Synthesis and Properties of High Tilted Antiferroelectric Esters with Partially Fluorinated Alkoxyalkoxy Terminal Chains

Novel chiral esters with partially fluorinated alkoxyalkoxy terminal chains are described. Their phase transition temperatures, enthalpies, and electrooptical properties are reported. A helical pitch in pure compounds and their mixtures based on selective reflection of light is also characterized

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

Effects of Dicer and Argonaute down-regulation on mRNA levels in human HEK293 cells

RNA interference and the microRNA (miRNA) pathway can induce sequence-specific mRNA degradation and/or translational repression. The human genome encodes hundreds of miRNAs that can post-transcriptionally repress thousands of genes. Using reporter constructs, we observed that degradation of mRNAs bearing sites imperfectly complementary to the endogenous let-7 miRNA is considerably stronger in human HEK293 than HeLa cells. The degradation did not result from the Ago2-mediated endonucleolytic cleavage but it was Dicer- and Ago2-dependent. We used this feature of HEK293 to address the size of a pool of transcripts regulated by RNA silencing in a single cell type. We generated HEK293 cell lines depleted of Dicer or individual Ago proteins. The cell lines were used for microarray analyses to obtain a comprehensive picture of RNA silencing. The 3'-untranslated region sequences of a few hundred transcripts that were commonly up-regulated upon Ago2 and Dicer knock-downs showed a significant enrichment of putative miRNA-binding sites. The up-regulation upon Ago2 and Dicer knock-downs was moderate and we found no evidence, at the mRNA level, for activation of silenced genes. Taken together, our data suggest that, independent of the effect on translation, miRNAs affect levels of a few hundred mRNAs in HEK293 cells

DDX3 depletion selectively represses translation of structured mRNAs

DDX3 is an RNA chaperone of the DEAD-box family that regulates translation. Its yeast ortholog Ded1 controls the translation of nearly all mRNAs, whereas DDX3 is thought to regulate only a subset of mRNAs. However, the set of mRNAs that are regulated by DDX3 are unknown, along with the relationship between DDX3 binding and activity. Here, we use ribosome profiling, RNA-seq, and PAR-CLIP to define the set of mRNAs that are regulated by DDX3 in human cells. We find that while DDX3 binds most expressed mRNAs, depletion of DDX3 affects the translation level of only a small subset of the transcriptome. We further find that DDX3 binds a site on helix 16 of the human ribosome, placing it immediately adjacent to the mRNA entry channel and translation factor eIF4B. Translation changes caused by depleting DDX3 levels or through chemical inhibition mimicking a dominant negative allele are different. Taken together, our data defines the subset of the transcriptome that is responsive to DDX3 inhibition, with relevance for basic biology and disease states where DDX3 expression is altered

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