Differentiable Game Mechanics

Deep learning is built on the foundational guarantee that gradient descent on an objective function converges to local minima. Unfortunately, this guarantee fails in settings, such as generative adversarial nets, that exhibit multiple interacting losses. The behavior of gradient-based methods in games is not well understood -- and is becoming increasingly important as adversarial and multi-objective architectures proliferate. In this paper, we develop new tools to understand and control the dynamics in n-player differentiable games. The key result is to decompose the game Jacobian into two components. The first, symmetric component, is related to potential games, which reduce to gradient descent on an implicit function. The second, antisymmetric component, relates to Hamiltonian games, a new class of games that obey a conservation law akin to conservation laws in classical mechanical systems. The decomposition motivates Symplectic Gradient Adjustment (SGA), a new algorithm for finding stable fixed points in differentiable games. Basic experiments show SGA is competitive with recently proposed algorithms for finding stable fixed points in GANs -- while at the same time being applicable to, and having guarantees in, much more general cases.Comment: JMLR 2019, journal version of arXiv:1802.0564

Investigation of the evaporation process of liquefied hydrocarbons in front of a compressor

International audienceInlet fogging and wet compression are well known methods to lower the inlet temperature of air compressors of gas turbines and in this way lead to a more efficient compression process. Injection of water into the gas stream is another established method to reduce the compressor stage inlet temperature during the compression of crack gas. The lower inlet temperature of the compressor stage reduces its power demand and additionally, the discharge temperature remains in a suitable range. Applying the method of liquid injection, all injected droplets should be evaporated before entering the compressor impeller to avoid damage at the blades. A good knowledge about the evaporation process of injected liquid in a free stream is necessary to determine the required distance for complete evaporation of all droplets. The aim of this paper is to provide clear statements on technical possibilities and requirements for an optimized and reliable compression process under liquid injection. The evaporation process of injected hydrocarbon droplets into a gas stream is investigated under realistic boundary conditions. Using conservation laws of mass and energy, a 1D numerical model is derived which allows the calculation of the liquid hydrocarbon evaporation in a free stream. The required fluid properties are taken from the National Institute of Standards and Technology (NIST). A comparison between the 1D model and a 3D Navier-Stokes solution for injected CH 4 droplets into a CH 4 gas stream shows good agreement regarding the decrease of the droplet diameter during the evaporation with respect to the amount of injected mass of liquid fluid and gives a good indication of the requested distance for complete evaporation. In addition, the 1D model predicts the temperature decrease of the gas during evaporation in good accordance to a 3D Navier-Stokes solver. Applying the simple 1D model, it is possible to evaluate the thermodynamic inlet parameters of a compressor for given boundary conditions quickly. In addition, the results allow a statement regarding the complete evaporation of all sizes of injected droplets at the compressor inlet and the formation of liquid films at the walls

The ubiquitin-editing enzyme A20 controls NK cell homeostasis through regulation of mTOR activity and TNF

The ubiquitin-editing enzyme A20 is a well-known regulator of immune cell function and homeostasis. In addition, A20 protects cells from death in an ill-defined manner. While most studies focus on its role in the TNF-receptor complex, we here identify a novel component in the A20-mediated decision between life and death. Loss of A20 in NK cells led to spontaneous NK cell death and severe NK cell lymphopenia. The few remaining NK cells showed an immature, hyperactivated phenotype, hallmarked by the basal release of cytokines and cytotoxic molecules. NK-A20(-/-) cells were hypersensitive to TNF-induced cell death and could be rescued, at least partially, by a combined deficiency with TNF. Unexpectedly, rapamycin, a well-established inhibitor of mTOR, also strongly protected NK-A20(-/-) cells from death, and further studies revealed that A20 restricts mTOR activation in NK cells. This study therefore maps A20 as a crucial regulator of mTOR signaling and underscores the need for a tightly balanced mTOR pathway in NK cell homeostasis

The Mechanics of n-Player Differentiable Games

The cornerstone underpinning deep learning is the guarantee that gradient descent on an objective converges to local minima. Unfortunately, this guarantee fails in settings, such as generative adversarial nets, where there are multiple interacting losses. The behavior of gradient-based methods in games is not well understood – and is becoming increasingly important as adversarial and multiobjective architectures proliferate. In this paper, we develop new techniques to understand and control the dynamics in general games. The key result is to decompose the second-order dynamics into two components. The first is related to potential games, which reduce to gradient descent on an implicit function; the second relates to Hamiltonian games, a new class of games that obey a conservation law, akin to conservation laws in classical mechanical systems. The decomposition motivates Symplectic Gradient Adjustment (SGA), a new algorithm for finding stable fixed points in general games. Basic experiments show SGA is competitive with recently proposed algorithms for finding stable fixed points in GANs – whilst at the same time being applicable to – and having guarantees in – much more general games

Identification and Diagnostic Performance of a Small RNA within the PCA3 and BMCC1 Gene Locus That Potentially Targets mRNA

Background: PCA3 is a long noncoding RNA (lncRNA) with unknown function, upregulated in prostate cancer. LncRNAs may be processed into smaller active species. We hypothesized this for PCA3. Methods: We computed feasible RNA hairpins within the BMCC1 gene (encompassing PCA3) and searched a prostate transcriptome for these. We measured expression using qRT-PCR in three cohorts of prostate cancer tissues (n = 60), exfoliated urinary cells (n = 484 with cancer and n = 166 controls), and in cell lines (n = 22). We used in silico predictions and RNA knockup to identify potential mRNA targets of short transcribed RNAs. Results: We predicted 13 hairpins, of which PCA3-shRNA2 was most abundant within the prostate transcriptome. PCA3-shRNA2 is located within intron 1 of PCA3 and appears regulated by androgens. Expression of PCA3-shRNA2 was upregulated in malignant prostatic tissues, exfoliated urinary cells from men with prostate cancer (13–273 fold change; t test P < 0.003), and closely correlated to PCA3 expression (r = 0.84–0.93; P < 0.001). Urinary PCA3-shRNA2 (C-index, 0.75–0.81) and PCA3 (C-index, 0.78) could predict the presence of cancer in most men. PCA3-shRNA2 knockup altered the expression of predicted target mRNAs, including COPS2, SOX11, WDR48, TEAD1, and Noggin. PCA3-shRNA2 expression was negatively correlated with COPS2 in patient samples (r = −0.32; P < 0.001). Conclusion: We identified a short RNA within PCA3, whose expression is correlated to PCA3, which may target mRNAs implicated in prostate biology

Changes in fecal pellet characteristics with depth as indicators of zooplankton repackaging of particles in the mesopelagic zone of the subtropical and subarctic North Pacific Ocean

Author Posting. © Elsevier B.V., 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part II: Topical Studies in Oceanography 55 (2008): 1636-1647, doi:10.1016/j.dsr2.2008.04.019.We investigated how fecal pellet characteristics change with depth in order to quantify the extent of particle repackaging by mesopelagic zooplankton in two contrasting open-ocean systems. Material from neutrally buoyant sediment traps deployed in the summer of 2004 and 2005 at 150, 300, and 500 m was analyzed from both a mesotrophic (Japanese time-series station K2) and an oligotrophic (Hawaii Ocean Time series-HOT station ALOHA) environment in the Pacific Ocean as part of the VERtical Transport In the Global Ocean (VERTIGO) project. We quantified changes in the flux, size, shape, and color of particles recognizable as zooplankton fecal pellets to determine how these parameters varied with depth and location. Flux of K2 fecal pellet particulate organic carbon (POC) at 150 and 300 m was 4-5 times higher than at ALOHA, and at all depths, fecal pellets were 2-5 times larger at K2, reflective of the disparate zooplankton community structure at the two sites. At K2, the proportion of POC flux that consisted of fecal pellets generally decreased with depth from 20% at 150 m to 5% at 500 m, whereas at ALOHA this proportion increased with depth (and was more variable) from 14% to 35%. This difference in the fecal fraction of POC with increasing depth is hypothesized to be due to differences in the extent of zooplankton-mediated fragmentation (coprohexy) and in zooplankton community structure between the two locations. Both regions provided indications of sinking particle repackaging and zooplankton carnivory in the mesopelagic. At ALOHA this was reflected in a significant increase in the mean flux of larvacean fecal pellets from 150 to 500 m of 3 to 46 μg C m-2 d-1, respectively, and at K2 a large peak in larvacean mean pellet flux at 300 m of 3.1 mg C m-2 d-1. Peaks in red pellets produced by carnivores occurred at 300 m at K2, and a variety of other fecal pellet classes showed significant changes in their distribution with depth. There was also evidence of substantially higher pellet fragmentation at K2 with nearly double the ratio of broken:intact pellets at 150 and 300 m (mean of 67% and 64%, respectively ) than at ALOHA where the proportion of broken pellets remained constant with depth (mean 35%). Variations in zooplankton size and community structure within the mesopelagic zone can thus differentially alter the transfer efficiency of sinking POC.This study was supported by grants from the U.S. National Science Foundation NSF OCE-0324402 (Biological Oceanography) to D.K.S and OCE-0301139 (Chemical Oceanography) to K.O.B

Metabolic flexibility of enigmatic SAR 324 revealed through metagenomics and metatranscriptomics

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102166/1/emi12165.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102166/2/emi12165-sup-0001-figure.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102166/3/emi12165-sup-0002-table.pd

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Ca2+ Regulates the Drosophila Stoned-A and Stoned-B Proteins Interaction with the C2B Domain of Synaptotagmin-1

The dicistronic Drosophila stoned gene is involved in exocytosis and/or endocytosis of synaptic vesicles. Mutations in either stonedA or stonedB cause a severe disruption of neurotransmission in fruit flies. Previous studies have shown that the coiled-coil domain of the Stoned-A and the µ-homology domain of the Stoned-B protein can interact with the C2B domain of Synaptotagmin-1. However, very little is known about the mechanism of interaction between the Stoned proteins and the C2B domain of Synaptotagmin-1. Here we report that these interactions are increased in the presence of Ca2+. The Ca2+-dependent interaction between the µ-homology domain of Stoned-B and C2B domain of Synaptotagmin-1 is affected by phospholipids. The C-terminal region of the C2B domain, including the tryptophan-containing motif, and the Ca2+ binding loop region that modulate the Ca2+-dependent oligomerization, regulates the binding of the Stoned-A and Stoned-B proteins to the C2B domain. Stoned-B, but not Stoned-A, interacts with the Ca2+-binding loop region of C2B domain. The results indicate that Ca2+-induced self-association of the C2B domain regulates the binding of both Stoned-A and Stoned-B proteins to Synaptotagmin-1. The Stoned proteins may regulate sustainable neurotransmission in vivo by binding to Ca2+-bound Synaptotagmin-1 associated synaptic vesicles