Investigating charge-up and fragmentation dynamics of oxygen molecules after interaction with strong X-ray free-electron laser pulses.

During the last decade, X-ray free-electron lasers (XFELs) have enabled the study of light-matter interaction under extreme conditions. Atoms which are subject to XFEL radiation are charged by a complex interplay of (several subsequent) photoionization events and electronic decay processes within a few femtoseconds. The interaction with molecules is even more intriguing, since intricate nuclear dynamics occur as the molecules start to dissociate during the charge-up process. Here, we demonstrate that by analyzing photoelectron angular emission distributions and kinetic energy release of charge states of ionic molecular fragments, we can obtain a detailed understanding of the charge-up and fragmentation dynamics. Our novel approach allows for gathering such information without the need of complex ab initio modeling. As an example, we provide a detailed view on the processes happening on a femtosecond time scale in oxygen molecules exposed to intense XFEL pulses.

Electric Nondipole Effect in Strong-Field Ionization.

Strong-field ionization of atoms by circularly polarized femtosecond laser pulses produces a donut-shaped electron momentum distribution. Within the dipole approximation this distribution is symmetric with respect to the polarization plane. The magnetic component of the light field is known to shift this distribution forward. Here, we show that this magnetic nondipole effect is not the only nondipole effect in strong-field ionization. We find that an electric nondipole effect arises that is due to the position dependence of the electric field and which can be understood in analogy to the Doppler effect. This electric nondipole effect manifests as an increase of the radius of the donut-shaped photoelectron momentum distribution for forward-directed momenta and as a decrease of this radius for backwards-directed electrons. We present experimental data showing this fingerprint of the electric nondipole effect and compare our findings with a classical model and quantum calculations.

Strong Differential Photoion Circular Dichroism in Strong-Field Ionization of Chiral Molecules.

We investigate the differential ionization probability of chiral molecules in the strong-field regime as a function of the helicity of the incident light. To this end, we analyze the fourfold ionization of bromochlorofluoromethane (CHBrClF) with subsequent fragmentation into four charged fragments and different dissociation channels of the singly ionized methyloxirane. By resolving for the molecular orientation, we show that the photoion circular dichroism signal strength is increased by 2 orders of magnitude.

Fourfold Differential Photoelectron Circular Dichroism.

We report on a joint experimental and theoretical study of photoelectron circular dichroism (PECD) in methyloxirane. By detecting O 1s photoelectrons in coincidence with fragment ions, we deduce the molecule's orientation and photoelectron emission direction in the laboratory frame. Thereby, we retrieve a fourfold differential PECD clearly beyond 50%. This strong chiral asymmetry is reproduced by ab initio electronic structure calculations. Providing such a pronounced contrast makes PECD of fixed-in-space chiral molecules an even more sensitive tool for chiral recognition in the gas phase.

Spin and Angular Momentum in Strong-Field Ionization.

The spin polarization of electrons from multiphoton ionization of Xe by 395 nm circularly polarized laser pulses at 6×10^{13} W/cm^{2} has been measured. At this photon energy of 3.14 eV the above-threshold ionization peaks connected to Xe^{+} ions in the ground state (J=3/2, ionization potential I_{p}=12.1 eV) and the first excited state (J=1/2, I_{p}=13.4 eV) are clearly separated in the electron energy distribution. These two combs of above-threshold ionization peaks show opposite spin polarizations. The magnitude of the spin polarization is a factor of 2 higher for the J=1/2 than for the J=3/2 final ionic state. In turn, the data show that the ionization probability is strongly dependent on the sign of the magnetic quantum number.

Direct Experimental Access to the Nonadiabatic Initial Momentum Offset upon Tunnel Ionization.

We report on the nonadiabatic offset of the initial electron momentum distribution in the plane of polarization upon single ionization of argon by strong field tunneling and show how to experimentally control the degree of nonadiabaticity. Two-color counter- and corotating fields (390 and 780 nm) are compared to show that the nonadiabatic offset strongly depends on the temporal evolution of the laser electric field. We introduce a simple method for the direct access to the nonadiabatic offset using two-color counter- and corotating fields. Further, for a single-color circularly polarized field at 780 nm, we show that the radius of the experimentally observed donutlike distribution increases for increasing momentum in the light propagation direction. Our observed initial momentum offsets are well reproduced by the strong-field approximation. A mechanistic picture is introduced that links the measured nonadiabatic offset to the magnetic quantum number of virtually populated intermediate states.

Nonsequential Double Ionization by Counterrotating Circularly Polarized Two-Color Laser Fields.

We report on nonsequential double ionization of Ar by a laser pulse consisting of two counterrotating circularly polarized fields (390 and 780 nm). The double-ionization probability depends strongly on the relative intensity of the two fields and shows a kneelike structure as a function of intensity. We conclude that double ionization is driven by a beam of nearly monoenergetic recolliding electrons, which can be controlled in intensity and energy by the field parameters. The electron momentum distributions show the recolliding electron as well as a second electron which escapes from an intermediate excited state of Ar^{+}.

Trajectory-resolved Coulomb focusing in tunnel ionization of atoms with intense, elliptically polarized laser pulses.

In strong-field light-matter interactions, the strong laser field dominates the dynamics. However, recent experiments indicate that the Coulomb force can play an important role as well. In this Letter, we have studied the photoelectron momentum distributions produced from noble gases in elliptically polarized, 800 nm laser light. By performing a complete mapping of the three-dimensional electron momentum, we find that Coulomb focusing significantly narrows the lateral momentum spread. We find a surprisingly sensitive dependence of Coulomb focusing on the initial transverse momentum distribution, i.e., the momentum at the moment of birth of the photoelectron. We also observe a strong signature of the low-energy structure in the above threshold ionization spectrum.

CXCR4 activation maintains a stem cell population in tamoxifen-resistant breast cancer cells through AhR signalling.

BACKGROUND: Tamoxifen is commonly used for breast cancer therapy. However, tamoxifen resistance is an important clinical problem. Continuous treatment with conventional therapy may contribute to cancer progression in recurring cancers through the accumulation of drug-resistant cancer progenitors. METHODS: To investigate signalling mechanisms important for the maintenance and viability of drug-resistant cancer progenitors, we used microarray analysis, PCR array for genes involved in cancer drug resistance and metabolism, flow cytometry, soft agar colony formation assay, in vivo tumourigenicity assay and immunohistochemical analysis using tamoxifen-sensitive and tamoxifen-resistant breast cancer MCF7 cells. RESULTS: Downregulation of CXCR4 signalling by small molecule antagonist AMD3100 specifically inhibits growth of progenitor cell population in MCF7(TAM-R) cells both in vitro and in vivo. Microarray analysis revealed aryl hydrocarbon receptor (AhR) signalling as one of the top networks that is differentially regulated in MCF7(TAM-R) and MCF7 xenograft tumours treated with AMD3100. Further, small molecule antagonists of AhR signalling specifically inhibit the progenitor population in MCF7(TAM-R) cells and growth of MCF7(TAM-R) xenografts in vivo. CONCLUSION: The chemokine receptor CXCR4 maintains a cancer progenitor population in tamoxifen-resistant MCF7 cells through AhR signalling and could be a putative target for the treatment of tamoxifen-resistant breast cancers.

Relevance of air-to-liquid mass ratio effect on final granule properties of an Enalapril maleate formulation.

BACKGROUND: In the production of enalapril maleate tablets, the granulation process is the most crucial step. Numerous variables are known to influence the fluid bed granulation process and thus the final granule quality. In this study a novel descriptor for the nozzle parameter "air-to-liquid mass ratio" is presented. Granules manufacturing processes were designed by application of statistical experimental design. AIM: The influence of the critical process parameter (CPP)--air-to-liquid mass ratio--on pharmaceutic properties of granules was studied. Air-to-liquid mass ratio can be considered as important variable influencing the droplet size of atomized liquid binder solution. RESULTS/CONCLUSION: A significant influence of air-to-liquid mass ratio on granule final particle size distribution was found. Increasing air-to-liquid mass ratio resulted in increased granules particle size distribution. Decreasing air-to-liquid mass ratio led to granules with reduced tapped density. Thus, it can be concluded that the parameter "air-to-liquid mass ratio" is a critical process parameter in the production of enalapril maleate granules.

Ultrafast temporal evolution of interatomic Coulombic decay in NeKr dimers.

We investigate interatomic Coulombic decay in NeKr dimers after neon inner-valence photoionization [Ne+(2s-1)] using a synchrotron light source. We measure with high energy resolution the two singly charged ions of the Coulomb-exploding dimer dication and the photoelectron in coincidence. By carefully tracing the post-collision interaction between the photoelectron and the emitted ICD electron we are able to probe the temporal evolution of the state as it decays. Although the ionizing light pulses are 80 picoseconds long, we determine the lifetime of the intermediate dimer cation state and visualize the contraction of the nuclear structure on the femtosecond time scale.

Enantioselective fragmentation of an achiral molecule in a strong laser field.

Chirality is omnipresent in living nature. On the single molecule level, the response of a chiral species to a chiral probe depends on their respective handedness. A prominent example is the difference in the interaction of a chiral molecule with left or right circularly polarized light. In the present study, we show by Coulomb explosion imaging that circularly polarized light can also induce a chiral fragmentation of a planar and thus achiral molecule. The observed enantiomer strongly depends on the orientation of the molecule with respect to the light propagation direction and the helicity of the ionizing light. This finding might trigger new approaches to improve laser-driven enantioselective chemical synthesis.

Th2-mediated atopic disease protection in Th1-mediated rheumatoid arthritis.

OBJECTIVE: The balance between CD4+ T-helper (h) cell subsets (Th1 and Th2) plays an important role in the pathogenesis of rheumatoid arthritis (RA) and atopy. While RA is believed to be a Th1 mediated disease, Th2 cells predominate in atopic disorders. The purpose of this study was to investigate differences in the occurrence of allergy, hay fever, house dust mite sensitivity and asthma, as well as total serum IgE levels in RA patients and controls. METHODS: The case history of atopic disorders was assessed in 134 RA patients and compared to those found in 305 healthy blood donors. RA patients also answered clinical questions concerning disease activity and severity. Total serum IgE levels were measured in both groups, taking into consideration disease modifying therapy. RESULTS: A significantly lower occurrence of medical history of hay fever (2.3%) and house dust mite sensitivity (3.1%) was found among RA patients compared to controls (24.2% and 12.2%, respectively; p < 0.0001 and p < 0.003 respectively). Moreover, RA patients had significantly lower total serum IgE levels than control subjects (p < 0.0001). RA was less severe in patients with atopy compared to non-atopic RA patients. CONCLUSION: These results support the concept that RA and atopy antagonize each other and that a change in the cytokine patterns of Th1 and Th2 cells could provide an indication for curative effects on RA.

[Visualization of coronary arteries in CT as assessed by a new 16 slice technology and reduced gantry rotation time: first experiences]. / Darstellung der Herzkranzgefässe im CT mittels neuer 16-Zeilen-Technologie und reduzierter Rotationszeit: Erste Erfahrungen.

PURPOSE: First evaluation of image quality of a new 16-slice multidetector-row computed tomography (MDCT) for the assessment of coronary artery disease and lesion detection of the coronary arteries. MATERIALS AND METHODS: On a newly developed 16-slice CT scanner (SOMATOM Sensation 16, Siemens, Forchheim, Germany) a calcium score as well as a contrast-enhanced CT angiography (CTA) were performed on 4 patients with retrospective ECG-gating and a gantry rotation time of 420 ms to exclude or follow-up coronary heart disease. CTA was performed after injecting 120 ml contrast media intravenously. After medication with a ss-Blocker, the heart rate was between 55 and 67 bpm. RESULTS: The scan time for calcium score was 12 s, for CTA 18 s (scan range 15 and 12 cm, respectively). Volume score was between 0 and 256.4. In the CT angiography the entire coronary tree could be visualized in all patients up to the very distal subsegmental branches. In two patients a complete occlusion of the RCA and the LAD were depicted, respectively. In one of these patients, a large aneurysm of the left anterior ventricular wall was also delineated. CONCLUSION: Considering our first experiences with the new 16-slice technology, an excellent visualization of the entire coronary tree including the very distal and side branches due to substantially increased spatial resolution seems to be achievable. In these patients the acquired image quality raises the hope for improved, non-invasive cardiac diagnostics. In larger studies, the clinical impact of this new technology needs to be further investigated.

[Three isoflurane preparations from various manufacturers. A comparison of isoflurane concentrations in fresh gas after vaporization with a Drager vaporizer type 19.3]. / Drei Isofluranpräparate verschiedener Hersteller. Ein Vergleich der Isoflurankonzentrationen im Frischgas nach Verdampfung mit dem Dräger-Vapor 19.3.

OBJECTIVES: The purpose of this study was to check the precision of the Dräger vaporizer model 19.3 when filled with three different preparations of isoflurane. METHODS: Six Dräger vaporizers model 19.3 calibrated with forene were filled with forene (Abbott), isoflurane (Lilly) and isoflurane (Pharmacia); gas output was measured by infrared absorption (Irina, Dräger) at vaporizer settings of 0.2, 0.4, 0.6, 0.8, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0 and 5.0 vol%, starting with a fresh gas flow of 2 1/min followed by 4, 6 and 12 1/min. Thus each of the three isoflurane preparations was checked in six different vaporizers and with four different fresh gas flows. RESULTS: Within the concentration range used in clinical practice there was no significant difference in the delivery of the three isoflurane preparations. Each of the six vaporizers produced a controllable and predictable concentration of the three preparations. CONCLUSION: Vaporizers of Dräger type 19.n calibrated with forene deliver the same predictable concentration of the volatile anaesthetic when filled with isoflurane from Lilly or isoflurane from Pharmacia instead of forene and may be used without impairment in patient safety. In addition, no specific calibration with one of the new isoflurane preparations is required.

Effects of allelopathic substances produced by asparagus on incidence and severity of asparagus decline due toFusarium crown rot.

The effects of toxic components isolated from asparagus tissue onFusarium spp. and other soil microorganisms and their effects on the susceptibility of asparagus toFusarium crown rot was investigated to determine what role allelopathic substances may play in the asparagus ecosystem and in asparagus crown rot decline. Dried sterilized asparagus crown and root tissues were incorporated into pots of 3-month-old asparagus seedlings with and withoutFusarium inoculum. Root tissue alone and treatments in which crown and root tissues were combined with theFusarium inoculum showed significant reduction of plant growth over nontreated controls. Root and crown tissues were partitioned with polar and nonpolar solvents and bioassayed on pregerminated asparagus and cress seeds. Inhibition of radicle growth was confined to the polar fractions. Further separation with paper chromatography gave several fractions that were inhibitory to radish, cress, tomato seed germination as well as inhibitory to growth of pregerminated asparagus seeds. Crude extracts from roots and crown residues were bioassayed on many different fungal isolates on Petri plates and were found to inhibit the growth of oomycetous fungi. Extracts from the roots were found to be more active than extracts from other portions of the asparagus plants.

Isolation and characterization of phytotoxic compounds from asparagus (Asparagus officinalis L.) roots.

Potential allelochemicals from aqueous extracts of dried asparagus (Asparagus officinalis L.) roots were isolated and characterized. Active fractions separated by HPLC included ferulic, isoferulic, malic, citric, and fumaric acids. Soxhlet extraction of the residues also produced phytotoxic caffeic acid. Although none of these compounds, when applied singly, was active enough to account for the phytotoxicity of asparagus extracts, their combined effect might be additive or synergistic. An extract from lyophilized fresh root tissues contained a fraction that was one order of magnitude more toxic than any compound obtained from the dried roots. The most active component was isolated by TLC and characterized by [(1)H]NMR as methylenedioxycinnamic acid (MDCA). This compound provided severe inhibition of curly cress (Lepidium sativum L.) root and shoot growth at concentrations of 25 ppm or above.

No linkage of the interleukin-4 receptor locus on chromosome 16p11.2-12.1 with sarcoidosis in German multiplex families.

We typed 241 members of 62 sarcoidosis families with 136 affected siblings for three single nucleotide polymorphisms of the interleukin-4 receptor alpha-chain gene (IL4R). Allele frequencies in patients were compared to those of healthy unrelated control individuals. The segregation of the three-point IL4R haplotypes completed by two flanking highly polymorphic microsatellite polymorphisms revealed no evidence for linkage of the IL4R gene locus with sarcoidosis.