@article{1728, abstract = {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.}, author = {Cohen, Michael H and Anna Kicheva and Ribeiro, Ana C and Blassberg, Robert A and Page, Karen M and Barnes, Chris P and Briscoe, James}, journal = {Nature Communications}, publisher = {Nature Publishing Group}, title = {{Ptch1 and Gli regulate Shh signalling dynamics via multiple mechanisms}}, doi = {10.1038/ncomms7709}, volume = {6}, year = {2015}, } @article{1735, abstract = {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.}, author = {Ando, Ryoichi and Thürey, Nils and Wojtan, Christopher J}, journal = {Computer Graphics Forum}, number = {2}, pages = {473 -- 480}, publisher = {Wiley}, title = {{A dimension-reduced pressure solver for liquid simulations}}, doi = {10.1111/cgf.12576}, volume = {34}, year = {2015}, } @article{1734, abstract = {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.}, author = {Klehm, Oliver and Rousselle, Fabrice and Papas, Marios and Bradley, Derek and Hery, Christophe and Bickel, Bernd and Jarosz, Wojciech and Beeler, Thabo}, journal = {Computer Graphics Forum}, number = {2}, pages = {709 -- 733}, publisher = {Wiley-Blackwell}, title = {{Recent advances in facial appearance capture}}, doi = {10.1111/cgf.12594}, volume = {34}, year = {2015}, } @article{1789, abstract = {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.}, author = {Kuechler, Alma and Zink, Alexander and Wieland, Thomas and Lüdecke, Hermann and Cremer, Kirsten and Salviati, Leonardo and Magini, Pamela and Najafi, Kimia and Zweier, Christiane and Czeschik, Johanna and Aretz, Stefan and Endele, Sabine and Tamburrino, Federica and Pinato, Claudia and Clementi, Maurizio and Gundlach, Jasmin and Maylahn, Carina and Mazzanti, Laura and Wohlleber, Eva and Schwarzmayr, Thomas and Kariminejad, Roxana and Schlessinger, Avner and Wieczorek, Dagmar and Strom, Tim and Novarino, Gaia and Engels, Hartmut}, journal = {European Journal of Human Genetics}, number = {6}, pages = {753 -- 760}, publisher = {Nature Publishing Group}, title = {{Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome}}, doi = {10.1038/ejhg.2014.165}, volume = {23}, year = {2015}, } @article{1788, abstract = {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.}, author = {Pitanti, Alessandro and Johannes Fink and Safavi-Naeini, Amir H and Hill, Jeff T and Lei, Chan U and Tredicucci, Alessandro and Painter, Oskar J}, journal = {Optics Express}, number = {3}, pages = {3196 -- 3208}, publisher = {Optical Society of America}, title = {{Strong opto-electro-mechanical coupling in a silicon photonic crystal cavity}}, doi = {10.1364/OE.23.003196}, volume = {23}, year = {2015}, }