Supramolecular Assembly of Aminoethylene‐Lipopeptide PMO Conjugates into RNA Splice‐Switching Nanomicelles

Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile.     

Polymer Fiber Probes Enable Optical Control of Spinal Cord and Muscle Function In Vivo

Restoration of motor and sensory functions in paralyzed patients requires the development of tools for simultaneous recording and stimulation of neural activity in the spinal cord. In addition to its complex neurophysiology, the spinal cord presents technical challenges stemming from its flexible fibrous structure and repeated elastic deformation during normal motion. To address these engineering constraints, we developed highly flexible fiber probes, consisting entirely of polymers, for combined optical stimulation and recording of neural activity. The fabricated fiber probes exhibit low‐loss light transmission even under repeated extreme bending deformations. Using our fiber probes, we demonstrate simultaneous recording and optogenetic stimulation of neural activity in the spinal cord of transgenic mice expressing the light sensitive protein channelrhodopsin 2 (ChR2). Furthermore, optical stimulation of the spinal cord with the polymer fiber probes induces on‐demand limb movements that correlate with electromyographical (EMG) activity.     

Spontaneous Current Oscillations during Hard Anodization of Aluminum under Potentiostatic Conditions

Nanoporous anodic aluminum oxide is prepared by hard anodization of aluminum under potentiostatic conditions using 0.3 M H₂C₂O₄. Under unstirred electrolyte condition, spontaneous current oscillations are observed. The amplitude and period of these current oscillations are observed to increase with anodization time. As a consequence of the oscillatory behavior, the resulting anodic alumina exhibits modulated pore structures, in which the diameter contrast and the length of pore modulation increase with the amplitude and the period of current oscillations, respectively, and the current peak profile determines the internal geometry of oxide nanopores. The mechanism responsible for the oscillatory behavior is suggested to be a diffusion‐controlled anodic oxidation of aluminum.     

Perceptual-based quality assessment for audio–visual services: A survey

Accurate measurement of the perceived quality of audio–visual services at the end-user is becoming a crucial issue in digital applications due to the growing demand for compression and transmission of audio–visual services over communication networks. Content providers strive to offer the best quality of experience for customers linked to their different quality of service (QoS) solutions. Therefore, developing accurate, perceptual-based quality metrics is a key requirement in multimedia services. In this paper, we survey state-of-the-art signal-driven perceptual audio and video quality assessment methods independently, and investigate relevant issues in developing joint audio–visual quality metrics. Experiments with respect to subjective quality results have been conducted for analyzing and comparing the performance of the quality metrics. We consider emerging trends in audio–visual quality assessment, and propose feasible solutions for future work in perceptual-based audio–visual quality metrics.     

Topology control for fault-tolerant communication in wireless ad hoc networks

Fault-tolerant communication and energy efficiency are important requirements for future-generation wireless ad hoc networks, which are increasingly being considered also for critical application domains like embedded systems in automotive and aerospace. Topology control, which enables multi-hop communication between any two network nodes via a suitably constructed overlay network, is the primary target for increasing connectivity and saving energy here. In this paper, we present a fault-tolerant distributed topology control algorithm that constructs and continuously maintains a k-regular and k-node-connected overlay for energy-efficient multi-hop communication. As a by-product, it also builds a hierarchy of clusters that reflects the node density in the network, with guaranteed and localized fault-tolerant communication between any pair of cluster members. The construction algorithm automatically adapts to a dynamically changing environment, is guaranteed to converge, and exhibits good performance as well.     

Optical reconstruction of high-speed surface dynamics in an uncontrollable environment

The ability to communicate with our voice can be regarded as the concatenation of the two processes "phonation" and "modulation." These take place in the larynx and palatal and oral region, respectively. During phonation the audible primary voice signal is created by mutual reaction of vocal folds with the exhaled air stream of the lungs. The underlying interactions of masses, fluids and acoustics have yet to be identified and understood. One part of the primary signal's acoustical source are vortex induced vibrations, as e.g., created by the Coand?effect in the air stream. The development of these vorteces is determined by the shape and 3-D movements of the vocal folds in the larynx. Current clinical in vivo research methods for vocal folds do not deliver data of satisfactory quality for fundamental research, e.g., an endoscope is limited to 2-D image information. Based hereupon, a few improved methods have been presented, however delivering only selective 3-D information, either for a single point or a line. This stands in contrast to the 3-D motions of the entire vocal fold surface. More complex imaging methods, such as MRI, do not deliver information in real-time. Thus, it is necessary to develop an easily applicable, more improved examination method, which allows for 3-D data of the vocal folds surfaces to be obtained. We present a method to calibrate a 3-D reconstruction setup including a laser projection system and a high-speed camera. The setup is designed with miniaturization and an in vivo application in mind. The laser projection system generates a divergent grid of 196 laser dots by diffraction gratings. It is calibrated with a planar calibration target through planar homography. In general, the setup allows to reconstruct the topology of a surface at high frame rates (up to 4000 frames per second) and in uncontrollable environments, as e.g., given by the lighting situation (little to no ambient light) and varying texture (e.g., varying grade of reflection) in the human larynx. In particular, this system measures the 3-D vocal fold surface dynamics during phonation. Applied to synthetic data, the calibration is shown to be robust (error approximately 0.5 μm) regarding noise and systematic errors. Experimental data gained with a linear z -stage proved that the system reconstructs the 3-D coordinates of points with an error at approximately 15 μm. The method was applied exemplarily to reconstruct porcine and artificial vocal folds' surfaces during phonation. Local differences such as asymmetry between left and right fold dynamics, as well as global parameters, such as opening and closing speed and maximum displacements, were identified and quantified.     

An integrated 8-12 GHz fractional-N frequency synthesizer in SiGe BiCMOS for satellite communications

We present an integrated fractional-N low-noise frequency synthesizer for satellite applications. By using two integrated VCOs and combining digital and analog tuning techniques, a PLL lock range from 8 to 12 GHz is achieved. Due to a small VCO fine tuning gain and optimized charge pump output biasing, the phase noise is low and almost constant over the tuning range. All 16 sub-bands show a tuning range above 900 MHz each, allowing temperature compensation without sub-band switching. This makes the synthesizer robust against variations of the device parameters with process, supply voltage, temperature and aging. The measured phase noise is ?87 dBc/Hz and ?106 dBc/Hz at 10 kHz and 1 MHz offset, respectively. In integer-N mode, phase noise values down to ?98 dBc/Hz at 10 kHz and ?111 dBc/Hz at 1 MHz offset, respectively, were measured.