TY - JOUR AB - How much cutting is needed to simplify the topology of a surface? We provide bounds for several instances of this question, for the minimum length of topologically non-trivial closed curves, pants decompositions, and cut graphs with a given combinatorial map in triangulated combinatorial surfaces (or their dual cross-metric counterpart). Our work builds upon Riemannian systolic inequalities, which bound the minimum length of non-trivial closed curves in terms of the genus and the area of the surface. We first describe a systematic way to translate Riemannian systolic inequalities to a discrete setting, and vice-versa. This implies a conjecture by Przytycka and Przytycki (Graph structure theory. Contemporary Mathematics, vol. 147, 1993), a number of new systolic inequalities in the discrete setting, and the fact that a theorem of Hutchinson on the edge-width of triangulated surfaces and Gromov’s systolic inequality for surfaces are essentially equivalent. We also discuss how these proofs generalize to higher dimensions. Then we focus on topological decompositions of surfaces. Relying on ideas of Buser, we prove the existence of pants decompositions of length O(g^(3/2)n^(1/2)) for any triangulated combinatorial surface of genus g with n triangles, and describe an O(gn)-time algorithm to compute such a decomposition. Finally, we consider the problem of embedding a cut graph (or more generally a cellular graph) with a given combinatorial map on a given surface. Using random triangulations, we prove (essentially) that, for any choice of a combinatorial map, there are some surfaces on which any cellular embedding with that combinatorial map has length superlinear in the number of triangles of the triangulated combinatorial surface. There is also a similar result for graphs embedded on polyhedral triangulations. AU - Colin De Verdière, Éric AU - Hubard, Alfredo AU - De Mesmay, Arnaud N ID - 1730 IS - 3 JF - Discrete & Computational Geometry TI - Discrete systolic inequalities and decompositions of triangulated surfaces VL - 53 ER - TY - JOUR AB - In the vertebrate neural tube, the morphogen Sonic Hedgehog (Shh) establishes a characteristic pattern of gene expression. Here we quantify the Shh gradient in the developing mouse neural tube and show that while the amplitude of the gradient increases over time, the activity of the pathway transcriptional effectors, Gli proteins, initially increases but later decreases. Computational analysis of the pathway suggests three mechanisms that could contribute to this adaptation: transcriptional upregulation of the inhibitory receptor Ptch1, transcriptional downregulation of Gli and the differential stability of active and inactive Gli isoforms. Consistent with this, Gli2 protein expression is downregulated during neural tube patterning and adaptation continues when the pathway is stimulated downstream of Ptch1. Moreover, the Shh-induced upregulation of Gli2 transcription prevents Gli activity levels from adapting in a different cell type, NIH3T3 fibroblasts, despite the upregulation of Ptch1. Multiple mechanisms therefore contribute to the intracellular dynamics of Shh signalling, resulting in different signalling dynamics in different cell types. AU - Cohen, Michael H AU - Anna Kicheva AU - Ribeiro, Ana C AU - Blassberg, Robert A AU - Page, Karen M AU - Barnes, Chris P AU - Briscoe, James ID - 1728 JF - Nature Communications TI - Ptch1 and Gli regulate Shh signalling dynamics via multiple mechanisms VL - 6 ER - TY - JOUR AB - This work presents a method for efficiently simplifying the pressure projection step in a liquid simulation. We first devise a straightforward dimension reduction technique that dramatically reduces the cost of solving the pressure projection. Next, we introduce a novel change of basis that satisfies free-surface boundary conditions exactly, regardless of the accuracy of the pressure solve. When combined, these ideas greatly reduce the computational complexity of the pressure solve without compromising free surface boundary conditions at the highest level of detail. Our techniques are easy to parallelize, and they effectively eliminate the computational bottleneck for large liquid simulations. AU - Ando, Ryoichi AU - Thürey, Nils AU - Wojtan, Christopher J ID - 1735 IS - 2 JF - Computer Graphics Forum TI - A dimension-reduced pressure solver for liquid simulations VL - 34 ER - TY - JOUR AB - Facial appearance capture is now firmly established within academic research and used extensively across various application domains, perhaps most prominently in the entertainment industry through the design of virtual characters in video games and films. While significant progress has occurred over the last two decades, no single survey currently exists that discusses the similarities, differences, and practical considerations of the available appearance capture techniques as applied to human faces. A central difficulty of facial appearance capture is the way light interacts with skin-which has a complex multi-layered structure-and the interactions that occur below the skin surface can, by definition, only be observed indirectly. In this report, we distinguish between two broad strategies for dealing with this complexity. "Image-based methods" try to exhaustively capture the exact face appearance under different lighting and viewing conditions, and then render the face through weighted image combinations. "Parametric methods" instead fit the captured reflectance data to some parametric appearance model used during rendering, allowing for a more lightweight and flexible representation but at the cost of potentially increased rendering complexity or inexact reproduction. The goal of this report is to provide an overview that can guide practitioners and researchers in assessing the tradeoffs between current approaches and identifying directions for future advances in facial appearance capture. AU - Klehm, Oliver AU - Rousselle, Fabrice AU - Papas, Marios AU - Bradley, Derek AU - Hery, Christophe AU - Bickel, Bernd AU - Jarosz, Wojciech AU - Beeler, Thabo ID - 1734 IS - 2 JF - Computer Graphics Forum TI - Recent advances in facial appearance capture VL - 34 ER - TY - JOUR AB - Intellectual disability (ID) has an estimated prevalence of 2-3%. Due to its extreme heterogeneity, the genetic basis of ID remains elusive in many cases. Recently, whole exome sequencing (WES) studies revealed that a large proportion of sporadic cases are caused by de novo gene variants. To identify further genes involved in ID, we performed WES in 250 patients with unexplained ID and their unaffected parents and included exomes of 51 previously sequenced child-parents trios in the analysis. Exome analysis revealed de novo intragenic variants in SET domain-containing 5 (SETD5) in two patients. One patient carried a nonsense variant, and the other an 81 bp deletion located across a splice-donor site. Chromosomal microarray diagnostics further identified four de novo non-recurrent microdeletions encompassing SETD5. CRISPR/Cas9 mutation modelling of the two intragenic variants demonstrated nonsense-mediated decay of the resulting transcripts, pointing to a loss-of-function (LoF) and haploinsufficiency as the common disease-causing mechanism of intragenic SETD5 sequence variants and SETD5-containing microdeletions. In silico domain prediction of SETD5, a predicted SET domain-containing histone methyltransferase (HMT), substantiated the presence of a SET domain and identified a novel putative PHD domain, strengthening a functional link to well-known histone-modifying ID genes. All six patients presented with ID and certain facial dysmorphisms, suggesting that SETD5 sequence variants contribute substantially to the microdeletion 3p25.3 phenotype. The present report of two SETD5 LoF variants in 301 patients demonstrates a prevalence of 0.7% and thus SETD5 variants as a relatively frequent cause of ID. AU - Kuechler, Alma AU - Zink, Alexander AU - Wieland, Thomas AU - Lüdecke, Hermann AU - Cremer, Kirsten AU - Salviati, Leonardo AU - Magini, Pamela AU - Najafi, Kimia AU - Zweier, Christiane AU - Czeschik, Johanna AU - Aretz, Stefan AU - Endele, Sabine AU - Tamburrino, Federica AU - Pinato, Claudia AU - Clementi, Maurizio AU - Gundlach, Jasmin AU - Maylahn, Carina AU - Mazzanti, Laura AU - Wohlleber, Eva AU - Schwarzmayr, Thomas AU - Kariminejad, Roxana AU - Schlessinger, Avner AU - Wieczorek, Dagmar AU - Strom, Tim AU - Novarino, Gaia AU - Engels, Hartmut ID - 1789 IS - 6 JF - European Journal of Human Genetics TI - Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome VL - 23 ER - TY - JOUR AB - We fabricate and characterize a microscale silicon opto-electromechanical system whose mechanical motion is coupled capacitively to an electrical circuit and optically via radiation pressure to a photonic crystal cavity. To achieve large electromechanical interaction strength, we implement an inverse shadow mask fabrication scheme which obtains capacitor gaps as small as 30 nm while maintaining a silicon surface quality necessary for minimizing optical loss. Using the sensitive optical read-out of the photonic crystal cavity, we characterize the linear and nonlinear capacitive coupling to the fundamental ωm=2π = 63 MHz in-plane flexural motion of the structure, showing that the large electromechanical coupling in such devices may be suitable for realizing efficient microwave-to-optical signal conversion. AU - Pitanti, Alessandro AU - Johannes Fink AU - Safavi-Naeini, Amir H AU - Hill, Jeff T AU - Lei, Chan U AU - Tredicucci, Alessandro AU - Painter, Oskar J ID - 1788 IS - 3 JF - Optics Express TI - Strong opto-electro-mechanical coupling in a silicon photonic crystal cavity VL - 23 ER - TY - JOUR AB - It is known that in classical fluids turbulence typically occurs at high Reynolds numbers. But can turbulence occur at low Reynolds numbers? Here we investigate the transition to turbulence in the classic Taylor-Couette system in which the rotating fluids are manufactured ferrofluids with magnetized nanoparticles embedded in liquid carriers. We find that, in the presence of a magnetic field transverse to the symmetry axis of the system, turbulence can occur at Reynolds numbers that are at least one order of magnitude smaller than those in conventional fluids. This is established by extensive computational ferrohydrodynamics through a detailed investigation of transitions in the flow structure, and characterization of behaviors of physical quantities such as the energy, the wave number, and the angular momentum through the bifurcations. A finding is that, as the magnetic field is increased, onset of turbulence can be determined accurately and reliably. Our results imply that experimental investigation of turbulence may be feasible by using ferrofluids. Our study of transition to and evolution of turbulence in the Taylor-Couette ferrofluidic flow system provides insights into the challenging problem of turbulence control. AU - Altmeyer, Sebastian AU - Do, Younghae AU - Lai, Ying ID - 1804 JF - Scientific Reports TI - Transition to turbulence in Taylor-Couette ferrofluidic flow VL - 5 ER - TY - JOUR AB - Repeated stress has been suggested to underlie learning and memory deficits via the basolateral amygdala (BLA) and the hippocampus; however, the functional contribution of BLA inputs to the hippocampus and their molecular repercussions are not well understood. Here we show that repeated stress is accompanied by generation of the Cdk5 (cyclin-dependent kinase 5)-activator p25, up-regulation and phosphorylation of glucocorticoid receptors, increased HDAC2 expression, and reduced expression of memoryrelated genes in the hippocampus. A combination of optogenetic and pharmacosynthetic approaches shows that BLA activation is both necessary and sufficient for stress-associated molecular changes and memory impairments. Furthermore, we show that this effect relies on direct glutamatergic projections from the BLA to the dorsal hippocampus. Finally, we show that p25 generation is necessary for the stress-induced memory dysfunction. Taken together, our data provide a neural circuit model for stress-induced hippocampal memory deficits through BLA activity-dependent p25 generation. AU - Rei, Damien AU - Mason, Xenos AU - Seo, Jinsoo AU - Gräff, Johannes AU - Rudenko, Andrii AU - Wang, Jùn AU - Rueda, Richard AU - Sandra Siegert AU - Cho, Sukhee AU - Canter, Rebecca G AU - Mungenast, Alison E AU - Deisseroth, Karl A AU - Tsai, Lihuei ID - 1803 IS - 23 JF - PNAS TI - Basolateral amygdala bidirectionally modulates stress induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway VL - 112 ER - TY - JOUR AB - We study a double Cahn-Hilliard type functional related to the Gross-Pitaevskii energy of two-components Bose-Einstein condensates. In the case of large but same order intercomponent and intracomponent coupling strengths, we prove Γ-convergence to a perimeter minimisation functional with an inhomogeneous surface tension. We study the asymptotic behavior of the surface tension as the ratio between the intercomponent and intracomponent coupling strengths becomes very small or very large and obtain good agreement with the physical literature. We obtain as a consequence, symmetry breaking of the minimisers for the harmonic potential. AU - Goldman, Michael AU - Royo-Letelier, Jimena ID - 1807 IS - 3 JF - ESAIM - Control, Optimisation and Calculus of Variations TI - Sharp interface limit for two components Bose-Einstein condensates VL - 21 ER - TY - JOUR AB - Noncoding variants in the human MIR137 gene locus increase schizophrenia risk with genome-wide significance. However, the functional consequence of these risk alleles is unknown. Here we examined induced human neurons harboring the minor alleles of four disease-associated single nucleotide polymorphisms in MIR137. We observed increased MIR137 levels compared to those in major allele–carrying cells. microRNA-137 gain of function caused downregulation of the presynaptic target genes complexin-1 (Cplx1), Nsf and synaptotagmin-1 (Syt1), leading to impaired vesicle release. In vivo, miR-137 gain of function resulted in changes in synaptic vesicle pool distribution, impaired induction of mossy fiber long-term potentiation and deficits in hippocampus-dependent learning and memory. By sequestering endogenous miR-137, we were able to ameliorate the synaptic phenotypes. Moreover, reinstatement of Syt1 expression partially restored synaptic plasticity, demonstrating the importance of Syt1 as a miR-137 target. Our data provide new insight into the mechanism by which miR-137 dysregulation can impair synaptic plasticity in the hippocampus. AU - Sandra Siegert AU - Seo, Jinsoo AU - Kwon, Ester J AU - Rudenko, Andrii AU - Cho, Sukhee AU - Wang, Wenyuan AU - Flood, Zachary C AU - Martorell, Anthony J AU - Ericsson, Maria AU - Mungenast, Alison E AU - Tsai, Lihuei ID - 1802 JF - Nature Neuroscience TI - The schizophrenia risk gene product miR-137 alters presynaptic plasticity VL - 18 ER -