Direct single-molecule observation of calcium-dependent misfolding in human neuronal calcium sensor-1

Neurodegenerative disorders are strongly linked to protein misfolding, and crucial to their explication is a detailed understanding of the underlying structural rearrangements and pathways that govern the formation of misfolded states. Here we use single-molecule optical tweezers to monitor misfolding reactions of the human neuronal calcium sensor-1, a multispecific EF-hand protein involved in neurotransmitter release and linked to severe neurological diseases. We directly observed two misfolding trajectories leading to distinct kinetically trapped misfolded conformations. Both trajectories originate from an on-pathway intermediate state and compete with native folding in a calcium-dependent manner. The relative probability of the different trajectories could be affected by modulating the relaxation rate of applied force, demonstrating an unprecedented real-time control over the free-energy landscape of a protein. Constant-force experiments in combination with hidden Markov analysis revealed the free-energy landscape of the misfolding transitions under both physiological and pathological calcium concentrations. Remarkably for a calcium sensor, we found that higher calcium concentrations increased the lifetimes of the misfolded conformations, slowing productive folding to the native state. We propose a rugged, multidimensional energy landscape for neuronal calcium sensor-1 and speculate on a direct link between protein misfolding and calcium dysregulation that could play a role in neurodegeneration

An Optical Backplane Demonstrator System Based on FET-SEED Smart Pixel Arrays and Diffractive Lenslet Arrays

We have demonstrated a representative portion of an optical backplane using FET-SEED smart pixels and free-space optics to interconnect printed circuit boards (PCB\u27s) in a two board, unidirectional link configuration. 4×4 arrays of FET-SEED transceivers were designed, fabricated, and packaged all the PCB level, The optical interconnection was constructed using diffractive microoptics, and custom optomechanics. The system was operated in two modes, one showing high data throughput, 100 MBit/sec, and the other demonstrating large connection densities, 2222 channel/cm2

Integrating Human Indoor Air Pollutant Exposure within Life Cycle Impact Assessment

Neglecting health effects from indoor pollutant emissions and exposure, as currently done in Life Cycle Assessment (LCA), may result in product or process optimizations at the expense of workers’ or consumers’ health. To close this gap, methods for considering indoor exposure to chemicals are needed to complement the methods for outdoor human exposure assessment already in use. This paper summarizes the work of an international expert group on the integration of human indoor and outdoor exposure in LCA, within the UNEP/SETAC Life Cycle Initiative. A new methodological framework is proposed for a general procedure to include human-health effects from indoor exposure in LCA. Exposure models from occupational hygiene and household indoor air quality studies and practices are critically reviewed and recommendations are provided on the appropriateness of various model alternatives in the context of LCA. A single-compartment box model is recommended for use as a default in LCA, enabling one to screen occupational and household exposures consistent with the existing models to assess outdoor emission in a multimedia environment. An initial set of model parameter values was collected. The comparison between indoor and outdoor human exposure per unit of emission shows that for many pollutants, intake per unit of indoor emission may be several orders of magnitude higher than for outdoor emissions. It is concluded that indoor exposure should be routinely addressed within LCA

Universal and efficient compressed sensing by spread spectrum and application to realistic Fourier imaging techniques

We advocate a compressed sensing strategy that consists of multiplying the signal of interest by a wide bandwidth modulation before projection onto randomly selected vectors of an orthonormal basis. Firstly, in a digital setting with random modulation, considering a whole class of sensing bases including the Fourier basis, we prove that the technique is universal in the sense that the required number of measurements for accurate recovery is optimal and independent of the sparsity basis. This universality stems from a drastic decrease of coherence between the sparsity and the sensing bases, which for a Fourier sensing basis relates to a spread of the original signal spectrum by the modulation (hence the name "spread spectrum"). The approach is also efficient as sensing matrices with fast matrix multiplication algorithms can be used, in particular in the case of Fourier measurements. Secondly, these results are confirmed by a numerical analysis of the phase transition of the l1- minimization problem. Finally, we show that the spread spectrum technique remains effective in an analog setting with chirp modulation for application to realistic Fourier imaging. We illustrate these findings in the context of radio interferometry and magnetic resonance imaging.Comment: Submitted for publication in EURASIP Journal on Advances in Signal Processin