Abstract:We construct the five-dimensional supergravity dual of the N = 1 * mass deformation of the N = 4 supersymmetric Yang-Mills theory on S 4 and use it to calculate the universal contribution to the corresponding S 4 free energy at large 't Hooft coupling in the planar limit. The holographic RG flow solutions are smooth and preserve four supercharges. As a novel feature compared to the holographic duals of N = 1 * on R 4 , in our backgrounds the five-dimensional dilaton has a non-trivial profile, and the gaugino condensate is fixed in terms of the mass-deformation parameters. Important aspects of the analysis involve characterizing the ambiguities in the partition function of non-conformal N = 1 supersymmetric theories on S 4 as well as the action of S-duality on the N = 1 * theory.

Mutagenesis screening is a powerful forward genetic approach that has been successfully applied in lower-model organisms to discover genetic factors for biological processes. This phenotype-based approach has yet to be established in vertebrates for probing major human diseases, largely because of the complexity of colony management. Herein, we report a rapid strategy for identifying genetic modifiers of cardiomyopathy (CM). Based on the application of doxorubicin stress to zebrafish insertional cardiac (ZIC) mutants, we identified 4 candidate CM-modifying genes, of which 3 have been linked previously to CM. The long isoform of DnaJ (Hsp40) homolog, subfamily B, member 6b (dnajb6b(L)) was identified as a CM susceptibility gene, supported by identification of rare variants in its human ortholog DNAJB6 from CM patients. Mechanistic studies indicated that the deleterious, loss-of-function modifying effects of dnajb6b(L) can be ameliorated by inhibition of ER stress. In contrast, overexpression of dnajb6(L) exerts cardioprotective effects on both fish and mouse CM models. Together, our findings establish a mutagenesis screening strategy that is scalable for systematic identification of genetic modifiers of CM, feasible to suggest therapeutic targets, and expandable to other major human diseases.

Motivated by the recent dilaton-based proof of the 4d a-theorem, we study the dilaton effective action for RG flows in d dimensions. When d is even, the action consists of a WessZumino (WZ) term, whose Weyl-variation encodes the trace-anomaly, plus all Weyl-invariants. For d odd, the action consists of Weyl-invariants only. We present explicit results for the flat-space limit of the dilaton effective action in d-dimensions up to and including 8-derivative terms. GJMS-operators from conformal geometry motivate a form of the action that unifies the Weyl-invariants and anomaly-terms into a compact general-d structure.A new feature in 8d is the presence of an 8-derivative Weyl-invariant that pollutes the O(p 8 )-contribution from the WZ action to the dilaton scattering amplitudes; this may challenge a dilaton-based proof of an a-theorem in 8d.We use the example of a free massive scalar for two purposes: 1) it allows us to confirm the structure of the d-dimensional dilaton effective action explicitly; we carry out this check for d = 3, 4, 5, . . . , 10; and 2) in 8d we demonstrate how the flow ∆a = a UV − a IR can be extracted systematically from the O(p 8 )-amplitudes despite the contamination from the 8-derivative Weylinvariant. This computation gives a value for the a-anomaly of the 8d free conformal scalar that is shown to match the value obtained from zeta-function regularization of the log-term in the free energy.arXiv:1209.3424v2 [hep-th]

Scattering amplitudes in 4d N = 4 super Yang-Mills theory (SYM) can be described by Grassmannian contour integrals whose form depends on whether the external data is encoded in momentum space, twistor space, or momentum twistor space. After a pedagogical review, we present a new, streamlined proof of the equivalence of the three integral formulations. A similar strategy allows us to derive a new Grassmannian integral for 3d N = 6 ABJM theory amplitudes in momentum twistor space: it is a contour integral in an orthogonal Grassmannian with the novel property that the internal metric depends on the external data. The result can be viewed as a central step towards developing an amplituhedron formulation for ABJM amplitudes. Various properties of Grassmannian integrals are examined, including boundary properties, pole structure, and a homological interpretation of the global residue theorems for N = 4 SYM.

Dilated cardiomyopathy (DCM) is a heritable, genetically heterogeneous disorder characterized by progressive heart failure. DCM typically remains clinically silent until adulthood, yet symptomatic disease can develop in childhood. We sought to identify the genetic basis of pediatric DCM in 15 sporadic and three affected-siblings cases, comprised of 21 affected children (mean age, five years) whose parents had normal echocardiograms (mean age, 39 years). Twelve underwent cardiac transplantation and five died with severe heart failure. Parent-offspring whole exome sequencing (WES) data were filtered for rare, deleterious, de novo and recessive variants. In prior work, we reported de novo mutations in TNNT2 and RRAGC and compound heterozygous mutations in ALMS1 and TAF1A among four cases in our cohort. Here, de novo mutations in established DCM genes—RBM20, LMNA, TNNT2, and PRDM16—were identified among five additional cases. The RBM20 mutation was previously reported in familial DCM. An identical unreported LMNA mutation was identified in two unrelated cases, both harboring gene-specific defects in cardiomyocyte nuclear morphology. Collectively, WES had a 50% diagnostic yield in our cohort, providing an explanation for pediatric heart failure and enabling informed family planning. Research is ongoing to discover novel DCM genes among the remaining families.