A Simulated Microgravity Environment Causes a Sustained Defect in Epithelial Barrier Function.

Intestinal epithelial cell (IEC) junctions constitute a robust barrier to invasion by viruses, bacteria and exposure to ingested agents. Previous studies showed that microgravity compromises the human immune system and increases enteropathogen virulence. However, the effects of microgravity on epithelial barrier function are poorly understood. The aims of this study were to identify if simulated microgravity alters intestinal epithelial barrier function (permeability), and susceptibility to barrier-disrupting agents. IECs (HT-29.cl19a) were cultured on microcarrier beads in simulated microgravity using a rotating wall vessel (RWV) for 18 days prior to seeding on semipermeable supports to measure ion flux (transepithelial electrical resistance (TER)) and FITC-dextran (FD4) permeability over 14 days. RWV cells showed delayed apical junction localization of the tight junction proteins, occludin and ZO-1. The alcohol metabolite, acetaldehyde, significantly decreased TER and reduced junctional ZO-1 localization, while increasing FD4 permeability in RWV cells compared with static, motion and flask control cells. In conclusion, simulated microgravity induced an underlying and sustained susceptibility to epithelial barrier disruption upon removal from the microgravity environment. This has implications for gastrointestinal homeostasis of astronauts in space, as well as their capability to withstand the effects of agents that compromise intestinal epithelial barrier function following return to Earth

Chloride channels regulate differentiation and barrier functions of the mammalian airway.

The conducting airway forms a protective mucosal barrier and is the primary target of airway disorders. The molecular events required for the formation and function of the airway mucosal barrier, as well as the mechanisms by which barrier dysfunction leads to early onset airway diseases, remain unclear. In this study, we systematically characterized the developmental landscape of the mouse airway using single-cell RNA sequencing and identified remarkably conserved cellular programs operating during human fetal development. We demonstrated that in mouse, genetic inactivation of chloride channel Ano1/Tmem16a compromises airway barrier function, results in early signs of inflammation, and alters the airway cellular landscape by depleting epithelial progenitors. Mouse Ano1-/-mutants exhibited mucus obstruction and abnormal mucociliary clearance that resemble the airway defects associated with cystic fibrosis. The data reveal critical and non-redundant roles for Ano1 in organogenesis, and show that chloride channels are essential for mammalian airway formation and function

Potential Barrier Classification by Short-Time Measurement

We investigate the short-time dynamics of a delta-function potential barrier on an initially confined wave-packet. There are mainly two conclusions: A) At short times the probability density of the first particles that passed through the barrier is unaffected by it. B) When the barrier is absorptive (i.e., its potential is imaginary) it affects the transmitted wave function at shorter times than a real potential barrier. Therefore, it is possible to distinguish between an imaginary and a real potential barrier by measuring its effect at short times only on the transmitting wavefunction.Comment: 6 pages, 5 figure

Dynamic splitting of a Bose-Einstein Condensate

We study the dynamic process of splitting a condensate by raising a potential barrier in the center of a harmonic trap. We use a two-mode model to describe the phase coherence between the two halves of the condensate. Furthermore, we explicitly consider the spatial dependence of the mode funtions, which varies depending on the potential barrier. This allows to get the tunneling coupling between the two wells and the on-site energy as a function of the barrier height. Moreover we can get some insight on the collective modes which are excited by raising the barrier. We describe the internal and external degrees of freedom by variational ansatz. We distinguish the possible regimes as a function of the characteristic parameters of the problem and identify the adiabaticity conditions.Comment: 17 pages, 8 figure

Wave function of the Universe in the early stage of its evolution

In quantum cosmological models, constructed in the framework of Friedmann-Robertson-Walker metrics, a nucleation of the Universe with its further expansion is described as a tunneling transition through an effective barrier between regions with small and large values of the scale factor $a$ at non-zero (or zero) energy. The approach for describing this tunneling consists of constructing a wave function satisfying an appropriate boundary condition. There are various ways for defining the boundary condition that lead to different estimates of the barrier penetrability and the tunneling time. In order to describe the escape from the tunneling region as accurately as possible and to construct the total wave function on the basis of its two partial solutions unambiguously, we use the tunneling boundary condition that the total wave function must represent only the outgoing wave at the point of escape from the barrier, where the following definition for the wave is introduced: the wave is represented by the wave function whose modulus changes minimally under a variation of the scale factor $a$. We construct a new method for a direct non-semiclassical calculation of the total stationary wave function of the Universe, analyze the behavior of this wave function in the tunneling region, near the escape point and in the asymptotic region, and estimate the barrier penetrability. We observe oscillations of modulus of wave function in the external region starting from the turning point which decrease with increasing of $a$ and which are not shown in semiclassical calculations. The period of such an oscillation decreases uniformly with increasing $a$ and can be used as a fully quantum dynamical characteristic of the expansion of the Universe.Comment: 19 pages, 21 files for 10 EPS figures, LaTeX svjour style. The Sec.2 (formalism of Wheeler-De Witt equation) is reduced. In Sec.3.1 definition of the outgoing wave from barrier is defined more accurately. In Sec.4.1 semiclassical calculations of wavew function and penetrability are performed and comparison with results in fully quantum approach is adde

Akt-dependent Pp2a activity is required for epidermal barrier formation during late embryonic development

Acquisition of epidermal barrier function occurs late in mouse gestation. Several days before birth a wave of barrier acquisition sweeps across murine fetal skin, converging on dorsal and ventral midlines. We investigated the molecular pathways active during epidermal barrier formation. Akt signaling increased as the barrier wave crossed epidermis and Jun was transiently dephosphorylated. Inhibitor experiments on embryonic explants showed that the dephosphorylation of Jun was dependent on both Akt and protein phosphatase 2A (Pp2a). Inhibition of Pp2a and Akt signaling also caused defects in epidermal barrier formation. These data are compatible with a model for developmental barrier acquisition mediated by Pp2a regulation of Jun dephosphorylation, downstream of Akt signaling. Support for this model was provided by siRNA-mediated knockdown of Ppp2r2a (Pr55α or B55α), a regulatory subunit of Pp2a expressed in an Akt-dependent manner in epidermis during barrier formation. Ppp2r2a reduction caused significant increase in Jun phosphorylation and interfered with the acquisition of barrier function, with barrier acquisition being restored by inhibition of Jun phosphorylation. Our data provide strong evidence that Ppp2r2a is a regulatory subunit of Pp2a that targets this phosphatase to Jun, and that Pp2a action is necessary for barrier formation. We therefore describe a novel Akt-dependent Pp2a activity that acts at least partly through Jun to affect initial barrier formation during late embryonic epidermal development

Theory of tunneling conductance of graphene NIS junctions

We calculate the tunneling conductance of a graphene normal metal-insulator-superconductor (NIS) junction with a barrier of thickness $d$ and with an arbitrary voltage $V_0$ applied across the barrier region. We demonstrate that the tunneling conductance of such a NIS junction is an oscillatory function of both $d$ and $V_0$. We also show that the periodicity and amplitude of such oscillations deviate from their universal values in the thin barrier limit as obtained in earlier work [Phys. Rev. Lett. {\bf 97}, 217001 (2006)] and become a function of the applied voltage $V_0$. Our results reproduces the earlier results on tunneling conductance of such junctions in the thin [Phys. Rev. Lett. {\bf 97}, 217001 (2006)] and zero [Phys. Rev. Lett. {\bf 97}, 067007 (2006)] barrier limits as special limiting cases. We discuss experimental relevance of our results.Comment: Revised versio

Tunneling of a Massless Field through a 3D Gaussian Barrier

We propose a method for the approximate computation of the Green function of a scalar massless field Phi subjected to potential barriers of given size and shape in spacetime. This technique is applied to the case of a 3D gaussian ellipsoid-like barrier, placed on the axis between two pointlike sources of the field. Instead of the Green function we compute its temporal integral, that gives the static potential energy of the interaction of the two sources. Such interaction takes place in part by tunneling of the quanta of Phi across the barrier. We evaluate numerically the correction to the potential in dependence on the size of the barrier and on the barrier-sources distance.Comment: 16 pages, LaTeX, 3 PostScript figures; improved presentation, to appear in J. Math. Phy

Composite fermions traversing a potential barrier

Using a composite fermion picture, we study the lateral transport between two two-dimensional electron gases, at filling factor 1/2, separated by a potential barrier. In the mean field approximation, composite fermions far from the barrier do not feel a magnetic field while in the barrier region the effective magnetic field is different from zero. This produces a cutoff in the conductance when represented as a function of the thickness and height of the barrier. There is a range of barrier heights for which an incompressible liquid, at $\nu =1/3$, exists in the barrier region.Comment: 3 pages, latex, 4 figures available upon request from [email protected]. To appear in Physical Review B (RC) June 15t

Resonant escape over an oscillating barrier in single-electron ratchet transfer

Single-electron escape from a metastable state over an oscillating barrier is experimentally investigated in silicon-based ratchet transfer. When the barrier is oscillating on a time scale characteristic of the single-electron escape, synchronization occurs between the deterministic barrier modulation and the stochastic escape events. The average escape time as a function of its oscillation frequency exhibits a minimum providing a primary signature for resonant activation of single electrons.Comment: 4 pages, 5 figure