TY - JOUR AB - We study chains of lattice ideals that are invariant under a symmetric group action. In our setting, the ambient rings for these ideals are polynomial rings which are increasing in (Krull) dimension. Thus, these chains will fail to stabilize in the traditional commutative algebra sense. However, we prove a theorem which says that “up to the action of the group”, these chains locally stabilize. We also give an algorithm, which we have implemented in software, for explicitly constructing these stabilization generators for a family of Laurent toric ideals involved in applications to algebraic statistics. We close with several open problems and conjectures arising from our theoretical and computational investigations. AU - Hillar, Christopher J. AU - Martin del Campo Sanchez, Abraham ID - 5920 JF - Journal of Symbolic Computation SN - 0747-7171 TI - Finiteness theorems and algorithms for permutation invariant chains of Laurent lattice ideals VL - 50 ER - TY - JOUR AB - We present two methods for the precise independent focusing of orthogonal linear polarizations of light at arbitrary relative locations. Our first scheme uses a displaced lens in a polarization Sagnac interferometer to provide adjustable longitudinal and lateral focal displacements via simple geometry; the second uses uniaxial crystals to achieve the same effect in a compact collinear setup. We develop the theoretical applications and limitations of our schemes, and provide experimental confirmation of our calculations. AU - Schmid, David AU - Huang, Ting-Yu AU - Hazrat, Shiraz AU - Dirks, Radhika AU - Onur Hosten AU - Quint, Stephan AU - Thian, Dickson AU - Kwiat, Paul G ID - 591 IS - 13 JF - Optics Express TI - Adjustable and robust methods for polarization-dependent focusing VL - 21 ER - TY - JOUR AU - Bernecky, Carrie A AU - Cramer, Patrick ID - 595 IS - 6 JF - EMBO Journal TI - Struggling to let go: A non-coding RNA directs its own extension and destruction VL - 32 ER - TY - JOUR AB - Different interoceptive systems must be integrated to ensure that multiple homeostatic insults evoke appropriate behavioral and physiological responses. Little is known about how this is achieved. Using C. elegans, we dissect cross-modulation between systems that monitor temperature, O2 and CO2. CO2 is less aversive to animals acclimated to 15°C than those grown at 22°C. This difference requires the AFD neurons, which respond to both temperature and CO2 changes. CO2 evokes distinct AFD Ca2+ responses in animals acclimated at 15°C or 22°C. Mutants defective in synaptic transmission can reprogram AFD CO2 responses according to temperature experience, suggesting reprogramming occurs cell autonomously. AFD is exquisitely sensitive to CO2. Surprisingly, gradients of 0.01% CO2/second evoke very different Ca2+ responses from gradients of 0.04% CO2/second. Ambient O2 provides further contextual modulation of CO2 avoidance. At 21% O2 tonic signalling from the O2-sensing neuron URX inhibits CO2 avoidance. This inhibition can be graded according to O2 levels. In a natural wild isolate, a switch from 21% to 19% O2 is sufficient to convert CO2 from a neutral to an aversive cue. This sharp tuning is conferred partly by the neuroglobin GLB-5. The modulatory effects of O2 on CO2 avoidance involve the RIA interneurons, which are post-synaptic to URX and exhibit CO2-evoked Ca2+ responses. Ambient O2 and acclimation temperature act combinatorially to modulate CO2 responsiveness. Our work highlights the integrated architecture of homeostatic responses in C. elegans. AU - Kodama-Namba, Eiji AU - Fenk, Lorenz A. AU - Bretscher, Andrew J. AU - Gross, Einav AU - Busch, K. Emanuel AU - de Bono, Mario ID - 6128 IS - 12 JF - PLoS Genetics SN - 1553-7404 TI - Cross-modulation of homeostatic responses to temperature, oxygen and carbon dioxide in C. elegans VL - 9 ER - TY - JOUR AB - Cas9 is an RNA-guided double-stranded DNA nuclease that participates in clustered regularly interspaced short palindromic repeats (CRISPR)-mediated adaptive immunity in prokaryotes. CRISPR–Cas9 has recently been used to generate insertion and deletion mutations in Caenorhabditis elegans, but not to create tailored changes (knock-ins). We show that the CRISPR–CRISPR-associated (Cas) system can be adapted for efficient and precise editing of the C. elegans genome. The targeted double-strand breaks generated by CRISPR are substrates for transgene-instructed gene conversion. This allows customized changes in the C. elegans genome by homologous recombination: sequences contained in the repair template (the transgene) are copied by gene conversion into the genome. The possibility to edit the C. elegans genome at selected locations will facilitate the systematic study of gene function in this widely used model organism. AU - Chen, Changchun AU - Fenk, Lorenz A. AU - de Bono, Mario ID - 6130 IS - 20 JF - Nucleic Acids Research SN - 1362-4962 TI - Efficient genome editing in Caenorhabditis elegans by CRISPR-targeted homologous recombination VL - 41 ER - TY - JOUR AB - cGMP signaling is widespread in the nervous system. However, it has proved difficult to visualize and genetically probe endogenously evoked cGMP dynamics in neurons in vivo. Here, we combine cGMP and Ca2+ biosensors to image and dissect a cGMP signaling network in a Caenorhabditis elegans oxygen-sensing neuron. We show that a rise in O2 can evoke a tonic increase in cGMP that requires an atypical O2-binding soluble guanylate cyclase and that is sustained until oxygen levels fall. Increased cGMP leads to a sustained Ca2+ response in the neuron that depends on cGMP-gated ion channels. Elevated levels of cGMP and Ca2+ stimulate competing negative feedback loops that shape cGMP dynamics. Ca2+-dependent negative feedback loops, including activation of phosphodiesterase-1 (PDE-1), dampen the rise of cGMP. A different negative feedback loop, mediated by phosphodiesterase-2 (PDE-2) and stimulated by cGMP-dependent kinase (PKG), unexpectedly promotes cGMP accumulation following a rise in O2, apparently by keeping in check gating of cGMP channels and limiting activation of Ca2+-dependent negative feedback loops. Simultaneous imaging of Ca2+ and cGMP suggests that cGMP levels can rise close to cGMP channels while falling elsewhere. O2-evoked cGMP and Ca2+ responses are highly reproducible when the same neuron in an individual animal is stimulated repeatedly, suggesting that cGMP transduction has high intrinsic reliability. However, responses vary substantially across individuals, despite animals being genetically identical and similarly reared. This variability may reflect stochastic differences in expression of cGMP signaling components. Our work provides in vivo insights into the architecture of neuronal cGMP signaling. AU - Couto, A. AU - Oda, S. AU - Nikolaev, V. O. AU - Soltesz, Z. AU - de Bono, Mario ID - 6133 IS - 35 JF - Proceedings of the National Academy of Sciences SN - 0027-8424 TI - In vivo genetic dissection of O2-evoked cGMP dynamics in a Caenorhabditis elegans gas sensor VL - 110 ER - TY - JOUR AB - Many organisms have stress response pathways, components of which share homology with players in complex human disease pathways. Research on stress response in the nematode worm Caenorhabditis elegans has provided detailed insights into the genetic and molecular mechanisms underlying complex human diseases. In this review we focus on four different types of environmental stress responses – heat shock, oxidative stress, hypoxia, and osmotic stress – and on how these can be used to study the genetics of complex human diseases. All four types of responses involve the genetic machineries that underlie a number of complex human diseases such as cancer and neurodegenerative diseases, including Alzheimer's and Parkinson's. We highlight the types of stress response experiments required to detect the genes and pathways underlying human disease and suggest that studying stress biology in worms can be translated to understanding human disease and provide potential targets for drug discovery. AU - Rodriguez, Miriam AU - Snoek, L. Basten AU - de Bono, Mario AU - Kammenga, Jan E. ID - 6135 IS - 6 JF - Trends in Genetics SN - 0168-9525 TI - Worms under stress: C. elegans stress response and its relevance to complex human disease and aging VL - 29 ER - TY - CHAP AU - de Bono, Mario AU - Schafer, W.R. AU - Gottschalk, A. ED - Hegemann, Peter ED - Sigrist, Stephan ID - 6132 SN - 9783110270723; 9783110270716 T2 - Optogenetics TI - Optogenetic actuation, inhibition, modulation and readout for neuronal networks generating behavior in the nematode Caenorhabditis elegans ER - TY - JOUR AB - The molecular and supramolecular origins of the superior nonlinear optical (NLO) properties observed in the organic phenolic triene material, OH1 (2-(3-(4-hydroxystyryl)-5,5-dimethylcyclohex-2-enylidene)malononitrile), are presented. The molecular charge-transfer distribution is topographically mapped, demonstrating that a uniformly delocalized passive electronic medium facilitates the charge-transfer between the phenolic electron donor and the cyano electron acceptors which lie at opposite ends of the molecule. Its ability to act as a “push–pull” π-conjugated molecule is quantified, relative to similar materials, by supporting empirical calculations; these include bond-length alternation and harmonic-oscillator stabilization energy (HOSE) tests. Such tests, together with frontier molecular orbital considerations, reveal that OH1 can exist readily in its aromatic (neutral) or quinoidal (charge-separated) state, thereby overcoming the “nonlinearity-thermal stability trade-off”. The HOSE calculation also reveals a correlation between the quinoidal resonance contribution to the overall structure of OH1 and the UV–vis absorption peak wavelength in the wider family of configurationally locked polyene framework materials. Solid-state tensorial coefficients of the molecular dipole, polarizability, and the first hyperpolarizability for OH1 are derived from the first-, second-, and third-order electronic moments of the experimental charge-density distribution. The overall solid-state molecular dipole moment is compared with those from gas-phase calculations, revealing that crystal field effects are very significant in OH1. The solid-state hyperpolarizability derived from this charge-density study affords good agreement with gas-phase calculations as well as optical measurements based on hyper-Rayleigh scattering (HRS) and electric-field-induced second harmonic (EFISH) generation. This lends support to the further use of charge-density studies to calculate solid-state hyperpolarizability coefficients in other organic NLO materials. Finally, this charge-density study is also employed to provide an advanced classification of hydrogen bonds in OH1, which requires more stringent criteria than those from conventional structure analysis. As a result, only the strongest OH···NC interaction is so classified as a true hydrogen bond. Indeed, it is this electrostatic interaction that influences the molecular charge transfer: the other four, weaker, nonbonded contacts nonetheless affect the crystal packing. Overall, the establishment of these structure–property relationships lays a blueprint for designing further, more NLO efficient, materials in this industrially leading organic family of compounds. AU - Lin, Tze-Chia AU - Cole, Jacqueline M. AU - Higginbotham, Andrew P AU - Edwards, Alison J. AU - Piltz, Ross O. AU - Pérez-Moreno, Javier AU - Seo, Ji-Youn AU - Lee, Seung-Chul AU - Clays, Koen AU - Kwon, O-Pil ID - 6370 IS - 18 JF - The Journal of Physical Chemistry C SN - 1932-7447 TI - Molecular origins of the high-performance nonlinear optical susceptibility in a phenolic polyene chromophore: Electron density distributions, hydrogen bonding, and ab initio calculations VL - 117 ER - TY - GEN AB - In order to guarantee that each method of a data structure updates the logical state exactly once, al-most all non-blocking implementations employ Compare-And-Swap (CAS) based synchronization. For FIFO queue implementations this translates into concurrent enqueue or dequeue methods competing among themselves to update the same variable, the tail or the head, respectively, leading to high contention and poor scalability. Recent non-blocking queue implementations try to alleviate high contentionby increasing the number of contention points, all the while using CAS-based synchronization. Furthermore, obtaining a wait-free implementation with competition is achieved by additional synchronization which leads to further degradation of performance.In this paper we formalize the notion of competitiveness of a synchronizing statement which can beused as a measure for the scalability of concurrent implementations. We present a new queue implementation, the Speculative Pairing (SP) queue, which, as we show, decreases competitiveness by using Fetch-And-Increment (FAI) instead of CAS. We prove that the SP queue is linearizable and lock-free.We also show that replacing CAS with FAI leads to wait-freedom for dequeue methods without an adverse effect on performance. In fact, our experiments suggest that the SP queue can perform and scale better than the state-of-the-art queue implementations. AU - Henzinger, Thomas A AU - Payer, Hannes AU - Sezgin, Ali ID - 6440 SN - 2664-1690 TI - Replacing competition with cooperation to achieve scalable lock-free FIFO queues ER -