IER2-induced senescence drives melanoma invasion through osteopontin

Expression of the immediate-early response gene IER2 has been associated with the progression of several types of cancer, but its functional role is poorly understood. We found that increased IER2 expression in human melanoma is associated with shorter overall survival, and subsequently investigated the mechanisms through which IER2 exerts this effect. In experimental melanoma models, sustained expression of IER2 induced senescence in a subset of melanoma cells in a p53/MAPK/AKT-dependent manner. The senescent cells produced a characteristic secretome that included high levels of the extracellular phosphoglycoprotein osteopontin. Nuclear localization of the IER2 protein was critical for both the induction of senescence and osteopontin secretion. Osteopontin secreted by IER2-expressing senescent cells strongly stimulated the migration and invasion of non-senescent melanoma cells. Consistently, we observed coordinate expression of IER2, p53/p21, and osteopontin in primary human melanomas and metastases, highlighting the pathophysiological relevance of IER2-mediated senescence in melanoma progression. Together, our study reveals that sustained IER2 expression drives melanoma invasion and progression through stimulating osteopontin secretion via the stochastic induction of senescence

Auger electron wave packet interferometry on extreme timescales with coherent soft x rays

Wave packet interferometry provides benchmark information on light-induced electronic quantum states by monitoring their relative amplitudes and phases during coherent excitation, propagation,and decay. The relative phase control of soft x-ray pulse replicas on the single-digit attosecond timescale achieved in our experiments makes this method a powerful tool to probe ultrafast quantum phenomena such as the excitation of Auger shake-up states with sub-cycle precision. In this contribution we present first results obtained for different Auger decay channels upon generating L-shell vacancies in argon atoms using Michelson-type all-reflective interferometric autocorrelation at a central free-electron laser photon energy of 274.7 eV

Electronic quantum coherence in glycine molecules probed with ultrashort x ray pulses in real time

Here, we use x rays to create and probe quantum coherence in the photoionized amino acid glycine. The outgoing photoelectron leaves behind the cation in a coherent superposition of quantum mechanical eigenstates. Delayed x ray pulses track the induced coherence through resonant x ray absorption that induces Auger decay and by photoelectron emission from sequential double photoionization. Sinusoidal temporal modulation of the detected signal at early times 0 to 25 fs is observed in both measurements. Advanced ab initio many electron simulations allow us to explain the first 25 fs of the detected coherent quantum evolution in terms of the electronic coherence. In the kinematically complete x ray absorption measurement, we monitor its dynamics for a period of 175 fs and observe an evolving modulation that may implicate the coupling of electronic to vibronic coherence at longer time scales. Our experiment provides a direct support for the existence of long lived electronic coherence in photoionized biomolecule

Simultaneous Operation of Three Laser Systems at the FLASH Photoinjector

The free-electron laser facility FLASH at DESY (Hamburg, Germany) operates two undulator beamlines simultaneously. Both undulator beamlines are driven by a common linear superconducting accelerator with a beam energy of up to 1.25 GeV. The superconducting technology allows the acceleration of trains of several hundred microsecond spaced bunches with a repetition rate of 10 Hz. A fast kickers-septum system is installed to distribute one part of the electron bunch train to FLASH1 and the other part to FLASH2 keeping the full 10 Hz repetition rate for both beamlines. In order to deliver different beam properties to each beamline, the FLASH photoinjector uses two independent laser systems to generate different bunch pattern and bunch charges. One laser serves the FLASH1 beamline, the other the FLASH2 beamline. A third laser with adjus ö laser pulse duration is used to generate ultra-short bunches for single spike lasing

Reflective Optical System for Time-Resolved Electron Bunch Measurements at PITZ

The Photo-Injector Test facility at DESY, Zeuthen site (PITZ), produces pulsed electron beams with low transverse emittance and is equipped with diagnostic devices for measuring various electron bunch properties, including the longitudinal and transverse electron phase space distributions. The longitudinal bunch structure is recorded using a streak camera located outside the accelerator tunnel, connected to the diagnostics in the beam-line stations by an optical system of about 30 m length. This system mainly consists of telescopes of achromatic lenses, which transport the light pulses and image them onto the entrance slit of the streak camera. Due to dispersion in the lenses, the temporal resolution degrades during transport. This article presents general considerations for time-resolving optical systems as well as simulations and measurements of specific candidate systems. It then describes the development of an imaging system based on mirror telescopes which will improve the temporal resolution, with an emphasis on off-axis parabolic mirror systems working at unit magnification. A hybrid system of lenses and mirrors will serve as a proof of principle.Comment: 11 pages, 12 figures, submitted to NIM

Study of temporal, spectral, arrival time and energy fluctuations of SASE FEL pulsesb

Self-amplified spontaneous emission (SASE) pulses delivered by free electron lasers (FELs) are inherently fluctuating sources; each pulse varies in energy, duration, arrival time and spectral shape. Therefore, there is strong demand for a full characterization of the properties of SASE radiation, which will facilitate more precise interpretation of the experimental data taken at SASE FELs. In this paper, we present an investigation into the fluctuations of pulse duration, spectral distribution, arrival time and pulse energy of SASE XUV pulses at FLASH, both on a shot-to-shot basis and on average over many pulses. With the aid of simulations, we derived scaling laws for these parameters and disentangled the statistical SASE fluctuations from accelerator-based fluctuations and measurement uncertainties