Counter Machines and Distributed Automata: A Story about Exchanging Space and Time

We prove the equivalence of two classes of counter machines and one class of distributed automata. Our counter machines operate on finite words, which they read from left to right while incrementing or decrementing a fixed number of counters. The two classes differ in the extra features they offer: one allows to copy counter values, whereas the other allows to compute copyless sums of counters. Our distributed automata, on the other hand, operate on directed path graphs that represent words. All nodes of a path synchronously execute the same finite-state machine, whose state diagram must be acyclic except for self-loops, and each node receives as input the state of its direct predecessor. These devices form a subclass of linear-time one-way cellular automata.Comment: 15 pages (+ 13 pages of appendices), 5 figures; To appear in the proceedings of AUTOMATA 2018

Pretubulysin derived probes as novel tools for monitoring the microtubule network via activity-based protein profiling and fluorescence microscopy

Microtubules (mt) are highly dynamic polymers composed of alpha- and beta-tubulin monomers that are present in all dividing and non-dividing cells. A broad variety of natural products exists that are known to interfere with the microtubule network, by either stabilizing or de-stabilizing these rope-like polymers. Among those tubulysins represent a new and potent class of cytostatic tetrapeptides originating from myxobacteria. Early studies suggested that tubulysins interact with the eukaryotic cytoskeleton by inhibition of tubulin polymerization with EC50 values in the picomolar range. Recently, pretubulysins have been described to retain the high tubulindegradation activity of their more complex tubulysin relatives and represent an easier synthetic target with an efficient synthesis already in place. Although tubulin has been suggested as the dedicated target of tubulysin a comprehensive molecular target analysis of pretubulysin in the context of the whole proteome has not been carried out so far. Here we utilize synthetic chemistry to develop two pretubulysin photoaffinity probes which were applied in cellular activity-based protein profiling and imaging studies in order to unravel and visualize dedicated targets. Our results clearly show a remarkable selectivity of pretubulysin for beta-tubulin which we independently confirmed by a mass-spectrometry based proteomic profiling platform as well as by tubulin antibody based co-staining on intact cells

A Bit-String Model for Biological Aging

We present a simple model for biological aging. We studied it through computer simulations and we have found this model to reflect some features of real populations.Comment: LaTeX file, 4 PS figures include

Besondere bildgebende Befunde bei primär generalisierten Epilepsien

Konventionelle bildgebende Verfahren sind bei Patienten mit idiopathischen generalisierten Epilepsien per definitionem unauffällig. MRT-basierte (Magnetresonanztomographie), morphometrische Verfahren konnten jedoch in Gruppenanalysen subtile strukturelle Veränderungen insbesondere im mesialen Frontallappen, supplementär motorischen Areal und Thalamus nachweisen. Ergänzende funktionelle MRT- und Diffusions-Tensor-Bildgebungs(DTI)-Untersuchungen bei Patienten mit juveniler myoklonischer Epilepsie (JME) zeigen eine erhöhte funktionelle und strukturelle Konnektivität zwischen präfrontalen kognitiven und motorischen Kortexarealen, die Erklärungen für krankheitstypische Anfallsreflexmechanismen bieten. Studien an neu diagnostizierten Patienten, longitudinale Studien sowie Untersuchungen an gesunden Geschwistern von JME-Patienten weisen darauf hin, dass diese Veränderungen am ehesten Ursache im Sinne einer genetisch determinierten Entwicklungsstörung sind und nicht eine sekundäre Folge der chronischen Epilepsie

Ictal SPECT in Sturge-Weber syndrome

We report on a patient with right-sided Sturge-Weber syndrome (SWS), in whom earlier functional hemispherectomy failed. Subtraction of ictal and interictal single-photon-emission-computed-tomography (SPECT) superimposed on individual MRI showed a right fronto-orbital hyperperfusion, with a left-sided EEG seizure pattern. Ictal SPECT supported our assumption that right frontal originated seizure pattern propagated to left hemisphere via the remaining right frontal bridge. Right orbito-frontal resection and disconnection from corpus callosum resulted in seizure freedom

A novel technique for selective NF-kappa B inhibition in Kupffer cells: contrary effects in fulminant hepatitis and ischaemia-reperfusion.

Background and aims: The transcription factor nuclear factor kappa B (NF-kB) has risen as a promising target for anti-inflammatory therapeutics. In the liver, however, NFkB inhibition mediates both damaging and protective effects. The outcome is deemed to depend on the liver cell type addressed. Recent gene knock-out studies focused on the role of NF-kB in hepatocytes, whereas the role of NF-kB in Kupffer cells has not yet been investigated in vivo. Here we present a novel approach, which may be suitable for clinical application, to selectively target NF-kB in Kupffer cells and analyse the effects in experimental models of liver injury. Methods: NF-kB inhibiting decoy oligodeoxynucleotides were loaded upon gelatin nanoparticles (D-NPs) and their in vivo distribution was determined by confocal microscopy. Liver damage, NF-kB activity, cytokine levels and apoptotic protein expression were evaluated after lipopolysaccharide (LPS), D-galactosamine (GalN)/LPS, or concanavalin A (ConA) challenge and partial warm ischaemia and subsequent reperfusion, respectively. Results: D-NPs were selectively taken up by Kupffer cells and inhibited NF-kB activation. Inhibition of NF-kB in Kupffer cells improved survival and reduced liver injury after GalN/LPS as well as after ConA challenge. While anti-apoptotic protein expression in liver tissue was not reduced, pro-apoptotic players such as cJun N-terminal kinase (JNK) were inhibited. In contrast, selective inhibition of NF-kB augmented reperfusion injury. Conclusions: NF-kB inhibiting decoy oligodeoxynucleotide- loaded gelatin nanoparticles is a novel tool to selectively inhibit NF-kB activation in Kupffer cells in vivo. Thus, liver injury can be reduced in experimental fulminant hepatitis, but increased at ischaemia–reperfusion

Feasibility of multimodal 3D neuroimaging to guide implantation of intracranial EEG electrodes

Since intracranial electrode implantation has limited spatial sampling and carries significant risk, placement has to be effective and efficient. Structural and functional imaging of several different modalities contributes to localising the seizure onset zone (SoZ) and eloquent cortex. There is a need to summarise and present this information throughout the pre/intra/post-surgical course