Determination of 2´-5´-Oligoadenylate Synthetase in Serum and Peripheral Blood Mononuclear Cells before and after Subcutaneous Application of Recombinant Interferon beta and gamma

Peer Reviewe

Quantum properties of dichroic silicon vacancies in silicon carbide

The controlled generation and manipulation of atom-like defects in solids has a wide range of applications in quantum technology. Although various defect centres have displayed promise as either quantum sensors, single photon emitters or light-matter interfaces, the search for an ideal defect with multi-functional ability remains open. In this spirit, we investigate here the optical and spin properties of the V1 defect centre, one of the silicon vacancy defects in the 4H polytype of silicon carbide (SiC). The V1 centre in 4H-SiC features two well-distinguishable sharp optical transitions and a unique S=3/2 electronic spin, which holds promise to implement a robust spin-photon interface. Here, we investigate the V1 defect at low temperatures using optical excitation and magnetic resonance techniques. The measurements, which are performed on ensemble, as well as on single centres, prove that this centre combines coherent optical emission, with up to 40% of the radiation emitted into the zero-phonon line (ZPL), a strong optical spin signal and long spin coherence time. These results single out the V1 defect in SiC as a promising system for spin-based quantum technologies

Pedestrians moving in dark: Balancing measures and playing games on lattices

We present two conceptually new modeling approaches aimed at describing the motion of pedestrians in obscured corridors: * a Becker-D\"{o}ring-type dynamics * a probabilistic cellular automaton model. In both models the group formation is affected by a threshold. The pedestrians are supposed to have very limited knowledge about their current position and their neighborhood; they can form groups up to a certain size and they can leave them. Their main goal is to find the exit of the corridor. Although being of mathematically different character, the discussion of both models shows that it seems to be a disadvantage for the individual to adhere to larger groups. We illustrate this effect numerically by solving both model systems. Finally we list some of our main open questions and conjectures

Remote control of municipal solid waste

Percutaneous image-guided interventions, such as radiofrequency ablation (RFA), biopsy, seed implantation, and several types of drainage, employ needle shaped instruments which have to be inserted into the patient's body. Precise planning of needle placement is a key to a successful intervention. The planning of the access path has to be carried out with respect to a variety of criteria for all possible trajectories to the selected target. Since the planning is performed in 2D slices, it demands considerable experience and constitutes a significant mental task. To support the process of finding a suitable path for hepatic interventions, we propose a fast automatic method that computes a list of path proposals for a given target point inside the liver with respect to multiple criteria that affect safety and practicability. Prerequisites include segmentation masks of the liver, of all relevant risk structures and, depending on the kind of procedure, of the tumor. The path proposals are computed based on a weighted combination of cylindrical projections. Each projection represents one path criterion and is generated using the graphics hardware of the workstation. The list of path proposals is generated in less than one second. Hence, updates of the proposals upon changes of the target point and other relevant input parameters can be carried out interactively. The results of a preliminary evaluation indicate that the proposed paths are comparable to those chosen by experienced radiologists and therefore are suited to support planning in the clinical environment. Our implementation focuses on RFA and biopsy in the liver but may be adapted to other types of interventions

NCAM180 Regulates Ric8A Membrane Localization and Potentiates β-Adrenergic Response

Cooperation between receptors allows integrated intracellular signaling leading to appropriate physiological responses. The Neural Cell Adhesion Molecule (NCAM) has three main isoforms of 120, 140 and 180 kDa, with adhesive and signaling properties, but their respective functions remains to be fully identified. Here we show that the human NCAM180 intracellular domain is a novel interactor of the human guanosine exchange factor (GEF) Ric8A using the yeast two hybrid system and immunoprecipitation. Furthermore, NCAM, Ric8A and Gαs form a tripartite complex. Colocalization experiments by confocal microscopy revealed that human NCAM180 specifically induces the recruitment of Ric8A to the membrane. In addition, using an in vitro recombinant system, and in vivo by comparing NCAM knock-out mouse brain to NCAM heterozygous and wild type brains, we show that NCAM expression dose dependently regulates Ric8A redistribution in detergent resistent membrane microdomains (DRM). Previous studies have demonstrated essential roles for Ric8 in Gα protein activity at G protein coupled receptors (GPCR), during neurotransmitter release and for asymmetric cell division. We observed that inhibition of Ric8A by siRNA or its overexpression, decreases or increases respectively, cAMP production following β-adrenergic receptor stimulation. Furthermore, in human HEK293T recombinant cells, NCAM180 potentiates the Gαs coupled β-adrenergic receptor response, in a Ric8A dependent manner, whereas NCAM120 or NCAM140 do not. Finally, in mouse hippocampal neurons expressing endogenously NCAM, NCAM is required for the agonist isoproterenol to induce cAMP production, and this requirement depends on Ric8A. These data illustrate a functional crosstalk between a GPCR and an IgCAM in the nervous system

Simulation of Vehicle-Pedestrian Interaction

The literature on vehicle crash reconstruction provides a number of empirical or classical theoretical models for the distance pedestrians are thrown in impacts with various types of vehicles and impact speeds. The aim of this research was to compare the predictions offered by computer simulation to those obtained using the empirical and classical theoretical models traditionally utilised in vehicle-pedestrian accident reconstruction. Particular attention was paid to the pedestrian throw distance versus vehicle impact speed relationship and the determination of pedestrian injury patterns and associated severity. It was discovered that computer simulation offered improved pedestrian kinematic prediction in comparison to traditional vehicle-pedestrian accident reconstruction techniques. The superior kinematic prediction was found to result in a more reliable pedestrian throw distance versus vehicle impact speed relationship, particularly in regard to varying vehicle and pedestrian parameters such as shape, size and orientation. The pedestrian injury prediction capability of computer simulation was found to be very good for head and lower extremity injury determination. Such injury prediction capabilities were noted to be useful in providing additional correlation of vehicle impact speed predictions, whether these predictions were made using computer simulation, traditional vehicle-pedestrian accident reconstruction methods or a combination of both. A generalised approach to the use of computer simulation for the reconstruction of vehicle-pedestrian accidents was also offered. It is hoped that this approach is developed and improved by other researchers so that over time guidelines for a standardised approach to the simulation of vehicle-pedestrian accidents might evolve. Thoracic injury prediction, particularly for frontal impacts, was found to be less than ideal. It is suspected that the relatively poor thoracic biofidelity stems from the development of pedestrian mathematical models from occupant mathematical models, which were in turn developed from cadaver and dummy tests. It is hoped that future research will result in improved thoracic biofidelity in human mathematical models

The Batten Disease Palmitoyl Protein Thioesterase 1 Gene Regulates Neural Specification and Axon Connectivity during Drosophila Embryonic Development

Palmitoyl Protein Thioesterase 1 (PPT1) is an essential lysosomal protein in the mammalian nervous system whereby defects result in a fatal pediatric disease called Infantile Neuronal Ceroids Lipofuscinosis (INCL). Flies bearing mutations in the Drosophila ortholog Ppt1 exhibit phenotypes similar to the human disease: accumulation of autofluorescence deposits and shortened adult lifespan. Since INCL patients die as young children, early developmental neural defects due to the loss of PPT1 are postulated but have yet to be elucidated. Here we show that Drosophila Ppt1 is required during embryonic neural development. Ppt1 embryos display numerous neural defects ranging from abnormal cell fate specification in a number of identified precursor lineages in the CNS, missing and disorganized neurons, faulty motoneuronal axon trajectory, and discontinuous, misaligned, and incorrect midline crossings of the longitudinal axon bundles of the ventral nerve cord. Defects in the PNS include a decreased number of sensory neurons, disorganized chordotonal neural clusters, and abnormally shaped neurons with aberrant dendritic projections. These results indicate that Ppt1 is essential for proper neuronal cell fates and organization; and to establish the local environment for proper axon guidance and fasciculation. Ppt1 function is well conserved from humans to flies; thus the INCL pathologies may be due, in part, to the accumulation of various embryonic neural defects similar to that of Drosophila. These findings may be relevant for understanding the developmental origin of neural deficiencies in INCL

Hydrogen Peroxide Promotes Injury-Induced Peripheral Sensory Axon Regeneration in the Zebrafish Skin

Production of H2O2 by injured zebrafish skin cells promotes the regeneration of nearby somatosensory axon terminals, thus coordinating wound healing of the skin with sensory reinnervation

Amputation-induced reactive oxygen species are required for successful Xenopus tadpole tail regeneration.

Understanding the molecular mechanisms that promote successful tissue regeneration is critical for continued advancements in regenerative medicine. Vertebrate amphibian tadpoles of the species Xenopus laevis and Xenopus tropicalis have remarkable abilities to regenerate their tails following amputation, through the coordinated activity of numerous growth factor signalling pathways, including the Wnt, Fgf, Bmp, Notch and TGF-β pathways. Little is known, however, about the events that act upstream of these signalling pathways following injury. Here, we show that Xenopus tadpole tail amputation induces a sustained production of reactive oxygen species (ROS) during tail regeneration. Lowering ROS levels, using pharmacological or genetic approaches, reduces the level of cell proliferation and impairs tail regeneration. Genetic rescue experiments restored both ROS production and the initiation of the regenerative response. Sustained increased ROS levels are required for Wnt/β-catenin signalling and the activation of one of its main downstream targets, fgf20 (ref. 7), which, in turn, is essential for proper tail regeneration. These findings demonstrate that injury-induced ROS production is an important regulator of tissue regeneration