393 research outputs found
Learning the Tangent Space of Dynamical Instabilities from Data
For a large class of dynamical systems, the optimally time-dependent (OTD)
modes, a set of deformable orthonormal tangent vectors that track directions of
instabilities along any trajectory, are known to depend "pointwise" on the
state of the system on the attractor, and not on the history of the trajectory.
We leverage the power of neural networks to learn this "pointwise" mapping from
phase space to OTD space directly from data. The result of the learning process
is a cartography of directions associated with strongest instabilities in phase
space. Implications for data-driven prediction and control of dynamical
instabilities are discussed
Interactive Training System for Interventional Electrocardiology Procedures
International audienceRecent progress in cardiac catheterization and devices al-lowed to develop new therapies for severe cardiac diseases like arrhyth-mias and heart failure. The skills required for such interventions are still very challenging to learn, and typically acquired over several years. Vir-tual reality simulators can reduce this burden by allowing to practice such procedures without consequences on patients. In this paper, we propose the first training system dedicated to cardiac electrophysiology, includ-ing pacing and ablation procedures. Our framework involves an efficient GPU-based electrophysiological model. Thanks to an innovative mul-tithreading approach, we reach high computational performances that allow to account for user interactions in real-time. Based on a scenario of cardiac arrhythmia, we demonstrate the ability of the user-guided simulator to navigate inside vessels and cardiac cavities with a catheter and to reproduce an ablation procedure involving: extra-cellular poten-tial measurements, endocardial surface reconstruction, electrophysiology mapping, radio-frequency (RF) ablation, as well as electrical stimulation. This works is a step towards computerized medical learning curriculum
Synthesis of Carboxamides Tranylcypromine Analogues as LSD1 (KDM1A) Inhibitors for AML
Lysine-specific demethylase 1 (LSD1/KDM1A) oxidatively removes methyl groups from histone proteins and its aberrant activity has been correlated with cancers including acute myeloid leukemia (AML). We report a novel series of tranylcypromine analogues containing a carboxamide at the 4-position of the aryl ring and novel carbamates. These compounds were potent submicromolar LSD1 inhibitors in enzyme assays and were anti-proliferative against a panel of AML cell lines. LSD1 target engagement in cells was demonstrated through the effects on H3K4me2 protein expression, CD86, CD11b and CD14 levels
A systems-level framework for drug discovery identifies Csf1R as an anti-epileptic drug target
The identification of drug targets is highly challenging, particularly for diseases of the brain. To address this problem, we developed and experimentally validated a general computational framework for drug target discovery that combines gene regulatory information with causal reasoning (âCausal Reasoning Analytical Framework for Target discoveryââCRAFT). Using a systems genetics approach and starting from gene expression data from the target tissue, CRAFT provides a predictive framework for identifying cell membrane receptors with a direction-specified influence over disease-related gene expression profiles. As proof of concept, we applied CRAFT to epilepsy and predicted the tyrosine kinase receptor Csf1R as a potential therapeutic target. The predicted effect of Csf1R blockade in attenuating epilepsy seizures was validated in three pre-clinical models of epilepsy. These results highlight CRAFT as a systems-level framework for target discovery and suggest Csf1R blockade as a novel therapeutic strategy in epilepsy. CRAFT is applicable to disease settings other than epilepsy
Apex scavengers from different European populations converge at threatened savannah landscapes
Over millennia, human intervention has transformed European habitats mainly through extensive livestock grazing. âDehesas/Montadosâ are an Iberian savannah-like ecosystem dominated by oak-trees, bushes and grass species that are subject to agricultural and extensive livestock uses. They are a good example of how large-scale, low intensive transformations can maintain high biodiversity levels as well as socio-economic and cultural values. However, the role that these human-modified habitats can play for individuals or species living beyond their borders is unknown. Here, using a dataset of 106 adult GPS-tagged Eurasian griffon vultures (Gyps fulvus) monitored over seven years, we show how individuals breeding in western European populations from Northern, Central, and Southern Spain, and Southern France made long-range forays (LRFs) of up to 800 km to converge in the threatened Iberian âdehesasâ to forage. There, extensive livestock and wild ungulates provide large amounts of carcasses, which are available to scavengers from traditional exploitations and rewilding processes. Our results highlight that maintaining Iberian âdehesasâ is critical not only for local biodiversity but also for long-term conservation and the ecosystem services provided by avian scavengers across the continent
Physical limits of flight performance in the heaviest soaring bird
Flight costs are predicted to vary with environmental conditions, and this should ultimately determine the movement capacity and distributions of large soaring birds. Despite this, little is known about how flight effort varies with environmental parameters. We deployed bio-logging devices on the worldâs heaviest soaring bird, the Andean condor (Vultur gryphus), to assess the extent to which these birds can operate without resorting to powered flight. Our records of individual wingbeats in >216 hours of flight show that condors can sustain soaring across a wide range of wind and thermal conditions, only flapping for 1 % of their flight time. This is amongst the very lowest estimated movement costs in vertebrates. One bird even flew for > 5 hours without flapping, covering ~ 172 km. Overall, > 70 % of flapping flight was associated with take-offs. Movement between weak thermal updrafts at the start of the day also imposed a metabolic cost, with birds flapping towards the end of glides to reach ephemeral thermal updrafts. Nonetheless, the investment required was still remarkably low, and even in winter conditions with weak thermals, condors are only predicted to flap for ~ 2 s per km. The overall flight effort in the largest soaring birds therefore appears to be constrained by the requirements for take-off
Alternative splicing of hepatitis B virus: A novel virus/host interaction altering liver immunity
This work was supported by grants from Institut National de la Sante et de la Recherche Medicale (Inserm) â France, Universite Pierre et Marie Curie (UPMC) â France, Agence National de la Recherche sur le Sida et les Hepatites (ANRS) â France (n° N14015DR) and PHC-Tassili (11MDU826). MD was supported by ANRS (grant ASA14013DRA). YM was supported by French Ministry for Higher Education and Research and by the Ligue contre le Cancer (grant n° GB/MA/VSP-10504)
The Interplay Between Post-Critical Beliefs and Anxiety: An Exploratory Study in a Polish Sample
The present research investigates the relationship between anxiety and the religiosity dimensions that Wulff (Psychology of religion: classic and contemporary views, Wiley, New York, 1991; Psychology of religion. Classic and contemporary views, Wiley, New York, 1997; Psychologia religii. Klasyczna i wspĂłĹczesna, Wydawnictwo Szkolne i Pedagogiczne, Warszawa, 1999) described as Exclusion vs. Inclusion of Transcendence and Literal vs. Symbolic. The researchers used the Post-Critical Belief scale (Hutsebaut in J Empir Theol 9(2):48â66, 1996; J Empir Theol 10(1):39â54, 1997) to measure Wulffâs religiosity dimensions and the IPAT scale (Krug et al. 1967) to measure anxiety. Results from an adult sample (N = 83) suggest that three dimensions show significant relations with anxiety. Orthodoxy correlated negatively with suspiciousness (L) and positively with guilt proneness (O) factorâin the whole sample. Among women, Historical Relativism negatively correlated with suspiciousness (L), lack of integration (Q3), general anxiety and covert anxiety. Among men, Historical Relativism positively correlated with tension (Q4) and emotional instability (C), general anxiety, covert anxiety and overt anxiety. External Critique was correlated with suspiciousness (L) by men
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