Shaping picosecond ellipsoidal laser pulses with periodic intensity modulation for electron photoinjectors.

A method for shaping periodic intensity distributions of strongly chirped picosecond laser pulses in the infrared range by periodic phase modulation of the spectrum is proposed. The dependence of the time modulation period and depth on the parameters of periodic phase modulation of the spectrum is analyzed by analytical and numerical methods. It is demonstrated that the intensity distribution structure obtained at second- and fourth-harmonic generation can be retained by introducing an angular chirp. The electron bunch dynamics at the photoinjector test facility at DESY in Zeuthen (PITZ) was modeled numerically using ellipsoidal laser pulses with intensity modulation.

Observation of the Self-Modulation Instability via Time-Resolved Measurements.

Self-modulation of an electron beam in a plasma has been observed. The propagation of a long (several plasma wavelengths) electron bunch in an overdense plasma resulted in the production of multiple bunches via the self-modulation instability. Using a combination of a radio-frequency deflector and a dipole spectrometer, the time and energy structure of the self-modulated beam was measured. The longitudinal phase space measurement showed the modulation of a long electron bunch into three bunches with an approximately 200 keV/c amplitude momentum modulation. Demonstrating this effect is a breakthrough for proton-driven plasma accelerator schemes aiming to utilize the same physical effect.

Shaping of cylindrical and 3D ellipsoidal beams for electron photoinjector laser drivers.

With the use of spatial light modulators it became possible to implement in experiments the method of controlling the space-time intensity distribution of femtosecond laser pulses stretched to picosecond duration. Cylindrical and quasi-ellipsoidal intensity distributions were obtained and characterized by means of a 2D spectrograph and a cross-correlator.

Disk Yb:KGW amplifier of profiled pulses of laser driver for electron photoinjector.

We investigated a diode-pumped multipass disk Yb:KGW amplifier intended for amplifying a train of 3D ellipsoidal pulses of a laser driver for a photocathode of a linear electron accelerator. The multipass amplification geometry permitted increasing the energy of broadband (about 10 nm) pulses with a repetition rate of 1 MHz from 0.12 µJ to 39 µJ, despite large losses (two orders of magnitude) introduced by a beam shaper of 3D ellipsoidal beam. The distortions of the pulse train envelope were minimal due to optimal delay between the moment of pump switching on and arrival of the first pulse of the train.

beta-catenin signaling pathway and the tolerance of breast cancer cells to hypoxic conditions.

We have previously shown that Snail, a regulator of epithelial-mesenchymal transition, is activated in the hypoxia-resistant breast cancer cell line HBL100. The purpose of this study was to evaluate the role of beta-catenin signaling pathway in the maintenance of breast cancer cells 'tolerance to hypoxia. The breast cancer cell lines MCF-7 and HBL-100 were used in this study; HBL-100 cells were characterized by increased resistance to hypoxia. We have demonstrated that the transcription factor beta-catenin is activated in hypoxic conditions and the beta-catenin activity is supported by Snail, a regulator of epithelial-mesenchymal transition. The activated beta-catenin regulates the expression of genes of the cell response to hypoxia and thus, it maintains the growth of breast cancer in the reduced oxygen conditions. The coordinated activation of Snail/beta-catenin/HIF-1alpha proteins in cell may be considered as an important factor of tumor resistance to hypoxia.

Phosphorylated Akt1 in human breast cancer measured by direct sandwich enzyme-linked immunosorbent assay: Correlation with clinicopathological features and tumor VEGF-signaling system component levels.

Protein kinase B (Akt) plays a major role in the regulation of breast cancer growth, survival, hormone, drug and radiosensitivity, but the clinical value of its expression and activation in human tumors is unclear. Activated Akt1 (pAkt1) expression was quantified in a series of 46 breast cancer and adjacent mammary gland samples by a direct Path-Scan PhosphoAkt1 (Ser473) sandwich ELISA kit. VEGF, sVEGFR1 and sVEGFR2 levels were measured simultaneously by standard ELISA kits. Forty-nine percent of the tumors had an increased pAkt1 level as compared to adjacent tissue. pAkt1 levels were significantly higher in stage IIb than in stage I-IIa tumors. The frequency of pAkt1 elevation was positively associated with tumor size and malignancy grade. pAkt1 was also twice as frequently increased in PgR-negative as in PgR-positive tumors, while its mean level was significantly higher in ER-positive than in ER-negative tumors. VEGF, sVEGFR1 and sVEGFR2 were increased in 73-85% of the tumors, but no associations with most clinicobiological factors and pAkt1 level were found. In conclusion, activation of Akt1 is not associated with VEGF signaling protein expression in breast cancer but is related to tumor size, grade of malignancy, and steroid receptor status.

Cooperation between STAT3 and c-jun suppresses Fas transcription.

Decreased Fas expression during tumor progression often results in a loss of Fas-ligand (FasL)-mediated apoptosis. Human and mouse melanoma exhibit an inverse correlation between the degree of Fas cell surface expression, tumorigenicity, and metastatic capacity. The expression of dominant negative Stat3 or c-Jun in melanoma cells efficiently increased Fas expression and sensitized cells to FasL-induced apoptosis. Stat3+/- as well as c-Jun-/- cells exhibited increased Fas cell surface expression and higher sensitivity to FasL-mediated apoptosis. Suppression of Fas expression by Stat3 and c-Jun is uncoupled from Stat3-mediated transcriptional activation. Our findings indicate that Stat3 oncogenic activities could also be mediated through its cooperation with c-Jun, resulting in downregulation of Fas surface expression, which is implicated in the tumor's ability to resist therapy and metastasize.

A novel group IIA phospholipase A2 interacts with v-Src oncoprotein from RSV-transformed hamster cells.

We have isolated a novel isoform of phospholipase A(2). This enzyme was designated srPLA(2) because it was discovered while analyzing the proteins interacting with different forms of the v-Src oncoproteins isolated from Rous sarcoma virus-transformed hamster cells. It contains all the functional regions of the PLA(2) group IIA proteins but differs at its C-terminal end where there is an additional stretch of 8 amino acids. The SrPLA(2) isoform was detected as a 17-kDa precursor in cells and as a mature 14-kDa form secreted in culture medium. A direct interaction of the 17-kDa precursor with the Src protein was observed in lysates of transformed cells. Both the 17- and 14-kDa forms were found to be phosphorylated on tyrosine. To our knowledge, this is the first report of a PLA(2) group II protein that is tyrosine phosphorylated. We surmise that srPLA(2) interacts with the Src protein at the cell membrane during the process of its maturation.

Phosphatidylinositol-3 kinase dependent pathways: the role in control of cell growth, survival, and malignant transformation.

Phosphatidylinositol-3 kinase (PI3K) is one of the most important regulatory proteins that is involved in different signaling pathways and controlling of key functions of the cell. The double-enzymatic activity of PI3K (lipid kinase and protein kinase) as well as the ability of this enzyme to activate a number of signal proteins including some oncoproteins determines its fundamental significance in regulation of cell functions such as growth and survival, aging, and malignant transformation. Among the main effectors of PI3K are the mitogen-transducing signal proteins (protein kinase C, phosphoinositide-dependent kinases, small G-proteins, MAP (mitogen activated protein) kinases), which are activated either via their interaction with lipid products of PI3K or through PI3K-dependent phosphorylation of proteins. The anti-apoptotic effect of PI3K is realized by activation of proteins from another signaling pathway--protein kinase B (PKB) and/or PKB-dependent enzymes (GSK-3, ILK). PI3K plays a critical role in malignant transformation. PI3K itself possesses oncogenic activity and also forms complexes with some viral or cellular oncoproteins (src, ras, rac, alb, T-antigen), whose transforming activities are realized only in presence of PI3K. The transforming effect of PI3K is supposed to occur on the basis of complex alterations in cellular signaling pathways: appearance of constitutively generated PI3K-dependent mitogen signal and activation of some protooncogenes (src, ras, rac, etc.), PI3K/PKB-pathway stimulation resulting in delay of apoptosis and increase of cell survival, and actin cytoskeleton reorganization.

Contribution of phosphatidylinositol 3-kinase to radiation resistance in human melanoma cells.

The activity of phosphatidylinositol 3-kinase (PI3K), a key component of multiple signal transduction pathways, was investigated in early- and late-stage melanoma cells that have varying degrees of radiation resistance. Analysis of PI3K biproducts (PI-3,4-P2 and PI-3,4,5-triphosphate) revealed a direct correlation between radiation resistance and levels of PI3K activity. Treating melanoma cells with wortmanin or LY294002, two different PI3K inhibitors, decreased PI3K activity and caused a dose-dependent decrease in resistance to ultraviolet radiation. Lower resistance to radiation elicited by LY294002 coincided with increased apoptosis. To further establish the role of PI3K in radiation resistance, we transfected early-stage melanoma cells with the cDNA of p85, the regulatory subunit of PI3K. Clones that constitutively overexpressed p85 exhibited a higher degree of PI-3,4-P2 synthesis and a corresponding increase in their resistance to ultraviolet radiation. The results of this study point to the role of PI3K and its biproducts in radiation resistance of human melanoma cells.