Lorentzian Threads as Gatelines and Holographic Complexity

The continuous min flow-max cut principle is used to reformulate the "complexity=volume" conjecture using Lorentzian flows-divergenceless norm-bounded timelike vector fields whose minimum flux through a boundary subregion is equal to the volume of the homologous maximal bulk Cauchy slice. The nesting property is used to show the rate of complexity is bounded below by "conditional complexity," describing a multistep optimization with intermediate and final target states. Conceptually, discretized Lorentzian flows are interpreted in terms of threads or gatelines such that complexity is equal to the minimum number of gatelines used to prepare a conformal field theory (CFT) state by an optimal tensor network (TN) discretizing the state. We propose a refined measure of complexity, capturing the role of suboptimal TNs, as an ensemble average. The bulk symplectic potential provides a "canonical" thread configuration characterizing perturbations around arbitrary CFT states. Its consistency requires the bulk to obey linearized Einstein's equations, which are shown to be equivalent to the holographic first law of complexity, thereby advocating a notion of "spacetime complexity.

Computing spacetime

Inspired by the universality of computation, we advocate for a principle of spacetime complexity, where gravity arises as a consequence of spacetime optimizing the computational cost of its own quantum dynamics. This principle is explicitly realized in the context of the Anti-de Sitter/Conformal Field Theory correspondence, where complexity is naturally understood in terms of state preparation via Euclidean path integrals, and Einstein's equations emerge from the laws of quantum complexity. We visualize spacetime complexity using Lorentzian threads which, conceptually, represent the operations needed to prepare a quantum state in a tensor network discretizing spacetime. Thus, spacetime itself evolves via optimized computation.Comment: 9 pages, 2 figures, Received honorable mention for the 2022 Essay Competition of the Gravity Research Foundation; References added, to appear in the October 2022 Special Issue of the International Journal of Modern Physics

PP-Wave / CFT_2 Duality

We investigate the pp-wave limit of the AdS_3\times S^3\times K3 compactification of Type IIB string theory from the point of view of the dual Sym_N(K3) CFT. It is proposed that a fundamental string in this pp-wave geometry is dual to the c=6 effective string of the Sym_N(K3) CFT, with the string bits of the latter being composed of twist operators. The massive fundamental string oscillators correspond to certain twisted Virasoro generators in the effective string. It is shown that both the ground states and the genus expansion parameter (at least in the orbifold limit of the CFT) coincide. Surprisingly the latter scales like J^2/N rather than the J^4/N^2 which might have been expected. We demonstrate a leading-order agreement between the pp-wave and CFT particle spectra. For a degenerate special case (one NS 5-brane) an intriguing complete agreement is found.Comment: JHEP3 LaTeX, 20 pages; discussion of WZW levels clarified, reference adde

NCS-1 Inhibits insulin stimulated GLUT4 translocation in 3T3L1 adipocytes through a phosphatidylinositol 4-kinase dependent pathway

Expression of NCS-1 (neuronal calcium sensor-1, also termed frequenin) in 3T3L1 adipocytes strongly inhibited insulin-stimulated translocation of GLUT4 and insulin-responsive aminopeptidase. The effect of NCS-1 was specific for GLUT4 and the insulin-responsive aminopeptidase translocation as there was no effect on the trafficking of the cation-independent mannose 6-phosphate receptor or the GLUT1 glucose transporter isoform. Moreover, NCS-1 showed partial colocalization with GLUT4-EGFP in the perinuclear region. The inhibitory action of NCS-1 was independent of calcium sequestration since neither treatment with ionomycin nor endothelin-1, both of which elevated the intracellular calcium concentration, restored insulin-stimulated GLUT4 translocation. Furthermore, NCS-1 did not alter the insulin-stimulated protein kinase B (PKB/Akt) phosphorylation or the recruitment of Cbl to the plasma membrane. In contrast, expression of the NCS-1 effector phosphatidylinositol 4-kinase (PI 4-kinase) inhibited insulin-stimulated GLUT4 translocation, whereas co-transfection with an inactive PI 4-kinase mutant prevented the NCS-1-induced inhibition. These data demonstrate that PI 4-kinase functions to negatively regulate GLUT4 translocation through its interaction with NCS-1

Fabular: regression formulas as probabilistic programming

Regression formulas are a domain-specific language adopted by several R packages for describing an important and useful class of statistical models: hierarchical linear regressions. Formulas are succinct, expressive, and clearly popular, so are they a useful addition to probabilistic programming languages? And what do they mean? We propose a core calculus of hierarchical linear regression, in which regression coefficients are themselves defined by nested regressions (unlike in R). We explain how our calculus captures the essence of the formula DSL found in R. We describe the design and implementation of Fabular, a version of the Tabular schema-driven probabilistic programming language, enriched with formulas based on our regression calculus. To the best of our knowledge, this is the first formal description of the core ideas of R's formula notation, the first development of a calculus of regression formulas, and the first demonstration of the benefits of composing regression formulas and latent variables in a probabilistic programming language.Adam Ścibior received travel support from the DARPA PPAML programme. Marcin Szymczak was supported by Microsoft Research through its PhD Scholarship Programme.This is the author accepted manuscript. The final version is available from the Association of Computer Machinery via http://dx.doi.org/10.1145/2837614.283765

Characterization of Antibodies against Receptor Activity-Modifying Protein 1 (RAMP1): A Cautionary Tale

Calcitonin gene-related peptide (CGRP) is a key component of migraine pathophysiology, yielding effective migraine therapeutics. CGRP receptors contain a core accessory protein subunit: receptor activity-modifying protein 1 (RAMP1). Understanding of RAMP1 expression is incomplete, partly due to the challenges in identifying specific and validated antibody tools. We profiled antibodies for immunodetection of RAMP1 using Western blotting, immunocytochemistry and immunohistochemistry, including using RAMP1 knockout mouse tissue. Most antibodies could detect RAMP1 in Western blotting and immunocytochemistry using transfected cells. Two antibodies (844, ab256575) could detect a RAMP1-like band in Western blots of rodent brain but not RAMP1 knockout mice. However, cross-reactivity with other proteins was evident for all antibodies. This cross-reactivity prevented clear conclusions about RAMP1 anatomical localization, as each antibody detected a distinct pattern of immunoreactivity in rodent brain. We cannot confidently attribute immunoreactivity produced by RAMP1 antibodies (including 844) to the presence of RAMP1 protein in immunohistochemical applications in brain tissue. RAMP1 expression in brain and other tissues therefore needs to be revisited using RAMP1 antibodies that have been comprehensively validated using multiple strategies to establish multiple lines of convincing evidence. As RAMP1 is important for other GPCR/ligand pairings, our results have broader significance beyond the CGRP field

The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission

1Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin and glutathione (GSH) systems that are thought to play a major role as antioxidants during blood stage infection. In this report, we analyzed a critical component of the GSH biosynthesis pathway using reverse genetics. Plasmodium berghei parasites lacking expression of gamma-glutamylcysteine synthetase (γ-GCS), the rate limiting enzyme in de novo synthesis of GSH, were generated through targeted gene disruption thus demonstrating, quite unexpectedly, that γ-GCS is not essential for blood stage development. Despite a significant reduction in GSH levels, blood stage forms of pbggcs− parasites showed only a defect in growth as compared to wild type. In contrast, a dramatic effect on development of the parasites in the mosquito was observed. Infection of mosquitoes with pbggcs− parasites resulted in reduced numbers of stunted oocysts that did not produce sporozoites. These results have important implications for the design of drugs aiming at interfering with the GSH redox-system in blood stages and demonstrate that de novo synthesis of GSH is pivotal for development of Plasmodium in the mosquito