Hamiltonian BRST Quantization of the Conformal String

We present a new formulation of the tensionless string ($T= 0$) where the space-time conformal symmetry is manifest. Using a Hamiltonian BRST scheme we quantize this {\em Conformal String} and find that it has critical dimension $D=2$. This is in keeping with our classical result that the model describes massless particles in this dimension. It is also consistent with our previous results which indicate that quantized conformally symmetric tensionless strings describe a topological phase away {}from $D=2$. We reach our result by demanding nilpotency of the BRST charge and consistency with the Jacobi identities. The derivation is presented in two different ways: in operator language and using mode expansions. Careful attention is payed to regularization, a crucial ingredient in our calculations.Comment: 33pp (LaTeX), USITP-94-0

Classical and Quantized Tensionless Strings

{}From the ordinary tensile string we derive a geometric action for the tensionless ($T=0$) string and discuss its symmetries and field equations. The Weyl symmetry of the usual string is shown to be replaced by a global space-time conformal symmetry in the $T\to 0$ limit. We present the explicit expressions for the generators of this group in the light-cone gauge. Using these, we quantize the theory in an operator form and require the conformal symmetry to remain a symmetry of the quantum theory. Modulo details concerning zero-modes that are discussed in the paper, this leads to the stringent restriction that the physical states should be singlets under space-time diffeomorphisms, hinting at a topological theory. We present the details of the calculation that leads to this conclusion.Comment: 34 pages, Latex, USITP 93-1

Space-Time Symmetries of Quantized Tensionless Strings

The tensionless limit of the free bosonic string is space-time conformally symmetric classically. Requiring invariance of the quantum theory in the light cone gauge tests the reparametrization symmetry needed to fix this gauge. The full conformal symmetry gives stronger constraints than the Poincar\'e subalgebra. We find that the symmetry may be preserved in any space-time dimension, but only if the spectrum is drastically reduced (part of this reduction is natural in a zero tension limit of the ordinary string spectrum). The quantum states are required to be symmetric ({\it i.e.} singlets) under space-time diffeomorphisms, except for the centre of mass wave function.Comment: 15pp, plain latex, USITP-92-

A Role for the SmpB-SsrA System in Yersinia pseudotuberculosis Pathogenesis

Yersinia utilizes a sophisticated type III secretion system to enhance its chances of survival and to overcome the host immune system. SmpB (small protein B) and SsrA (small stable RNA A) are components of a unique bacterial translational control system that help maintain the bacterial translational machinery in a fully operational state. We have found that loss of the SmpB-SsrA function causes acute defects in the ability of Yersinia pseudotuberculosis to survive in hostile environments. Most significantly, we show that mutations in smpB-ssrA genes render the bacterium avirulent and unable to cause mortality in mice. Consistent with these observations, we show that the mutant strain is unable to proliferate in macrophages and exhibits delayed Yop-mediated host cell cytotoxicity. Correspondingly, we demonstrate that the smpB-ssrA mutant suffers severe deficiencies in expression and secretion of Yersinia virulence effector proteins, and that this defect is at the level of transcription. Of further interest is the finding that the SmpB-SsrA system might play a similar role in the related type III secretion system that governs flagella assembly and bacterial motility. These findings highlight the significance of the SmpB-SsrA system in bacterial pathogenesis, survival under adverse environmental conditions, and motility

Mode Shift to Arlanda Airport for Sustainable Development

For the past 20 years, the GPCRDB (G protein-coupled receptors database; http://www.gpcr.org/7tm/) has been a 'one-stop shop' for G protein-coupled receptor (GPCR)-related data. The GPCRDB contains experimental data on sequences, ligand-binding constants, mutations and oligomers, as well as many different types of computationally derived data, such as multiple sequence alignments and homology models. The GPCRDB also provides visualization and analysis tools, plus a number of query systems. In the latest GPCRDB release, all multiple sequence alignments, and >65,000 homology models, have been significantly improved, thanks to a recent flurry of GPCR X-ray structure data. Tools were introduced to browse X-ray structures, compare binding sites, profile similar receptors and generate amino acid conservation statistics. Snake plots and helix box diagrams can now be custom coloured (e.g. by chemical properties or mutation data) and saved as figures. A series of sequence alignment visualization tools has been added, and sequence alignments can now be created for subsets of sequences and sequence positions, and alignment statistics can be produced for any of these subsets

Schild's Null Strings in Flat and Curved Backgrounds

Schild's null (tensionless) strings are discussed in certain flat and curved backgrounds. We find closed, stationary, null strings as natural configurations existing on the horizons of spacetimes which possess such null hypersurfaces. Examples of these are obtained in Schwarzschild and Rindler spacetimes. A dynamic null string is also identified in Rindler spacetime. Furthermore, a general prescription (with explicit examples) is outlined by means of which null string configurations can be obtained in a large class of cosmological backgrounds.Comment: RevTex 3.0, 14 Pages, no figure

Effective dynamics of an electrically charged string with a current

Equations of motion for an electrically charged string with a current in an external electromagnetic field with regard to the first correction due to the self-action are derived. It is shown that the reparametrization invariance of the free action of the string imposes constraints on the possible form of the current. The effective equations of motion are obtained for an absolutely elastic charged string in the form of a ring (circle). Equations for the external electromagnetic fields that admit stationary states of such a ring are revealed. Solutions to the effective equations of motion of an absolutely elastic charged ring in the absence of external fields as well as in an external uniform magnetic field are obtained. In the latter case, the frequency at which one can observe radiation emitted by the ring is evaluated. A model of an absolutely nonstretchable charged string with a current is proposed. The effective equations of motion are derived within this model, and a class of solutions to these equations is found.Comment: 14 pages, 3 figures, format changed, minor change

Salmonella Pathogenicity Island 2 Is Expressed Prior to Penetrating the Intestine

Salmonella enterica serovar Typhimurium is a facultative intracellular pathogen that causes disease in mice that resembles human typhoid. Typhoid pathogenesis consists of distinct phases in the intestine and a subsequent systemic phase in which bacteria replicate in macrophages of the liver and spleen. The type III secretion system encoded by Salmonella pathogenicity island 2 (SPI-2) is a major virulence factor contributing to the systemic phase of typhoid pathogenesis. Understanding how pathogens regulate virulence mechanisms in response to the environment, including different host tissues, is key to our understanding of pathogenesis. A recombinase-based in vivo expression technology system was developed to assess SPI-2 expression during murine typhoid. SPI-2 expression was detectable at very early times in bacteria that were resident in the lumen of the ileum and was independent of active bacterial invasion of the epithelium. We also provide direct evidence for the regulation of SPI-2 by the Salmonella transcription factors ompR and ssrB in vivo. Together these results demonstrate that SPI-2 expression precedes penetration of the intestinal epithelium. This induction of expression precedes any documented SPI-2-dependent phases of typhoid and may be involved in preparing Salmonella to successfully resist the antimicrobial environment encountered within macrophages

Higher Spin Gauge Theory and Holography: The Three-Point Functions

In this paper we calculate the tree level three-point functions of Vasiliev's higher spin gauge theory in AdS4 and find agreement with the correlators of the free field theory of N massless scalars in three dimensions in the O(N) singlet sector. This provides substantial evidence that Vasiliev theory is dual to the free field theory, thus verifying a conjecture of Klebanov and Polyakov. We also find agreement with the critical O(N) vector model, when the bulk scalar field is subject to the alternative boundary condition such that its dual operator has classical dimension 2.Comment: 90 pages, 5 figures; v4, minor changes in the introductio

Novel Agonist Bioisosteres and Common Structure-Activity Relationships for The Orphan G Protein-Coupled Receptor GPR139

GPR139 is an orphan class A G protein-coupled receptor found mainly in the central nervous system. It has its highest expression levels in the hypothalamus and striatum, regions regulating metabolism and locomotion, respectively, and has therefore been suggested as a potential target for obesity and Parkinson’s disease. The two aromatic amino acids (L)-Trp and (L)-Phe have been proposed as putative endogenous agonists, and three structurally related benzohydrazide, glycine benzamide, and benzotriazine surrogate agonist series have been published. Herein, we assayed 158 new analogues selected from a pharmacophore model, and identified 12 new GPR139 agonists, containing previously untested bioisosteres. Furthermore, we present the first combined structure-activity relationships, and a refined pharmacophore model to serve as a rationale for future ligand identification and optimization