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Biomedical subjects

W Hofmann

Publications and source records attributed to W Hofmann.

At least 19 recordsLinked to original sources
PubMed2007

Modeling lung cancer incidence in rats following exposure to radon progeny.

Lung cancer incidence in Sprague-Dawley rats was simulated by a biologically based carcinogenesis model, which is formulated mathematically in terms of a stochastic state-vector model. Doses to the sensitive target cells in the bronchial epithelium of the rat lung were calculated by a stochastic dosimetry model, considering the distinct monopodial branching structure and the crossfire of alpha particles from alveolar tissue to bronchial epithelium. Bronchial and alveolar cellular doses could reasonably be approximated by lognormal distributions, with geometric standard deviations (GSD) between 7 and 10, depending on exposure conditions. Based on a dose-exposure conversion factor of 8.5 mGy WLM(-1) and a GSD of 8, lung cancer incidences were calculated for each cumulative exposure category in the rat inhalation study, consisting of different exposure rates and exposure times. The fair agreement between theoretical predictions and experimental data over the whole exposure range emphasises the necessity to incorporate the full cellular dose distributions rather than their mean values.

Animals↗
PubMed2006

A model for the induction of chromosome aberrations through direct and bystander mechanisms.

A state vector model (SVM) for chromosome aberrations and neoplastic transformation has been adapted to describe detrimental bystander effects. The model describes initiation (formation of translocations) and promotion (clonal expansion and loss of contact inhibition of initiated cells). Additional terms either in the initiation model or in the rate of clonal expansion of initiated cells, describe detrimental bystander effects for chromosome aberrations as reported in the scientific literature. In the present study, the SVM with bystander effects is tested on a suitable dataset. In addition to the simulation of non-linear effects, a classical dataset for neoplastic transformation in C3H 10T1/2 cells after alpha particle irradiation is used to show that the model without bystander features can also describe LNT-like dose responses. A published model for bystander induced neoplastic transformation was adapted for chromosome aberration induction and used to compare the results obtained with the different models.

Animals↗
PubMed2006

Incorporation of microdosimetric concepts into a biologically-based model of radiation carcinogenesis.

The generalised state-vector model of radiation carcinogenesis (SVM) simulates radiation induced biological effects by expressing the transition rates between the various initiation and promotion stages in terms of dose rate for low and high linear energy transfer (LET) particles. In the present work, the SVM has been reformulated to incorporate single track characteristics of particles with varying LET. Transition rates of the initiation phase were expressed as functions of LET by describing the complexity and clustering of DNA double strand breaks (DSBs) and its effect on repair kinetics, while the promotion phase was reformulated based on a multi-target single-hit hypothesis. Such an approach allows the consideration of hit frequencies and the variability of the specific energy and LET spectra of radon progeny alpha particles in bronchial target cells for different exposure conditions.

Alpha Particles↗
PubMed2006

HESS observations of the galactic center region and their possible dark matter interpretation.

The detection of gamma rays from the source HESS J1745-290 in the Galactic Center (GC) region with the High Energy Spectroscopic System (HESS) array of Cherenkov telescopes in 2004 is presented. After subtraction of the diffuse gamma-ray emission from the GC ridge, the source is compatible with a point source with spatial extent less than 1.2;{'}(stat) (95% C.L.). The measured energy spectrum above 160 GeV is compatible with a power law with photon index of 2.25+/-0.04(stat)+/-0.10(syst) and no significant flux variation is detected. It is finally found that the bulk of the very high energy emission must have non-dark-matter origin.

Journal Article↗
PubMed2006

Fast variability of tera-electron volt gamma rays from the radio galaxy M87.

The detection of fast variations of the tera-electron volt (TeV) (10(12) eV) gamma-ray flux, on time scales of days, from the nearby radio galaxy M87 is reported. These variations are about 10 times as fast as those observed in any other wave band and imply a very compact emission region with a dimension similar to the Schwarzschild radius of the central black hole. We thus can exclude several other sites and processes of the gamma-ray production. The observations confirm that TeV gamma rays are emitted by extragalactic sources other than blazars, where jets are not relativistically beamed toward the observer.

Journal Article↗
PubMed2006

Stochastic modeling predictions for the clearance of insoluble particles from the tracheobronchial tree of the human lung.

Bronchial clearance of deposited particles was simulated using a stochastic model of the tracheobronchial tree. The clearance model introduced in this study considers (1) a continuous decrease of the mucus thickness from the trachea to the terminal bronchioles according to a linear or an exponential function, (2) the possibility of mucus discontinuities, which are mainly found in intermediate and distal airways of the tracheobronchial compartment, (3) mucus production in proximal airways, (4) a slow bronchial clearance phase due to the capture of a defined particle fraction f (s) in the periciliary sol phase, and (5) an eventual delay of the mucociliary transport at carinal ridges of airway bifurcations. Based on the concept of mucus volume conservation in single bifurcations, a reduction of the thickness of the mucus blanket from proximal to distal airways causes a significant increase of the mucus velocities in small ciliated airways compared to other stochastic modeling predictions assuming a constant thickness of the mucus layer throughout the conducting airways. This effect is further enhanced by the consideration of mucus discontinuities. In contrast, the ability of bronchial airways to produce a certain volume of mucus has a decreasing effect on the mucus velocities. In all generated clearance velocity models, mucociliary clearance is completely terminated within 24 h after exposure, consistent with the experimental evidence. Implementation of a slow bronchial clearance phase predicts a long-term retention fraction, which is fully cleared from the lung after several weeks. For 1-microm MMAD particles, 24-h retention varies between 0.42 and 0.52, in line with the suggestions of the ICRP. Mucus delay at carinal ridges only affects short-term clearance by increasing the retained particle fraction at a given time, while long-term retention is not influenced.

Bronchi↗
PubMed2006

Modelling the effect of non-uniform radon progeny activities on transformation frequencies in human bronchial airways.

The effects of radiological and morphological source heterogeneities in straight and Y-shaped bronchial airways on hit frequencies and microdosimetric quantities in epithelial cells have been investigated previously. The goal of the present study is to relate these physical quantities to transformation frequencies in sensitive target cells and to radon-induced lung cancer risk. Based on an effect-specific track length model, computed linear energy transfer (LET) spectra were converted to corresponding transformation frequencies for different activity distributions and source-target configurations. Average transformation probabilities were considerably enhanced for radon progeny accumulations and target cells at the carinal ridge, relative to uniform activity distributions and target cells located along the curved and straight airway portions at the same exposure level. Although uncorrelated transformation probabilities produce a linear dose-effect relationship, correlated transformations first increase depending on the LET, but then decrease significantly when exceeding a defined number of hits or cumulative exposure level.

Air Pollutants, Radioactive↗
PubMed2006

A low level of extragalactic background light as revealed by gamma-rays from blazars.

The diffuse extragalactic background light consists of the sum of the starlight emitted by galaxies through the history of the Universe, and it could also have an important contribution from the 'first stars', which may have formed before galaxy formation began. Direct measurements are difficult and not yet conclusive, owing to the large uncertainties caused by the bright foreground emission associated with zodiacal light. An alternative approach is to study the absorption features imprinted on the gamma-ray spectra of distant extragalactic objects by interactions of those photons with the background light photons. Here we report the discovery of gamma-ray emission from the blazars H 2356 - 309 and 1ES 1101 - 232, at redshifts z = 0.165 and z = 0.186, respectively. Their unexpectedly hard spectra provide an upper limit on the background light at optical/near-infrared wavelengths that appears to be very close to the lower limit given by the integrated light of resolved galaxies. The background flux at these wavelengths accordingly seems to be strongly dominated by the direct starlight from galaxies, thus excluding a large contribution from other sources-in particular from the first stars formed. This result also indicates that intergalactic space is more transparent to gamma-rays than previously thought.

Journal Article↗
PubMed2006

Discovery of very-high-energy gamma-rays from the Galactic Centre ridge.

The source of Galactic cosmic rays (with energies up to 10(15) eV) remains unclear, although it is widely believed that they originate in the shock waves of expanding supernova remnants. At present the best way to investigate their acceleration and propagation is by observing the gamma-rays produced when cosmic rays interact with interstellar gas. Here we report observations of an extended region of very-high-energy (> 10(11) eV) gamma-ray emission correlated spatially with a complex of giant molecular clouds in the central 200 parsecs of the Milky Way. The hardness of the gamma-ray spectrum and the conditions in those molecular clouds indicate that the cosmic rays giving rise to the gamma-rays are likely to be protons and nuclei rather than electrons. The energy associated with the cosmic rays could have come from a single supernova explosion around 10(4) years ago.

Journal Article↗
PubMed2005

A multi-compartment model for slow bronchial clearance of insoluble particles--extension of the ICRP human respiratory tract models.

To incorporate the various mechanisms that are presently assumed to be responsible for the experimentally observed slow bronchial clearance into the HRTM, a multi-compartment model was developed to simulate the clearance of insoluble particles in the tracheobronchial tree of the human lung. The new model considers specific mass transfer paths that may play an important role for slow bronchial clearance. These include the accumulation of particulate mass in the periciliary sol layer, phagocytosis of stored particles by airway macrophages and uptake of deposited mass by epithelial cells. Besides the gel layer representing fast mucociliary clearance, all cellular and non-cellular units involved in the slow clearance process are described by respective compartments that are connected by specific transfer rates. The gastrointestinal tract and lymph nodes are included into the model as final accumulation compartments, to which mass is transferred via the airway route and the transepithelial path. Predicted retention curves correspond well with previously published data.

Absorption↗
PubMed2005

Discovery of very high energy gamma rays associated with an x-ray binary.

X-ray binaries are composed of a normal star in orbit around a neutron star or stellar-mass black hole. Radio and x-ray observations have led to the presumption that some x-ray binaries called microquasars behave as scaled-down active galactic nuclei. Microquasars have resolved radio emission that is thought to arise from a relativistic outflow akin to active galactic nuclei jets, in which particles can be accelerated to large energies. Very high energy gamma-rays produced by the interactions of these particles have been observed from several active galactic nuclei. Using the High Energy Stereoscopic System, we find evidence for gamma-ray emission of >100 gigaelectron volts from a candidate microquasar, LS 5039, showing that particles are also accelerated to very high energies in these systems.

Journal Article↗
PubMed2005

Microdosimetry of radon progeny alpha particles in bronchial airway bifurcations.

A Monte Carlo code, initially developed for the calculation of microdosimetric spectra for alpha particles in cylindrical airways, has been extended to allow the computation of microdosimetric parameters for multiple source-target configurations in bronchial airway bifurcations. The objective of the present study was to investigate the effects of uniform and non-uniform radon progeny surface activity distributions in symmetric and asymmetric bronchial airway bifurcations on absorbed dose, hit frequency, lineal energy, single hit specific energy and LET spectra. In order to assess the effects of multiple hits, dose-dependent specific energy spectra were calculated by solving the compound Poisson process by iterative convolution. While the simulations showed significant differences of cellular dose quantities at different cell locations for uniformly distributed surface activities, even higher variations, as high as several orders of magnitude, were observed for non-uniform surface activity distributions, depending on the location of the cell and the local activity distribution.

Air Pollutants, Radioactive↗
PubMed2005

Radiocaesium in flowing waters of highly contaminated Austrian alpine areas.

In this study the runoff of (137)Cs, mainly originated from the Chernobyl fallout, from highly contaminated alpine regions in Salzburg (Austria) is discussed. Twenty-five water-samples and 25 sediment-samples were taken from creeks of different size to determine the runoff of dissolved (137)Cs and Cs-binding characteristics to different particle size classes in the sediments. The hypothesis, that specific activity of the sediments depended on particle size and the surface of the particle, was proved with some modifications. Caesium activity concentration in water showed a negative correlation with electrical conductivity, while no significant correlations were detectable with other variables (pH, temperature, and altitude). Enormous differences and the variations found in the (137)Cs-concentrations in water can be explained by the electrical conductivity without any dependency on the inventory of the catchment. The sediment samples analysed showed a negative correlation between specific activity [Bq/kg] and particle-diameter, mainly explained by (137)Cs-uptake proportional to the particle surface per mass.

Altitude↗
PubMed2005

A new population of very high energy gamma-ray sources in the Milky Way.

Very high energy gamma-rays probe the long-standing mystery of the origin of cosmic rays. Produced in the interactions of accelerated particles in astrophysical objects, they can be used to image cosmic particle accelerators. A first sensitive survey of the inner part of the Milky Way with the High Energy Stereoscopic System (HESS) reveals a population of eight previously unknown firmly detected sources of very high energy gamma-rays. At least two have no known radio or x-ray counterpart and may be representative of a new class of "dark" nucleonic cosmic ray sources.

Journal Article↗
PubMed2005

Microdosimetry of inhomogeneous radon progeny distributions in bronchial airways.

A Monte Carlo code, initially developed for the calculation of microdosimetric spectra for alpha particles in cylindrical airways, has been extended to allow the computation (i) of additional microdosimetric parameters and (ii) for realistic exposure conditions in human bronchial airways with respect to surface activity distribution and airway geometry. The objective of the present study was to investigate the effects of non-uniform distributions of radon progeny activities in bronchial airways on cellular energy deposition parameters. Significant variations of hit frequencies, doses and microscopic energy deposition patterns were observed for epithelial cell nuclei, depending strongly on the assumed activity distributions. Thus, epithelial cells located at different positions in a given bronchial airway may experience a wide range of biological responses. The results obtained suggest that the hit frequency may be the primary physical parameter for alpha particles, supplemented by microdosimetric single event spectra, to be related to biological effects for chronic low level exposures.

Administration, Inhalation↗
PubMed2005

Cystatin C as a marker of GFR--history, indications, and future research.

OBJECTIVE: To summarize recent knowledge on the small molecular weight protein cystatin C (cys-C) and its use as a marker of the glomerular filtration rate (GFR). METHODS: A multinational expert meeting was held in April 2002 in Marburg, Germany. Contributors summarized their main findings. CONCLUSIONS: Cys-C is at least equal if not superior to serum creatinine as a marker of GFR. The independence from height, gender, age, and muscle mass is advantageous. Select patient groups such as children, the elderly, and patients with reduced muscle mass benefit in particular.

Adolescent↗
PubMed2005

3D-Visualization of particle deposition patterns in the human lung generated by Monte Carlo modeling: methodology and applications.

An advanced stochastic model is described which enables the generation of three-dimensional particle deposition patterns in the human lung. While particle trajectories are represented as a combination of randomly oriented vectors in a coordinate system with the trachea defining the z direction, deposition sites of single particles are determined by using a grid of specific volume elements (voxels). After storage in an array, the spatial coordinates are visualized with an appropriate graphic editor, enabling the combination of respective deposition images with lung outlines and the creation of two-dimensional distributions by sectioning the three-dimensional structures at pre-defined positions.

Aerosols↗