768 research outputs found

    Quiver Structure of Heterotic Moduli

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    We analyse the vector bundle moduli arising from generic heterotic compactifications from the point of view of quiver representations. Phenomena such as stability walls, crossing between chambers of supersymmetry, splitting of non-Abelian bundles and dynamic generation of D-terms are succinctly encoded into finite quivers. By studying the Poincar\'e polynomial of the quiver moduli space using the Reineke formula, we can learn about such useful concepts as Donaldson-Thomas invariants, instanton transitions and supersymmetry breaking.Comment: 38 pages, 5 figures, 1 tabl

    Heterologous expression screens in Nicotiana benthamiana identify a candidate effector of the wheat Yellow Rust Pathogen that associates with processing bodies

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    Rust fungal pathogens of wheat (Triticum spp.) affect crop yields worldwide. The molecular mechanisms underlying the virulence of these pathogens remain elusive, due to the limited availability of suitable molecular genetic research tools. Notably, the inability to perform high-throughput analyses of candidate virulence proteins (also known as effectors) impairs progress. We previously established a pipeline for the fast-forward screens of rust fungal candidate effectors in the model plant Nicotiana benthamiana. This pipeline involves selecting candidate effectors in silico and performing cell biology and protein-protein interaction assays in planta to gain insight into the putative functions of candidate effectors. In this study, we used this pipeline to identify and characterize sixteen candidate effectors from the wheat yellow rust fungal pathogen Puccinia striiformis f sp tritici. Nine candidate effectors targeted a specific plant subcellular compartment or protein complex, providing valuable information on their putative functions in plant cells. One candidate effector, PST02549, accumulated in processing bodies (P-bodies), protein complexes involved in mRNA decapping, degradation, and storage. PST02549 also associates with the P-body-resident ENHANCER OF mRNA DECAPPING PROTEIN 4 (EDC4) from N. benthamiana and wheat. We propose that P-bodies are a novel plant cell compartment targeted by pathogen effectors

    Room temperature triplet state spectroscopy of organic semiconductors

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    Organic light-emitting devices and solar cells are devices that create, manipulate, and convert excited states in organic semiconductors. It is crucial to characterize these excited states, or excitons, to optimize device performance in applications like displays and solar energy harvesting. This is complicated if the excited state is a triplet because the electronic transition is ‘dark’ with a vanishing oscillator strength. As a consequence, triplet state spectroscopy must usually be performed at cryogenic temperatures to reduce competition from non-radiative rates. Here, we control non-radiative rates by engineering a solid-state host matrix containing the target molecule, allowing the observation of phosphorescence at room temperature and alleviating constraints of cryogenic experiments. We test these techniques on a wide range of materials with functionalities spanning multi-exciton generation (singlet exciton fission), organic light emitting device host materials, and thermally activated delayed fluorescence type emitters. Control of non-radiative modes in the matrix surrounding a target molecule may also have broader applications in light-emitting and photovoltaic devices.United States. Dept. of Energy. Center for Excitonics (Award DE-SC0001088

    Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

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    The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation

    How to Compute Worst-Case Execution Time by Optimization Modulo Theory and a Clever Encoding of Program Semantics

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    International audienceIn systems with hard real-time constraints, it is necessary to compute upper bounds on the worst-case execution time (WCET) of programs; the closer the bound to the real WCET, the better. This is especially the case of synchronous reactive control loops with a fixed clock; the WCET of the loop body must not exceed the clock period. We compute the WCET (or at least a close upper bound thereof) as the solution of an optimization modulo theory problem that takes into account the semantics of the program, in contrast to other methods that compute the longest path whether or not it is feasible according to these semantics. Optimization modulo theory extends satisfiability modulo theory (SMT) to maximization problems. Immediate encodings of WCET problems into SMT yield formulas intractable for all current production-grade solvers; this is inherent to the DPLL(T) approach to SMT implemented in these solvers. By conjoining some appropriate "cuts" to these formulas, we considerably reduce the computation time of the SMT-solver. We experimented our approach on a variety of control programs, using the OTAWA analyzer both as baseline and as underlying microarchitectural analysis for our analysis, and show notable improvement on the WCET bound on a variety of benchmarks and control programs

    Strongly exchange-coupled triplet pairs in an organic semiconductor

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    From biological complexes to devices based on organic semiconductors, spin interactions play a key role in the function of molecular systems. For instance, triplet-pair reactions impact operation of organic light-emitting diodes as well as photovoltaic devices. Conventional models for triplet pairs assume they interact only weakly. Here, using electron spin resonance, we observe long-lived, strongly-interacting triplet pairs in an organic semiconductor, generated via singlet fission. Using coherent spin-manipulation of these two-triplet states, we identify exchange-coupled (spin-2) quintet complexes co-existing with weakly coupled (spin-1) triplets. We measure strongly coupled pairs with a lifetime approaching 3 µs and a spin coherence time approaching 1 µs, at 10 K. Our results pave the way for the utilization of high-spin systems in organic semiconductors.Gates-Cambridge Trust, Winton Programme for the Physics of Sustainability, Freie Universität Berlin within the Excellence Initiative of the German Research Foundation, Engineering and Physical Sciences Research Council (Grant ID: EP/G060738/1)This is the author accepted manuscript. The final version is available from Nature Publishing Group at http://dx.doi.org/10.1038/nphys3908

    Inhibition of autophagy, lysosome and VCP function impairs stress granule assembly

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    Stress granules (SGs) are mRNA-protein aggregates induced during stress, which accumulate in many neurodegenerative diseases. Previously, the autophagy-lysosome pathway and valosin-containing protein (VCP), key players of the protein quality control (PQC), were shown to regulate SG degradation. This is consistent with the idea that PQC may survey and/or assist SG dynamics. However, despite these observations, it is currently unknown whether the PQC actively participates in SG assembly. Here, we describe that inhibition of autophagy, lysosomes and VCP causes defective SG formation after induction. Silencing the VCP co-factors UFD1L and PLAA, which degrade defective ribosomal products (DRIPs) and 60S ribosomes, also impaired SG assembly. Intriguingly, DRIPs and 60S, which are released from disassembling polysomes and are normally excluded from SGs, were significantly retained within SGs in cells with impaired autophagy, lysosome or VCP function. Our results suggest that deregulated autophagy, lysosomal or VCP activities, which occur in several neurodegenerative (VCP-associated) diseases, may alter SG morphology and composition

    Nanooptics of molecular-shunted plasmonic nanojunctions.

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    Gold nanoparticles are separated above a planar gold film by 1.1 nm thick self-assembled molecular monolayers of different conductivities. Incremental replacement of the nonconductive molecules with a chemically equivalent conductive version differing by only one atom produces a strong 50 nm blue-shift of the coupled plasmon. With modeling this gives a conductance of 0.17G(0) per biphenyl-4,4'-dithiol molecule and a total conductance across the plasmonic junction of 30G(0). Our approach provides a reliable tool quantifying the number of molecules in each plasmonic hotspot, here <200.We acknowledge financial support from EPSRC grant EP/ G060649/1, EP/I012060/1, EP/L027151/1, EP/K028510/1, ERC grant LINASS 320503. F.B. acknowledges support from the Winton Programme for the Physics of Sustainability. C.T. and J.A. acknowledge financial support from Project FIS2013- 41184-P from MINECO, ETORTEK 2014-15 of the Basque Department of Industry and IT756-13 from the Basque consolidated groups.This paper was originally published in Nano Letters under a CC-BY licence (F Benz, C Tserkezis, LO Herrmann, B de Nijs, A Sanders, DO Sigle, L Pukenas, SD Evans, J Aizpurua, JJ Baumberg, Nano Letters 2015, 15, 669−674

    Whole-body tissue stabilization and selective extractions via tissue-hydrogel hybrids for high-resolution intact circuit mapping and phenotyping

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    To facilitate fine-scale phenotyping of whole specimens, we describe here a set of tissue fixation-embedding, detergent-clearing and staining protocols that can be used to transform excised organs and whole organisms into optically transparent samples within 1–2 weeks without compromising their cellular architecture or endogenous fluorescence. PACT (passive CLARITY technique) and PARS (perfusion-assisted agent release in situ) use tissue-hydrogel hybrids to stabilize tissue biomolecules during selective lipid extraction, resulting in enhanced clearing efficiency and sample integrity. Furthermore, the macromolecule permeability of PACT- and PARS-processed tissue hybrids supports the diffusion of immunolabels throughout intact tissue, whereas RIMS (refractive index matching solution) grants high-resolution imaging at depth by further reducing light scattering in cleared and uncleared samples alike. These methods are adaptable to difficult-to-image tissues, such as bone (PACT-deCAL), and to magnified single-cell visualization (ePACT). Together, these protocols and solutions enable phenotyping of subcellular components and tracing cellular connectivity in intact biological networks
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