TY - JOUR AB - Combining antibiotics is a promising strategy for increasing treatment efficacy and for controlling resistance evolution. When drugs are combined, their effects on cells may be amplified or weakened, that is the drugs may show synergistic or antagonistic interactions. Recent work revealed the underlying mechanisms of such drug interactions by elucidating the drugs'; joint effects on cell physiology. Moreover, new treatment strategies that use drug combinations to exploit evolutionary tradeoffs were shown to affect the rate of resistance evolution in predictable ways. High throughput studies have further identified drug candidates based on their interactions with established antibiotics and general principles that enable the prediction of drug interactions were suggested. Overall, the conceptual and technical foundation for the rational design of potent drug combinations is rapidly developing. AU - Bollenbach, Mark Tobias ID - 1810 JF - Current Opinion in Microbiology TI - Antimicrobial interactions: Mechanisms and implications for drug discovery and resistance evolution VL - 27 ER - TY - JOUR AB - We investigate the occurrence of rotons in a quadrupolar Bose–Einstein condensate confined to two dimensions. Depending on the particle density, the ratio of the contact and quadrupole–quadrupole interactions, and the alignment of the quadrupole moments with respect to the confinement plane, the dispersion relation features two or four point-like roton minima or one ring-shaped minimum. We map out the entire parameter space of the roton behavior and identify the instability regions. We propose to observe the exotic rotons by monitoring the characteristic density wave dynamics resulting from a short local perturbation, and discuss the possibilities to detect the predicted effects in state-of-the-art experiments with ultracold homonuclear molecules. AU - Lahrz, Martin AU - Lemeshko, Mikhail AU - Mathey, Ludwig ID - 1812 IS - 4 JF - New Journal of Physics TI - Exotic roton excitations in quadrupolar Bose–Einstein condensates VL - 17 ER - TY - JOUR AB - Atomic form factors are widely used for the characterization of targets and specimens, from crystallography to biology. By using recent mathematical results, here we derive an analytical expression for the atomic form factor within the independent particle model constructed from nonrelativistic screened hydrogenic wave functions. The range of validity of this analytical expression is checked by comparing the analytically obtained form factors with the ones obtained within the Hartee-Fock method. As an example, we apply our analytical expression for the atomic form factor to evaluate the differential cross section for Rayleigh scattering off neutral atoms. AU - Safari, Laleh AU - Santos, José AU - Amaro, Pedro AU - Jänkälä, Kari AU - Fratini, Filippo ID - 1811 IS - 5 JF - Journal of Mathematical Physics TI - Analytical evaluation of atomic form factors: Application to Rayleigh scattering VL - 56 ER - TY - JOUR AB - We develop a microscopic theory describing a quantum impurity whose rotational degree of freedom is coupled to a many-particle bath. We approach the problem by introducing the concept of an “angulon”—a quantum rotor dressed by a quantum field—and reveal its quasiparticle properties using a combination of variational and diagrammatic techniques. Our theory predicts renormalization of the impurity rotational structure, such as that observed in experiments with molecules in superfluid helium droplets, in terms of a rotational Lamb shift induced by the many-particle environment. Furthermore, we discover a rich many-body-induced fine structure, emerging in rotational spectra due to a redistribution of angular momentum within the quantum many-body system. AU - Schmidt, Richard AU - Lemeshko, Mikhail ID - 1813 IS - 20 JF - Physical Review Letters TI - Rotation of quantum impurities in the presence of a many-body environment VL - 114 ER - TY - JOUR AU - Gupta, Ashutosh AU - Henzinger, Thomas A ID - 1808 IS - 2 JF - ACM Transactions on Modeling and Computer Simulation TI - Guest editors' introduction to special issue on computational methods in systems biology VL - 25 ER - TY - JOUR AB - Vertebrates have a unique 3D body shape in which correct tissue and organ shape and alignment are essential for function. For example, vision requires the lens to be centred in the eye cup which must in turn be correctly positioned in the head. Tissue morphogenesis depends on force generation, force transmission through the tissue, and response of tissues and extracellular matrix to force. Although a century ago D'Arcy Thompson postulated that terrestrial animal body shapes are conditioned by gravity, there has been no animal model directly demonstrating how the aforementioned mechano-morphogenetic processes are coordinated to generate a body shape that withstands gravity. Here we report a unique medaka fish (Oryzias latipes) mutant, hirame (hir), which is sensitive to deformation by gravity. hir embryos display a markedly flattened body caused by mutation of YAP, a nuclear executor of Hippo signalling that regulates organ size. We show that actomyosin-mediated tissue tension is reduced in hir embryos, leading to tissue flattening and tissue misalignment, both of which contribute to body flattening. By analysing YAP function in 3D spheroids of human cells, we identify the Rho GTPase activating protein ARHGAP18 as an effector of YAP in controlling tissue tension. Together, these findings reveal a previously unrecognised function of YAP in regulating tissue shape and alignment required for proper 3D body shape. Understanding this morphogenetic function of YAP could facilitate the use of embryonic stem cells to generate complex organs requiring correct alignment of multiple tissues. AU - Porazinski, Sean AU - Wang, Huijia AU - Asaoka, Yoichi AU - Behrndt, Martin AU - Miyamoto, Tatsuo AU - Morita, Hitoshi AU - Hata, Shoji AU - Sasaki, Takashi AU - Krens, Gabriel AU - Osada, Yumi AU - Asaka, Satoshi AU - Momoi, Akihiro AU - Linton, Sarah AU - Miesfeld, Joel AU - Link, Brian AU - Senga, Takeshi AU - Castillo Morales, Atahualpa AU - Urrutia, Araxi AU - Shimizu, Nobuyoshi AU - Nagase, Hideaki AU - Matsuura, Shinya AU - Bagby, Stefan AU - Kondoh, Hisato AU - Nishina, Hiroshi AU - Heisenberg, Carl-Philipp J AU - Furutani Seiki, Makoto ID - 1817 IS - 7551 JF - Nature TI - YAP is essential for tissue tension to ensure vertebrate 3D body shape VL - 521 ER - TY - CONF AB - We consider partially observable Markov decision processes (POMDPs) with a set of target states and every transition is associated with an integer cost. The optimization objec- tive we study asks to minimize the expected total cost till the target set is reached, while ensuring that the target set is reached almost-surely (with probability 1). We show that for integer costs approximating the optimal cost is undecidable. For positive costs, our results are as follows: (i) we establish matching lower and upper bounds for the optimal cost and the bound is double exponential; (ii) we show that the problem of approximating the optimal cost is decidable and present ap- proximation algorithms developing on the existing algorithms for POMDPs with finite-horizon objectives. While the worst- case running time of our algorithm is double exponential, we present efficient stopping criteria for the algorithm and show experimentally that it performs well in many examples. AU - Chatterjee, Krishnendu AU - Chmelik, Martin AU - Gupta, Raghav AU - Kanodia, Ayush ID - 1820 T2 - Proceedings of the Twenty-Ninth AAAI Conference on Artificial Intelligence TI - Optimal cost almost-sure reachability in POMDPs VL - 5 ER - TY - JOUR AB - We present an efficient wavefront tracking algorithm for animating bodies of water that interact with their environment. Our contributions include: a novel wavefront tracking technique that enables dispersion, refraction, reflection, and diffraction in the same simulation; a unique multivalued function interpolation method that enables our simulations to elegantly sidestep the Nyquist limit; a dispersion approximation for efficiently amplifying the number of simulated waves by several orders of magnitude; and additional extensions that allow for time-dependent effects and interactive artistic editing of the resulting animation. Our contributions combine to give us multitudes more wave details than similar algorithms, while maintaining high frame rates and allowing close camera zooms. AU - Jeschke, Stefan AU - Wojtan, Christopher J ID - 1814 IS - 3 JF - ACM Transactions on Graphics TI - Water wave animation via wavefront parameter interpolation VL - 34 ER - TY - JOUR AB - Why do species not adapt to ever-wider ranges of conditions, gradually expanding their ecological niche and geographic range? Gene flow across environments has two conflicting effects: although it increases genetic variation, which is a prerequisite for adaptation, gene flow may swamp adaptation to local conditions. In 1956, Haldane proposed that, when the environment varies across space, "swamping" by gene flow creates a positive feedback between low population size and maladaptation, leading to a sharp range margin. However, current deterministic theory shows that, when variance can evolve, there is no such limit. Using simple analytical tools and simulations, we show that genetic drift can generate a sharp margin to a species' range, by reducing genetic variance below the level needed for adaptation to spatially variable conditions. Aided by separation of ecological and evolutionary timescales, the identified effective dimensionless parameters reveal a simple threshold that predicts when adaptation at the range margin fails. Two observable parameters determine the threshold: (i) the effective environmental gradient, which can be measured by the loss of fitness due to dispersal to a different environment; and (ii) the efficacy of selection relative to genetic drift. The theory predicts sharp range margins even in the absence of abrupt changes in the environment. Furthermore, it implies that gradual worsening of conditions across a species' habitat may lead to a sudden range fragmentation, when adaptation to a wide span of conditions within a single species becomes impossible. AU - Polechova, Jitka AU - Barton, Nicholas H ID - 1818 IS - 20 JF - PNAS TI - Limits to adaptation along environmental gradients VL - 112 ER - TY - JOUR AB - The sessile life style of plants creates the need to deal with an often adverse environment, in which water availability can change on a daily basis, challenging the cellular physiology and integrity. Changes in osmotic conditions disrupt the equilibrium of the plasma membrane: hypoosmotic conditions increase and hyperosmotic environment decrease the cell volume. Here, we show that short-term extracellular osmotic treatments are closely followed by a shift in the balance between endocytosis and exocytosis in root meristem cells. Acute hyperosmotic treatments (ionic and nonionic) enhance clathrin-mediated endocytosis simultaneously attenuating exocytosis, whereas hypoosmotic treatments have the opposite effects. In addition to clathrin recruitment to the plasma membrane, components of early endocytic trafficking are essential during hyperosmotic stress responses. Consequently, growth of seedlings defective in elements of clathrin or early endocytic machinery is more sensitive to hyperosmotic treatments. We also found that the endocytotic response to a change of osmotic status in the environment is dominant over the presumably evolutionary more recent regulatory effect of plant hormones, such as auxin. These results imply that osmotic perturbation influences the balance between endocytosis and exocytosis acting through clathrin-mediated endocytosis. We propose that tension on the plasma membrane determines the addition or removal of membranes at the cell surface, thus preserving cell integrity. AU - Zwiewka, Marta AU - Nodzyński, Tomasz AU - Robert, Stéphanie AU - Vanneste, Steffen AU - Friml, Jiřĺ ID - 1819 IS - 8 JF - Molecular Plant TI - Osmotic stress modulates the balance between exocytosis and clathrin mediated endocytosis in Arabidopsis thaliana VL - 8 ER -