1,630 research outputs found

    CRISPR RNA-guided activation of endogenous human genes

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    Catalytically inactive CRISPR-associated 9 nuclease (dCas9) can be directed by short guide RNAs (gRNAs) to repress endogenous genes in bacteria and human cells. Here we show that a dCas9-VP64 transcriptional activation domain fusion protein can be directed by single or multiple gRNAs to increase expression of specific endogenous human genes. These results provide an important proof-of-principle that CRISPR-Cas systems can be used to target heterologous effector domains in human cells

    Duality and Braiding in Twisted Quantum Field Theory

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    We re-examine various issues surrounding the definition of twisted quantum field theories on flat noncommutative spaces. We propose an interpretation based on nonlocal commutative field redefinitions which clarifies previously observed properties such as the formal equivalence of Green's functions in the noncommutative and commutative theories, causality, and the absence of UV/IR mixing. We use these fields to define the functional integral formulation of twisted quantum field theory. We exploit techniques from braided tensor algebra to argue that the twisted Fock space states of these free fields obey conventional statistics. We support our claims with a detailed analysis of the modifications induced in the presence of background magnetic fields, which induces additional twists by magnetic translation operators and alters the effective noncommutative geometry seen by the twisted quantum fields. When two such field theories are dual to one another, we demonstrate that only our braided physical states are covariant under the duality.Comment: 35 pages; v2: Typos correcte

    Motion in Quantum Gravity

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    We tackle the question of motion in Quantum Gravity: what does motion mean at the Planck scale? Although we are still far from a complete answer we consider here a toy model in which the problem can be formulated and resolved precisely. The setting of the toy model is three dimensional Euclidean gravity. Before studying the model in detail, we argue that Loop Quantum Gravity may provide a very useful approach when discussing the question of motion in Quantum Gravity.Comment: 30 pages, to appear in the book "Mass and Motion in General Relativity", proceedings of the C.N.R.S. School in Orleans, France, eds. L. Blanchet, A. Spallicci and B. Whitin

    Lineage-based identification of cellular states and expression programs

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    We present a method, LineageProgram, that uses the developmental lineage relationship of observed gene expression measurements to improve the learning of developmentally relevant cellular states and expression programs. We find that incorporating lineage information allows us to significantly improve both the predictive power and interpretability of expression programs that are derived from expression measurements from in vitro differentiation experiments. The lineage tree of a differentiation experiment is a tree graph whose nodes describe all of the unique expression states in the input expression measurements, and edges describe the experimental perturbations applied to cells. Our method, LineageProgram, is based on a log-linear model with parameters that reflect changes along the lineage tree. Regularization with L1 that based methods controls the parameters in three distinct ways: the number of genes change between two cellular states, the number of unique cellular states, and the number of underlying factors responsible for changes in cell state. The model is estimated with proximal operators to quickly discover a small number of key cell states and gene sets. Comparisons with existing factorization, techniques, such as singular value decomposition and non-negative matrix factorization show that our method provides higher predictive power in held, out tests while inducing sparse and biologically relevant gene sets.National Institutes of Health (U.S.) (P01-NS055923)National Institutes of Health (U.S.) (1-UL1-RR024920

    A Note on B-observables in Ponzano-Regge 3d Quantum Gravity

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    We study the insertion and value of metric observables in the (discrete) path integral formulation of the Ponzano-Regge spinfoam model for 3d quantum gravity. In particular, we discuss the length spectrum and the relation between insertion of such B-observables and gauge fixing in the path integral.Comment: 17 page
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