Annkatrin Sommer

Controlling dielectrics with the electric field of light

The control of the electric and optical properties of semiconductors with microwave fields forms the basis of modern electronics, information processing and optical communications. The extension of such control to optical frequencies calls for wideband materials such as dielectrics, which require strong electric fields to alter their physical properties. Few-cycle laser pulses permit damage-free exposure of dielectrics to electric fields of several volts per ångström and significant modifications in their electronic system. Fields of such strength and temporal confinement can turn a dielectric from an insulating state to a conducting state within the optical period. However, to extend electric signal control and processing to light frequencies depends on the feasibility of reversing these effects approximately as fast as they can be induced. Here we study the underlying electron processes with sub-femtosecond solid-state spectroscopy, which reveals the feasibility of manipulating the electronic structure and electric polarizability of a dielectric reversibly with the electric field of light. We irradiate a dielectric (fused silica) with a waveform-controlled near-infrared few-cycle light field of several volts per angström and probe changes in extreme-ultraviolet absorptivity and near-infrared reflectivity on a timescale of approximately a hundred attoseconds to a few femtoseconds. The field-induced changes follow, in a highly nonlinear fashion, the turn-on and turn-off behaviour of the driving field, in agreement with the predictions of a quantum mechanical model. The ultrafast reversibility of the effects implies that the physical properties of a dielectric can be controlled with the electric field of light, offering the potential for petahertz-bandwidth signal manipulation.

Attosecond nonlinear polarization and light-matter energy transfer in solids

Electric-field-induced charge separation (polarization) is the most fundamental manifestation of the interaction of light with matter and a phenomenon of great technological relevance. Nonlinear optical polarization produces coherent radiation in spectral ranges inaccessible by lasers and constitutes the key to ultimate-speed signal manipulation. Terahertz techniques have provided experimental access to this important observable up to frequencies of several terahertz. Here we demonstrate that attosecond metrology extends the resolution to petahertz frequencies of visible light. Attosecond polarization spectroscopy allows measurement of the response of the electronic system of silica to strong (more than one volt per ångström) few-cycle optical (about 750 nanometres) fields. Our proof-of-concept study provides time-resolved insight into the attosecond nonlinear polarization and the light-matter energy transfer dynamics behind the optical Kerr effect and multi-photon absorption. Timing the nonlinear polarization relative to the driving laser electric field with sub-30-attosecond accuracy yields direct quantitative access to both the reversible and irreversible energy exchange between visible-infrared light and electrons. Quantitative determination of dissipation within a signal manipulation cycle of only a few femtoseconds duration (by measurement and ab initio calculation) reveals the feasibility of dielectric optical switching at clock rates above 100 terahertz. The observed sub-femtosecond rise of energy transfer from the field to the material (for a peak electric field strength exceeding 2.5 volts per ångström) in turn indicates the viability of petahertz-bandwidth metrology with a solid-state device.

Waveform-controlled near-single-cycle milli-joule laser pulses generate sub-10 nm extreme ultraviolet continua.

We demonstrate the generation of waveform-controlled laser pulses with 1 mJ pulse energy and a full-width-half-maximum duration of ∼4  fs, therefore lasting less than two cycles of the electric field oscillating at their carrier frequency. The laser source is carrier-envelope-phase stabilized and used as the backbone of a kHz repetition rate source of high-harmonic continua with unprecedented flux at photon energies between 100 and 200 eV (corresponding to a wavelength range between 12-6 nm respectively). In combination we use these tools for the complete temporal characterization of the laser pulses via attosecond streaking spectroscopy.

Salinomycin co-treatment enhances tamoxifen cytotoxicity in luminal A breast tumor cells by facilitating lysosomal degradation of receptor tyrosine kinases

Luminal A breast cancer is the most common breast cancer subtype which is usually treated with selective estrogen receptor modulators (SERMS) like tamoxifen. Nevertheless, one third of estrogen receptor positive breast cancer patients initially do not respond to endocrine therapy and about 40% of luminal A breast tumors recur in five years. In this study, we investigated an alternative treatment approach by combining tamoxifen and salinomycin in luminal A breast cancer cell lines. We have found that salinomycin induces an additional cytotoxic effect by inhibiting the ligand independent activation of ERα. Thereby salinomycin increases the intracellular calcium level. This leads to a premature fusion of endosomes with lysosomes and thus to the degradation of Egfr family members. Since this process is essential for luminal A breast cancer cells to circumvent tamoxifen treatment, the combination of both drugs induces cytotoxicity in tamoxifen sensitive as well as resistant luminal A breast cancer cell lines.

MiRNA-27a sensitizes breast cancer cells to treatment with Selective Estrogen Receptor Modulators

BACKGROUND MicroRNA-27a (miR-27a) is a small non-coding RNA, shown to play a role in multiple cancers, including the regulation of ERα expression in breast cancer. Most ERα positive tumors are treated with Selective Estrogen Receptor Modulators (SERMs) and thus the role of miR-27a expression in response to SERM treatment is of interest. METHODS Tamoxifen resistant cells were generated by molecular evolution with six cycles of tamoxifen treatment. MCF7 and T47D luminal A breast cancer cell lines were either treated with miR-27a mimics, or ER-signaling was modulated ectopically. The changes were analyzed with RT-qPCR, western blotting and transcriptional activity ERE-reporter assays. Moreover, the response to SERM treatments (tamoxifen, endoxifen and toremifen) was investigated by cell viability and apoptosis measurements. An in silico analysis of survival data from the METABRIC study was performed in order to assess the prognostic value of miR-27a for response to SERM treatment. RESULTS Tamoxifen-resistant cells showed decreased expression of ERα and miR-27a. The overexpression of miR-27a increased the levels of ERα, while modulation of ERα decreased miR-27a expression. High miR-27a expression increased the sensitivity of MCF7 and T47D cells to SERM treatments and re-sensitized the cells to tamoxifen. Patient survival of luminal A breast cancer patients that underwent endocrine therapies was better in groups with high miR-27a expression. CONCLUSION MiR-27a sensitizes luminal A breast cancer cells to SERM treatments based on a positive feedback loop with ERα. An increased overall-survival of ER-positive breast cancer patients that underwent endocrine treatments and displayed high miR-27a levels was found.

A proteomic analysis of an in vitro knock-out of miR-200c

Loss of miR-200c is correlated to advanced cancer-subtypes due to increased EMT and decreased treatment efficacy by chemotherapeutics. As miRNAs regulate a multitude of targets, the analysis of differentially expressed proteins upon a genomic knock-out (KO) is of interest. In this study, we generated a TALENs KO of miR-200c in MCF7 breast cancer cells, excluded its compensation by family-members and evaluated the impact on the proteome by analyzing three individual KO-clones. We identified 26 key proteins and a variety of enrichments in metabolic and cytoskeletal pathways. In six of these targets (AGR2, FLNA/B, ALDH7A1, SCIN, GSTM3) the differential expression was additionally detected at mRNA level. Together, these alterations in protein abundance accounted for the observed biological phenotypes, i.e. increased migration and chemoresistance and altered metabolism, found in the miR-200c-KO clones. These findings provide novel insights into miR-200c and pave the way for further studies.

Attosecond nonlinear polarization and energy transfer in solids

Attosecond polarization spectroscopy is a new experimental technique resolving the nonlinear polarization and energy-transfer induced by visible few-cycle strong fields in solids. It reveals the intensity dependent response time of the system with attosecond resolution.

Octave spanning wedge dispersive mirrors with low dispersion oscillations

A novel concept for octave spanning dispersive mirrors with low spectral dispersion oscillations is presented. The key element of the so-called wedge dispersive mirror is a slightly wedged layer which is coated on a specially optimized dispersive multilayer stack by a common sputter coating process. The group delay dispersion (GDD) of a pulse reflected on a wedge dispersive mirror is nearly free of oscillations. Fabricated mirrors with negative GDD demonstrate the compression of a pulse down to 3.8 fs as good as double angled mirrors optimized for the same bandwidth.

Attosecond Polarization Spectroscopy

The aim of this thesis is to examine whether optical few cycle pulses and dielectrics can be used in ultrafast signal processing. The findings presented so far already provide several answers to the questions raised in Chap. 1. Ultrashort pulses can manipulate distinct optical properties of insulators reversibly on femtosecond timescales. The induced dynamics are able to follow the petahertz driving field and exhibit highly nonlinear features.

Time Integrated Investigation of the Nonlinear Kerr Coefficient

Most of the nonlinear phenomena described in Sect. 2 are well understood if the oscillation period of the exciting field clearly exceeds the time constant of the induced dynamics Buckland, Boyd Opt Lett 21:1117, 1996, [1].