intravertebrate stages show a partial dosage compensation. We also highlight regional differences of gene expression along the Z chromosome in cercariae, but not in the intravertebrate stages. Finally, we feature a consistent permissive chromatin landscape of the Z chromosome in both sexes and stages. We argue that dosage compensation in schistosomes is characterized by chromatin remodeling mechanisms in the Z-specific region.}, author = {Picard, Marion A L and Vicoso, Beatriz and Roquis, David and Bulla, Ingo and Augusto, Ronaldo C. and Arancibia, Nathalie and Grunau, Christoph and Boissier, Jérôme and Cosseau, Céline}, issn = {1759-6653}, journal = {Genome biology and evolution}, number = {7}, pages = {1909--1922}, publisher = {Oxford Academic Press}, title = {{Dosage compensation throughout the Schistosoma mansoni lifecycle: Specific chromatin landscape of the Z chromosome}}, doi = {10.1093/gbe/evz133}, volume = {11}, year = {2019}, } @article{6752, abstract = {Two-player games on graphs are widely studied in formal methods, as they model the interaction between a system and its environment. The game is played by moving a token throughout a graph to produce an infinite path. There are several common modes to determine how the players move the token through the graph; e.g., in turn-based games the players alternate turns in moving the token. We study the bidding mode of moving the token, which, to the best of our knowledge, has never been studied in infinite-duration games. The following bidding rule was previously defined and called Richman bidding. Both players have separate budgets, which sum up to 1. In each turn, a bidding takes place: Both players submit bids simultaneously, where a bid is legal if it does not exceed the available budget, and the higher bidder pays his bid to the other player and moves the token. The central question studied in bidding games is a necessary and sufficient initial budget for winning the game: a threshold budget in a vertex is a value t ∈ [0, 1] such that if Player 1’s budget exceeds t, he can win the game; and if Player 2’s budget exceeds 1 − t, he can win the game. Threshold budgets were previously shown to exist in every vertex of a reachability game, which have an interesting connection with random-turn games—a sub-class of simple stochastic games in which the player who moves is chosen randomly. We show the existence of threshold budgets for a qualitative class of infinite-duration games, namely parity games, and a quantitative class, namely mean-payoff games. The key component of the proof is a quantitative solution to strongly connected mean-payoff bidding games in which we extend the connection with random-turn games to these games, and construct explicit optimal strategies for both players.}, author = {Avni, Guy and Henzinger, Thomas A and Chonev, Ventsislav K}, issn = {1557735X}, journal = {Journal of the ACM}, number = {4}, publisher = {ACM}, title = {{Infinite-duration bidding games}}, doi = {10.1145/3340295}, volume = {66}, year = {2019}, } @inproceedings{7010, abstract = {Numerous biophysical questions require the quantification of short-range interactions between (functionalized) surfaces and synthetic or biological objects such as cells. Here, we present an original, custom built setup for reflection interference contrast microscopy that can assess distances between a substrate and a flowing object at high speed with nanometric accuracy. We demonstrate its use to decipher the complex biochemical and mechanical interplay regulating blood cell homing at the vessel wall in the microcirculation using an in vitro approach. We show that in the absence of specific biochemical interactions, flowing cells are repelled from the soft layer lining the vessel wall, contributing to red blood cell repulsion in vivo. In contrast, this so-called glycocalyx stabilizes rolling of cells under flow in the presence of a specific receptor naturally present on activated leucocytes and a number of cancer cell lines.}, author = {Davies, Heather S. and Baranova, Natalia S. and El Amri, Nouha and Coche-Guérente, Liliane and Verdier, Claude and Bureau, Lionel and Richter, Ralf P. and Débarre, Delphine}, booktitle = {Advances in Microscopic Imaging II}, isbn = {9781510628458}, issn = {1605-7422}, location = {Munich, Germany}, publisher = {SPIE}, title = {{Blood cell-vessel wall interactions probed by reflection interference contrast microscopy}}, doi = {10.1117/12.2527058}, volume = {11076}, year = {2019}, } @article{6763, abstract = {When grape-sized aqueous dimers are irradiated in a microwave oven, an intense electromagnetic hotspot forms at their point of contact, often igniting a plasma. Here we show that this irradiation can result in the injection of mechanical energy. By examining irradiated hydrogel dimers through high-speed imaging, we find that they repeatedly bounce off of each other while irradiated. We determine that an average of 1 lJ of mechanical energy is injected into the pair during each collision. Furthermore, a characteristic high-pitched audio signal is found to accompany each collision. We show that both the audio signal and the energy injection arise via an interplay between vaporization and elastic deformations in the region of contact, the so-called ‘elastic Liedenfrost effect’. Our results establish a novel, non-contact method of injecting mechanical energy into soft matter systems, suggesting application in fields such as soft robotics.}, author = {Khattak, Hamza K. and Waitukaitis, Scott R and Slepkov, Aaron D.}, issn = {17446848}, journal = {Soft Matter}, number = {29}, pages = {5804--5809}, publisher = {Royal Society of Chemistry}, title = {{Microwave induced mechanical activation of hydrogel dimers}}, doi = {10.1039/c9sm00756c}, volume = {15}, year = {2019}, } @article{6784, abstract = {Mathematical models have been used successfully at diverse scales of biological organization, ranging from ecology and population dynamics to stochastic reaction events occurring between individual molecules in single cells. Generally, many biological processes unfold across multiple scales, with mutations being the best studied example of how stochasticity at the molecular scale can influence outcomes at the population scale. In many other contexts, however, an analogous link between micro- and macro-scale remains elusive, primarily due to the challenges involved in setting up and analyzing multi-scale models. Here, we employ such a model to investigate how stochasticity propagates from individual biochemical reaction events in the bacterial innate immune system to the ecology of bacteria and bacterial viruses. We show analytically how the dynamics of bacterial populations are shaped by the activities of immunity-conferring enzymes in single cells and how the ecological consequences imply optimal bacterial defense strategies against viruses. Our results suggest that bacterial populations in the presence of viruses can either optimize their initial growth rate or their population size, with the first strategy favoring simple immunity featuring a single restriction modification system and the second strategy favoring complex bacterial innate immunity featuring several simultaneously active restriction modification systems.}, author = {Ruess, Jakob and Pleska, Maros and Guet, Calin C and Tkačik, Gašper}, issn = {1553-7358}, journal = {PLoS Computational Biology}, number = {7}, publisher = {Public Library of Science}, title = {{Molecular noise of innate immunity shapes bacteria-phage ecologies}}, doi = {10.1371/journal.pcbi.1007168}, volume = {15}, year = {2019}, } @article{6778, abstract = {An important adaptation during colonization of land by plants is gravitropic growth of roots, which enabled roots to reach water and nutrients, and firmly anchor plants in the ground. Here we provide insights into the evolution of an efficient root gravitropic mechanism in the seed plants. Architectural innovation, with gravity perception constrained in the root tips along with a shootward transport route for the phytohormone auxin, appeared only upon the emergence of seed plants. Interspecies complementation and protein domain swapping revealed functional innovations within the PIN family of auxin transporters leading to the evolution of gravitropism-specific PINs. The unique apical/shootward subcellular localization of PIN proteins is the major evolutionary innovation that connected the anatomically separated sites of gravity perception and growth response via the mobile auxin signal. We conclude that the crucial anatomical and functional components emerged hand-in-hand to facilitate the evolution of fast gravitropic response, which is one of the major adaptations of seed plants to dry land.}, author = {Zhang, Yuzhou and Xiao, G and Wang, X and Zhang, Xixi and Friml, Jiří}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Evolution of fast root gravitropism in seed plants}}, doi = {10.1038/s41467-019-11471-8}, volume = {10}, year = {2019}, } @article{6821, abstract = {To determine the visual sensitivities of an organism of interest, quantitative reverse transcription–polymerase chain reaction (qRT–PCR) is often used to quantify expression of the light‐sensitive opsins in the retina. While qRT–PCR is an affordable, high‐throughput method for measuring expression, it comes with inherent normalization issues that affect the interpretation of results, especially as opsin expression can vary greatly based on developmental stage, light environment or diurnal cycles. We tested for diurnal cycles of opsin expression over a period of 24 hr at 1‐hr increments and examined how normalization affects a data set with fluctuating expression levels using qRT–PCR and transcriptome data from the retinae of the cichlid Pelmatolapia mariae. We compared five methods of normalizing opsin expression relative to (a) the average of three stably expressed housekeeping genes (Ube2z, EF1‐α and β‐actin), (b) total RNA concentration, (c) GNAT2, (the cone‐specific subunit of transducin), (d) total opsin expression and (e) only opsins expressed in the same cone type. Normalizing by proportion of cone type produced the least variation and would be best for removing time‐of‐day variation. In contrast, normalizing by housekeeping genes produced the highest daily variation in expression and demonstrated that the peak of cone opsin expression was in the late afternoon. A weighted correlation network analysis showed that the expression of different cone opsins follows a very similar daily cycle. With the knowledge of how these normalization methods affect opsin expression data, we make recommendations for designing sampling approaches and quantification methods based upon the scientific question being examined.}, author = {Yourick, Miranda R. and Sandkam, Benjamin A. and Gammerdinger, William J and Escobar-Camacho, Daniel and Nandamuri, Sri Pratima and Clark, Frances E. and Joyce, Brendan and Conte, Matthew A. and Kocher, Thomas D. and Carleton, Karen L.}, issn = {1755-0998}, journal = {Molecular Ecology Resources}, number = {6}, pages = {1447--1460}, publisher = {Wiley}, title = {{Diurnal variation in opsin expression and common housekeeping genes necessitates comprehensive normalization methods for quantitative real-time PCR analyses}}, doi = {10.1111/1755-0998.13062}, volume = {19}, year = {2019}, } @article{6788, abstract = {We consider the Nelson model with ultraviolet cutoff, which describes the interaction between non-relativistic particles and a positive or zero mass quantized scalar field. We take the non-relativistic particles to obey Fermi statistics and discuss the time evolution in a mean-field limit of many fermions. In this case, the limit is known to be also a semiclassical limit. We prove convergence in terms of reduced density matrices of the many-body state to a tensor product of a Slater determinant with semiclassical structure and a coherent state, which evolve according to a fermionic version of the Schrödinger–Klein–Gordon equations.}, author = {Leopold, Nikolai K and Petrat, Sören P}, issn = {1424-0661}, journal = {Annales Henri Poincare}, number = {10}, pages = {3471–3508}, publisher = {Springer Nature}, title = {{Mean-field dynamics for the Nelson model with fermions}}, doi = {10.1007/s00023-019-00828-w}, volume = {20}, year = {2019}, } @article{6795, abstract = {The green‐beard effect is one proposed mechanism predicted to underpin the evolu‐tion of altruistic behavior. It relies on the recognition and the selective help of altruists to each other in order to promote and sustain altruistic behavior. However, this mechanism has often been dismissed as unlikely or uncommon, as it is assumed that both the signaling trait and altruistic trait need to be encoded by the same gene or through tightly linked genes. Here, we use models of indirect genetic effects (IGEs) to find the minimum correlation between the signaling and altruistic trait required for the evolution of the latter. We show that this correlation threshold depends on the strength of the interaction (influence of the green beard on the expression of the altruistic trait), as well as the costs and benefits of the altruistic behavior. We further show that this correlation does not necessarily have to be high and support our analytical results by simulations.}, author = {Trubenova, Barbora and Hager, Reinmar}, issn = {20457758}, journal = {Ecology and Evolution}, number = {17}, pages = {9597--9608}, publisher = {Wiley}, title = {{Green beards in the light of indirect genetic effects}}, doi = {10.1002/ece3.5484}, volume = {9}, year = {2019}, } @article{6793, abstract = {The Regge symmetry is a set of remarkable relations between two tetrahedra whose edge lengths are related in a simple fashion. It was first discovered as a consequence of an asymptotic formula in mathematical physics. Here, we give a simple geometric proof of Regge symmetries in Euclidean, spherical, and hyperbolic geometry.}, author = {Akopyan, Arseniy and Izmestiev, Ivan}, issn = {14692120}, journal = {Bulletin of the London Mathematical Society}, number = {5}, pages = {765--775}, publisher = {London Mathematical Society}, title = {{The Regge symmetry, confocal conics, and the Schläfli formula}}, doi = {10.1112/blms.12276}, volume = {51}, year = {2019}, } @misc{9786, author = {Ruess, Jakob and Pleska, Maros and Guet, Calin C and Tkačik, Gašper}, publisher = {Public Library of Science}, title = {{Supporting text and results}}, doi = {10.1371/journal.pcbi.1007168.s001}, year = {2019}, } @article{6831, abstract = {* Understanding the mechanisms causing phenotypic differences between females and males has long fascinated evolutionary biologists. An extensive literature exists on animal sexual dimorphism but less information is known about sex differences in plants, particularly the extent of geographical variation in sexual dimorphism and its life‐cycle dynamics. * Here, we investigated patterns of genetically based sexual dimorphism in vegetative and reproductive traits of a wind‐pollinated dioecious plant, Rumex hastatulus, across three life‐cycle stages using open‐pollinated families from 30 populations spanning the geographic range and chromosomal variation (XY and XY1Y2) of the species. * The direction and degree of sexual dimorphism was highly variable among populations and life‐cycle stages. Sex‐specific differences in reproductive function explained a significant amount of temporal change in sexual dimorphism. For several traits, geographical variation in sexual dimorphism was associated with bioclimatic parameters, likely due to the differential responses of the sexes to climate. We found no systematic differences in sexual dimorphism between chromosome races. * Sex‐specific trait differences in dioecious plants largely result from a balance between sexual and natural selection on resource allocation. Our results indicate that abiotic factors associated with geographical context also play a role in modifying sexual dimorphism during the plant life‐cycle.}, author = {Puixeu Sala, Gemma and Pickup, Melinda and Field, David and Barrett, Spencer C.H.}, issn = {1469-8137}, journal = {New Phytologist}, number = {3}, pages = {1108--1120}, publisher = {Wiley}, title = {{Variation in sexual dimorphism in a wind-pollinated plant: The influence of geographical context and life-cycle dynamics}}, doi = {10.1111/nph.16050}, volume = {224}, year = {2019}, } @article{6824, abstract = {Platelets are small anucleate cellular fragments that are released by megakaryocytes and safeguard vascular integrity through a process termed ‘haemostasis’. However, platelets have important roles beyond haemostasis as they contribute to the initiation and coordination of intravascular immune responses. They continuously monitor blood vessel integrity and tightly coordinate vascular trafficking and functions of multiple cell types. In this way platelets act as ‘patrolling officers of the vascular highway’ that help to establish effective immune responses to infections and cancer. Here we discuss the distinct biological features of platelets that allow them to shape immune responses to pathogens and tumour cells, highlighting the parallels between these responses.}, author = {Gärtner, Florian R and Massberg, Steffen}, issn = {1474-1741}, journal = {Nature Reviews Immunology}, number = {12}, pages = {747–760}, publisher = {Springer Nature}, title = {{Patrolling the vascular borders: Platelets in immunity to infection and cancer}}, doi = {10.1038/s41577-019-0202-z}, volume = {19}, year = {2019}, } @article{6832, abstract = {Steady-state turnover is a hallmark of epithelial tissues throughout adult life. Intestinal epithelial turnover is marked by continuous cell migration, which is assumed to be driven by mitotic pressure from the crypts. However, the balance of forces in renewal remains ill-defined. Combining biophysical modeling and quantitative three-dimensional tissue imaging with genetic and physical manipulations, we revealed the existence of an actin-related protein 2/3 complex–dependent active migratory force, which explains quantitatively the profiles of cell speed, density, and tissue tension along the villi. Cells migrate collectively with minimal rearrangements while displaying dual—apicobasal and front-back—polarity characterized by actin-rich basal protrusions oriented in the direction of migration. We propose that active migration is a critical component of gut epithelial turnover.}, author = {Krndija, Denis and Marjou, Fatima El and Guirao, Boris and Richon, Sophie and Leroy, Olivier and Bellaiche, Yohanns and Hannezo, Edouard B and Vignjevic, Danijela Matic}, journal = {Science}, number = {6454}, pages = {705--710}, publisher = {American Association for the Advancement of Science}, title = {{Active cell migration is critical for steady-state epithelial turnover in the gut}}, doi = {10.1126/science.aau3429}, volume = {365}, year = {2019}, } @article{6818, abstract = {Indigoidine is a blue natural pigment, which can be efficiently synthetized in E. coli. In addition to its antioxidant and antimicrobial activities indigoidine due to its stability and deep blue color can find an application as an industrial, environmentally friendly dye. Moreover, similarly to its counterpart regular indigo dye, due to its molecular structure, indigoidine is an organic semiconductor. Fully conjugated aromatic moiety and intermolecular hydrogen bonding of indigoidine result in an unusually narrow bandgap for such a small molecule. This, in its turn, result is tight molecular packing in the solid state and opens a path for a wide range of application in organic and bio-electronics, such as electrochemical and field effect transistors, organic solar cells, light and bio-sensors etc.}, author = {Yumusak, Cigdem and Prochazkova, Anna Jancik and Apaydin, Dogukan H and Seelajaroen, Hathaichanok and Sariciftci, Niyazi Serdar and Weiter, Martin and Krajcovic, Jozef and Qin, Yong and Zhang, Wei and Zhan, Jixun and Kovalenko, Alexander}, issn = {0143-7208}, journal = {Dyes and Pigments}, publisher = {Elsevier}, title = {{Indigoidine - Biosynthesized organic semiconductor}}, doi = {10.1016/j.dyepig.2019.107768}, volume = {171}, year = {2019}, } @article{6828, abstract = {In this paper we construct a family of exact functors from the category of Whittaker modules of the simple complex Lie algebra of type to the category of finite-dimensional modules of the graded affine Hecke algebra of type . Using results of Backelin [2] and of Arakawa-Suzuki [1], we prove that these functors map standard modules to standard modules (or zero) and simple modules to simple modules (or zero). Moreover, we show that each simple module of the graded affine Hecke algebra appears as the image of a simple Whittaker module. Since the Whittaker category contains the BGG category as a full subcategory, our results generalize results of Arakawa-Suzuki [1], which in turn generalize Schur-Weyl duality between finite-dimensional representations of and representations of the symmetric group .}, author = {Brown, Adam}, issn = {0021-8693}, journal = {Journal of Algebra}, pages = {261--289}, publisher = {Elsevier}, title = {{Arakawa-Suzuki functors for Whittaker modules}}, doi = {10.1016/j.jalgebra.2019.07.027}, volume = {538}, year = {2019}, } @misc{9803, abstract = {Understanding the mechanisms causing phenotypic differences between females and males has long fascinated evolutionary biologists. An extensive literature exists on animal sexual dimorphism but less is known about sex differences in plants, particularly the extent of geographical variation in sexual dimorphism and its life-cycle dynamics. Here, we investigate patterns of genetically-based sexual dimorphism in vegetative and reproductive traits of a wind-pollinated dioecious plant, Rumex hastatulus, across three life-cycle stages using open-pollinated families from 30 populations spanning the geographic range and chromosomal variation (XY and XY1Y2) of the species. The direction and degree of sexual dimorphism was highly variable among populations and life-cycle stages. Sex-specific differences in reproductive function explained a significant amount of temporal change in sexual dimorphism. For several traits, geographical variation in sexual dimorphism was associated with bioclimatic parameters, likely due to the differential responses of the sexes to climate. We found no systematic differences in sexual dimorphism between chromosome races. Sex-specific trait differences in dioecious plants largely result from a balance between sexual and natural selection on resource allocation. Our results indicate that abiotic factors associated with geographical context also play a role in modifying sexual dimorphism during the plant life cycle.}, author = {Puixeu Sala, Gemma and Pickup, Melinda and Field, David and Barrett, Spencer C.H.}, publisher = {Dryad}, title = {{Data from: Variation in sexual dimorphism in a wind-pollinated plant: the influence of geographical context and life-cycle dynamics}}, doi = {10.5061/dryad.n1701c9}, year = {2019}, } @article{6836, abstract = {Direct reciprocity is a powerful mechanism for the evolution of cooperation on the basis of repeated interactions1,2,3,4. It requires that interacting individuals are sufficiently equal, such that everyone faces similar consequences when they cooperate or defect. Yet inequality is ubiquitous among humans5,6 and is generally considered to undermine cooperation and welfare7,8,9,10. Most previous models of reciprocity do not include inequality11,12,13,14,15. These models assume that individuals are the same in all relevant aspects. Here we introduce a general framework to study direct reciprocity among unequal individuals. Our model allows for multiple sources of inequality. Subjects can differ in their endowments, their productivities and in how much they benefit from public goods. We find that extreme inequality prevents cooperation. But if subjects differ in productivity, some endowment inequality can be necessary for cooperation to prevail. Our mathematical predictions are supported by a behavioural experiment in which we vary the endowments and productivities of the subjects. We observe that overall welfare is maximized when the two sources of heterogeneity are aligned, such that more productive individuals receive higher endowments. By contrast, when endowments and productivities are misaligned, cooperation quickly breaks down. Our findings have implications for policy-makers concerned with equity, efficiency and the provisioning of public goods.}, author = {Hauser, Oliver P. and Hilbe, Christian and Chatterjee, Krishnendu and Nowak, Martin A.}, issn = {14764687}, journal = {Nature}, number = {7770}, pages = {524--527}, publisher = {Springer Nature}, title = {{Social dilemmas among unequals}}, doi = {10.1038/s41586-019-1488-5}, volume = {572}, year = {2019}, } @article{6844, abstract = {Studying the progression of the proliferative and differentiative patterns of neural stem cells at the individual cell level is crucial to the understanding of cortex development and how the disruption of such patterns can lead to malformations and neurodevelopmental diseases. However, our understanding of the precise lineage progression programme at single-cell resolution is still incomplete due to the technical variations in lineage- tracing approaches. One of the key challenges involves developing a robust theoretical framework in which we can integrate experimental observations and introduce correction factors to obtain a reliable and representative description of the temporal modulation of proliferation and differentiation. In order to obtain more conclusive insights, we carry out virtual clonal analysis using mathematical modelling and compare our results against experimental data. Using a dataset obtained with Mosaic Analysis with Double Markers, we illustrate how the theoretical description can be exploited to interpret and reconcile the disparity between virtual and experimental results.}, author = {Picco, Noemi and Hippenmeyer, Simon and Rodarte, Julio and Streicher, Carmen and Molnár, Zoltán and Maini, Philip K. and Woolley, Thomas E.}, issn = {1469-7580}, journal = {Journal of Anatomy}, number = {3}, pages = {686--696}, publisher = {Wiley}, title = {{A mathematical insight into cell labelling experiments for clonal analysis}}, doi = {10.1111/joa.13001}, volume = {235}, year = {2019}, } @article{6855, abstract = {Many traits of interest are highly heritable and genetically complex, meaning that much of the variation they exhibit arises from differences at numerous loci in the genome. Complex traits and their evolution have been studied for more than a century, but only in the last decade have genome-wide association studies (GWASs) in humans begun to reveal their genetic basis. Here, we bring these threads of research together to ask how findings from GWASs can further our understanding of the processes that give rise to heritable variation in complex traits and of the genetic basis of complex trait evolution in response to changing selection pressures (i.e., of polygenic adaptation). Conversely, we ask how evolutionary thinking helps us to interpret findings from GWASs and informs related efforts of practical importance.}, author = {Sella, Guy and Barton, Nicholas H}, issn = {1545-293X}, journal = {Annual Review of Genomics and Human Genetics}, pages = {461--493}, publisher = {Annual Reviews}, title = {{Thinking about the evolution of complex traits in the era of genome-wide association studies}}, doi = {10.1146/annurev-genom-083115-022316}, volume = {20}, year = {2019}, } @article{6840, abstract = {We discuss thermodynamic properties of harmonically trapped imperfect quantum gases. The spatial inhomogeneity of these systems imposes a redefinition of the mean-field interparticle potential energy as compared to the homogeneous case. In our approach, it takes the form a 2N2 ωd, where N is the number of particles, ω—the harmonic trap frequency, d—system’s dimensionality, and a is a parameter characterizing the interparticle interaction. We provide arguments that this model corresponds to the limiting case of a long-ranged interparticle potential of vanishingly small amplitude. This conclusion is drawn from a computation similar to the well-known Kac scaling procedure, which is presented here in a form adapted to the case of an isotropic harmonic trap. We show that within the model, the imperfect gas of trapped repulsive bosons undergoes the Bose–Einstein condensation provided d > 1. The main result of our analysis is that in d = 1 the gas of attractive imperfect fermions with a = −aF < 0 is thermodynamically equivalent to the gas of repulsive bosons with a = aB > 0 provided the parameters aF and aB fulfill the relation aB + aF = . This result supplements similar recent conclusion about thermodynamic equivalence of two-dimensional (2D) uniform imperfect repulsive Bose and attractive Fermi gases.}, author = {Mysliwy, Krzysztof and Napiórkowski, Marek}, issn = {1742-5468}, journal = {Journal of Statistical Mechanics: Theory and Experiment}, number = {6}, publisher = {IOP Publishing}, title = {{Thermodynamics of inhomogeneous imperfect quantum gases in harmonic traps}}, doi = {10.1088/1742-5468/ab190d}, volume = {2019}, year = {2019}, } @article{6843, abstract = {The aim of this short paper is to offer a complete characterization of all (not necessarily surjective) isometric embeddings of the Wasserstein space Wp(X), where S is a countable discrete metric space and 0> r eff and show that these systems obey universal scaling laws different from neutral particles. An accurate description of these states requires both the Coulomb-modified scattering length and the effective range unless the Coulomb interaction is very weak (D -> ). Our findings are relevant for bound states whose spatial extent is significantly larger than the range of the attractive potential. These states enjoy universality – their character is independent of the shape of the short-range potential.}, author = {Schmickler, C.H. and Hammer, H.-W. and Volosniev, Artem}, issn = {0370-2693}, journal = {Physics Letters B}, publisher = {Elsevier}, title = {{Universal physics of bound states of a few charged particles}}, doi = {10.1016/j.physletb.2019.135016}, volume = {798}, year = {2019}, } @article{7005, abstract = {Activity-dependent bulk endocytosis generates synaptic vesicles (SVs) during intense neuronal activity via a two-step process. First, bulk endosomes are formed direct from the plasma membrane from which SVs are then generated. SV generation from bulk endosomes requires the efflux of previously accumulated calcium and activation of the protein phosphatase calcineurin. However, it is still unknown how calcineurin mediates SV generation. We addressed this question using a series of acute interventions that decoupled the generation of SVs from bulk endosomes in rat primary neuronal culture. This was achieved by either disruption of protein–protein interactions via delivery of competitive peptides, or inhibition of enzyme activity by known inhibitors. SV generation was monitored using either a morphological horseradish peroxidase assay or an optical assay that monitors the replenishment of the reserve SV pool. We found that SV generation was inhibited by, (i) peptides that disrupt calcineurin interactions, (ii) an inhibitor of dynamin I GTPase activity and (iii) peptides that disrupt the phosphorylation-dependent dynamin I–syndapin I interaction. Peptides that disrupted syndapin I interactions with eps15 homology domain-containing proteins had no effect. This revealed that (i) calcineurin must be localized at bulk endosomes to mediate its effect, (ii) dynamin I GTPase activity is essential for SV fission and (iii) the calcineurin-dependent interaction between dynamin I and syndapin I is essential for SV generation. We therefore propose that a calcineurin-dependent dephosphorylation cascade that requires both dynamin I GTPase and syndapin I lipid-deforming activity is essential for SV generation from bulk endosomes.}, author = {Cheung, Giselle T and Cousin, Michael A.}, issn = {1471-4159}, journal = {Journal of Neurochemistry}, number = {5}, pages = {570--583}, publisher = {Wiley}, title = {{Synaptic vesicle generation from activity‐dependent bulk endosomes requires a dephosphorylation‐dependent dynamin–syndapin interaction}}, doi = {10.1111/jnc.14862}, volume = {151}, year = {2019}, } @article{7000, abstract = {The main contributions of this paper are the proposition and the convergence analysis of a class of inertial projection-type algorithm for solving variational inequality problems in real Hilbert spaces where the underline operator is monotone and uniformly continuous. We carry out a unified analysis of the proposed method under very mild assumptions. In particular, weak convergence of the generated sequence is established and nonasymptotic O(1 / n) rate of convergence is established, where n denotes the iteration counter. We also present some experimental results to illustrate the profits gained by introducing the inertial extrapolation steps.}, author = {Shehu, Yekini and Iyiola, Olaniyi S. and Li, Xiao-Huan and Dong, Qiao-Li}, issn = {1807-0302}, journal = {Computational and Applied Mathematics}, number = {4}, publisher = {Springer Nature}, title = {{Convergence analysis of projection method for variational inequalities}}, doi = {10.1007/s40314-019-0955-9}, volume = {38}, year = {2019}, } @article{7009, abstract = {Cell migration is essential for physiological processes as diverse as development, immune defence and wound healing. It is also a hallmark of cancer malignancy. Thousands of publications have elucidated detailed molecular and biophysical mechanisms of cultured cells migrating on flat, 2D substrates of glass and plastic. However, much less is known about how cells successfully navigate the complex 3D environments of living tissues. In these more complex, native environments, cells use multiple modes of migration, including mesenchymal, amoeboid, lobopodial and collective, and these are governed by the local extracellular microenvironment, specific modalities of Rho GTPase signalling and non- muscle myosin contractility. Migration through 3D environments is challenging because it requires the cell to squeeze through complex or dense extracellular structures. Doing so requires specific cellular adaptations to mechanical features of the extracellular matrix (ECM) or its remodelling. In addition, besides navigating through diverse ECM environments and overcoming extracellular barriers, cells often interact with neighbouring cells and tissues through physical and signalling interactions. Accordingly, cells need to call on an impressively wide diversity of mechanisms to meet these challenges. This Review examines how cells use both classical and novel mechanisms of locomotion as they traverse challenging 3D matrices and cellular environments. It focuses on principles rather than details of migratory mechanisms and draws comparisons between 1D, 2D and 3D migration.}, author = {Yamada, KM and Sixt, Michael K}, issn = {1471-0080}, journal = {Nature Reviews Molecular Cell Biology}, number = {12}, pages = {738–752}, publisher = {Springer Nature}, title = {{Mechanisms of 3D cell migration}}, doi = {10.1038/s41580-019-0172-9}, volume = {20}, year = {2019}, } @article{6988, abstract = {Platelets are central players in thrombosis and hemostasis but are increasingly recognized as key components of the immune system. They shape ensuing immune responses by recruiting leukocytes, and support the development of adaptive immunity. Recent data shed new light on the complex role of platelets in immunity. Here, we summarize experimental and clinical data on the role of platelets in host defense against bacteria. Platelets bind, contain, and kill bacteria directly; however, platelet proinflammatory effector functions and cross-talk with the coagulation system, can also result in damage to the host (e.g., acute lung injury and sepsis). Novel clinical insights support this dichotomy: platelet inhibition/thrombocytopenia can be either harmful or protective, depending on pathophysiological context. Clinical studies are currently addressing this aspect in greater depth.}, author = {Nicolai, Leo and Gärtner, Florian R and Massberg, Steffen}, issn = {1471-4906}, journal = {Trends in Immunology}, number = {10}, pages = {922--938}, publisher = {Cell Press}, title = {{Platelets in host defense: Experimental and clinical insights}}, doi = {10.1016/j.it.2019.08.004}, volume = {40}, year = {2019}, } @article{7002, abstract = {Multiple Importance Sampling (MIS) is a key technique for achieving robustness of Monte Carlo estimators in computer graphics and other fields. We derive optimal weighting functions for MIS that provably minimize the variance of an MIS estimator, given a set of sampling techniques. We show that the resulting variance reduction over the balance heuristic can be higher than predicted by the variance bounds derived by Veach and Guibas, who assumed only non-negative weights in their proof. We theoretically analyze the variance of the optimal MIS weights and show the relation to the variance of the balance heuristic. Furthermore, we establish a connection between the new weighting functions and control variates as previously applied to mixture sampling. We apply the new optimal weights to integration problems in light transport and show that they allow for new design considerations when choosing the appropriate sampling techniques for a given integration problem.}, author = {Kondapaneni, Ivo and Vevoda, Petr and Grittmann, Pascal and Skrivan, Tomas and Slusallek, Philipp and Křivánek, Jaroslav}, issn = {0730-0301}, journal = {ACM Transactions on Graphics}, number = {4}, publisher = {ACM}, title = {{Optimal multiple importance sampling}}, doi = {10.1145/3306346.3323009}, volume = {38}, year = {2019}, } @article{6978, abstract = {In pipes and channels, the onset of turbulence is initially dominated by localizedtransients, which lead to sustained turbulence through their collective dynamics. In thepresent work, we study numerically the localized turbulence in pipe flow and elucidate astate space structure that gives rise to transient chaos. Starting from the basin boundaryseparating laminar and turbulent flow, we identify transverse homoclinic orbits, thepresence of which necessitates a homoclinic tangle and chaos. A direct consequence ofthe homoclinic tangle is the fractal nature of the laminar-turbulent boundary, which wasconjectured in various earlier studies. By mapping the transverse intersections between thestable and unstable manifold of a periodic orbit, we identify the gateways that promote anescape from turbulence.}, author = {Budanur, Nazmi B and Dogra, Akshunna and Hof, Björn}, journal = {Physical Review Fluids}, number = {10}, pages = {102401}, publisher = {American Physical Society}, title = {{Geometry of transient chaos in streamwise-localized pipe flow turbulence}}, doi = {10.1103/PhysRevFluids.4.102401}, volume = {4}, year = {2019}, } @article{7026, abstract = {Effective design of combination therapies requires understanding the changes in cell physiology that result from drug interactions. Here, we show that the genome-wide transcriptional response to combinations of two drugs, measured at a rigorously controlled growth rate, can predict higher-order antagonism with a third drug in Saccharomyces cerevisiae. Using isogrowth profiling, over 90% of the variation in cellular response can be decomposed into three principal components (PCs) that have clear biological interpretations. We demonstrate that the third PC captures emergent transcriptional programs that are dependent on both drugs and can predict antagonism with a third drug targeting the emergent pathway. We further show that emergent gene expression patterns are most pronounced at a drug ratio where the drug interaction is strongest, providing a guideline for future measurements. Our results provide a readily applicable recipe for uncovering emergent responses in other systems and for higher-order drug combinations. A record of this paper’s transparent peer review process is included in the Supplemental Information.}, author = {Lukacisin, Martin and Bollenbach, Tobias}, issn = {2405-4712}, journal = {Cell Systems}, number = {5}, pages = {423--433.e1--e3}, publisher = {Cell Press}, title = {{Emergent gene expression responses to drug combinations predict higher-order drug interactions}}, doi = {10.1016/j.cels.2019.10.004}, volume = {9}, year = {2019}, }