Implementation of Algorithm of Petri Nets Distributed Synthesis into FPGA

In the paper an implementation of algorithm of Petri net array-based synthesis is presented. The method is based on decomposition of colored interpreted macro Petri net into subnets. The structured encoding of places in subnets is done of using minimal numbers of bits. Microoperations, which are assigned to places, are written into distributed and flexible memories. It leads to realization of a logic circuit in a two-level concurrent structure, where the combinational circuit of the first level is responsible for firing transitions, and the second level memories are used for generation of microoperations. This algorithm is implemented in C# and delivered as a stand alone library

Source localization algorithm based on topographic matching pursuit

Spatio-temporal decomposition methods in combination with source localization algorithms can contribute to an improved description and allocation of neural activity from electrical and magnetic multichannel measurements. We introduce a new algorithm, which combines Topographic Matching Pursuit as spatio-temporal decomposition method with a dipole-source localization. The new algorithm is applied to EEG-data obtained from a photic driving experiment with eleven volunteers. In comparison to a hitherto published Multichannel Matching Pursuit (MMP) source localization the new algorithm shows, for a Mirrored-Dipole configuration, higher Goodness-of-Fit values, if temporal asynchrony exists in the EEG-channels. We conclude that the suggested algorithm is more appropriate for source reconstruction in case of temporal asynchrony than MMP-based procedures used so far

Matching pursuit based removal of cardiac pulse-related artifacts in EEG/fMRI

Cardiac pulse-related artifacts in the EEG recorded simultaneously with fMRI are complex and highly variable. Their effective removal is an unsolved problem. Our aim is to develop an adaptive removal algorithm based on the matching pursuit (MP) technique and to compare it to established methods using a visual evoked potential (VEP). We recorded the VEP inside the static magnetic field of an MR scanner (with artifacts) as well as in an electrically shielded room (artifact free). The MP-based artifact removal outperformed average artifact subtraction (AAS) and optimal basis set removal (OBS) in terms of restoring the EEG field map topography of the VEP. Subsequently, a dipole model was fitted to the VEP under each condition using a realistic boundary element head model. The source location of the VEP recorded inside the MR scanner was closest to that of the artifact free VEP after cleaning with the MP-based algorithm as well as with AAS. While none of the tested algorithms offered complete removal, MP showed promising results due to its ability to adapt to variations of latency, frequency and amplitude of individual artifact occurrences while still utilizing a common template

Influence of traumatic brain injury on extracellular tau elimination at the blood–brain barrier

Repetitive head trauma has been associated with the accumulation of tau species in the brain. Our prior work showed brain vascular mural cells contribute to tau processing in the brain, and that these cells progressively degenerate following repetitive mild traumatic brain injury (r-mTBI). The current studies investigated the role of the cerebrovasculature in the elimination of extracellular tau from the brain, and the influence of r-mTBI on these processes. Following intracranial injection of biotin-labeled tau, the levels of exogenous labeled tau residing in the brain were elevated in a mouse model of r-mTBI at 12 months post-injury compared to r-sham mice, indicating reduced tau elimination from the brain following head trauma. This may be the result of decreased caveolin-1 mediated tau efflux at the blood–brain barrier (BBB), as the caveolin inhibitor, methyl-β-cyclodextrin, significantly reduced tau uptake in isolated cerebrovessels and significantly decreased the basolateral-to-apical transit of tau across an in vitro model of the BBB. Moreover, we found that the upstream regulator of endothelial caveolin-1, Mfsd2a, was elevated in r-mTBI cerebrovessels compared to r-sham, which coincided with a decreased expression of cerebrovascular caveolin-1 in the chronic phase following r-mTBI (> 3 months post-injury). Lastly, angiopoietin-1, a mural cell-derived protein governing endothelial Mfsd2a expression, was secreted from r-mTBI cerebrovessels to a greater extent than r-sham animals. Altogether, in the chronic phase post-injury, release of angiopoietin-1 from degenerating mural cells downregulates caveolin-1 expression in brain endothelia, resulting in decreased tau elimination across the BBB, which may describe the accumulation of tau species in the brain following head trauma

NMR Investigation of Structures of G-Protein Coupled Receptor Folding Intermediates

Folding of G-protein coupled receptors (GPCRs) according to the two-stage model (Popot et al., Biochemistry 29(1990), 4031) is postulated to proceed in 2 steps: Partitioning of the polypeptide into the membrane followed by diffusion until native contacts are formed. Herein we investigate conformational preferences of fragments of the yeast Ste2p receptor using NMR. Constructs comprising the first, the first two and the first three transmembrane (TM) segments, as well as a construct comprising TM1-TM2 covalently linked to TM7 were examined. We observed that the isolated TM1 does not form a stable helix nor does it integrate well into the micelle. TM1 is significantly stabilized upon interaction with TM2, forming a helical hairpin reported previously (Neumoin et al., Biophys. J. 96(2009), 3187), and in this case the protein integrates into the hydrophobic interior of the micelle. TM123 displays a strong tendency to oligomerize, but hydrogen exchange data reveal that the center of TM3 is solvent exposed. In all GPCRs so-far structurally characterized TM7 forms many contacts with TM1 and TM2. In our study TM127 integrates well into the hydrophobic environment, but TM7 does not stably pack against the remaining helices. Topology mapping in microsomal membranes also indicates that TM1 does not integrate in a membrane-spanning fashion, but that TM12, TM123 and TM127 adopt predominantly native-like topologies. The data from our study would be consistent with the retention of individual helices of incompletely synthesized GPCRs in the vicinity of the translocon until the complete receptor is released into the membrane interior