Compensation Mechanisms for Altered Membrane Sterol Compositions in the Yeast: Saccharomyces cerevisiae

Cell Membranes are composed of several different lipid and sterol products. Among these are, chiefly, phospholipids, glycolipids, sphingolipids, various proteins and sterols. The sterol that is prevalent in fungi, including yeast, is ergosterol. It plays the same physiological role as cholesterol in mammalian cells. That is, mainly, to control membrane fluidity. Membranes in general are extremely important to the normal functioning of any cell and its sub-cellular compartments. The primary factor in the normal functioning of a membrane is the relative composition of the previously mentioned components. Even though there is a high amount of traffic between different membranes within a cell, each one requires its own distinct composition in order to function properly. How cells maintain these distinct compositions is of great interest because abnormal sterol levels have been linked to many diseases in humans, including heart disease and Alzheimer’s disease. In a previous study, a yeast knockout library was screened for sensitivity to a class of anti-fungal drugs called triterpene glycosides. Triterpene glycosides, or TTG, are drugs that work by disturbing membranes. Of the yeast mutants that were found to be hyper-sensitive to TTG, two, ERG4 and ERG5, were found to be involved in the ergosterol biosynthesis pathway. Erg4p, called C-24(28) reductase, is the last enzyme in the ergosterol biosynthesis pathway. When this gene is knocked out, there is a complete lack of ergosterol in the membrane. Instead, the enzyme’s substrate, ergosta-5,7,22,24(28)-tetraen-3beta-ol, accumulates in the membrane. Likewise, when the ERG5 gene is deleted, the enzyme’s substrate, ergosta-5,7,24-trien-3beta-ol, accumulates in the place of ergosterol. The Erg5p is known as C-22 desaturase and immediately precedes C-24(28) reductase in the biosynthetic pathway. Another gene displaying the hyper-sensitive phenotype, OSH3, is involved in the transport of sterols to and from the plasma membrane, and the esterification of exogenous sterol products, though its exact function is yet uncharacterized. We have begun high copy suppression screens, usingTTG, which seek to identify compensation mechanisms between the major components of membranes. Unfortunately, one of these screens did not give enough data to justify continuing the project. The other, however, has been successful, yielding several suppression candidates, and the first phase of the screen is drawing to a close. Now that suppressors have been found, the lab will then work to understand how these particular genes compensate for the complete lack of ergosterol in the yeast membranes and rescue the hypersensitive phenotype. These studies seek to lay the groundwork for understanding the interplay of the various membrane components, the importance of their relative composition in a membrane, and the process by which cells regulate the compositions of membrane particles, particularly the primary yeast sterol, ergosterol

Stabilising the supersymmetric Standard Model on the Z_6' orientifold

Four stacks of intersecting supersymmetric fractional D6-branes on the Z_6' orientifold have previously been used to construct consistent models having the spectrum of the supersymmetric Standard Model, including a single pair of Higgs doublets, plus three right-chiral neutrino singlets. However, various moduli, Kahler moduli and complex-structure moduli, twisted and untwisted, remain unfixed. Further, some of the Yukawa couplings needed to generated quark and lepton masses are forbidden by a residual global symmetry of the model. In this paper we study the stabilisation of moduli using background fluxes, and show that the moduli may be stabilised within the Kahler cone. In principle, missing Yukawa couplings may be restored, albeit with a coupling that is suppressed by non-perturbative effects, by the use Euclidean D2-branes that are pointlike in spacetime, i.e. E2-instantons. However, for the models under investigation, we show that this is not possible.Comment: 32 pages, LaTeX. Small addition made prior to submission for publicatio

Mapping 6D N = 1 supergravities to F-theory

We develop a systematic framework for realizing general anomaly-free chiral 6D supergravity theories in F-theory. We focus on 6D (1, 0) models with one tensor multiplet whose gauge group is a product of simple factors (modulo a finite abelian group) with matter in arbitrary representations. Such theories can be decomposed into blocks associated with the simple factors in the gauge group; each block depends only on the group factor and the matter charged under it. All 6D chiral supergravity models can be constructed by gluing such blocks together in accordance with constraints from anomalies. Associating a geometric structure to each block gives a dictionary for translating a supergravity model into a set of topological data for an F-theory construction. We construct the dictionary of F-theory divisors explicitly for some simple gauge group factors and associated matter representations. Using these building blocks we analyze a variety of models. We identify some 6D supergravity models which do not map to integral F-theory divisors, possibly indicating quantum inconsistency of these 6D theories.Comment: 37 pages, no figures; v2: references added, minor typos corrected; v3: minor corrections to DOF counting in section

Brane cosmology with a bulk scalar field

We consider ``cosmologically symmetric'' (i.e. solutions with homogeneity and isotropy along three spatial dimensions) five-dimensional spacetimes with a scalar field and a three-brane representing our universe. We write Einstein's equations in a conformal gauge, using light-cone coordinates. We obtain explicit solutions: a. assuming proportionality between the scalar field and the logarithm of the (bulk) scale factor; b. assuming separable solutions. We then discuss the cosmology in the brane nduced by these solutions.Comment: 24 pages, Latex, no figur

Integrable open spin chains from giant gravitons

We prove that in the presence of a maximal giant graviton state in N=4 SYM, the states dual to open strings attached to the giant graviton give rise to an PSU(2,2|4) open spin chain model with integrable boundary conditions in the SO(6) sector of the spin chain to one loop order.Comment: 18 pages, 2 figures, uses JHEP

A study of open strings ending on giant gravitons, spin chains and integrability

We systematically study the spectrum of open strings attached to half BPS giant gravitons in the N=4 SYM AdS/CFT setup. We find that some null trajectories along the giant graviton are actually null geodesics of AdS_5x S^5, so that we can study the problem in a plane wave limit setup. We also find the description of these states at weak 't Hooft coupling in the dual CFT. We show how the dual description is given by an open spin chain with variable number of sites. We analyze this system in detail and find numerical evidence for integrability. We also discover an interesting instability of long open strings in Ramond-Ramond backgrounds that is characterized by having a continuum spectrum of the string, which is separated from the ground state by a gap. This instability arises from accelerating the D-brane on which the strings end via the Ramond-Ramond field. From the integrable spin chain point of view, this instability prevents us from formulating the integrable structure in terms of a Bethe Ansatz construction.Comment: 38 pages+appendices, 9 figures. Uses JHEP3. v2: added reference

String-Inspired Higher-Curvature Terms and the Randall-Sundrum Scenario

We consider the O(a') string effective action, with Gauss-Bonnet curvature-squared and fourth-order dilaton-derivative terms, which is derived by a matching procedure with string amplitudes in five space-time dimensions. We show that a non-factorizable metric of the Randall-Sundrum (RS) type, with four-dimensional conformal factor Exp(-2 k|z|), can be a solution of the pertinent equations of motion. The parameter k is found proportional to the string coupling g_s and thus the solution appears to be non-perturbative. It is crucial that the Gauss-Bonnet combination has the right (positive in our conventions) sign, relative to the Einstein term, which is the case necessitated by compatibility with string (tree) amplitude computations. We study the general solution for the dilaton and metric functions, and thus construct the appropriate phase-space diagram in the solution space. In the case of an anti-de-Sitter bulk, we demonstrate that there exists a continuous interpolation between (part of) the RS solution at z=infinity and an (integrable) naked singularity at z=0. This implies the dynamical formation of domain walls (separated by an infinite distance), thus restricting the physical bulk space time to the positive z axis. Some brief comments on the possibility of fine-tuning the four-dimensional cosmological constant to zero are also presented.Comment: 28 pages Latex, three eps figures incorporated, minor change

Multiple Inflation, Cosmic String Networks and the String Landscape

Motivated by the string landscape we examine scenarios for which inflation is a two-step process, with a comparatively short inflationary epoch near the string scale and a longer period at a much lower energy (like the TeV scale). We quantify the number of $e$-foldings of inflation which are required to yield successful inflation within this picture. The constraints are very sensitive to the equation of state during the epoch between the two inflationary periods, as the extra-horizon modes can come back inside the horizon and become reprocessed. We find that the number of $e$-foldings during the first inflationary epoch can be as small as 12, but only if the inter-inflationary period is dominated by a network of cosmic strings (such as might be produced if the initial inflationary period is due to the brane-antibrane mechanism). In this case a further 20 $e$-foldings of inflation would be required at lower energies to solve the late universe's flatness and horizon problems.Comment: 27 pages, 6 figures; v2: refences adde

Classical/quantum integrability in AdS/CFT

We discuss the AdS/CFT duality from the perspective of integrable systems and establish a direct relationship between the dimension of single trace local operators composed of two types of scalar fields in N=4 super Yang-Mills and the energy of their dual semiclassical string states in AdS(5) X S(5). The anomalous dimensions can be computed using a set of Bethe equations, which for ``long'' operators reduces to a Riemann-Hilbert problem. We develop a unified approach to the long wavelength Bethe equations, the classical ferromagnet and the classical string solutions in the SU(2) sector and present a general solution, governed by complex curves endowed with meromorphic differentials with integer periods. Using this solution we compute the anomalous dimensions of these long operators up to two loops and demonstrate that they agree with string-theory predictions.Comment: 49 pages, 5 figures, LaTeX; v2: complete proof of the two-loop equivalence between the sigma model and the gauge theory is added. References added; v4,v5,v6: misprints correcte

F-Theory and the Mordell-Weil Group of Elliptically-Fibered Calabi-Yau Threefolds

The Mordell-Weil group of an elliptically fibered Calabi-Yau threefold X contains information about the abelian sector of the six-dimensional theory obtained by compactifying F-theory on X. After examining features of the abelian anomaly coefficient matrix and U(1) charge quantization conditions of general F-theory vacua, we study Calabi-Yau threefolds with Mordell-Weil rank-one as a first step towards understanding the features of the Mordell-Weil group of threefolds in more detail. In particular, we generate an interesting class of F-theory models with U(1) gauge symmetry that have matter with both charges 1 and 2. The anomaly equations --- which relate the Neron-Tate height of a section to intersection numbers between the section and fibral rational curves of the manifold --- serve as an important tool in our analysis.Comment: 29 pages + appendices, 5 figures; v2: minor correction