A slice of AdS_5 as the large N limit of Seiberg duality

A slice of AdS_5 is used to provide a 5D gravitational description of 4D strongly-coupled Seiberg dual gauge theories. An (electric) SU(N) gauge theory in the conformal window at large N is described by the 5D bulk, while its weakly coupled (magnetic) dual is confined to the IR brane. This framework can be used to construct an N = 1 MSSM on the IR brane, reminiscent of the original Randall-Sundrum model. In addition, we use our framework to study strongly-coupled scenarios of supersymmetry breaking mediated by gauge forces. This leads to a unified scenario that connects the extra-ordinary gauge mediation limit to the gaugino mediation limit in warped space.Comment: 47 Pages, axodraw4j.st

Non-Perturbative Superpotentials in F-theory and String Duality

We use open-closed string duality between F-theory on K3xK3 and type II strings on CY manifolds without branes to study non-perturbative superpotentials in generalized flux compactifications. On the F-theory side we obtain the full flux potential including D3-instanton contributions and show that it leads to an explicit and simple realization of the three ingredients of the KKLT model for stringy dS vacua. The D3-instanton contribution is highly non-trivial, can be systematically computed including the determinant factors and demonstrates that a particular flux lifts very effectively zero modes on the instanton. On the closed string side, we propose a generalization of the Gukov-Vafa-Witten superpotential for type II strings on generalized CY manifolds, depending on all moduli multiplets.Comment: 49 pages, harvmac, 1 figure; references & figures adde

Stable Non-Supersymmetric Throats in String Theory

We construct a large class of non-supersymmetric AdS-like throat geometries in string theory by taking non-supersymmetric orbifolds of supersymmetric backgrounds. The scale of SUSY breaking is the AdS radius, and the dual field theory has explicitly broken supersymmetry. The large hierarchy of energy scales in these geometries is stable. We establish this by showing that the dual gauge theories do not have any relevant operators which are singlets under the global symmetries. When the geometries are embedded in a compact internal space, a large enough discrete subgroup of the global symmetries can still survive to prevent any singlet relevant operators from arising. We illustrate this by embedding one case in a non-supersymmetric orbifold of a Calabi-Yau manifold. These examples can serve as a starting point for obtaining Randall-Sundrum models in string theory, and more generally for constructing composite Higgs or technicolor-like models where strongly coupled dynamics leads to the breaking of electro-weak symmetry. Towards the end of the paper, we briefly discuss how bulk gauge fields can be incorporated by introducing D7-branes in the bulk, and also show how the strongly coupled dynamics can lead to an emergent weakly coupled gauge theory in the IR with matter fields including scalars.Comment: 28 pages,2 figure

Low-Energy Probes of a Warped Extra Dimension

We investigate a natural realization of a light Abelian hidden sector in an extended Randall-Sundrum (RS) model. In addition to the usual RS bulk we consider a second warped space containing a bulk U(1)_x gauge theory with a characteristic IR scale of order a GeV. This Abelian hidden sector can couple to the standard model via gauge kinetic mixing on a common UV brane. We show that if such a coupling induces significant mixing between the lightest U(1)_x gauge mode and the standard model photon and Z, it can also induce significant mixing with the heavier U(1)_x Kaluza-Klein (KK) modes. As a result it might be possible to probe several KK modes in upcoming fixed-target experiments and meson factories, thereby offering a new way to investigate the structure of an extra spacetime dimension.Comment: 26 pages, 1 figure, added references, corrected minor typos, same as journal versio

An approach for particle sinking velocity measurements in the 3–400 μm size range and considerations on the effect of temperature on sinking rates

The flux of organic particles below the mixed layer is one major pathway of carbon from the surface into the deep ocean. The magnitude of this export flux depends on two major processes—remineralization rates and sinking velocities. Here, we present an efficient method to measure sinking velocities of particles in the size range from approximately 3–400 μm by means of video microscopy (FlowCAM®). The method allows rapid measurement and automated analysis of mixed samples and was tested with polystyrene beads, different phytoplankton species, and sediment trap material. Sinking velocities of polystyrene beads were close to theoretical values calculated from Stokes’ Law. Sinking velocities of the investigated phytoplankton species were in reasonable agreement with published literature values and sinking velocities of material collected in sediment trap increased with particle size. Temperature had a strong effect on sinking velocities due to its influence on seawater viscosity and density. An increase in 9 °C led to a measured increase in sinking velocities of ~40 %. According to this temperature effect, an average temperature increase in 2 °C as projected for the sea surface by the end of this century could increase sinking velocities by about 6 % which might have feedbacks on carbon export into the deep ocean

Inhibiting mevalonate pathway enzymes increases stromal cell resilience to a cholesterol-dependent cytolysin

Animal health depends on the ability of immune cells to kill invading pathogens, and on the resilience of tissues to tolerate the presence of pathogens. Trueperella pyogenes causes tissue pathology in many mammals by secreting a cholesterol-dependent cytolysin, pyolysin (PLO), which targets stromal cells. Cellular cholesterol is derived from squalene, which is synthesized via the mevalonate pathway enzymes, including HMGCR, FDPS and FDFT1. The present study tested the hypothesis that inhibiting enzymes in the mevalonate pathway to reduce cellular cholesterol increases the resilience of stromal cells to PLO. We first verified that depleting cellular cholesterol with methyl-β-cyclodextrin increased the resilience of stromal cells to PLO. We then used siRNA to deplete mevalonate pathway enzyme gene expression, and used pharmaceutical inhibitors, atorvastatin, alendronate or zaragozic acid to inhibit the activity of HMGCR, FDPS and FDFT1, respectively. These approaches successfully reduced cellular cholesterol abundance, but mevalonate pathway enzymes did not affect cellular resilience equally. Inhibiting FDFT1 was most effective, with zaragozic acid reducing the impact of PLO on cell viability. The present study provides evidence that inhibiting FDFT1 increases stromal cell resilience to a cholesterol-dependent cytolysin

Th17 cells are more protective than Th1 cells against the intracellular parasite Trypanosoma cruzi

Th17 cells are a subset of CD4+ T cells known to play a central role in the pathogenesis of many autoimmune diseases, as well as in the defense against some extracellular bacteria and fungi. However, Th17 cells are not believed to have a significant function against intracellular infections. In contrast to this paradigm, we have discovered that Th17 cells provide robust protection against Trypanosoma cruzi, the intracellular protozoan parasite that causes Chagas disease. Th17 cells confer significantly stronger protection against T. cruzi-related mortality than even Th1 cells, traditionally thought to be the CD4+ T cell subset most important for immunity to T. cruzi and other intracellular microorganisms. Mechanistically, Th17 cells can directly protect infected cells through the IL-17A-dependent induction of NADPH oxidase, involved in the phagocyte respiratory burst response, and provide indirect help through IL-21-dependent activation of CD8+ T cells. The discovery of these novel Th17 cell-mediated direct protective and indirect helper effects important for intracellular immunity highlights the diversity of Th17 cell roles, and increases understanding of protective T. cruzi immunity, aiding the development of therapeutics and vaccines for Chagas disease

Measuring kinetic drivers of pneumolysin pore structure

Most membrane attack complex-perforin/cholesterol-dependent cytolysin (MACPF/CDC) proteins are thought to form pores in target membranes by assembling into pre-pore oligomers before undergoing a pre-pore to pore transition. Assembly during pore formation is into both full rings of subunits and incomplete rings (arcs). The balance between arcs and full rings is determined by a mechanism dependent on protein concentration in which arc pores arise due to kinetic trapping of the pre-pore forms by the depletion of free protein subunits during oligomerisation. Here we describe the use of a kinetic assay to study pore formation in red blood cells by the MACPF/CDC pneumolysin from Streptococcus pneumoniae. We show that cell lysis displays two kinds of dependence on protein concentration. At lower concentrations it is dependent on the pre-pore topore transition of arc oligomers, which we show to be a cooperative process. At higher concentrations it is dependent on the amount of pneumolysin bound to the membrane and reflects the affinity of the protein for its receptor, cholesterol. A lag occurs before cell lysis begins; this is dependent on oligomerisation of pneumolysin. Kinetic dissection of cell lysis by pneumolysin demonstrates the capacity of MACPF/CDCs to generate pore-forming oligomericstructures of variable size with, most likely, different functional roles in biology

Exploring new physics frontiers through numerical relativity

The demand to obtain answers to highly complex problems within strong-field gravity has been met with significant progress in the numerical solution of Einstein's equations - along with some spectacular results - in various setups. We review techniques for solving Einstein's equations in generic spacetimes, focusing on fully nonlinear evolutions but also on how to benchmark those results with perturbative approaches. The results address problems in high-energy physics, holography, mathematical physics, fundamental physics, astrophysics and cosmology