Quantitative structural information from single-molecule FRET.

Single-molecule studies can be used to study biological processes directly and in real-time. In particular, the fluorescence energy transfer between reporter dye molecules attached to specific sites on macromolecular complexes can be used to infer distance information. When several measurements are combined, the information can be used to determine the position and conformation of certain domains with respect to the complex. However, data analysis schemes that include all experimental uncertainties are highly complex, and the outcome depends on assumptions about the state of the dye molecules. Here, we present a new analysis algorithm using Bayesian parameter estimation based on Markov Chain Monte Carlo sampling and parallel tempering termed Fast-NPS that can analyse large smFRET networks in a relatively short time and yields the position of the dye molecules together with their respective uncertainties. Moreover, we show what effects different assumptions about the dye molecules have on the outcome. We discuss the possibilities and pitfalls in structure determination based on smFRET using experimental data for an archaeal transcription pre-initiation complex, whose architecture has recently been unravelled by smFRET measurements.

A full subtraction approach for finite element method based source analysis using constrained Delaunay tetrahedralisation.

A mathematical dipole is widely used as a model for the primary current source in electroencephalography (EEG) source analysis. In the governing Poisson-type differential equation, the dipole leads to a singularity on the right-hand side, which has to be treated specifically. In this paper, we will present a full subtraction approach where the total potential is divided into a singularity and a correction potential. The singularity potential is due to a dipole in an infinite region of homogeneous conductivity. The correction potential is computed using the finite element (FE) method. Special care is taken in order to evaluate the right-hand side integral appropriately with the objective of achieving highest possible convergence order for linear basis functions. Our new approach allows the construction of transfer matrices for fast computation of the inverse problem for anisotropic volume conductors. A constrained Delaunay tetrahedralisation (CDT) approach is used for the generation of high-quality FE meshes. We validate the new approach in a four-layer sphere model with a highly conductive cerebrospinal fluid (CSF) and an anisotropic skull compartment. For radial and tangential sources with eccentricities up to 1 mm below the CSF compartment, we achieve a maximal relative error of 0.71% in a CDT-FE model with 360 k nodes which is not locally refined around the source singularity and therefore useful for arbitrary dipole locations. The combination of the full subtraction approach with the high quality CDT meshes leads to accuracies that, to the best of the author's knowledge, have not yet been presented before.

Quantitative analysis of neurophysiological processes of the aging CNS.

Electrophysiological studies were performed on 65 aged subjects (62--91 years) and 48 control subjects (18--38 years). The power spectrum of the EEG in the aging persons shows different types, from spectra with a marked peak of alpha activity to spectra of a desynchronized type. Progressive deterioration of the periodicity of the occipital alpha rhythm and also a progressive time shift between the activities of both occipital lobes were found in the aging subjects. The SEP and VEP have prolonged latencies of all components. The amplitudes of all components of the SEP are significantly increased and those of the VEP are within normal limits. There is a more significant involvement of the dominant hemisphere. Transcallosal transmission of the SEP is qualitatively not involved. Quantitatively there is a marked prolongation of the duration of the transmission of certain SEP components. Transmission of the SEP from the specific cortical response area to different areas of the ipsilateral hemisphere is significantly increased. It is assumed that during aging there is an involvement of the cortical neuronal transmitter mechanisms and a progressive decrease of the specific cortical inhibitory processes.

[Determination of neurophysiological parameters of the aging CNS. I. Evoked potentials (author's transl)]. / Methoden zur Bestimmung neurophysiologischer Parameter des ZNS im Alter. I. Mitteilung: Evozierte Potentiale.

Somatosensory (SEP) and visual (VEP) evoked potentials were studied in 65 healthy subjects who ranged in age from 62-91 years and in 48 normal persons aged 18-38 years. The amplitudes and latencies of the different components of the evoked potentials were measured. The transmission of evoked potentials from the specific response area into different regions of the ipsi- and contralateral hemisphere were studied. The findings can be summarized as follows: The latencies of the SEP and VEP of aged subjects are significantly prolonged. The increase in latency is relatively slight for the first components, progressively higher for the following components. The amplitudes of the different components of the SEP and VEP are significantly increased in aged subjects. The modifications of the SEP-latencies and of the VEP-amplitudes are more important over the dominant hemisphere. In young subjects the SE are confirmed to the centro-parietal region. In aged persons the SEP spreads over the whole hemisphere. The hypothesis that the aging process involves the synaptic transmitter mechanisms at the cortical level is discussed in relation to the involvement of the latencies. The increase in amplitude of the evoked potentials could be explained by assuming that the inhibition - an essential property of the cortex - decreases during the aging process.

Somatosensory event-related potentials and selective attention impairment in young chronic schizophrenics.

Somatosensory event-related potentials (SERP) were recorded in 30 chronic young schizophrenic patients and in 15 age-matched controls. Objective SERP parameters were latencies, amplitudes and the determination of areas of the cognitive components N1 and P3 by integration. Highly significantly reduced areas and prolonged latencies of the N1 component and significantly prolonged reaction times (RT) discriminate schizophrenics in psychopathological remitted state from controls. A significant correlation between decreased N1 areas and prolonged RTs (p less than 0.01), respectively high self-rating subscores 'disturbance of selective attention' (p less than 0.05) can be found only in the SERPs of the left hemisphere. Nevertheless, a reduced N1 area cannot be interpreted as an indicator of vulnerability for schizophrenia, but only for selective attention impairment.

[Elementary electromyographic analysis and motion patterns of the myoglossus muscle]. / Elementare elektromyographische Analyse und Bewegungsmuster des M. myloglossus

In five fully dentulous and one edentulous patient, the m. myloglossus was examined by means of concentric needle electrodes and implanted wire electrodes. It was not possible to achieve absolute inertia with the conductors. The individual potentials of motoric units are bi- and triphasic. The duration was 3 to 5 msec, and the amplitude was 200 to 800 muvolt. The portion of polyphasic potentials is about 5%. With moderate innervation the discharge frequency is 2 to 8/sec. With maximum innervation, interference activity is observed. Kinetic studies showed that the m.myloglossus acts as typical antagonist in lateral tongue movements and as synergist when raising tongue and throat. From these findings conclusions may be drawn with regard to prosthetics.

[Electromyographic studies on the masticatory muscles after the preparation of terminal molars as denture abutments]. / Elektromyographische Untersuchungen an der Kaumuskulatur nach Präparation endständiger Molaren als Brückenpfeiler.

When the occlusal surfaces of terminal molars are ground off during bridge preparation, the occlusal support for the condyle of the affected side disappears and thus the intermaxillary distance declines. The effect of this process on the masticatory muscles was examined electromyographically in nine patients. It was found that the muscle activity especially in the m. temporalis is immediately reduced by 30 to 40%.