Domain walls and instantons in N=1, d=4 supergravity

We study the supersymmetric sources of (multi-) domain-wall and (multi-) instanton solutions of generic N=1, d=4 supergravities, that is: the worldvolume effective actions for said supersymmetric topological defects. The domain-wall solutions naturally couple to the two 3-forms recently found as part of the N=1, d=4 tensor hierarchy (i.e. they have two charges in general) and their tension is the absolute value of the superpotential section L. The introduction of sources (we study sources with finite and vanishing thickness) is equivalent to the introduction of local coupling constants and results in dramatic changes of the solutions. Our results call for a democratic reformulation of N=1,d=4 supergravity in which coupling constants are, off-shell, scalar fields. The effective actions for the instantons are always proportional to the coordinate orthogonal to the twist-free embedding of the null-geodesic (in the Wick-rotated scalar manifold) describing the instanton. We show their supersymmetry and find the associated supersymmetric (multi-) instanton solutions.Comment: 34 pages, 4 figures, references adde

Hamiltonian analysis of BHT massive gravity

We study the Hamiltonian structure of the Bergshoeff-Hohm-Townsend (BHT) massive gravity with a cosmological constant. In the space of coupling constants $(\Lambda_0,m^2)$, our canonical analysis reveals the special role of the condition $\Lambda_0/m^2\neq-1$. In this sector, the dimension of the physical phase space is found to be $N^*=4$, which corresponds to two Lagrangian degree of freedom. When applied to the AdS asymptotic region, the canonical approach yields the conserved charges of the BTZ black hole, and central charges of the asymptotic symmetry algebra.Comment: LATEX, 21 pages; v2: minor correction

AdS Black Hole Solutions in the Extended New Massive Gravity

We have obtained (warped) AdS black hole solutions in the three dimensional extended new massive gravity. We investigate some properties of black holes and obtain central charges of the two dimensional dual CFT. To obtain the central charges, we use the relation between entropy and temperature according to the AdS/CFT dictionary. For AdS black holes, one can also use the central charge function formalism which leads to the same results.Comment: 24pages, some organization corrected, minor corrections, references added, final published versio

Holographic two-point functions for 4d log-gravity

We compute holographic one- and two-point functions of critical higher-curvature gravity in four dimensions. The two most important operators are the stress tensor and its logarithmic partner, sourced by ordinary massless and by logarithmic non-normalisable gravitons, respectively. In addition, the logarithmic gravitons source two ordinary operators, one with spin-one and one with spin-zero. The one-point function of the stress tensor vanishes for all Einstein solutions, but has a non-zero contribution from logarithmic gravitons. The two-point functions of all operators match the expectations from a three-dimensional logarithmic conformal field theory.Comment: 35 pages; v2: typos corrected, added reference; v3: shorter introduction, minor changes in the text in section 3, added reference; published versio

Warped black holes in 3D general massive gravity

We study regular spacelike warped black holes in the three dimensional general massive gravity model, which contains both the gravitational Chern-Simons term and the linear combination of curvature squared terms characterizing the new massive gravity besides the Einstein-Hilbert term. The parameters of the metric are found by solving a quartic equation constrained by an inequality that imposes the absence of closed timelike curves. Explicit expressions for the central charges are suggested by exploiting the fact that these black holes are discrete quotients of spacelike warped AdS(3) and a known formula for the entropy. Previous results obtained separately in topological massive gravity and in new massive gravity are recovered as special cases.Comment: 38 pages, 7 figures. v2: minor changes, added refs and an appendix on self-dual and null z-warped black hole

Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone

A boundary stress tensor for higher-derivative gravity in AdS and Lifshitz backgrounds

We investigate the Brown-York stress tensor for curvature-squared theories. This requires a generalized Gibbons-Hawking term in order to establish a well-posed variational principle, which is achieved in a universal way by reducing the number of derivatives through the introduction of an auxiliary tensor field. We examine the boundary stress tensor thus defined for the special case of `massive gravity' in three dimensions, which augments the Einstein-Hilbert term by a particular curvature-squared term. It is shown that one obtains finite results for physical parameters on AdS upon adding a `boundary cosmological constant' as a counterterm, which vanishes at the so-called chiral point. We derive known and new results, like the value of the central charges or the mass of black hole solutions, thereby confirming our prescription for the computation of the stress tensor. Finally, we inspect recently constructed Lifshitz vacua and a new black hole solution that is asymptotically Lifshitz, and we propose a novel and covariant counterterm for this case.Comment: 25 pages, 1 figure; v2: minor corrections, references added, to appear in JHE

Nonlinear Dynamics of 3D Massive Gravity

We explore the nonlinear classical dynamics of the three-dimensional theory of "New Massive Gravity" proposed by Bergshoeff, Hohm and Townsend. We find that the theory passes remarkably highly nontrivial consistency checks at the nonlinear level. In particular, we show that: (1) In the decoupling limit of the theory, the interactions of the helicity-0 mode are described by a single cubic term -- the so-called cubic Galileon -- previously found in the context of the DGP model and in certain 4D massive gravities. (2) The conformal mode of the metric coincides with the helicity-0 mode in the decoupling limit. Away from this limit the nonlinear dynamics of the former is described by a certain generalization of Galileon interactions, which like the Galileons themselves have a well-posed Cauchy problem. (3) We give a non-perturbative argument based on the presence of additional symmetries that the full theory does not lead to any extra degrees of freedom, suggesting that a 3D analog of the 4D Boulware-Deser ghost is not present in this theory. Last but not least, we generalize "New Massive Gravity" and construct a class of 3D cubic order massive models that retain the above properties.Comment: 21 page

Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set

BACKGROUND: A multi-cancer early detection (MCED) test used to complement existing screening could increase the number of cancers detected through population screening, potentially improving clinical outcomes. The Circulating Cell-free Genome Atlas study (CCGA; NCT02889978) was a prospective, case-controlled, observational study and demonstrated that a blood-based MCED test utilizing cell-free DNA (cfDNA) sequencing in combination with machine learning could detect cancer signals across multiple cancer types and predict cancer signal origin (CSO) with high accuracy. The objective of this third and final CCGA substudy was to validate an MCED test version further refined for use as a screening tool. PATIENTS AND METHODS: This pre-specified substudy included 4077 participants in an independent validation set (cancer: n = 2823; non-cancer: n = 1254, non-cancer status confirmed at year-one follow-up). Specificity, sensitivity, and CSO prediction accuracy were measured. RESULTS: Specificity for cancer signal detection was 99.5% [95% confidence interval (CI): 99.0% to 99.8%]. Overall sensitivity for cancer signal detection was 51.5% (49.6% to 53.3%); sensitivity increased with stage [stage I: 16.8% (14.5% to 19.5%), stage II: 40.4% (36.8% to 44.1%), stage III: 77.0% (73.4% to 80.3%), stage IV: 90.1% (87.5% to 92.2%)]. Stage I-III sensitivity was 67.6% (64.4% to 70.6%) in 12 pre-specified cancers that account for approximately two-thirds of annual USA cancer deaths and was 40.7% (38.7% to 42.9%) in all cancers. Cancer signals were detected across >50 cancer types. Overall accuracy of CSO prediction in true positives was 88.7% (87.0% to 90.2%). CONCLUSION: In this pre-specified, large-scale, clinical validation substudy, the MCED test demonstrated high specificity and accuracy of CSO prediction and detected cancer signals across a wide diversity of cancers. These results support the feasibility of this blood-based MCED test as a complement to existing single-cancer screening tests. CLINICAL TRIAL NUMBER: NCT02889978