Intrathymic expression of Flt3 ligand enhances thymic recovery after irradiation

Hematopoietic stem cell transplantation (HSCT) requires conditioning treatments such as irradiation, which leads to a severely delayed recovery of T cell immunity and constitutes a major complication of this therapy. Currently, our understanding of the mechanisms regulating thymic recovery is limited. It is known that a subpopulation of bone marrow (BM)–derived thymic immigrant cells and the earliest intrathymic progenitors express the FMS-like tyrosine kinase 3 (Flt3) receptor; however, the functional significance of this expression in the thymus is not known. We used the BM transplant model to investigate the importance of Flt3 ligand (FL) for the regeneration of the T cell compartment. We show that FL is expressed in the adult mouse thymus on the surface of perivascular fibroblasts. These cells surround the proposed thymic entry site of Flt3 receptor–positive T cell progenitors. After irradiation, perivascular FL expression is up-regulated and results in an enhanced recovery of thymic cellularity. Thymic grafting experiments confirm an intrathymic requirement for FL. Collectively, these results show that thymic stromal cell–mediated FL–Flt3 receptor interactions are important in the reconstitution of thymopoiesis early after lethal irradiation and HSCT, and provide a functional relevance to the expression of the Flt3 receptor on intrathymic T cell progenitors

Dynamics, correlations and phases of the micromaser

The micromaser possesses a variety of dynamical phase transitions parametrized by the flux of atoms and the time-of-flight of the atom within the cavity. We discuss how these phases may be revealed to an observer outside the cavity using the long-time correlation length in the atomic beam. Some of the phase transitions are not reflected in the average excitation level of the outgoing atom, which is the commonly used observable. The correlation length is directly related to the leading eigenvalue of the time evolution operator, which we study in order to elucidate the phase structure. We find that as a function of the time-of-flight the transition from the thermal to the maser phase is characterized by a sharp peak in the correlation length. For longer times-of-flight there is a transition to a phase where the correlation length grows exponentially with the flux. We present a detailed numerical and analytical treatment of the different phases and discuss the physics behind them.Comment: 60 pages, 18 figure files, Latex + \special{} for the figures, (some redundant figures are eliminated and others are changed

Non-equilibrium states of a photon cavity pumped by an atomic beam

We consider a beam of two-level randomly excited atoms that pass one-by-one through a one-mode cavity. We show that in the case of an ideal cavity, i.e. no leaking of photons from the cavity, the pumping by the beam leads to an unlimited increase in the photon number in the cavity. We derive an expression for the mean photon number for all times. Taking into account leaking of the cavity, we prove that the mean photon number in the cavity stabilizes in time. The limiting state of the cavity in this case exists and it is independent of the initial state. We calculate the characteristic functional of this non-quasi-free non-equilibrium state. We also calculate the energy flux in both the ideal and open cavity and the entropy production for the ideal cavity.Comment: Corrected energy production calculations and made some changes to ease the readin

Stable transduction with lentiviral vectors and amplification of immature hematopoietic progenitors from cord blood of preterm human fetuses

Umbilical cord blood (CB) from the early gestational human fetus is recognized as a rich source of hematopoietic stem cells. To examine the value of fetal CB for gene therapy of inborn immunohematopoietic disorders, we tested the feasibility of genetic modification of CD34(+) cells from CB at weeks 24 to 34 of pregnancy, using lentiviral vector-mediated transfer of the green fluorescent protein (GFP) gene. The transduction rate of CD34(+) cells was 42 +/- 9%, resulting in GFP expression in 23 +/- 4% of colonies derived from colony-forming units (CFUs) and 11 +/- 1% from primitive long-term culture-initiating cells (LTC-ICs). Cell cycle analysis demonstrated transduction and GFP expression in cells in the G(0) phase, which contains immature hematopoietic progenitors. Transduced fetal CD34(+) cells could be expanded 1000-fold in long-term cultures supplemented with megakaryocyte growth and development factor along with Flt-3 ligand. At week 10, expression of GFP was observed in 40.5 +/- 11.7% of CFU-derived colonies. While prestimulation of CD34(+) cells with cytokines prior to transduction increased the efficiency of GFP transfer 2- to 3-fold, long-term maintenance of GFP-expressing CFUs occurred only in the absence of prestimulation. The GFP gene was found integrated into the genomic DNA of 35% of LTC-IC-derived colonies initiated at week 10, but GFP expression was not detectable, suggesting downregulation of transgene activity during the extended culture period. These results indicate that human fetal CB progenitors are amenable to genetic modification by lentiviral vectors and may serve as a target for gene therapy of hematopoietic disorders by prenatal autologous transplantation

Macroscopic Interference Effects in Resonant Cavities

We investigate the possibility of interference effects induced by macroscopic quantum-mechanical superpositions of almost othogonal coherent states - a Schroedinger cats state - in a resonant microcavity. Despite the fact that a single atom, used as a probe of the cat state, on the average only change the mean number of photons by one unit, we show that this single atom can change the system drastically. Interference between the initial and almost orthogonal macroscopic quantum states of the radiation field can now take place. Dissipation under current experimental conditions is taken into account and it is found that this does not necessarily change the intereference effects dramatically.Comment: 20 pages, 3 figure

Enhancing Acceleration Radiation from Ground-State Atoms via Cavity Quantum Electrodynamics

When ground state atoms are accelerated through a high Q microwave cavity, radiation is produced with an intensity which can exceed the intensity of Unruh acceleration radiation in free space by many orders of magnitude. The cavity field at steady state is described by a thermal density matrix under most conditions. However, under some conditions gain is possible, and when the atoms are injected in a regular fashion, the radiation can be produced in a squeezed state

Solvable model of a strongly-driven micromaser

We study the dynamics of a micromaser where the pumping atoms are strongly driven by a resonant classical field during their transit through the cavity mode. We derive a master equation for this strongly-driven micromaser, involving the contributions of the unitary atom-field interactions and the dissipative effects of a thermal bath. We find analytical solutions for the temporal evolution and the steady-state of this system by means of phase-space techniques, providing an unusual solvable model of an open quantum system, including pumping and decoherence. We derive closed expressions for all relevant expectation values, describing the statistics of the cavity field and the detected atomic levels. The transient regime shows the build-up of mixtures of mesoscopic fields evolving towards a superpoissonian steady-state field that, nevertheless, yields atomic correlations that exhibit stronger nonclassical features than the conventional micromaser.Comment: 9 pages, 16 figures. Submitted for publicatio