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M Rudolph

Publications and source records attributed to M Rudolph.

At least 19 recordsLinked to original sources
PubMed2005

An extended analytic expression for the membrane potential distribution of conductance-based synaptic noise.

Synaptically generated subthreshold membrane potential (Vm) fluctuations can be characterized within the framework of stochastic calculus. It is possible to obtain analytic expressions for the steady-state Vm distribution, even in the case of conductance-based synaptic currents. However, as we show here, the analytic expressions obtained may substantially deviate from numerical solutions if the stochastic membrane equations are solved exclusively based on expectation values of differentials of the stochastic variables, hence neglecting the spectral properties of the underlying stochastic processes. We suggest a simple solution that corrects these deviations, leading to extended analytic expressions of the Vm distribution valid for a parameter regime that covers several orders of magnitude around physiologically realistic values. These extended expressions should enable finer characterization of the stochasticity of synaptic currents by analyzing experimentally recorded Vm distributions and may be applicable to other classes of stochastic processes as well.

Animals↗
PubMed2004

Avipoxvirus infection in peregrine falcons (Falco peregrinus) from a reintroduction programme in Germany.

Poxvirus infections are common in domestic birds in Germany, but they are rare in birds of prey. Only species of falconidae imported from Arabian or Asian countries have so far tested positive for poxvirus, and, among these, only raptors kept for falconry. As part of a reintroduction programme in the northern county of Mecklenburg-Western Pomerania, which is adjacent to the Baltic Sea, 21 young peregrine falcons were released into the wild; six of them died and one was examined postmortem, its tissues being examined by light and electron microscopy. In addition, an ELISA for fowlpox, pigeonpox and canarypox was applied. No virus could be isolated and propagation in culture failed, but virus particles were detected by electron microscopy in lesions from its skin and tongue.

Animals↗
PubMed2004

[Speech impaired children. Anxiety, depression and quality of life of the mothers].

BACKGROUND: It is widely held that the well being of a mother significantly influences the way she brings up her child: Mothers with depression speak less to their child than healthy mothers do and so their emotional disorder has to be regarded an important cofactor for their child's speech development. On the other hand it is suspected that a mother's well being and quality of life may be influenced by her child especially in cases when the child suffers from impairment or developmental disturbance. As literature provides only little information on this topic the purpose of this study was to estimate both health related quality of life HRQOL and distinctive emotional reactions i.e. depression and anxiety in mothers of children with a speech developmental disorder. MATERIALS AND METHODS: 100 mothers (age 33.4+/-5.3 years, range: 22 to 47 years) of 100 preschool children (32 girls, 68 boys; age 4.2+/-1.5 years, range 1;3 to 7;7 years) with a speech impairment were investigated. Mothers of children with cochlear hearing loss, syndromes or other developmental disorders were excluded from the study. To estimate the prevalence of anxiety disorders and depression in the mothers the German version of the Hospital Anxiety and Depression Scale (HADS) was used. Data from 157 healthy women from the German test manual served as controls. HRQOL was assessed by the SF-36 questionnaire with age matched normal controls taken from the German test manual. Microsoft((R)) Excel and Matlab((R)) software packages were used for description, analysis, and evaluation. The differences in prevalence rates were tested by chi(2)-test and Wilcoxon's rank sum test. RESULTS: Assessed by the HADS-depression subscale 11% of the mothers of speech impaired children met criteria for depression compared to 2.5% in the control group. The prevalence in the study group was significantly higher ( p<0.01). The prevalence of anxiety disorders did not differ from normative data on a significant level ( p>5%). The SF-36 questionnaire revealed lower scores of most SF-36 subscales on different significance levels. The results of both tests correlated on a statistically significant level. CONCLUSIONS: Screening mothers of speech impaired children for a "soft" parameter like HRQOL and for epidemiologically relevant emotional disorders like depression and anxiety is of significant clinical interest. The SF-36 and the HADS are suitable tests. As the results of both tests are highly correlated for clinical purposes it seems reasonable to focus on depression and anxiety only. Up to now no data exist about how fathers of speech impaired children react emotionally, so this question has to be focused on in future. Although data allow no conclusion on whether the speech impairment is the reason or the consequence of a reduced HRQOL or an emotional disorder the results clearly indicate the necessity to take into account the mothers' well being when dealing with speech impaired children.

Adult↗
PubMed2003

Synaptic background noise controls the input/output characteristics of single cells in an in vitro model of in vivo activity.

In vivo, in vitro and computational studies were used to investigate the impact of the synaptic background activity observed in neocortical neurons in vivo. We simulated background activity in vitro using two stochastic Ornstein-Uhlenbeck processes describing glutamatergic and GABAergic synaptic conductances, which were injected into a cell in real time using the dynamic clamp technique. With parameters chosen to mimic in vivo conditions, layer 5 rat prefrontal cortex cells recorded in vitro were depolarized by about 15 mV, their membrane fluctuated with a S.D. of about 4 mV, their input resistances decreased five-fold, their spontaneous firing had a high coefficient of variation and an average firing rate of about 5-10 Hz. Brief changes in the variance of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) synaptic conductance fluctuations induced time-locked spiking without significantly changing the average membrane potential of the cell. These transients mimicked increases in the correlation of excitatory inputs. Background activity was highly effective in modulating the firing-rate/current curve of the cell: the variance of the simulated gamma-aminobutyric acid (GABA) and AMPA conductances individually set the input/output gain, the mean excitatory and inhibitory conductances set the working point, and the mean inhibitory conductance controlled the input resistance. An average ratio of inhibitory to excitatory mean conductances close to 4 was optimal in generating membrane potential fluctuations with high coefficients of variation. We conclude that background synaptic activity can dynamically modulate the input/output properties of individual neocortical neurons in vivo.

Animals↗
PubMed2003

The discharge variability of neocortical neurons during high-conductance states.

In vivo recordings have shown that the discharge of cortical neurons is often highly variable and can have statistics similar to a Poisson process with a coefficient of variation around unity. To investigate the determinants of this high variability, we analyzed the spontaneous discharge of Hodgkin-Huxley type models of cortical neurons, in which in vivo-like synaptic background activity was modeled by random release events at excitatory and inhibitory synapses. By using compartmental models with active dendrites, or single compartment models with fluctuating conductances and fluctuating currents, we found that a high discharge variability was always paralleled with a high-conductance state, while some active and passive cellular properties had only a minor impact. Furthermore, a balance between excitation and inhibition was not a necessary condition for high discharge variability. We conclude that the fluctuating high-conductance state caused by the ongoing activity in the cortical network in vivo may be viewed as a natural determinant of the highly variable discharges of these neurons.

Action Potentials↗
PubMed2003

Trajectory clustering: a non-parametric method for grouping gene expression time courses, with applications to mammary development.

Trajectory clustering is a novel and statistically well-founded method for clustering time series data from gene expression arrays. Trajectory clustering uses non-parametric statistics and is hence not sensitive to the particular distributions underlying gene expression data. Each cluster is clearly defined in terms of direction of change of expression for successive time points (its 'trajectory'), and therefore has easily appreciated biological meaning. Applying the method to a dataset from mouse mammary gland development, we demonstrate that it produces different clusters than Hierarchical, K-means, and Jackknife clustering methods, even when those methods are applied to differences between successive time points. Compared to all of the other methods, trajectory clustering was better able to match a manual clustering by a domain expert, and was better able to cluster groups of genes with known related functions.

Algorithms↗
PubMed2003

Characterization of subthreshold voltage fluctuations in neuronal membranes.

Synaptic noise due to intense network activity can have a significant impact on the electrophysiological properties of individual neurons. This is the case for the cerebral cortex, where ongoing activity leads to strong barrages of synaptic inputs, which act as the main source of synaptic noise affecting on neuronal dynamics. Here, we characterize the subthreshold behavior of neuronal models in which synaptic noise is represented by either additive or multiplicative noise, described by Ornstein-Uhlenbeck processes. We derive and solve the Fokker-Planck equation for this system, which describes the time evolution of the probability density function for the membrane potential. We obtain an analytic expression for the membrane potential distribution at steady state and compare this expression with the subthreshold activity obtained in Hodgkin-Huxley-type models with stochastic synaptic inputs. The differences between multiplicative and additive noise models suggest that multiplicative noise is adequate to describe the high-conductance states similar to in vivo conditions. Because the steady-state membrane potential distribution is easily obtained experimentally, this approach provides a possible method to estimate the mean and variance of synaptic conductances in real neurons.

Cell Membrane↗
PubMed2001

Correlation detection and resonance in neural systems with distributed noise sources.

We investigated the resonance behavior in model neurons receiving a large number of random synaptic inputs, whose distributed nature permits one to introduce correlations between them and investigate its effect on cellular responsiveness. A change in the strength of this background led to enhanced responsiveness, consistent with stochastic resonance. Altering the correlation revealed a type of resonance behavior in which the neuron is sensitive to statistical properties rather than the strength of the noise. Remarkably, the neuron could detect weak correlations among the distributed inputs within millisecond time scales.

Animals↗
PubMed2001

Fluctuating synaptic conductances recreate in vivo-like activity in neocortical neurons.

To investigate the basis of the fluctuating activity present in neocortical neurons in vivo, we have combined computational models with whole-cell recordings using the dynamic-clamp technique. A simplified 'point-conductance' model was used to represent the currents generated by thousands of stochastically releasing synapses. Synaptic activity was represented by two independent fast glutamatergic and GABAergic conductances described by stochastic random-walk processes. An advantage of this approach is that all the model parameters can be determined from voltage-clamp experiments. We show that the point-conductance model captures the amplitude and spectral characteristics of the synaptic conductances during background activity. To determine if it can recreate in vivo-like activity, we injected this point-conductance model into a single-compartment model, or in rat prefrontal cortical neurons in vitro using dynamic clamp. This procedure successfully recreated several properties of neurons intracellularly recorded in vivo, such as a depolarized membrane potential, the presence of high-amplitude membrane potential fluctuations, a low-input resistance and irregular spontaneous firing activity. In addition, the point-conductance model could simulate the enhancement of responsiveness due to background activity. We conclude that many of the characteristics of cortical neurons in vivo can be explained by fast glutamatergic and GABAergic conductances varying stochastically.

Action Potentials↗
PubMed2001

(Immuno)affinity chromatography: a versatile tool for fast and selective purification, concentration, isolation and analysis.

Today, thanks to the availability of tailor made biomolecules with the desired biological functions, separations based upon (immuno)affinity techniques are more and more common in a large field of applications. By using the high selectivity of biomolecules (antibodies, receptors, specific proteins), this technique offers the possibility of isolating compounds from complex samples with a selectivity which cannot be achieved by other chromatographic methods. In order to succeed, however, the solid phase support for the immobilisation of the ligand of interest plays a prominent role. For this reason, numerous supports have already been introduced while research on new materials with additional advantages is continued. Here, a new solid phase support will be discussed for (immuno)affinity applications. This material demonstrates low non-specific adsorption and high ligand accessibility, which enables an enhanced selectivity and capacity. Because the material is available in large quantities and exhibits superb mechanical and physical stability, selective isolations have been performed on analytical as well as preparative scale. To demonstrate the potential of this new support, several applications will be presented. Based upon immunoaffinity, two applications for the determination of oestradiol in serum respectively vitamin B12 in fermentation broth will be presented. Regarding affinity chromatography, an enzyme reactor in which the enzyme glucose oxidase is immobilised on the new material, is made for the detection of glucose by Flow Injection Analysis and electrochemical detection. Next, to isolate, identify and test components on their xeno-oestrogenic activity, an affinity column is produced in which human oestrogen receptor is covalently coupled. Several components are screened on their biological activity and the results obtained will be presented here.

Chromatography, Affinity↗
PubMed2001

Simulating tumour removal in neurosurgery.

In this article the software system ROBO-SIM is described. ROBO-SIM is a planning and simulation tool for minimally invasive neurosurgery. Different to the most other simulation tools, ROBO-SIM is able to use actual patient's datasets for simulation. Same as in real neurosurgery a planning step, which provides more functionality as up-to-date planning systems on the market, is performed before undergoing the simulated operation. The planning steps include the definition of the trepanation point for entry into the skull and the target point within the depth of the brain, checking the surgical track and doing virtual trepanations (virtual craniotomy). For use with an intra-operative active manipulator, which is guided by the surgeon during real surgery (robotic surgery), go- and non-go-areas can be defined. During operation, the robot restricts the surgeon from leaving these go-areas. After planning, an additional simulation system, which is understood as an extension to the planning step, is used to simulate whole surgical interventions directly on the patient's anatomy basing on the planning data and by using the same instruments as for the real intervention. First tests with ROBO-SIM are performed on a phantom developed for this purpose and on actual patient's datasets with ventricular tumours.

Brain Neoplasms↗
PubMed2001

Incorporation of decay-accelerating factor into the baculovirus envelope generates complement-resistant gene transfer vectors.

Baculovirus vectors are an efficient means to deliver genes into hepatocytes in vitro. In experiments that exclude components of the complement system, gene transfer is facilitated. Therefore, the complement system has been defined to represent a potent primary barrier to direct application of baculoviruses in vivo. Here we have genetically manipulated baculoviruses so that the complement-regulatory protein human decay- accelerating factor (DAF) is incorporated into the viral envelope. We found that this modification protected baculovirus vectors against complement-mediated inactivation. Complement-resistant baculovirus vectors were additionally analyzed by immunoblotting and electron microscopy, showing the extent of envelope-incorporated DAF and shape of complement-resistant baculoviruses after exposure to complement. This modified baculovirus vector allowed for an enhanced gene transfer into complement-sufficient neonatal rats in vivo, and thus represents a step in the development of improved alternative viral vectors for gene therapy.

Animals↗
PubMed2001

Lipid composition of virosomes modulates their fusion efficiency with cryopreserved bull sperm cells.

Virosomes derived from different fusogenic enveloped viruses have been generated for potential application in gene targeting to sperm cells. Comparative characterization of reconstitution products revealed that virosomes derived from influenza viruses are superior to those generated from Sendai viruses, with respect to the fusion rates with cryopreserved bull sperm cells and to sperm cell vitality after fusion. Modulation of the lipid composition during virosome reconstitution affects fusion sites on target sperms and allows optimization of the fusion rate and sperm cell vitality. A fluorescence-based microscopic fusion assay combined with a vital cell stain revealed that about 90% of sperm cells fused with influenza virosomes containing exogenous cholesterol, sphingomyelin, phosphatidylcholine, and phosphatidylethanolamine. About 85% of the fused sperm cells remained vital. Such optimized influenza-derived virosomes provide the basis for ongoing experiments, which aim at eventually generating biologically active transgenic sperms.

Animals↗
PubMed2001

European brown hare syndrome in free-ranging European brown and mountain hares from Switzerland.

From 1997 to 2000, complete necropsy and histopathologic investigations were performed on 157 free-ranging European brown hares (Lepus europaeus) found dead throughout Switzerland. Organ samples of all these individuals (157 livers and 107 spleens available) were tested for European brown hare syndrome virus (EBHSV)-antigen by enzyme-linked immunosorbent assay (ELISA) test kit. Furthermore, 60 additional blood samples were tested for antibodies against EBHSV by ELISA. In addition, liver samples of 87 free-ranging mountain hares (Lepus timidus) hunted in 1996 were tested for EBHSV-antigen. In two European brown hares from southern Switzerland lesions suggestive of changes induced by EBHSV were present, and high titers of EBHSV-antigen were detected in both liver and spleen samples of these animals. Based on negative staining electron microscopy investigations of liver and spleen homogenates, we observed calicivirus in one antigen-positive hare. Low EBHSV-antigen titers were found in three additional European brown hares from central and western Switzerland, but EBHS-lesions were absent. Antibodies against EBHSV were not detected in any of the sera of European brown hares, and EBHSV-antigen was not found in the samples of mountain hares. This is the first report of EBHS in European brown hares from Switzerland.

Animals↗
PubMed2001

Timing and location of zona pellucida synthesis during oogenesis in domestic cats--an ultrastructural immunohistological investigation.

The application of zona pellucida proteins for contraception of wildlife and feral animals, including stray cats, has been promoted since it was demonstrated to be effective for free-roaming feral mares. Active immunization with zona pellucida proteins leads to either reversible or irreversible infertility. Therefore, knowledge of the timing and location of zona pellucida synthesis during oogenesis in cats is a key aspect of designing an immunocontraceptive for felids. Domestic cat ovaries obtained after ovariohysterectomy were used to produce a specific rabbit antibody against feline zonae pellucidae. Ultrathin sections (70 nm) of cat ovaries were treated with the anti-zona antibody followed by incubation with gold-labelled anti-rabbit IgG for ultrastructural investigation. The gold label was related to the ultrastructure of oocytes and granulosa cells. Cat follicles at different stages of development were examined. The antibody reacted very specifically with zona pellucida proteins in fully grown oocytes with a compact zona pellucida. In secondary follicles, gold labels were found on the zona pellucida and inside granulosa cells in the vicinity of oocytes. Primary follicles were labelled inside their cubic granulosa cells and on fragments of zona pellucida in the cleft between granulosa cells and the oocyte. Some primordial follicles were characterized by labelling of the granulosa cells. In conclusion, these results indicate that cat zona pellucida is produced exclusively by granulosa cells and not by oocytes. Synthesis of zona pellucida takes place at every stage of follicular development.

Animals↗
PubMed2000

In vivo, thyroid and lens surface exposure with spiral and conventional computed tomography in dental implant radiography.

OBJECTIVE: To compare the surface dose exposure to the lens of the eye and the thyroid gland received by patients undergoing spiral and conventional computed tomography (CT) examinations during dental implant pretreatment evaluation in critical radiosensitive structures of the maxillofacial region. STUDY DESIGN: Two groups of 10 patients each had a dental implant CT examination performed, with 5 patients in each group having maxillary and 5 having mandibular examinations. One group was examined with conventional CT and the other with spiral CT. Seven examination parameters were standardized to both types of examinations. Lithium fluoride thermoluminescent dosimeters were placed over the thyroid gland, lateral orbit, and infraorbital foramen of each patient to measure the surface dose. The Wilcoxon rank sum test was used to compare doses, with statistical significance set at P <.05. RESULTS: For the maxillary examination, there was a 57.4% reduction in the surface dose at the lateral orbit, 47% at the infraorbital foramen, and 60.8% at the thyroid when spiral CT was used instead of conventional CT with the same parameters. Similarly, for the mandibular examination, there was a 57.4% reduction at the lateral orbit, 60% reduction at the infraorbital foramen, and 70.9% at the thyroid. All the dose reductions were statistically significant at P <.05. CONCLUSION: The use of spiral CT for preimplant evaluation reduces the surface absorbed dose in certain critical structures of the maxillofacial region compared with conventional CT.

Adult↗