TY - CHAP AB - We review the history of population genetics, starting with its origins a century ago from the synthesis between Mendel and Darwin's ideas, through to the recent development of sophisticated schemes of inference from sequence data, based on the coalescent. We explain the close relation between the coalescent and a diffusion process, which we illustrate by their application to understand spatial structure. We summarise the powerful methods available for analysis of multiple loci, when linkage equilibrium can be assumed, and then discuss approaches to the more challenging case, where associations between alleles require that we follow genotype, rather than allele, frequencies. Though we can hardly cover the whole of population genetics, we give an overview of the current state of the subject, and future challenges to it. AU - Barton, Nicholas H AU - Etheridge, Alison ED - Balding, David ED - Moltke, Ida ED - Marioni, John ID - 8281 SN - 9781119429142 T2 - Handbook of statistical genomics TI - Mathematical models in population genetics ER - TY - GEN AB - Denote by ∆N the N-dimensional simplex. A map f : ∆N → Rd is an almost r-embedding if fσ1∩. . .∩fσr = ∅ whenever σ1, . . . , σr are pairwise disjoint faces. A counterexample to the topological Tverberg conjecture asserts that if r is not a prime power and d ≥ 2r + 1, then there is an almost r-embedding ∆(d+1)(r−1) → Rd. This was improved by Blagojevi´c–Frick–Ziegler using a simple construction of higher-dimensional counterexamples by taking k-fold join power of lower-dimensional ones. We improve this further (for d large compared to r): If r is not a prime power and N := (d+ 1)r−r l d + 2 r + 1 m−2, then there is an almost r-embedding ∆N → Rd. For the r-fold van Kampen–Flores conjecture we also produce counterexamples which are stronger than previously known. Our proof is based on generalizations of the Mabillard–Wagner theorem on construction of almost r-embeddings from equivariant maps, and of the Ozaydin theorem on existence of equivariant maps. AU - Avvakumov, Sergey AU - Karasev, R. AU - Skopenkov, A. ID - 8184 T2 - arXiv TI - Stronger counterexamples to the topological Tverberg conjecture ER - TY - CONF AB - A proxy re-encryption (PRE) scheme is a public-key encryption scheme that allows the holder of a key pk to derive a re-encryption key for any other key 𝑝𝑘′. This re-encryption key lets anyone transform ciphertexts under pk into ciphertexts under 𝑝𝑘′ without having to know the underlying message, while transformations from 𝑝𝑘′ to pk should not be possible (unidirectional). Security is defined in a multi-user setting against an adversary that gets the users’ public keys and can ask for re-encryption keys and can corrupt users by requesting their secret keys. Any ciphertext that the adversary cannot trivially decrypt given the obtained secret and re-encryption keys should be secure. All existing security proofs for PRE only show selective security, where the adversary must first declare the users it wants to corrupt. This can be lifted to more meaningful adaptive security by guessing the set of corrupted users among the n users, which loses a factor exponential in Open image in new window , rendering the result meaningless already for moderate Open image in new window . Jafargholi et al. (CRYPTO’17) proposed a framework that in some cases allows to give adaptive security proofs for schemes which were previously only known to be selectively secure, while avoiding the exponential loss that results from guessing the adaptive choices made by an adversary. We apply their framework to PREs that satisfy some natural additional properties. Concretely, we give a more fine-grained reduction for several unidirectional PREs, proving adaptive security at a much smaller loss. The loss depends on the graph of users whose edges represent the re-encryption keys queried by the adversary. For trees and chains the loss is quasi-polynomial in the size and for general graphs it is exponential in their depth and indegree (instead of their size as for previous reductions). Fortunately, trees and low-depth graphs cover many, if not most, interesting applications. Our results apply e.g. to the bilinear-map based PRE schemes by Ateniese et al. (NDSS’05 and CT-RSA’09), Gentry’s FHE-based scheme (STOC’09) and the LWE-based scheme by Chandran et al. (PKC’14). AU - Fuchsbauer, Georg AU - Kamath Hosdurg, Chethan AU - Klein, Karen AU - Pietrzak, Krzysztof Z ID - 6430 SN - 03029743 TI - Adaptively secure proxy re-encryption VL - 11443 ER - TY - JOUR AB - Electron transport in two-dimensional conducting materials such as graphene, with dominant electron–electron interaction, exhibits unusual vortex flow that leads to a nonlocal current-field relation (negative resistance), distinct from the classical Ohm’s law. The transport behavior of these materials is best described by low Reynolds number hydrodynamics, where the constitutive pressure–speed relation is Stoke’s law. Here we report evidence of such vortices observed in a viscous flow of Newtonian fluid in a microfluidic device consisting of a rectangular cavity—analogous to the electronic system. We extend our experimental observations to elliptic cavities of different eccentricities, and validate them by numerically solving bi-harmonic equation obtained for the viscous flow with no-slip boundary conditions. We verify the existence of a predicted threshold at which vortices appear. Strikingly, we find that a two-dimensional theoretical model captures the essential features of three-dimensional Stokes flow in experiments. AU - Mayzel, Jonathan AU - Steinberg, Victor AU - Varshney, Atul ID - 6069 JF - Nature Communications SN - 2041-1723 TI - Stokes flow analogous to viscous electron current in graphene VL - 10 ER - TY - JOUR AB - Speed of sound waves in gases and liquids are governed by the compressibility of the medium. There exists another type of non-dispersive wave where the wave speed depends on stress instead of elasticity of the medium. A well-known example is the Alfven wave, which propagates through plasma permeated by a magnetic field with the speed determined by magnetic tension. An elastic analogue of Alfven waves has been predicted in a flow of dilute polymer solution where the elastic stress of the stretching polymers determines the elastic wave speed. Here we present quantitative evidence of elastic Alfven waves in elastic turbulence of a viscoelastic creeping flow between two obstacles in channel flow. The key finding in the experimental proof is a nonlinear dependence of the elastic wave speed cel on the Weissenberg number Wi, which deviates from predictions based on a model of linear polymer elasticity. AU - Varshney, Atul AU - Steinberg, Victor ID - 6014 JF - Nature Communications SN - 2041-1723 TI - Elastic alfven waves in elastic turbulence VL - 10 ER - TY - JOUR AB - Epidermal growth factor receptor (EGFR) signaling controls skin development and homeostasis inmice and humans, and its deficiency causes severe skin inflammation, which might affect epidermalstem cell behavior. Here, we describe the inflammation-independent effects of EGFR deficiency dur-ing skin morphogenesis and in adult hair follicle stem cells. Expression and alternative splicing analysisof RNA sequencing data from interfollicular epidermis and outer root sheath indicate that EGFR con-trols genes involved in epidermal differentiation and also in centrosome function, DNA damage, cellcycle, and apoptosis. Genetic experiments employingp53deletion in EGFR-deficient epidermis revealthat EGFR signaling exhibitsp53-dependent functions in proliferative epidermal compartments, aswell asp53-independent functions in differentiated hair shaft keratinocytes. Loss of EGFR leads toabsence of LEF1 protein specifically in the innermost epithelial hair layers, resulting in disorganizationof medulla cells. Thus, our results uncover important spatial and temporal features of cell-autonomousEGFR functions in the epidermis. AU - Amberg, Nicole AU - Sotiropoulou, Panagiota A. AU - Heller, Gerwin AU - Lichtenberger, Beate M. AU - Holcmann, Martin AU - Camurdanoglu, Bahar AU - Baykuscheva-Gentscheva, Temenuschka AU - Blanpain, Cedric AU - Sibilia, Maria ID - 6451 JF - iScience SN - 2589-0042 TI - EGFR controls hair shaft differentiation in a p53-independent manner VL - 15 ER - TY - JOUR AB - We study effects of a bounded and compactly supported perturbation on multidimensional continuum random Schrödinger operators in the region of complete localisation. Our main emphasis is on Anderson orthogonality for random Schrödinger operators. Among others, we prove that Anderson orthogonality does occur for Fermi energies in the region of complete localisation with a non-zero probability. This partially confirms recent non-rigorous findings [V. Khemani et al., Nature Phys. 11 (2015), 560–565]. The spectral shift function plays an important role in our analysis of Anderson orthogonality. We identify it with the index of the corresponding pair of spectral projections and explore the consequences thereof. All our results rely on the main technical estimate of this paper which guarantees separate exponential decay of the disorder-averaged Schatten p-norm of χa(f(H)−f(Hτ))χb in a and b. Here, Hτ is a perturbation of the random Schrödinger operator H, χa is the multiplication operator corresponding to the indicator function of a unit cube centred about a∈Rd, and f is in a suitable class of functions of bounded variation with distributional derivative supported in the region of complete localisation for H. AU - Dietlein, Adrian M AU - Gebert, Martin AU - Müller, Peter ID - 10879 IS - 3 JF - Journal of Spectral Theory KW - Random Schrödinger operators KW - spectral shift function KW - Anderson orthogonality SN - 1664-039X TI - Perturbations of continuum random Schrödinger operators with applications to Anderson orthogonality and the spectral shift function VL - 9 ER - TY - JOUR AB - Starting from a microscopic model for a system of neurons evolving in time which individually follow a stochastic integrate-and-fire type model, we study a mean-field limit of the system. Our model is described by a system of SDEs with discontinuous coefficients for the action potential of each neuron and takes into account the (random) spatial configuration of neurons allowing the interaction to depend on it. In the limit as the number of particles tends to infinity, we obtain a nonlinear Fokker-Planck type PDE in two variables, with derivatives only with respect to one variable and discontinuous coefficients. We also study strong well-posedness of the system of SDEs and prove the existence and uniqueness of a weak measure-valued solution to the PDE, obtained as the limit of the laws of the empirical measures for the system of particles. AU - Flandoli, Franco AU - Priola, Enrico AU - Zanco, Giovanni A ID - 10878 IS - 6 JF - Discrete and Continuous Dynamical Systems KW - Applied Mathematics KW - Discrete Mathematics and Combinatorics KW - Analysis SN - 1553-5231 TI - A mean-field model with discontinuous coefficients for neurons with spatial interaction VL - 39 ER - TY - CONF AB - This paper investigates the power of preprocessing in the CONGEST model. Schmid and Suomela (ACM HotSDN 2013) introduced the SUPPORTED CONGEST model to study the application of distributed algorithms in Software-Defined Networks (SDNs). In this paper, we show that a large class of lower bounds in the CONGEST model still hold in the SUPPORTED model, highlighting the robustness of these bounds. This also raises the question how much does preprocessing help in the CONGEST model. AU - Foerster, Klaus-Tycho AU - Korhonen, Janne AU - Rybicki, Joel AU - Schmid, Stefan ID - 6935 SN - 9781450362177 T2 - Proceedings of the 2019 ACM Symposium on Principles of Distributed Computing TI - Does preprocessing help under congestion? ER - TY - JOUR AB - Autoregulation is the direct modulation of gene expression by the product of the corresponding gene. Autoregulation of bacterial gene expression has been mostly studied at the transcriptional level, when a protein acts as the cognate transcriptional repressor. A recent study investigating dynamics of the bacterial toxin–antitoxin MazEF system has shown how autoregulation at both the transcriptional and post-transcriptional levels affects the heterogeneity of Escherichia coli populations. Toxin–antitoxin systems hold a crucial but still elusive part in bacterial response to stress. This perspective highlights how these modules can also serve as a great model system for investigating basic concepts in gene regulation. However, as the genomic background and environmental conditions substantially influence toxin activation, it is important to study (auto)regulation of toxin–antitoxin systems in well-defined setups as well as in conditions that resemble the environmental niche. AU - Nikolic, Nela ID - 138 IS - 1 JF - Current Genetics TI - Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin system VL - 65 ER - TY - JOUR AB - We construct planar bi-Sobolev mappings whose local volume distortion is bounded from below by a given function f∈Lp with p>1. More precisely, for any 1<q<(p+1)/2 we construct W1,q-bi-Sobolev maps with identity boundary conditions; for f∈L∞, we provide bi-Lipschitz maps. The basic building block of our construction are bi-Lipschitz maps which stretch a given compact subset of the unit square by a given factor while preserving the boundary. The construction of these stretching maps relies on a slight strengthening of the celebrated covering result of Alberti, Csörnyei, and Preiss for measurable planar sets in the case of compact sets. We apply our result to a model functional in nonlinear elasticity, the integrand of which features fast blowup as the Jacobian determinant of the deformation becomes small. For such functionals, the derivation of the equilibrium equations for minimizers requires an additional regularization of test functions, which our maps provide. AU - Fischer, Julian L AU - Kneuss, Olivier ID - 151 IS - 1 JF - Journal of Differential Equations TI - Bi-Sobolev solutions to the prescribed Jacobian inequality in the plane with L p data and applications to nonlinear elasticity VL - 266 ER - TY - JOUR AB - The cerebral cortex is composed of a large variety of distinct cell-types including projection neurons, interneurons and glial cells which emerge from distinct neural stem cell (NSC) lineages. The vast majority of cortical projection neurons and certain classes of glial cells are generated by radial glial progenitor cells (RGPs) in a highly orchestrated manner. Recent studies employing single cell analysis and clonal lineage tracing suggest that NSC and RGP lineage progression are regulated in a profound deterministic manner. In this review we focus on recent advances based mainly on correlative phenotypic data emerging from functional genetic studies in mice. We establish hypotheses to test in future research and outline a conceptual framework how epigenetic cues modulate the generation of cell-type diversity during cortical development. This article is protected by copyright. All rights reserved. AU - Amberg, Nicole AU - Laukoter, Susanne AU - Hippenmeyer, Simon ID - 27 IS - 1 JF - Journal of Neurochemistry TI - Epigenetic cues modulating the generation of cell type diversity in the cerebral cortex VL - 149 ER - TY - JOUR AB - Tissue morphogenesis is driven by mechanical forces that elicit changes in cell size, shape and motion. The extent by which forces deform tissues critically depends on the rheological properties of the recipient tissue. Yet, whether and how dynamic changes in tissue rheology affect tissue morphogenesis and how they are regulated within the developing organism remain unclear. Here, we show that blastoderm spreading at the onset of zebrafish morphogenesis relies on a rapid, pronounced and spatially patterned tissue fluidization. Blastoderm fluidization is temporally controlled by mitotic cell rounding-dependent cell–cell contact disassembly during the last rounds of cell cleavages. Moreover, fluidization is spatially restricted to the central blastoderm by local activation of non-canonical Wnt signalling within the blastoderm margin, increasing cell cohesion and thereby counteracting the effect of mitotic rounding on contact disassembly. Overall, our results identify a fluidity transition mediated by loss of cell cohesion as a critical regulator of embryo morphogenesis. AU - Petridou, Nicoletta AU - Grigolon, Silvia AU - Salbreux, Guillaume AU - Hannezo, Edouard B AU - Heisenberg, Carl-Philipp J ID - 5789 JF - Nature Cell Biology SN - 14657392 TI - Fluidization-mediated tissue spreading by mitotic cell rounding and non-canonical Wnt signalling VL - 21 ER - TY - JOUR AB - The abelian sandpile serves as a model to study self-organized criticality, a phenomenon occurring in biological, physical and social processes. The identity of the abelian group is a fractal composed of self-similar patches, and its limit is subject of extensive collaborative research. Here, we analyze the evolution of the sandpile identity under harmonic fields of different orders. We show that this evolution corresponds to periodic cycles through the abelian group characterized by the smooth transformation and apparent conservation of the patches constituting the identity. The dynamics induced by second and third order harmonics resemble smooth stretchings, respectively translations, of the identity, while the ones induced by fourth order harmonics resemble magnifications and rotations. Starting with order three, the dynamics pass through extended regions of seemingly random configurations which spontaneously reassemble into accentuated patterns. We show that the space of harmonic functions projects to the extended analogue of the sandpile group, thus providing a set of universal coordinates identifying configurations between different domains. Since the original sandpile group is a subgroup of the extended one, this directly implies that it admits a natural renormalization. Furthermore, we show that the harmonic fields can be induced by simple Markov processes, and that the corresponding stochastic dynamics show remarkable robustness over hundreds of periods. Finally, we encode information into seemingly random configurations, and decode this information with an algorithm requiring minimal prior knowledge. Our results suggest that harmonic fields might split the sandpile group into sub-sets showing different critical coefficients, and that it might be possible to extend the fractal structure of the identity beyond the boundaries of its domain. AU - Lang, Moritz AU - Shkolnikov, Mikhail ID - 196 IS - 8 JF - Proceedings of the National Academy of Sciences TI - Harmonic dynamics of the Abelian sandpile VL - 116 ER - TY - JOUR AB - We theoretically study the shapes of lipid vesicles confined to a spherical cavity, elaborating a framework based on the so-called limiting shapes constructed from geometrically simple structural elements such as double-membrane walls and edges. Partly inspired by numerical results, the proposed non-compartmentalized and compartmentalized limiting shapes are arranged in the bilayer-couple phase diagram which is then compared to its free-vesicle counterpart. We also compute the area-difference-elasticity phase diagram of the limiting shapes and we use it to interpret shape transitions experimentally observed in vesicles confined within another vesicle. The limiting-shape framework may be generalized to theoretically investigate the structure of certain cell organelles such as the mitochondrion. AU - Kavcic, Bor AU - Sakashita, A. AU - Noguchi, H. AU - Ziherl, P. ID - 5817 IS - 4 JF - Soft Matter SN - 1744-683X TI - Limiting shapes of confined lipid vesicles VL - 15 ER - TY - JOUR AB - We consider the space of probability measures on a discrete set X, endowed with a dynamical optimal transport metric. Given two probability measures supported in a subset Y⊆X, it is natural to ask whether they can be connected by a constant speed geodesic with support in Y at all times. Our main result answers this question affirmatively, under a suitable geometric condition on Y introduced in this paper. The proof relies on an extension result for subsolutions to discrete Hamilton-Jacobi equations, which is of independent interest. AU - Erbar, Matthias AU - Maas, Jan AU - Wirth, Melchior ID - 73 IS - 1 JF - Calculus of Variations and Partial Differential Equations SN - 09442669 TI - On the geometry of geodesics in discrete optimal transport VL - 58 ER - TY - JOUR AB - We present an efficient algorithm for a problem in the interface between clustering and graph embeddings. An embedding ϕ : G → M of a graph G into a 2-manifold M maps the vertices in V(G) to distinct points and the edges in E(G) to interior-disjoint Jordan arcs between the corresponding vertices. In applications in clustering, cartography, and visualization, nearby vertices and edges are often bundled to the same point or overlapping arcs due to data compression or low resolution. This raises the computational problem of deciding whether a given map ϕ : G → M comes from an embedding. A map ϕ : G → M is a weak embedding if it can be perturbed into an embedding ψ ϵ : G → M with ‖ ϕ − ψ ϵ ‖ < ϵ for every ϵ > 0, where ‖.‖ is the unform norm. A polynomial-time algorithm for recognizing weak embeddings has recently been found by Fulek and Kynčl. It reduces the problem to solving a system of linear equations over Z2. It runs in O(n2ω)≤ O(n4.75) time, where ω ∈ [2,2.373) is the matrix multiplication exponent and n is the number of vertices and edges of G. We improve the running time to O(n log n). Our algorithm is also conceptually simpler: We perform a sequence of local operations that gradually “untangles” the image ϕ(G) into an embedding ψ(G) or reports that ϕ is not a weak embedding. It combines local constraints on the orientation of subgraphs directly, thereby eliminating the need for solving large systems of linear equations. AU - Akitaya, Hugo AU - Fulek, Radoslav AU - Tóth, Csaba ID - 6982 IS - 4 JF - ACM Transactions on Algorithms TI - Recognizing weak embeddings of graphs VL - 15 ER - TY - THES AB - Hybrid automata combine finite automata and dynamical systems, and model the interaction of digital with physical systems. Formal analysis that can guarantee the safety of all behaviors or rigorously witness failures, while unsolvable in general, has been tackled algorithmically using, e.g., abstraction, bounded model-checking, assisted theorem proving. Nevertheless, very few methods have addressed the time-unbounded reachability analysis of hybrid automata and, for current sound and automatic tools, scalability remains critical. We develop methods for the polyhedral abstraction of hybrid automata, which construct coarse overapproximations and tightens them incrementally, in a CEGAR fashion. We use template polyhedra, i.e., polyhedra whose facets are normal to a given set of directions. While, previously, directions were given by the user, we introduce (1) the first method for computing template directions from spurious counterexamples, so as to generalize and eliminate them. The method applies naturally to convex hybrid automata, i.e., hybrid automata with (possibly non-linear) convex constraints on derivatives only, while for linear ODE requires further abstraction. Specifically, we introduce (2) the conic abstractions, which, partitioning the state space into appropriate (possibly non-uniform) cones, divide curvy trajectories into relatively straight sections, suitable for polyhedral abstractions. Finally, we introduce (3) space-time interpolation, which, combining interval arithmetic and template refinement, computes appropriate (possibly non-uniform) time partitioning and template directions along spurious trajectories, so as to eliminate them. We obtain sound and automatic methods for the reachability analysis over dense and unbounded time of convex hybrid automata and hybrid automata with linear ODE. We build prototype tools and compare—favorably—our methods against the respective state-of-the-art tools, on several benchmarks. AU - Giacobbe, Mirco ID - 6894 TI - Automatic time-unbounded reachability analysis of hybrid systems ER - TY - GEN AB - The spread of adaptive alleles is fundamental to evolution, and in theory, this process is well‐understood. However, only rarely can we follow this process—whether it originates from the spread of a new mutation, or by introgression from another population. In this issue of Molecular Ecology, Hanemaaijer et al. (2018) report on a 25‐year long study of the mosquitoes Anopheles gambiae (Figure 1) and Anopheles coluzzi in Mali, based on genotypes at 15 single‐nucleotide polymorphism (SNP). The species are usually reproductively isolated from each other, but in 2002 and 2006, bursts of hybridization were observed, when F1 hybrids became abundant. Alleles backcrossed from A. gambiae into A. coluzzi, but after the first event, these declined over the following years. In contrast, after 2006, an insecticide resistance allele that had established in A. gambiae spread into A. coluzzi, and rose to high frequency there, over 6 years (~75 generations). Whole genome sequences of 74 individuals showed that A. gambiae SNP from across the genome had become common in the A. coluzzi population, but that most of these were clustered in 34 genes around the resistance locus. A new set of SNP from 25 of these genes were assayed over time; over the 4 years since near‐fixation of the resistance allele; some remained common, whereas others declined. What do these patterns tell us about this introgression event? AU - Barton, Nicholas H ID - 9805 TI - Data from: The consequences of an introgression event ER - TY - JOUR AB - Despite their different origins, Drosophila glia and hemocytes are related cell populations that provide an immune function. Drosophila hemocytes patrol the body cavity and act as macrophages outside the nervous system whereas glia originate from the neuroepithelium and provide the scavenger population of the nervous system. Drosophila glia are hence the functional orthologs of vertebrate microglia, even though the latter are cells of immune origin that subsequently move into the brain during development. Interestingly, the Drosophila immune cells within (glia) and outside the nervous system (hemocytes) require the same transcription factor Glide/Gcm for their development. This raises the issue of how do glia specifically differentiate in the nervous system and hemocytes in the procephalic mesoderm. The Repo homeodomain transcription factor and pan-glial direct target of Glide/Gcm is known to ensure glial terminal differentiation. Here we show that Repo also takes center stage in the process that discriminates between glia and hemocytes. First, Repo expression is repressed in the hemocyte anlagen by mesoderm-specific factors. Second, Repo ectopic activation in the procephalic mesoderm is sufficient to repress the expression of hemocyte-specific genes. Third, the lack of Repo triggers the expression of hemocyte markers in glia. Thus, a complex network of tissue-specific cues biases the potential of Glide/Gcm. These data allow us to revise the concept of fate determinants and help us understand the bases of cell specification. Both sexes were analyzed.SIGNIFICANCE STATEMENTDistinct cell types often require the same pioneer transcription factor, raising the issue of how does one factor trigger different fates. In Drosophila, glia and hemocytes provide a scavenger activity within and outside the nervous system, respectively. While they both require the Glide/Gcm transcription factor, glia originate from the ectoderm, hemocytes from the mesoderm. Here we show that tissue-specific factors inhibit the gliogenic potential of Glide/Gcm in the mesoderm by repressing the expression of the homeodomain protein Repo, a major glial-specific target of Glide/Gcm. Repo expression in turn inhibits the expression of hemocyte-specific genes in the nervous system. These cell-specific networks secure the establishment of the glial fate only in the nervous system and allow cell diversification. AU - Trébuchet, Guillaume AU - Cattenoz, Pierre B AU - Zsámboki, János AU - Mazaud, David AU - Siekhaus, Daria E AU - Fanto, Manolis AU - Giangrande, Angela ID - 8 IS - 2 JF - Journal of Neuroscience TI - The Repo homeodomain transcription factor suppresses hematopoiesis in Drosophila and preserves the glial fate VL - 39 ER -