Performance tests of an organic amine carbon dioxide removal system Final report

Performance tests and operating parameters of regenerable two-bed organic amine carbon dioxide removal syste

Quantum walk of a trapped ion in phase space

We implement the proof of principle for the quantum walk of one ion in a linear ion trap. With a single-step fidelity exceeding 0.99, we perform three steps of an asymmetric walk on the line. We clearly reveal the differences to its classical counterpart if we allow the walker/ion to take all classical paths simultaneously. Quantum interferences enforce asymmetric, non-classical distributions in the highly entangled degrees of freedom (of coin and position states). We theoretically study and experimentally observe the limitation in the number of steps of our approach, that is imposed by motional squeezing. We propose an altered protocol based on methods of impulsive steps to overcome these restrictions, in principal allowing to scale the quantum walk to several hundreds of steps.Comment: 4 pages, 4 figure

Visualization of the Membranous Labyrinth and Nerve Fiber Pathways in Human and Animal Inner Ears Using MicroCT Imaging

Design and implantation of bionic implants for restoring impaired hair cell function relies on accurate knowledge about the microanatomy and nerve fiber pathways of the human inner ear and its variation. Non-destructive isotropic imaging of soft tissues of the inner ear with lab-based microscopic X-ray computed tomography (microCT) offers high resolution but requires contrast enhancement using compounds with high X-ray attenuation. We evaluated different contrast enhancement techniques in mice, cat, and human temporal bones to differentially visualize the membranous labyrinth, sensory epithelia, and their innervating nerves together with the facial nerve and middle ear. Lugol’s iodine potassium iodine (I2KI) gave high soft tissue contrast in ossified specimens but failed to provide unambiguous identification of smaller nerve fiber bundles inside small bony canals. Fixation or post-fixation with osmium tetroxide followed by decalcification in EDTA provided superior contrast for nerve fibers and membranous structures. We processed 50 human temporal bones and acquired microCT scans with 15 μm voxel size. Subsequently we segmented sensorineural structures and the endolymphatic compartment for 3D representations to serve for morphometric variation analysis. We tested higher resolution image acquisition down to 3.0 μm voxel size in human and 0.5 μm in mice, which provided a unique level of detail and enabled us to visualize single neurons and hair cells in the mouse inner ear, which could offer an alternative quantitative analysis of cell numbers in smaller animals. Bigger ossified human temporal bones comprising the middle ear and mastoid bone can be contrasted with I2KI and imaged in toto at 25 μm voxel size. These data are suitable for surgical planning for electrode prototype placements. A preliminary assessment of geometric changes through tissue processing resulted in 1.6% volume increase caused during decalcification by EDTA and 0.5% volume increase caused by partial dehydration to 70% ethanol, which proved to be the best mounting medium for microCT image acquisition

Experimental simulation and limitations of quantum walks with trapped ions

We examine the prospects of discrete quantum walks (QWs) with trapped ions. In particular, we analyze in detail the limitations of the protocol of Travaglione and Milburn (PRA 2002) that has been implemented by several experimental groups in recent years. Based on the first realization in our group (PRL 2009), we investigate the consequences of leaving the scope of the approximations originally made, such as the Lamb--Dicke approximation. We explain the consequential deviations from the idealized QW for different experimental realizations and an increasing number of steps by taking into account higher-order terms of the quantum evolution. It turns out that these become dominant after a few steps already, which is confirmed by experimental results and is currently limiting the scalability of this approach. Finally, we propose a new scheme using short laser pulses, derived from a protocol from the field of quantum computation. We show that the new scheme is not subject to the above-mentioned restrictions, and analytically and numerically evaluate its limitations, based on a realistic implementation with our specific setup. Implementing the protocol with state-of-the-art techniques should allow for substantially increasing the number of steps to 100 and beyond and should be extendable to higher-dimensional QWs.Comment: 29 pages, 15 figue

Drafting a Surgical Procedure Using a Computational Anatomy Driven Approach for Precise, Robust, and Safe Vestibular Neuroprosthesis Placement-When One Size Does Not Fit All

OBJECTIVE: To design and evaluate a new vestibular implant and surgical procedure that should reach correct electrode placement in 95% of patients in silico. DESIGN: Computational anatomy driven implant and surgery design study. SETTING: Tertiary referral center. PARTICIPANTS: The population comprised 81 patients that had undergone a CT scan of the Mastoid region in the Maastricht University Medical Center. The population was subdivided in a vestibular implant eligible group (28) and a control group (53) without known vestibular loss. INTERVENTIONS: Canal lengths and relationships between landmarks were calculated for every patient. The relationships in group-anatomy were used to model a fenestration site on all three semicircular canals. Each patient's simulated individual distance from the fenestration site to the ampulla was calculated and compared with the populations average to determine if placement would be successful. MAIN OUTCOME MEASURES: Lengths of the semicircular canals, distances from fenestration site to ampulla (intralabyrinthine electrode length), and rate of successful electrode placement (robustness). RESULTS: The canal lengths for the lateral, posterior, and superior canal were respectively 12.1 mm ± 1.07, 18.8 mm ± 1.62, and 17.5 mm ± 1.23, the distances from electrode fenestration site to the ampulla were respectively 3.73 mm ± 0.53, 9.02 mm ± 0.90, and 5.31 mm ± 0.73 and electrode insertions were successful for each respective semicircular canal in 92.6%, 66.7%, and 86.4% of insertions in silico. The implant electrode was subsequently revised to include two more electrodes per lead, resulting in a robustness of 100%. CONCLUSIONS: The computational anatomy approach can be used to design and test surgical procedures. With small changes in electrode design, the proposed surgical procedure's target robustness was reached

Apoptosis of the fibrocytes type 1 in the spiral ligament and blood labyrinth barrier disturbance cause hearing impairment in murine cerebral malaria

<p>Abstract</p> <p>Background</p> <p>Experimental murine malaria has been shown to result in significant hearing impairment. Microscopic evaluation of the temporal bones of these animals has revealed regular morphology of the cochlea duct. Furthermore, the known vascular pathologic changes being associated with malaria could not be found. Immunohistochemistry for ICAM1 showed a strong marking in the <it>stria vascularis</it>, indicating a disturbance of the endocochlear potential. The aim of this study was to evaluate the role of apoptosis and the disturbance of the blood labyrinth barrier in the murine malaria associated hearing impairment.</p> <p>Methods</p> <p>The temporal bones of seven mice with cerebral malaria-four with hearing impairment, three without hearing impairment-were evaluated with immunohistochemistry for cleaved caspase 3 to detect apoptosis and connexin 26, a gap junction protein being a cornerstone in the endocochlear potassium recirculation. Furthermore five animals with cerebral malaria were treated with Evans blue prior to sacrification to detect disturbances of the blood labyrinth barrier.</p> <p>Results</p> <p>Cleaved caspase 3 could clearly be detected by immunohistochemistry in the fibrocytes of the spiral ligament, more intensively in animals with hearing impairment, less intensively in those without. Apoptosis signal was equally distributed in the spiral ligament as was the connexin 26 gap junction protein. The Evans blue testing revealed a strong signal in the malaria animals and no signal in the healthy control animals.</p> <p>Conclusion</p> <p>Malfunction of the fibrocytes type 1 in the spiral ligament and disruption of the blood labyrinth barrier, resulting in a breakdown of the endocochlear potential, are major causes for hearing impairment in murine cerebral malaria.</p

Quantitative X-ray Tomography of the Mouse Cochlea

Imaging with hard X-rays allows visualizing cochlear structures while maintaining intrinsic qualities of the tissue, including structure and size. With coherent X-rays, soft tissues, including membranes, can be imaged as well as cells making use of the so-called in-line phase contrast. In the present experiments, partially coherent synchrotron radiation has been used for micro-tomography. Three-dimensional reconstructions of the mouse cochlea have been created using the EM3D software and the volume has been segmented in the Amira Software Suite. The structures that have been reconstructed include scala tympani, scala media, scala vestibuli, Reissner's membrane, basilar membrane, tectorial membrane, organ of Corti, spiral limbus, spiral ganglion and cochlear nerve. Cross-sectional areas of the scalae were measured. The results provide a realistic and quantitative reconstruction of the cochlea

Drug diffusion along an intact mammalian cochlea

Intratympanic drug administration depends on the ability of drugs to pass through the round window membrane (RW) at the base of the cochlea and diffuse from this location to the apex. While the RW permeability for many different drugs can be promoted, passive diffusion along the narrowing spiral of the cochlea is limited. Earlier measurements of the distribution of marker ions, corticosteroids and antibiotics demonstrated that the concentration of substances applied to the RW was two to three orders of magnitude higher in the base compared to the apex. The measurements, however, involved perforating the cochlear bony wall and, in some cases, sampling perilymph. These manipulations can change the flow rate of perilymph and lead to intake of perilymph through the cochlear aqueduct, thereby disguising concentration gradients of the delivered substances. In this study, the suppressive effect of salicylate on cochlear amplification via block of the outer hair cell (OHC) somatic motility was utilized to assess salicylate diffusion along an intact guinea pig cochlea in vivo. Salicylate solution was applied to the RW and threshold elevation of auditory nerve responses was measured at different times and frequencies after application. Resultant concentrations of salicylate along the cochlea were calculated by fitting the experimental data using a mathematical model of the diffusion and clearing of salicylate in a tube of variable diameter combined with a model describing salicylate action on cochlear amplification. Concentrations reach a steady-state at different times for different cochlear locations and it takes longer to reach the steady-state at more apical locations. Even at the steady state, the predicted concentration at the apex negligible. Model predictions for the geometry of the longer human cochlea show even higher differences in the steady-state concentrations of the drugs between cochlear base and apex. Our findings confirm conclusions that achieving therapeutic drug concentrations throughout the entire cochlear duct is hardly possible when the drugs are applied to the RW and are distributed via passive diffusion. Assisted methods of drug delivery are needed to reach a more uniform distribution of drugs along the cochlea

Peptide-mediated targeting of liposomes to TrkB receptor-expressing cells

Sanjeev Ranjan,1 Rohit Sood,1 Jozsef Dudas,2 Rudolf Glueckert,2 Anneliese Schrott-Fischer,2 Soumen Roy,2 Ilmari Pyykk&amp;ouml;,3 Paavo KJ Kinnunen11Helsinki Biophysics and Biomembrane Group, Department of Biomedical Engineering and Computational Science, Aalto University, Espoo, Finland; 2Department of Otorhinolaryngology, Innsbruck Medical University, Innsbruck, Austria; 3Department of Otolaryngology, University of Tampere Medical School, Tampere, FinlandBackground: The neurotrophic receptor tyrosine kinase B (TrkB) has diverse signaling roles in neurons and tumor cells. Accordingly, its suppressive targeting is of interest in neuroblastoma and other tumors, whereas its role in improving survival is focused in neurons. Here we describe targeting of TrkB-binding peptide-conjugated liposomes (PCL) to the TrkB-expressing mouse macrophage-like cell line RAW264, and to all-trans-retinoic acid-treated neuron-like TrkB+ SH-SY5Y human neuroblastoma cells.Methods: Binding and internalization of PCL was monitored by flow cytometry and confocal fluorescence microscopy.Results: Internalization of TrkB-targeted PCL by RAW264 cells was enhanced and faster when compared with PCL having the corresponding scrambled peptide. Likewise, binding and augmented uptake were confirmed for TrkB+ SH-SY5Y cells, with targeted PCL appearing in the cytoplasm after 20 minutes of incubation.Conclusion: We demonstrate here the feasibility of targeting liposomes to TrkB-expressing cells by 18-mer peptides, promoting cellular uptake (at least partly into endosomes) via receptor-mediated pathways.Keywords: liposomes, targeting, tyrosine kinase B, peptid