NRF2 promotes urothelial cell response to bacterial infection by regulating reactive oxygen species and RAB27B expression

Uropathogenic Escherichia coli (UPEC) cause urinary tract infections (UTIs) by invading urothelial cells. In response, the host mounts an inflammatory response to expel bacteria. Here, we show that the NF-E2-related factor 2 (NRF2) pathway is activated in response to UPEC-triggered reactive oxygen species (ROS) production. We demonstrate the molecular sequence of events wherein NRF2 activation in urothelial cells reduces ROS production, inflammation, and cell death, promotes UPEC expulsion, and reduces the bacterial load. In contrast, loss of NRF2 leads to increased ROS production, bacterial burden, and inflammation, both in vitro and in vivo. NRF2 promotes UPEC expulsion by regulating transcription of the RAB-GTPase RAB27B. Finally, dimethyl fumarate, a US Food and Administration-approved NRF2 inducer, reduces the inflammatory response, increases RAB27B expression, and lowers bacterial burden in urothelial cells and in a mouse UTI model. Our findings elucidate mechanisms underlying the host response to UPEC and provide a potential strategy to combat UTIs

DEFROST: A New Code for Simulating Preheating after Inflation

At the end of inflation, dynamical instability can rapidly deposit the energy of homogeneous cold inflaton into excitations of other fields. This process, known as preheating, is rather violent, inhomogeneous and non-linear, and has to be studied numerically. This paper presents a new code for simulating scalar field dynamics in expanding universe written for that purpose. Compared to available alternatives, it significantly improves both the speed and the accuracy of calculations, and is fully instrumented for 3D visualization. We reproduce previously published results on preheating in simple chaotic inflation models, and further investigate non-linear dynamics of the inflaton decay. Surprisingly, we find that the fields do not want to thermalize quite the way one would think. Instead of directly reaching equilibrium, the evolution appears to be stuck in a rather simple but quite inhomogeneous state. In particular, one-point distribution function of total energy density appears to be universal among various two-field preheating models, and is exceedingly well described by a lognormal distribution. It is tempting to attribute this state to scalar field turbulence.Comment: RevTeX 4.0; 16 pages, 9 figure

State Sum Models and Simplicial Cohomology

We study a class of subdivision invariant lattice models based on the gauge group $Z_{p}$, with particular emphasis on the four dimensional example. This model is based upon the assignment of field variables to both the $1$- and $2$-dimensional simplices of the simplicial complex. The property of subdivision invariance is achieved when the coupling parameter is quantized and the field configurations are restricted to satisfy a type of mod-$p$ flatness condition. By explicit computation of the partition function for the manifold $RP^{3} \times S^{1}$, we establish that the theory has a quantum Hilbert space which differs from the classical one.Comment: 28 pages, Latex, ITFA-94-13, (Expanded version with two new sections

Networks of cosmological histories, crossing of the phantom divide line and potentials with cusps

We discuss the phenomenon of the smooth dynamical gravity induced crossing of the phantom divide line in a framework of simple cosmological models where it appears to occur rather naturally, provided the potential of the unique scalar field has some kind of cusp. The behavior of cosmological trajectories in the vicinity of the cusp is studied in some detail and a simple mechanical analogy is presented. The phenomenon of certain complementarity between the smoothness of the spacetime geometry and matter equations of motion is elucidated. We introduce a network of cosmological histories and qualitatively describe some of its properties

Braneworld dynamics with the BraneCode

We give a full nonlinear numerical treatment of time-dependent 5d braneworld geometry, which is determined self-consistently by potentials for the scalar field in the bulk and at two orbifold branes, supplemented by boundary conditions at the branes. We describe the BraneCode, an algorithm which we designed to solve the dynamical equations numerically. We applied the BraneCode to braneworld models and found several novel phenomena of the brane dynamics. Starting with static warped geometry with de Sitter branes, we found numerically that this configuration is often unstable due to a tachyonic mass of the radion during inflation. If the model admits other static configurations with lower values of de Sitter curvature, this effect causes a violent re-structuring towards them, flattening the branes, which appears as a lowering of the 4d effective cosmological constant. Braneworld dynamics can often lead to brane collisions. We found that in the presence of the bulk scalar field, the 5d geometry between colliding branes approaches a universal, homogeneous, anisotropic strong gravity Kasner-like asymptotic, irrespective of the bulk/brane potentials. The Kasner indices of the brane directions are equal to each other but different from that of the extra dimension.Comment: 38 pages, 10 figure

DBI in the Sky

We analyze the spectrum of density perturbations generated in models of the recently discovered "D-cceleration" mechanism of inflation. In this scenario, strong coupling quantum field theoretic effects sum to provide a DBI-like action for the inflaton. We show that the model has a strict lower bound on the non-Gaussianity of the CMBR power spectrum at an observable level, and is thus falsifiable. This in particular observationally distinguishes this mechanism from traditional slow roll inflation generated by weakly interacting scalar fields. The model also favors a large observable tensor component to the CMBR spectrum.Comment: 30 pages latex. v2: references added. v3: correction in three point function. v4: sign of non-Gaussianity corrected; fNL is negativ

The Mass, Normalization and Late Time behavior of the Tachyon Field

We study the dynamics of the tachyon field $T$. We derive the mass of the tachyon as the pole of the propagator which does not coincide with the standard mass given in the literature in terms of the second derivative of $V(T)$ or $Log[V(T)]$. We determine the transformation of the tachyon in order to have a canonical scalar field $\phi$. This transformation reduces to the one obtained for small $\dot T$ but it is also valid for large values of $\dot T$. This is specially interesting for the study of dark energy where $\dot T\simeq 1$. We also show that the normalized tachyon field $\phi$ is constrained to the interval $T_2\leq T \leq T_1$ where $T_1,T_2$ are zeros of the original potential $V(T)$. This results shows that the field $\phi$ does not know of the unboundedness of $V(T)$, as suggested for bosonic open string tachyons. Finally we study the late time behavior of tachyon field using the L'H\^{o}pital rule.Comment: 9 pages, 10 figure

Anisotropic Inflation and the Origin of Four Large Dimensions

In the context of (4+d)-dimensional general relativity, we propose an inflationary scenario wherein 3 spatial dimensions grow large, while d extra dimensions remain small. Our model requires that a self-interacting d-form acquire a vacuum expectation value along the extra dimensions. This causes 3 spatial dimensions to inflate, whilst keeping the size of the extra dimensions nearly constant. We do not require an additional stabilization mechanism for the radion, as stable solutions exist for flat, and for negatively curved compact extra dimensions. From a four-dimensional perspective, the radion does not couple to the inflaton; and, the small amplitude of the CMB temperature anisotropies arises from an exponential suppression of fluctuations, due to the higher-dimensional origin of the inflaton. The mechanism triggering the end of inflation is responsible, both, for heating the universe, and for avoiding violations of the equivalence principle due to coupling between the radion and matter.Comment: 24 pages, 2 figures; uses RevTeX4. v2: Minor changes and added references. v3: Improved discussion of slow-rol

WZW orientifolds and finite group cohomology

The simplest orientifolds of the WZW models are obtained by gauging a Z_2 symmetry group generated by a combined involution of the target Lie group G and of the worldsheet. The action of the involution on the target is by a twisted inversion g \mapsto (\zeta g)^{-1}, where \zeta is an element of the center of G. It reverses the sign of the Kalb-Ramond torsion field H given by a bi-invariant closed 3-form on G. The action on the worldsheet reverses its orientation. An unambiguous definition of Feynman amplitudes of the orientifold theory requires a choice of a gerbe with curvature H on the target group G, together with a so-called Jandl structure introduced in hep-th/0512283. More generally, one may gauge orientifold symmetry groups \Gamma = Z_2 \ltimes Z that combine the Z_2-action described above with the target symmetry induced by a subgroup Z of the center of G. To define the orientifold theory in such a situation, one needs a gerbe on G with a Z-equivariant Jandl structure. We reduce the study of the existence of such structures and of their inequivalent choices to a problem in group-\Gamma cohomology that we solve for all simple simply-connected compact Lie groups G and all orientifold groups \Gamma = Z_2 \ltimes Z.Comment: 48+1 pages, 11 figure

Can Inflating Braneworlds be Stabilized?

We investigate scalar perturbations from inflation in braneworld cosmologies with extra dimensions. For this we calculate scalar metric fluctuations around five dimensional warped geometry with four dimensional de Sitter slices. The background metric is determined self-consistently by the (arbitrary) bulk scalar field potential, supplemented by the boundary conditions at both orbifold branes. Assuming that the inflating branes are stabilized (by the brane scalar field potentials), we estimate the lowest eigenvalue of the scalar fluctuations - the radion mass. In the limit of flat branes, we reproduce well known estimates of the positive radion mass for stabilized branes. Surprisingly, however, we found that for de Sitter (inflating) branes the square of the radion mass is typically negative, which leads to a strong tachyonic instability. Thus, parameters of stabilized inflating braneworlds must be constrained to avoid this tachyonic instability. Instability of "stabilized" de Sitter branes is confirmed by the BraneCode numerical calculations in the accompanying paper hep-th/0309001. If the model's parameters are such that the radion mass is smaller than the Hubble parameter, we encounter a new mechanism of generation of primordial scalar fluctuations, which have a scale free spectrum and acceptable amplitude.Comment: 7 pages, RevTeX 4.