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Biomedical subjects

H Horn

Publications and source records attributed to H Horn.

At least 19 recordsLinked to original sources

Sex differences in semantic processing: event-related brain potentials distinguish between lower and higher order semantic analysis during word reading.

Behavioral studies suggest that women and men differ in the strategic elaboration of verbally encoded information especially in the absence of external task demand. However, measuring such covert processing requires other than behavioral data. The present study used event-related potentials to compare sexes in lower and higher order semantic processing during the passive reading of semantically related and unrelated word pairs. Women and men showed the same early context effect in the P1-N1 transition period. This finding indicates that the initial lexical-semantic access is similar in men and women. In contrast, sexes differed in higher order semantic processing. Women showed an earlier and longer lasting context effect in the N400 accompanied by larger signal strength in temporal networks similarly recruited by men and women. The results suggest that women spontaneously conduct a deeper semantic analysis. This leads to faster processing of related words in the active neural networks as reflected in a shorter stability of the N400 map in women. Taken together, the findings demonstrate that there is a selective sex difference in the controlled semantic analysis during passive word reading that is not reflected in different functional organization but in the depth of processing.

Adult↗

Comparison of spatial and temporal pattern for fMRI obtained with BOLD and arterial spin labeling.

Functional magnetic resonance imaging (fMRI) is presently either performed using blood oxygenation level-dependent (BOLD) contrast or using cerebral blood flow (CBF), measured with arterial spin labeling (ASL) technique. The present fMRI study aimed to provide practical hints to favour one method over the other. It involved three different acquisition methods during visual checkerboard stimulation on nine healthy subjects: 1) CBF contrast obtained from ASL, 2) BOLD contrast extracted from ASL and 3) BOLD contrast from Echo planar imaging. Previous findings were replicated; i) no differences between the three measurements were found in the location of the activated region; ii) differences were found in the temporal characteristics of the signals and iii) BOLD has significantly higher sensitivity than ASL perfusion. ASL fMRI was favoured when the investigation demands for perfusion and task related signal changes. BOLD fMRI is more suitable in conjunction with fast event related design.

Arteries↗

Oxygen profiles and biomass distribution in biopellets of Aspergillus niger.

Morphology of fungal pellets has a significant influence on mass transfer and turnover processes in submerged cultures. There are many reports in literature that biomass is not distributed homogeneously over the pellet radius, yet quantitative data is rare. This study presents a method for the quantification of fungal pellet structure (Aspergillus niger). Confocal laser scanning microscopy (CLSM) is used in combination with image analysis freeware (Image J). Hyphal distribution is resolved spatially in radial direction. Quantitative morphological parameters are derived from digital images especially from the peripheral regions of the pellet that are not oxygen limited. This morphological information is combined with data of microelectrode measurements in the same pellets. Results show that the morphological parameters obtained can describe the impact of pellet structure on oxygen gradients much better than average biomass density. It is concluded that CLSM and image analysis are powerful tools not only to generate valuable data for quantitative description of pellet morphology. In addition, this data may be used in mathematical models to improve predictions of mass transfer and substrate conversion in mycelial aggregates.

Aspergillus niger↗

Volumetric measurements of bacterial cells and extracellular polymeric substance glycoconjugates in biofilms.

In this study an enrichment culture developed from activated sludge was used to investigate the architecture of fully hydrated multispecies biofilms. The assessment of biofilm structure and volume was carried out using confocal laser scanning microscopy (CLSM). Bacterial cell distribution was determined with the nucleic acid-specific stain SYTO 60, whereas glycoconjugates of extracellular polymeric substances (EPS) were stained with the Alexa-488-labeled lectin of Aleuria aurantia. Digital image analysis was employed for visualization and quantification of three-dimensional CLSM data sets. The specific volumes of the polymeric and cellular biofilm constituents were quantified. In addition, gravimetric measurements were done to determine dry mass and thickness of the biofilms. The data recorded by the CLSM technique and the gravimetric data were then compared. It was shown that the biofilm thicknesses determined with both methods agree well for slow-growing heterotrophic and chemoautotrophic biofilms. In addition, for slow-growing biofilms, the volumes and masses calculated from CLSM and the biomass calculated from gravimetric measurements were also comparable. For fast-growing heterotrophic biofilms cultivated with high glucose concentrations the data sets fit to a lesser degree, but still showed the same common trend. Compared with traditional gravimetric measurements, CLSM allowed differential recording of multiple biofilm parameters with subsequent three-dimensional visualization and quantification. The quantitative three-dimensional results recorded by CLSM are an important basis for understanding, controlling, exploiting, and modeling of biofilms.

Bacteria, Aerobic↗

Behaviour of biofilm systems under varying hydrodynamic conditions.

Heterotrophic biofilms were cultivated in long-term experiments in biofilm tube reactors. During the biofilm cultivation the substrate loading of glucose was kept constant while the hydrodynamic conditions were changed stepwise. To describe the behaviour of the biofilm structure under these varying flow conditions the mass transfer and transport at the bulk/biofilm interface and inside the biofilm was investigated with oxygen microelectrodes. Furthermore, the biofilm density was used to describe the biofilm compactness before and after the change of the hydrodynamic condition. The obtained results show that the biofilm density and also the substrate flux decreased with decreasing flow velocity in the bulk phase. Additionally the slope of the oxygen concentration profiles decreased and the thickness of the concentration boundary layer increased. On the other hand, increasing the flow velocity in the bulk phase led both to a higher biofilm density and a higher maximum substrate flux. The biofilm surface became more homogenous and the thickness of the concentration boundary layer decreased. The time for adaptation of the biofilm structure after changing the hydrodynamic conditions ranged between 1 and 3 weeks.

Biofilms↗

Growth, structure and oxygen penetration in particle supported autotrophic biofilms.

Particle supported autotrophic biofilms were cultivated in external-loop airlift reactors at two different pumice concentrations. Oxygen microelectrodes were used to investigate substrate transport and conversion. A special flow cell was designed for the measurement of oxygen concentration profiles in the particle supported biofilms under defined hydrodynamic conditions. The oxygen concentration profiles inside the biofilms were found to be steeper at high flow velocities in the bulk phase of the flow cell compared to those at low flow velocities. Furthermore, the oxygen flux increased and the thickness of the concentration boundary layer decreased with increasing flow velocity. This dependence was found to be more pronounced in less dense biofilms out of airlift reactors with lower pumice concentrations. In addition confocal laser scanning microscopy (CLSM) was used to visualize the biofilm structure. The volume fractions of bacteria and extracellular polymeric substances (lectin-specific EPS-glycoconjugates) were measured in living fully hydrated biofilms. Both the microelectrode and CLSM measurement showed the influence of shear stress on particle supported biofilms. A higher particle concentration led to dense biofilms with a homogeneous surface, lower thickness of the concentration boundary layer and steeper oxygen concentration profiles. The combination of both techniques allows a detailed and quantitative characterisation of particle associated biofilm structure and function.

Biofilms↗

RIONET: a water quality management tool for river basins.

The water quality management tool RIONET for river basins has been developed with regard to the EU Water Framework Directive. The management tool can simulate the water quality in catchment basins not only in the dimension of a single river but in whole river networks. A submodel of the IWA River Water Quality Model No. 1 is used in RIONET. The river model is based on the assumption that self purification processes in the river takes place both in the benthic biofilm and the bulk water phase. Laboratory experiments with sediment cores underline the major role of the benthic biofilm. The input parameters of the management tool such as volumetric flow rates from waste water treatment plants and flow velocities and discharge in the main river and its tributaries can be loaded directly from geographic information systems (GIS). The subcatchment basin of the river Bode in Saxon Anhalt was used for test runs of RIONET.

Biofilms↗

Simulation of biofilm growth, substrate conversion and mass transfer under different hydrodynamic conditions.

The hydrodynamic conditions and the substrate load in biofilm systems are two main parameters which influence the biofilm growth in particular the structure, density and thickness. In a long term study on heterotrophic biofilms in biofilm tube reactors the investigation has focussed on mass transfer at the bulk/biofilm interface, the biofilm density and the substrate conversion rates. To study the mass transfer phenomena at the bulk/biofilm interface oxygen profiles have been measured directly in tube reactors with microelectrodes. Microelectrode studies, substrate conversion rates and biofilm densities were used to formulate model equations for the simulation of biofilm growth under different hydrodynamic and substrate conditions. It can be shown that the mass transfer at any time is strongly coupled with the growth conditions during the biofilm cultivation. On the one side the calculated Sherwood numbers were coupled to the present hydraulic conditions, on the other side in addition the growth conditions such as growth rate and Reynolds number during biofilm cultivation were considered.

Biofilms↗

2D simulation of transport and degradation in the River Rhine.

A simple 2D model has been developed for the simulation of mass transport and degradation of substances in the river Rhine. The model describes mass transport in the flow direction with a convective and a dispersive term. Transversal transport is described by segmenting the river and formulating a transversal exchange coefficient between the segments. Degradation can be formulated with any kinetics from first order to complex enzyme kinetics. The model was verified with monitoring data from the river Rhine. The hydrodynamic parameters such as dispersion coefficients and exchange coefficients were fitted to the conductivity, which was assumed to be non-degradable. The degradation term was fitted to ammonia values. The model was used to simulate measured concentrations of a readily (Aniline) and a poorly biodegradable substance (1,4-Dioxan) 10 m from the left river bank. It was the objective of this research program to develop a model which allows a realistic estimation of the locally and regionally predicted environmental concentration of chemical substances in the EU risk assessment scheme.

Ammonia↗

FLASHFLOOD: a 3D field-based similarity search and alignment method for flexible molecules.

A three-dimensional field-based similarity search and alignment method for flexible molecules is introduced. The conformational space of a flexible molecule is represented in terms of fragments and torsional angles of allowed conformations. A user-definable property field is used to compute features of fragment pairs. Features are generalizations of CoMMA descriptors that characterize local regions of the property field by its local moments. The features are invariant under coordinate system transformations. Features taken from a query molecule are used to form alignments with fragment pairs in the database. An assembly algorithm is then used to merge the fragment pairs into full structures, aligned to the query. Key to the method is the use of a context adaptive descriptor scaling procedure as the basis for similarity. This allows the user to tune the weights of the various feature components based on examples relevant to the particular context under investigation. The property fields may range from simple, phenomenological fields, to fields derived from quantum mechanical calculations. We apply the method to the dihydrofolate/methotrexate benchmark system, and show that when one injects relevant contextual information into the descriptor scaling procedure, better results are obtained more efficiently. We also show how the method works and include computer times for a query from a database that represents approximately 23 million conformers of seventeen flexible molecules.

Algorithms↗

Modelling the structure and function of extracellular polymeric substances in biofilms with new numerical techniques.

The objective of this study is the mathematical description of the structure and function of the extracellular polymeric substances (EPS) in biofilms. The basic assumptions of the EPS biofilm model are: the production of EPS in biofilms is coupled to the growth of micro-organisms the production of EPS is additionally coupled to the substrate conditions the EPS represent a considerable volume fraction of the matrix in biofilms and thus the density of the biofilms is strongly influenced by the EPS sorption of biocides and pollutants in biofilms occurs mainly to EPS the EPS can be used as an energy source during substrate limited phases. The mathematical model has been derived as a system of partial differential equations. The numerical solution of these complex balance equations has been done by a self-adaptive Galerkin-h-p-method. It can be shown, that on the one hand the simulation of substrate conversion and biofilm growth with the EPS-biofilm model yields similar results as the known biofilm models without consideration of the EPS fraction. On the other hand the advantage of the EPS-biofilm model is a better understanding of biofilm structure, which is mainly influenced by the EPS fraction in the biofilm. Furthermore, the sorption of pollutants, such as heavy metals and chlorinated organic substances, can be simulated in more detail.

Adsorption↗

CNS infection with clostridium septicum.

We present an unusual case of Clostridium septicum brain infection in a 72-yr-old woman who had no underlying malignant disease. The infection spread from a localized sit to the CNS causing gas formation. The patient died rapidly.

Aged↗

Size-exclusion chromatography of plasma proteins with high molecular masses.

Two different hydrophilic materials with large pores, Superose 6 and Fractogel EMD BioSec (S), which are designed for size-exclusion chromatography (SEC) of plasma proteins with high molecular masses, are tested for their performance on a preparative scale. The model mixtures are preparations of the clotting factors VIII (FVIII) and IX (FIX). A combination of a Fractogel EMD BioSec (S) column and a Superose 6 column has proved to be particularly effective for separations in a wide molecular size range, from several millions down to about 20,000. Superose 6 showed good results on a small scale as well as on a large scale, even in the molecular mass range over 1,000,000. However, recovery of FVIII clotting activity was less than 70% with this material and therefore not satisfactory. Fractogel did not perform well in terms of separation on a small scale. However, in the case of biopolymers with high molecular masses, separation was improved by using larger columns. With Fractogel, recovery of activity of the two clotting factors FVIII and FIX was satisfactory, above 80%. On a large scale, the active fraction in the clotting factor concentrate was successfully separated from the non-active fraction with either size exclusion (SE) material. In the preparation under investigation, the clotting factor VIII is found in a complex with the von Willebrand factor (vWF). The FVIII-vWF complex has a molecular mass of several millions. It dissociates in the presence of high concentrations of Ca2+ ions. Under such conditions FVIII and vWF were successfully separated with both SEC columns.

Chromatography, Gel↗

A recurrent glycine substitution mutation, G2043R, in the type VII collagen gene (COL7A1) in dominant dystrophic epidermolysis bullosa.

Dystrophic epidermolysis bullosa (DEB) is caused by mutations in the type VII collagen gene (COL7A1). Nearly all cases of dominant DEB are caused by glycine substitution mutations occurring within the triple helical region of type VII collagen, and most of the mutations are unique to individual families. In this study, we identified a patient of Hispanic-Mexican origin with a mild form of DEB, which resulted from a de novo dominant glycine substitution, G2043R, in exon 73 of COL7A1. We also investigated a Scottish family with a three-generation pedigree of dominant DEB, in whom the same glycine to arginine substitution mutation was demonstrated. This particular mutation has also been detected previously in three other families with dominant DEB: one Italian, one Hungarian and one Norwegian. Given the widespread geographical distribution of this mutation and the demonstration of its occurrence as a de novo event, G2043R therefore represents the first example of a mutational hotspot in dominant DEB. Interestingly, although both the Mexican and Scottish families we studied had some clinical features in keeping with the Pasini form of the disorder, there was considerable interfamilial variability as well as intrafamilial diversity in the affected individuals.

Adult↗

Reliability of electromagnetic articulography recording during speaking sequences.

For the development of malocclusions and speech disorders, major aetiological significance is attributed to orofacial malfunctions, especially of the tongue. The position of the tongue to the alveolar arch and teeth, particularly within the area of the tip of the tongue, is of special interest for orthodontists. Electromagnetic articulography is a new technique used to examine tongue function and to record its movement in the midsagittal plane. The aim of the study was to determine whether this procedure offers suitable and reliable results. Thirty-one subjects aged 14.3-37.3 years had to repeat speaking sequences five times. The German syllables they had to repeat were /asa/, /ascha/, /ata/, /ala/, /ana/, /aka/. The tongue movements were registered with an 'Articulograph AG 100'. Distances, angles and encircled planes were evaluated, and the proportion of intra-individual to overall variability was calculated in order to check the reliability of the courses of movement. Angles and distances especially showed, depending on the position of the receiver coils, strong reliability during speaking sequences, whereas area produced unfavourable results. The analysis of long trajectories and angles appeared favourable in order to describe the courses of movement. This required, however, a systematic assessment of functional movement with electromagnetic articulography.

Adolescent↗

Degradation pathways, analytical characterization and formulation strategies of a peptide and a protein. Calcitonine and human growth hormone in comparison.

Peptides and proteins differ from conventional chemical entities in their sensitivity to numerous environmental factors and their susceptibility to different degradation pathways. Therefore, complex analytical methodologies are necessary to characterize their molecular entity as well as to detect and quantify the possible degradation products. The formulation of these molecules for a pharmaceutical product requires stabilization by various excipients. Most of the products are brought to market as solutions or lyophilisates. In the first part, this article presents a comparison between the degradation profile of a peptide (calcitonine) and a protein (human growth hormone), in solution and as a freeze-dried product. The various analytical methods used to characterize and identify the degradation products are reviewed and discussed. The second part contains an overview of the different formulation strategies for calcitonine and human growth hormone. Finally, the different stress conditions used to obtain stability data are discussed critically. This leads on to general comments on the design of stability studies for peptide and protein drugs as pharmaceuticals taking into consideration the official guidelines.

Amino Acid Sequence↗