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Biomedical subjects

U Heinzmann

Publications and source records attributed to U Heinzmann.

At least 19 recordsLinked to original sources

Design, fabrication, and analysis of chirped multilayer mirrors for reflection of extreme-ultraviolet attosecond pulses.

Chirped Mo/Si multilayer coatings have been designed, fabricated, and characterized for use in extreme-ultraviolet attosecond experiments. By numerically simulating the reflection of the attosecond pulse from a multilayer mirror during the optimization procedure based on a genetic algorithm, we obtain optimized layer designs. We show that normal incidence chirped multilayer mirrors capable of reflecting pulses of approximately 100 attoseconds (as) duration can be designed by enhancing the reflectivity bandwidth and optimizing the phase-shift behavior. The chirped multilayer coatings have been fabricated by electron-beam evaporation in an ultrahigh vacuum in combination with ion-beam polishing of the interfaces and in situ reflectivity measurement for layer thickness control. To analyze the aperiodic layer structure by hard-x-ray reflectometry, we have developed an automatic fitting procedure that allows us to determine the individual layer thicknesses with an error of less than 0.05 nm. The fabricated chirped mirror may be used for production of 150-160 as pulses.

Journal Article↗

An overview on bioaerosols viewed by scanning electron microscopy.

Bioaerosols suspended in ambient air were collected with single-stage impactors at a semiurban site in southern Germany during late summer and early autumn. Sampling was mostly carried out at a nozzle velocity of 35 m/s, corresponding to a minimum aerodynamic diameter (cut-off diameter) of aerosol particles of 0.8 mum. The collected particles, sampled for short periods ( approximately 15 min) to avoid pile-up, were characterized by scanning electron microscopy (SEM). The observed bioaerosols include brochosomes, fungal spores, hyphae, insect scales, hairs of plants and, less commonly, bacteria and epicuticular wax. Brochosomes, which serve as a highly water repellent body coating of leafhoppers, are hollow spheroids with diameters around 400 nm, resembling C(60) or footballs (soccer balls). They are usually airborne not as individuals but in the form of large clusters containing up to 10,000 individual species or even more. Various types of spores and scales were observed, but assignment turned out be difficult due to the large number of fungi and insects from which they may have originated. Pollens were observed only once. The absence these presumably elastic particles suggests that they are frequently lost, at the comparatively high velocities, due to bounce-off from the nonadhesive impaction surfaces.

Aerosols↗

Toward time-resolved soft X-ray microscopy using pulsed fs-high-harmonic radiation.

Coherent soft X-ray sources open the way to new capabilities in high-resolution imaging, site- and element-specific spectroscopy and biomicroscopy. In this paper we demonstrate imaging with a table-top soft X-ray microscope. By combining a laser driven high-harmonic light source, optimized for having the maximum brightness at around 100 eV, a pair of multilayer mirrors to select a narrow spectral band and acting simultaneously as a condenser and a Fresnel zone plate as microscope objective, we were able to resolve 200 nm structures of a diatom sample. Further, the pulsed nature of our X-ray source offers the possibility of time-resolved spectromicroscopy with a temporal resolution in the order of a few femtoseconds.

Animals↗

Direct measurement of light waves.

The electromagnetic field of visible light performs approximately 10(15) oscillations per second. Although many instruments are sensitive to the amplitude and frequency (or wavelength) of these oscillations, they cannot access the light field itself. We directly observed how the field built up and disappeared in a short, few-cycle pulse of visible laser light by probing the variation of the field strength with a 250-attosecond electron burst. Our apparatus allows complete characterization of few-cycle waves of visible, ultraviolet, and/or infrared light, thereby providing the possibility for controlled and reproducible synthesis of ultrabroadband light waveforms.

Journal Article↗

Structural organization of DMPC lipid layers on chemically micropatterned self-assembled monolayers as biomimetic systems.

The growth structure of DMPC lipid layers on hydrophobic and hydrophilic alkylsilane-based self-assembled monolayers adsorbed on silicon has been investigated by means of X-ray reflectometry and atomic force microscopy. Hydrophilic modification of hydrophobically terminated ODS-SAMs has been achieved by dose-controlled irradiation with DUV light. While island formation of small DMPC bilayer islands is observed on hydrophobic SAM surfaces, closed layers of DMPC monolayers are formed on hydrophilic SAM surfaces. Furthermore, DMPC adsorption on chemically micropatterned substrates with alternating hydrophobic/hydrophilic surface properties has been studied by imaging ellipsometry and photoemission microscopy. Indication for at least partial bridging of hydrophobic areas by an adsorbed DMPC monolayer has been found.

Adsorption↗

Large-scale homogeneous molecular templates for femtosecond time-resolved studies of the guest-host interaction.

Self-assembled monolayer films based on iodobenzoyloxy-functionalized resorc[4]arenes were prepared on gold substrates to serve as model systems for future time-resolved studies of molecular recognition, a mechanism of outstanding importance in bioorganic systems. The film properties were tested using X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and imaging ellipsometry. An apparatus for time-resolved electron spectroscopy utilizing femtosecond soft X-ray pulses is capable of detecting iodine core-level photolines and the photoinduced dissociation after ultraviolet illumination. The developed technique holds promise for tracking the temporal evolution of chemical shifts of atomic markers as local probes for the dynamics of the guest-host interaction.

Benzoates↗

Atomic transient recorder.

In Bohr's model of the hydrogen atom, the electron takes about 150 attoseconds (1 as = 10(-18) s) to orbit around the proton, defining the characteristic timescale for dynamics in the electronic shell of atoms. Recording atomic transients in real time requires excitation and probing on this scale. The recent observation of single sub-femtosecond (1 fs = 10(-15) s) extreme ultraviolet (XUV) light pulses has stimulated the extension of techniques of femtochemistry into the attosecond regime. Here we demonstrate the generation and measurement of single 250-attosecond XUV pulses. We use these pulses to excite atoms, which in turn emit electrons. An intense, waveform-controlled, few cycle laser pulse obtains 'tomographic images' of the time-momentum distribution of the ejected electrons. Tomographic images of primary (photo)electrons yield accurate information of the duration and frequency sweep of the excitation pulse, whereas the same measurements on secondary (Auger) electrons will provide insight into the relaxation dynamics of the electronic shell following excitation. With the current approximately 750-nm laser probe and approximately 100-eV excitation, our transient recorder is capable of resolving atomic electron dynamics within the Bohr orbit time.

Journal Article↗

Time-resolved atomic inner-shell spectroscopy.

The characteristic time constants of the relaxation dynamics of core-excited atoms have hitherto been inferred from the linewidths of electronic transitions measured by continuous-wave extreme ultraviolet or X-ray spectroscopy. Here we demonstrate that a laser-based sampling system, consisting of a few-femtosecond visible light pulse and a synchronized sub-femtosecond soft X-ray pulse, allows us to trace these dynamics directly in the time domain with attosecond resolution. We have measured a lifetime of 7.9(-0.9)(+1.0) fs of M-shell vacancies of krypton in such a pump-probe experiment.

Journal Article↗

Experimental verification of quadrupole-dipole interference in spin-resolved photoionization.

We have measured the spin polarization of Xe (4p)(-1) photoelectrons after ionization with circularly polarized light at photon energies close to the ionization threshold where a resonant enhancement of quadrupole transitions has recently been predicted. At a reaction angle of 90 degrees a nonvanishing longitudinal spin polarization component of about 4% clearly indicates a quadrupole contribution to the photoexcitation. This is the first experimental evidence for the influence of nondipole transitions on the photoionization process at excitation energies much below 1 keV in an observable other than the intensity angular distribution.

Journal Article↗

Steering attosecond electron wave packets with light.

Photoelectrons excited by extreme ultraviolet or x-ray photons in the presence of a strong laser field generally suffer a spread of their energies due to the absorption and emission of laser photons. We demonstrate that if the emitted electron wave packet is temporally confined to a small fraction of the oscillation period of the interacting light wave, its energy spectrum can be up- or downshifted by many times the laser photon energy without substantial broadening. The light wave can accelerate or decelerate the electron's drift velocity, i.e., steer the electron wave packet like a classical particle. This capability strictly relies on a sub-femtosecond duration of the ionizing x-ray pulse and on its timing to the phase of the light wave with a similar accuracy, offering a simple and potentially single-shot diagnostic tool for attosecond pump-probe spectroscopy.

Journal Article↗

Enhanced values of the RBE and H ratio for cytogenetic effects induced by secondary electrons from an X-irradiated gold gurface.

The low-energy secondary electrons emerging from the entrance surface of an X-irradiated gold foil increase the dose to cells in contact with or at micrometer distances from this surface (Radiat. Res. 150, 92-100, 1998). We examined the effect of the spectrum of these low-energy electrons on the RBE for cytogenetic effects and showed that this RBE was increased. A monolayer of surface-attached human T lymphocytes was exposed to 60 kV X rays in the absence or presence of a gold foil positioned immediately behind the cell layer or separated from it by a Mylar foil 0.9 or 2 microm thick. The enhancement of dose in the cell nuclei caused by the photoelectrons and Auger electrons emerging from the entrance surface of the gold foil was measured by TSEE dosimetry. Dose enhancement factors of 55.7, 46.6 and 37.5 were obtained with 0, 0.9 and 2 microm of Mylar inserted between the gold surface and the cell layer. This large enhancement results from the photoelectric effect in the gold foil, as shown by the accompanying Monte Carlo calculations of the secondary electron spectra at the gold surface. Auger electrons from the gold foil generally were not able to penetrate into the cell nuclei except for that fraction of the cells that had a very thin (< 0.7 microm) layer of cytoplasm and membranes between gold surface and cell nucleus. The dose-yield curves for dicentric chromosomes plus centric rings and for acentric fragments obtained after exposures without or with the gold foil were linear-quadratic. The coefficient alpha, the slope of the linear yield component, was increased in the presence of the gold foil and showed RBE values ranging from 1.7 to 2.2 compared to exposures in absence of the gold foil. The ratio of the yield of interstitial deletions and dicentrics (H ratio) was significantly increased from about 0.17 in the absence of the gold foil to about 0.22 in the presence of the gold foil. The increases in the RBE and the H ratio are interpreted in microdosimetric terms: The preferred occurrence of electron track ends in the vicinity of the gold surface causes an increase in the dose-mean restricted linear energy transfer in cell nuclei exposed to the photoelectrons and Auger electrons.

Chromosome Aberrations↗

Attosecond metrology.

The generation of ultrashort pulses is a key to exploring the dynamic behaviour of matter on ever-shorter timescales. Recent developments have pushed the duration of laser pulses close to its natural limit-the wave cycle, which lasts somewhat longer than one femtosecond (1 fs = 10-15 s) in the visible spectral range. Time-resolved measurements with these pulses are able to trace dynamics of molecular structure, but fail to capture electronic processes occurring on an attosecond (1 as = 10-18 s) timescale. Here we trace electronic dynamics with a time resolution of </= 150 as by using a subfemtosecond soft-X-ray pulse and a few-cycle visible light pulse. Our measurement indicates an attosecond response of the atomic system, a soft-X-ray pulse duration of 650 +/- 150 as and an attosecond synchronism of the soft-X-ray pulse with the light field. The demonstrated experimental tools and techniques open the door to attosecond spectroscopy of bound electrons.

Journal Article↗

Asymmetry in photoelectron emission from chiral molecules induced by circularly polarized light.

In photoionization of free, unoriented chiral molecules with circularly polarized radiation, a significant circular dichroism, i.e., an asymmetry in the forward-backward electron emission, has been observed in the photoelectron angular distribution. This leads also to an asymmetry in the momentum transfer to the photoions. The spectra for the left- and right-handed enantiomers of bromocamphor exhibit asymmetries up to several percent which vary as a function of orbital binding energy. This enantioselective effect can similarly occur for biomolecules with handedness, like amino acids, and may thus be a contributing factor related to the origin of the terrestrial biomolecular homochirality.

Journal Article↗

Ischemically compromised myocardium displays different time-courses of functional recovery: correlation with morphological alterations?

OBJECTIVE: It has been demonstrated that positron emission tomography (PET) predicts the functional recovery of viable but ischemically compromised myocardium. Reversible contractile dysfunction after revascularization has been reported for 'hibernating myocardium' and stunned myocardium, however, there are little data concerning the time-course and the extent of improvement of the two different pathophysiological conditions. METHODS: Twenty-nine patients with advanced coronary artery disease and severely reduced left ventricular function (EF 18--35%) who were referred for isolated coronary artery bypass grafting underwent preoperative PET viability assessment and were functionally assessed by two-dimensional echocardiography preoperatively at 11 days, 14 weeks, and more than 12 months after surgical revascularization. Intraoperative biopsies were taken from dysfunctional areas defined by PET as segments of normal perfusion and normal metabolism (stunned myocardium) and from areas with a 'mismatch' between perfusion and metabolism (hibernating myocardium). The degree of morphological alterations was evaluated by electron microscopy. RESULTS: In 70% of the 240 dysfunctional segments, 'stunned myocardium' was present whereas 'hibernating myocardium' could be detected in only 24% (P < 0.01). Hibernating myocardium was associated with more severe preoperative wall motion abnormalities and incomplete postoperative recovery. After 1 year, 31% of 'stunned' segments vs. only 18% of 'hibernating' segments showed complete functional restoration (P < 0.05). This incomplete improvement was associated with more severe morphological alterations including depletion of sarcomeres, accumulation of glycogen, loss of sarcoplasmatic reticulum, and cellular sequestration. CONCLUSIONS: These data indicate that in patients with severe ischemic left ventricular dysfunction 'stunned myocardium' is more prevalent than 'hibernation'. Functional normalization is more frequent in 'stunned' segments, whereas areas of 'hibernation' showed more severe tissue injury and protracted recovery. Different degrees of myocardial injury coexist in most patients, which determines the time-course and the extent of improvement after revascularization.

Aged↗

Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats.

The cardiovascular system is currently considered a target for particulate matter, especially for ultrafine particles. In addition to autonomic or cytokine mediated effects, the direct interaction of inhaled materials with the target tissue must be examined to understand the underlying mechanisms. In the first approach, pulmonary and systemic distribution of inhaled ultrafine elemental silver (EAg) particles was investigated on the basis of morphology and inductively coupled plasma mass spectrometry (ICP-MS) analysis. Rats were exposed for 6 hr at a concentration of 133 microg EAg m(3) (3 x 10(6) cm(3), 15 nm modal diameter) and were sacrificed on days 0, 1, 4, and 7. ICP-MS analysis showed that 1.7 microg Ag was found in the lungs immediately after the end of exposure. Amounts of Ag in the lungs decreased rapidly with time, and by day 7 only 4% of the initial burden remained. In the blood, significant amounts of Ag were detected on day 0 and thereafter decreased rapidly. In the liver, kidney, spleen, brain, and heart, low concentrations of Ag were observed. Nasal cavities, especially the posterior portion, and lung-associated lymph nodes showed relatively high concentrations of Ag. For comparison, rats received by intratracheal instillation either 150 microL aqueous solution of 7 microg silver nitrate (AgNO(3) (4.4 microg Ag) or 150 microL aqueous suspension of 50 microg agglomerated ultrafine EAg particles. A portion of the agglomerates remained undissolved in the alveolar macrophages and in the septum for at least 7 days. In contrast, rapid clearance of instilled water-soluble AgNO(3) from the lung was observed. These findings show that although instilled agglomerates of ultrafine EAg particles were retained in the lung, Ag was rapidly cleared from the lung after inhalation of ultrafine EAg particles, as well as after instillation of AgNO(3), and entered systemic pathways.

Administration, Inhalation↗

Sudden interchannel interaction in the Tl 6p ionization above the 5d threshold

The linear magnetic dichroism in the angular distribution of Tl 5d and 6p photoelectrons and their dynamical spin polarization have been measured between hnu = 30 and 50 eV. In contrast to the Xe 5p photoionization at the 4d threshold, our results show that above the Tl 5d threshold strong interchannel coupling effects induce a sudden increase in the asymptotic phase difference of the s and d waves for the Tl 6p ionization. This shows that the valence excitation is different for resonant (Xe 4d) and nonresonant (Tl 5d) excitation from subvalence shells.

Journal Article↗

Dissolution of copper-rich granules in hepatic lysosomes by D-penicillamine prevents the development of fulminant hepatitis in Long-Evans cinnamon rats.

BACKGROUND/AIM: The Long-Evans cinnamon rat has a mutation homologous to the human Wilson disease gene, leading to gross copper accumulation and the development of hepatitis. D-penicillamine, a copper-chelating drug widely and efficiently used in treating Wilson disease, has also been shown to prevent hepatitis in Long-Evans cinnamon rats. The objectives of this study were: i) to investigate the effectiveness of D-penicillamine when administered to the already affected animals, and ii) to elucidate the mechanism of action of the drug. METHODS: Long-Evans cinnamon rats were divided into groups according to age and treatment with D-penicillamine. The drug was administered orally before and after the onset of hepatitis. Livers were examined by light and electron microscopy. The effect of D-penicillamine on the subcellular distribution and binding of copper was investigated in more detail. Finally, the interaction between D-penicillamine and specific hepatic copper-binding proteins was studied in vitro. RESULTS: D-penicillamine when given to either healthy or diseased animals prevented or reversed hepatitis, respectively. The drug particularly inhibited the disease-specific accumulation of copper in lysosomes of hepatocytes, tissue macrophages and Kupffer cells. When administered to diseased animals, the drug sequestered copper particularly from insoluble lysosomal particles. According to results obtained in vitro, the mobilization of this copper is likely to proceed through the solubilization of these particles. In contrast and as supported by the in vitro data, D-penicillamine had only a minor effect on copper bound to metallothionein in the cytosol. CONCLUSION: Our findings on the Long-Evans cinnamon rat provide some conclusions on the mechanism of action of D-penicillamine in Wilson disease therapy. The drug prevents the formation or promotes the solubilization of copper-rich particles which occur in lysosomes of hepatocytes and Kupffer cells in the livers of patients with Wilson disease. Once chelated with D-penicillamine copper might then be excreted into urine. However, the mobilization of copper by D-penicillamine seems to be limited due to the binding of the metal to metallothionein in liver cytosol. This copper, even at relatively high concentrations, apparently may be well tolerated.

Animals↗

Loss of the differentiated phenotype precedes apoptosis of ROS 17/2.8 osteoblast-like cells.

Osteoblast cells, recruited from mesenchymal precursors, initiate the final phase of bone remodeling by secreting the protein components of the bone matrix. Upon completion of remodeling, some of these osteoblasts may further differentiate, giving rise to matrix-embedded osteocytes and bone lining cells. The fate of the remaining osteoblasts is unknown, although by analogy with other cell systems, apoptotic cell death may be involved. We induced and characterized the apoptotic process in ROS 17/2.8 osteosarcoma cells by growing and maintaining confluent cultures in low serum medium. At confluence, but prior to apoptosis, the levels of collagen type I, alkaline phosphatase, and osteocalcin mRNAs declined abruptly. Expression of two housekeeping genes (ribosomal protein RPS6 and GAPDH) remained unchanged. Some 72 hours later cells began to show morphological and biochemical features of apoptosis, namely, chromatin condensation, membrane budding, and internucleosomal degradation of genomic DNA. We conclude that serum starvation-induced apoptosis of ROS 17/2.8 cells can serve as a model for investigating the mechanisms of osteoblastic apoptosis.

Animals↗