Fast retrieval of temporal characteristics of FEL pulses using streaking by THz field.

A simple and very fast method for reconstruction of temporal structure of linearly polarized FEL pulses from the THz streaking spectra of photoelectrons is suggested. The method is based on a quantum mechanical approach within the strong-field approximation. The method is suitable for online retrieval of the temporal characteristics of the FEL pulses. It can be applied for any photon frequency in a broad range of FEL pulse duration with a proper selection of the streaking field. To enhance its accuracy, it is suggested to simultaneously analyze the streaking spectra for several emission angles.

Circular Dichroism in Multiphoton Ionization of Resonantly Excited He

Intense, circularly polarized extreme-ultraviolet and near-infrared (NIR) laser pulses are combined to double ionize atomic helium via the oriented intermediate He^{+}(3p) resonance state. Applying angle-resolved electron spectroscopy, we find a large photon helicity dependence of the spectrum and the angular distribution of the electrons ejected from the resonance by NIR multiphoton absorption. The measured circular dichroism is unexpectedly found to vary strongly as a function of the NIR intensity. The experimental data are well described by theoretical modeling and possible mechanisms are discussed.

Circular dichroism measurements at an x-ray free-electron laser with polarization control.

A non-destructive diagnostic method for the characterization of circularly polarized, ultraintense, short wavelength free-electron laser (FEL) light is presented. The recently installed Delta undulator at the LCLS (Linac Coherent Light Source) at SLAC National Accelerator Laboratory (USA) was used as showcase for this diagnostic scheme. By applying a combined two-color, multi-photon experiment with polarization control, the degree of circular polarization of the Delta undulator has been determined. Towards this goal, an oriented electronic state in the continuum was created by non-resonant ionization of the O2 1s core shell with circularly polarized FEL pulses at hν ≃ 700 eV. An also circularly polarized, highly intense UV laser pulse with hν ≃ 3.1 eV was temporally and spatially overlapped, causing the photoelectrons to redistribute into so-called sidebands that are energetically separated by the photon energy of the UV laser. By determining the circular dichroism of these redistributed electrons using angle resolving electron spectroscopy and modeling the results with the strong-field approximation, this scheme allows to unambiguously determine the absolute degree of circular polarization of any pulsed, ultraintense XUV or X-ray laser source.

Determining the polarization state of an extreme ultraviolet free-electron laser beam using atomic circular dichroism.

Ultrafast extreme ultraviolet and X-ray free-electron lasers are set to revolutionize many domains such as bio-photonics and materials science, in a manner similar to optical lasers over the past two decades. Although their number will grow steadily over the coming decade, their complete characterization remains an elusive goal. This represents a significant barrier to their wider adoption and hence to the full realization of their potential in modern photon sciences. Although a great deal of progress has been made on temporal characterization and wavefront measurements at ultrahigh extreme ultraviolet and X-ray intensities, only few, if any progress on accurately measuring other key parameters such as the state of polarization has emerged. Here we show that by combining ultra-short extreme ultraviolet free electron laser pulses from FERMI with near-infrared laser pulses, we can accurately measure the polarization state of a free electron laser beam in an elegant, non-invasive and straightforward manner using circular dichroism.

Angle-resolved electron spectroscopy of laser-assisted Auger decay induced by a few-femtosecond x-ray pulse.

Two-color (x-ray+infrared) electron spectroscopy is used for investigating laser-assisted KLL Auger decay following 1s photoionization of atomic Ne with few-femtosecond x-ray pulses from the Linac Coherent Light Source. In an angle-resolved experiment, the overall width of the laser-modified Auger-electron spectrum and its structure change significantly as a function of the emission angle. The spectra are characterized by a strong intensity variation of the sidebands revealing a gross structure. This variation is caused, as predicted by theory, by the interference of electrons emitted at different times within the duration of one optical cycle of the infrared dressing laser, which almost coincides with the lifetime of the Ne 1s vacancy.

Quantum plasmonics: nonlinear effects in the field enhancement of a plasmonic nanoparticle dimer.

A fully quantum mechanical investigation using time-dependent density functional theory reveals that the field enhancement in a coupled nanoparticle dimer can be strongly affected by nonlinear effects. We show that both classical as well as linear quantum mechanical descriptions of the system fail even for moderate incident light intensities. An interparticle current resulting from the strong field photoemission tends to neutralize the plasmon-induced surface charge densities on the opposite sides of the nanoparticle junction. Thus, the coupling between the two nanoparticles and the field enhancement is reduced as compared to linear theory. A substantial nonlinear effect is revealed already at incident powers of 10(9) W/cm(2) for interparticle separation distances as large as 1 nm and down to the touching limit.

Circular dichroism in laser-assisted short-pulse photoionization.

A remarkable effect of circular dichroism, i.e., a difference in photoelectron spectra produced by right and left circularly polarized light in two-color multiphoton ionization of atoms, is predicted for the case when the atom is ionized by an extreme ultraviolet or x-ray femtosecond pulse in the field of a strong infrared laser pulse, both pulses being circularly polarized. We show that the sidebands formed in the spectra exhibit different circular dichroism often of different signs both in angle-resolved and angle-integrated experimental conditions. The effect can be used for detecting and measuring circular polarization of x rays in a spectral range where other methods are not effective.

Time-dependent screening of a point charge at a metal surface.

The space-time evolution of the dynamical screening charge density caused by a suddenly created point charge at the Cu(111) surface is investigated in the linear response approximation. Considering a thin slab as a model for the Cu(111) surface, we investigate the confinement effects on dynamical screening as well. The results have been obtained on the basis of self-consistent evaluation of the energy-momentum-dependent response function, taking into account the realistic surface band structure of Cu(111). At the initial stage, we observe fast long-range charge density oscillations due to excitation of the surface plasmon modes. Then we observe the propagation of the shock wave of the electron-hole excitations along the slab with velocity determined by the Fermi velocity of bulk Cu. At longer times, we have identified the propagation along the two slab surfaces of a much slower (with velocity ∼ 0.3 au, close to the Fermi velocity of the Cu(111) surface state) charge disturbance due to acoustic surface plasmon. The role of the energy band gap in the direction perpendicular to the surface in establishing the screening is also addressed.

One-electron model for the electronic response of metal surfaces to subfemtosecond photoexcitation.

The recent work of Cavalieri et al. [Nature (London) 449, 1029 (2007)10.1038/nature06229] has provided the first experimental observation of electron dynamics at metal surfaces in the subfemtosecond range. We explain the experimental findings using a full time-dependent approach within a one-dimensional model that includes the main ingredients of the short time physics involved in the experiment.

Long-lived excited states at surfaces: Cs/Cu(111) and Cs/Cu(100) systems.

One-electron and multielectron contributions to the decay of transient states in the Cs/Cu(111) and (100) systems are studied by a joined wave-packet propagation and many-body metal response approach. The long lifetime of these states is due to the Cu L and X band gaps which reduce the electron tunneling between Cs and Cu. In the (111) case, the decay is mainly by inelastic e-e interaction, whereas in the (100) case, electron tunneling is dominating. This accounts very well for the experimental findings [Bauer et al., Phys. Rev. B 55, 10 040 (1997) and Ogawa et al., Phys. Rev. Lett. 82, 1931 (1999)].

Signal transducers and activators of transcription 5B potentiates v-Src-mediated transformation of NIH-3T3 cells.

Previously, we reported that whereas both signal transducers and activators of transcription (STAT) 5A and STAT5B can be activated with respect to tyrosine phosphorylation and DNA binding potential by Src kinase, only STAT5B was translocated to the nucleus, where it presumably activates unique downstream responses. To help elucidate the functional consequences of STAT5B activation by v-src, the properties of stably transfected NIH-3T3 cells containing both an intact and a dominant negative, COOH-terminal-truncated isoform of STAT5B were investigated. STAT5B enhanced the transforming potential of v-Src as reflected by both an increase in focus formation and growth in soft agar. STAT5B also enhanced v-Src-induced cell cycle progression and cell motility in NIH-3T3 cells. Furthermore, the dominant negative, COOH-terminal-truncated isoform of STAT5B was able to partially suppress v-Src-mediated cell transformation. These results support the hypothesis that STAT5B may enhance Src/Abl-induced tumorigenesis. Accordingly, the equilibrium between STAT5B and STAT5A and their naturally occurring truncated forms may therefore play a key role in the etiology of certain cancers.

Long-lived adsorbate states on metal surfaces.

It has been shown recently that the peculiarities of the band structure of a metal can qualitatively influence the electron tunnelling between an adsorbate and a metal surface, the so-called resonant charge transfer (RCT). The presence of a projected band gap along the normal to the surface in the case of Cu(111) has been shown to lead to a blocking of the RCT in the case of Cs/Cu(111), resulting in the existence of a very long-lived excited state. Such long-lived states are potentially very important for surface reaction mechanisms invoking a transient state as an intermediate. Various systems: Cs, model M- negative ion of p pi symmetry, CO adsorbed on Cu(111), are investigated in order to determine the conditions for the blocking of the RCT and the existence of long-lived states.

Effect of the projected band gap on the formation of negative ions in grazing collisions from Cu surfaces.

The formation of negative ions (H-, O-, S-, F-, Cl-) is studied for grazing scattering of fast ions from Cu(110) and Cu(111) surfaces. In a detailed experimental and theoretical investigation we reveal that the projected L-band gap of the Cu metal affects charge transfer in a specific manner. From the analysis of the negative ion fractions as functions of projectile velocity we conclude that, for the Cu(111) surface the electronic 2D surface state continuum plays an essential role in the projectile-surface electron transfer.

Differential effects of prolactin and src/abl kinases on the nuclear translocation of STAT5B and STAT5A.

In this study, DNA binding and tyrosine phosphorylation of STAT5A and STAT5B were compared with their subcellular localization determined using indirect immunofluorescence microscopy. Following prolactin activation, both STAT5A and STAT5B were rapidly translocated into the nucleus and displayed a detergent-resistant, punctate nuclear staining pattern. Similar to prolactin induction, src activation resulted in tyrosine phosphorylation and DNA binding of both STAT5A and STAT5B. However, nuclear translocation of only STAT5B but not STAT5A was observed. This selective nuclear translocation appears to be mediated via the carboxyl-terminal sequences in STAT5B. Furthermore, overexpression of a dominant negative kinase-inactive mutant of JAK2 prevented prolactin-induced tyrosine phosphorylation and nuclear translocation of STAT5A and STAT5B but did not block src kinase activation and nuclear translocation of STAT5B. In co-transfection assays, prolactin-mediated activation but not src kinase-mediated activation of STAT5B resulted in the induction of a beta-casein promoter-driven reporter construct. These results suggest that STAT5 activation by src may occur by a mechanism distinct from that employed in cytokine activation of the JAK/STAT pathway, resulting in the selective nuclear translocation of STAT5B.

Composite response elements mediate hormonal and developmental regulation of milk protein gene expression.

Our laboratory has been studying the mechanisms by which hormones regulate the expression of differentiated function in the normal mammary gland and how these regulatory mechanisms have deviated in breast cancer. Two rat milk protein genes, encoding beta-casein and whey acidic protein, have been employed as molecular markers of mammary epithelial cell differentiation. Composite response elements containing multiple binding sites for several transcription factors mediate the hormonal and developmental regulation of milk protein gene expression. In the whey protein gene promoters, these include binding sites for nuclear factor (NF)-I, as well as the glucocorticoid receptor (GR) and signal transducers and activators of transcription (Stat5). In the casein promoters, these include binding sites for Stat5, Yin Yang 1 (YY1), GR and the CCAAT/enhancer binding protein (C/EBP). The C/EBP family of DNA binding proteins may play a pivotal role in maintaining the balance between cell proliferation and terminal differentiation in mammary epithelial cells. During normal mammary gland development, expression of LIP (liver-enriched inhibitory protein, a dominant-negative isoform of C/EBP beta) is hormonally regulated and correlates with cell proliferation during pregnancy. LIP can form heterodimers with other C/EBP family members and suppress their transcriptional activity. In contrast, C/EBP alpha is predominantly expressed during lactation following terminal differentiation. Elevated LIP levels have been detected in mouse, rat and human breast tumours of different aetiologies. This provides a mechanism, therefore, to block terminal differentiation and facilitate continued proliferation.

Prolactin induction of the alpha 2-Macroglobulin gene in rat ovarian granulosa cells: stat 5 activation and binding to the interleukin-6 response element.

alpha 2-Macroglobulin (alpha 2M) is expressed at high levels in the corpus luteum of pregnant rats in response to PRL and rat placental lactogens. These studies document that PRL induction of alpha 2M mRNA occurs rapidly in granulosa cells differentiated to the preovulatory phenotype in the presence of FSH and steroid, is hormone specific [induced by PRL but not by LH or interleukin-6 (IL-6)], and involves tyrosine kinase activity. To analyze the cellular signaling events stimulated by PRL, transient transfections of granulosa cells and electrophoretic mobility shift assays were done using the IL-6 response element (IL-6RE) of the alpha 2M promoter. The IL-6RE consists of two gamma-activating like sequences (GAS) that bind the acute phase response factor (APRF/Stat 3) in rat liver and the mammary gland factor (MGF/Stat 5) from mammary tissue. By transfecting various alpha 2M promoter-luciferase reporter transgenes into the granulosa cell cultures, we show that the GAS-like sites together with the minimal -48 base pairs of the alpha 2M promoter can confer PRL inducibility to the luciferase reporter gene. These same GAS-like sequences of the alpha 2M promoter were used to analyze the DNA-binding activity of proteins in whole cell extracts prepared from differentiated granulosa cells exposed to PRL for 0.25, 0.5, 4, and 20 h. PRL rapidly stimulated the binding of a specific protein to labeled alpha 2M GAS-like oligonucleotide, and this PRL-induced binding activity was shown to contain Stat 5 but not Stat 1 or Stat 3, using specific antibodies in the electrophoretic mobility shift assays. Because both Stat 5 and Stat 3 proteins are present in the whole cell extracts of differentiated granulosa cells, PRL appears to activate detectable amounts of Stat 5 (and not Stat 3). Thus, the initial induction of the alpha 2M gene by PRL in differentiated rat granulosa cells involves, at least in part, the activation (tyrosine phosphorylation?) of Stat 5.

Regulation of mammary gland factor/Stat5a during mammary gland development.

The rat homolog of sheep mammary gland factor (MGF)/Stat5 has been isolated and used to study the regulation of Stat5 during mammary gland development and PRL regulation in COS cells transfected with Stat5a and the PRL receptor. Two alternatively spliced isoforms, designated Stat5a1 and Stat5a2, were identified, the latter encoding a carboxy-terminal truncated protein. A polyclonal antibody to a carboxy-terminal peptide of Stat5a1 was generated and used to measure the level of this isoform during mammary gland development and after PRL induction in COS cells transiently transfected with Stat5a and the long form of the PRL receptor. Surprisingly, Stat5a mRNA and protein were readily detected both in virgin rats and after mammary gland involution. The levels of Stat5a increased during pregnancy, were highest in late pregnancy, and then, unexpectedly, decreased during lactation, the time at which the highest levels of milk protein gene expression are observed. Electrophoretic mobility shift assays using the specific anti-Stat5a1 antisera demonstrated that Stat5a1 comprises part of the heterogeneous, PRL-inducible, protein-DNA complex associated with the beta-casein GAS site. Immunocytochemical analysis detected considerable cytoplasmic and some nuclear staining for Stat5a1 during late pregnancy and predominantly nuclear staining during early lactation. The lack of correspondence of Stat5a gene expression and beta-casein gene expression suggests that Stat5 activation may facilitate the interaction of other factors binding within composite response elements identified recently in the milk protein gene promoters that are then responsible for the stable expression of milk protein genes in terminally differentiated mammary epithelial cells.

YY1 represses beta-casein gene expression by preventing the formation of a lactation-associated complex.

Site-specific mutagenesis of the highly conserved milk box (-140 to -110) region suggested that beta-casein expression is regulated by a hormone-mediated relief of repression (M. Schmitt-Ney, W. Doppler, R. K. Ball, and B. Groner, Mol. Cell. Biol. 11:3745-3755, 1991). However, when this sequence was placed upstream of a heterologous thymidine kinase promoter, it activated reporter gene expression. This apparent paradox was resolved when the trans-acting factor YY1, capable of acting as both a positive and negative regulator, was shown to interact with the milk box region, using bacterially expressed YY1 and specific oligonucleotide and antibody competition experiments. Second, it was demonstrated that extracts prepared from several cell types contained a protein(s) interacting with the mammary gland-specific factor (MGF) binding site, previously shown to be required for beta-casein promoter activity (Schmitt-Ney et al., Mol. Cell. Biol. 11:3745-3755, 1991). Sequence analysis of this site revealed similarity to the gamma interferon-activated sequence, suggesting that MGF may be related to the stat91 signaling protein. Finally, using an oligonucleotide encompassing both the YY1 and MGF sites, we detected a slow-mobility complex only in extracts from mammary glands at late pregnancy and lactation (lactation-associated complex [LAC]). Site-specific mutation of the YY1 binding site led to an enhancement in LAC DNA binding activity, while mutation of the MGF site decreased detectable LAC. These results support a model in which lactogenic stimuli lead to a decrease in YY1 binding, and subsequent increased formation of LAC at a nearby binding site, to stimulate beta-casein transcription.

High-velocity mechanical DNA transfer of the chloramphenicolacetyl transferase gene into rodent liver, kidney and mammary gland cells in organ explants and in vivo.

Mouse and rat liver, kidney and mammary gland explants were bombarded with high-velocity microprojectiles carrying a chloramphenicolacetyl transferase gene under different promoters (pTAT-cat, p chi-Casein-cat, p beta-Casein-cat). The expression of a CAT gene was revealed in all organ explants 24 h after transfection. The most pronounced expression was found when a TAT-CAT construction was used. In experiments in vivo rat liver was bombarded in situ with microprojectiles carrying pTAT-cat DNA. A marked activity of the CAT gene was detected 24 h after the bombardment.