Signal-to-pump back-action and self-oscillation in Double-Pump Josephson Parametric Amplifier

We present the theory of a Josephson parametric amplifier employing two pump sources. Our calculations are based on Input-Output Theory, and can easily be generalized to any coupled system involving parametric interactions. We analyze the operation of the device, taking into account the feedback introduced by the reaction of the signal and noise on the pump power, and in this framework, compute the response functions of interest - signal and idler gains, internal gain of the amplifier, and self-oscillation signal amplitude. To account for this back-action between signal and pump, we adopt a mean-field approach and self-consistently explore the boundary between amplification and self-oscillation. The coincidence of bifurcation and self-oscillation thresholds reveals that the origin of coherent emission of the amplifier lies in the multi-wave mixing of the noise components. Incorporation of the back-action leads the system to exhibit hysteresis, dependent on parameters like temperature and detuning from resonance. Our analysis also shows that the resonance condition itself changes in the presence of back-action and this can be understood in terms of the change in plasma frequency of the junction. The potential of the double pump amplifier for quantum-limited measurements and as a squeezer is also discussed.Comment: 25 pages, 20 figures, three appendice

Exponential quantum enhancement for distributed addition with local nonlinearity

We consider classical and entanglement-assisted versions of a distributed computation scheme that computes nonlinear Boolean functions of a set of input bits supplied by separated parties. Communication between the parties is restricted to take place through a specific apparatus which enforces the constraints that all nonlinear, nonlocal classical logic is performed by a single receiver, and that all communication occurs through a limited number of one-bit channels. In the entanglement-assisted version, the number of channels required to compute a Boolean function of fixed nonlinearity can become exponentially smaller than in the classical version. We demonstrate this exponential enhancement for the problem of distributed integer addition.Comment: To appear in Quantum Information Processin

Developing Next-generation Brain Sensing Technologies - A Review.

Advances in sensing technology raise the possibility of creating neural interfaces that can more effectively restore or repair neural function and reveal fundamental properties of neural information processing. To realize the potential of these bioelectronic devices, it is necessary to understand the capabilities of emerging technologies and identify the best strategies to translate these technologies into products and therapies that will improve the lives of patients with neurological and other disorders. Here we discuss emerging technologies for sensing brain activity, anticipated challenges for translation, and perspectives for how to best transition these technologies from academic research labs to useful products for neuroscience researchers and human patients

A National Network of Neurotechnology Centers for the BRAIN Initiative

We propose the creation of a national network of neurotechnology centers to enhance and accelerate the BRAIN Initiative and optimally leverage the effort and creativity of individual laboratories involved in it. As ‘‘brain observatories,’’ these centers could provide the critical interdisciplinary environment both for realizing ambitious and complex technologies and for providing individual investigators with access to them

Simultaneous whole-animal 3D-imaging of neuronal activity using light field microscopy

3D functional imaging of neuronal activity in entire organisms at single cell level and physiologically relevant time scales faces major obstacles due to trade-offs between the size of the imaged volumes, and spatial and temporal resolution. Here, using light-field microscopy in combination with 3D deconvolution, we demonstrate intrinsically simultaneous volumetric functional imaging of neuronal population activity at single neuron resolution for an entire organism, the nematode Caenorhabditis elegans. The simplicity of our technique and possibility of the integration into epi-fluoresence microscopes makes it an attractive tool for high-speed volumetric calcium imaging.Comment: 25 pages, 7 figures, incl. supplementary informatio

Catalyzing next-generation Artificial Intelligence through NeuroAI

Neuroscience has long been an essential driver of progress in artificial intelligence (AI). We propose that to accelerate progress in AI, we must invest in fundamental research in NeuroAI. A core component of this is the embodied Turing test, which challenges AI animal models to interact with the sensorimotor world at skill levels akin to their living counterparts. The embodied Turing test shifts the focus from those capabilities like game playing and language that are especially well-developed or uniquely human to those capabilities - inherited from over 500 million years of evolution - that are shared with all animals. Building models that can pass the embodied Turing test will provide a roadmap for the next generation of AI

Physical principles for scalable neural recording

Simultaneously measuring the activities of all neurons in a mammalian brain at millisecond resolution is a challenge beyond the limits of existing techniques in neuroscience. Entirely new approaches may be required, motivating an analysis of the fundamental physical constraints on the problem. We outline the physical principles governing brain activity mapping using optical, electrical, magnetic resonance, and molecular modalities of neural recording. Focusing on the mouse brain, we analyze the scalability of each method, concentrating on the limitations imposed by spatiotemporal resolution, energy dissipation, and volume displacement. Based on this analysis, all existing approaches require orders of magnitude improvement in key parameters. Electrical recording is limited by the low multiplexing capacity of electrodes and their lack of intrinsic spatial resolution, optical methods are constrained by the scattering of visible light in brain tissue, magnetic resonance is hindered by the diffusion and relaxation timescales of water protons, and the implementation of molecular recording is complicated by the stochastic kinetics of enzymes. Understanding the physical limits of brain activity mapping may provide insight into opportunities for novel solutions. For example, unconventional methods for delivering electrodes may enable unprecedented numbers of recording sites, embedded optical devices could allow optical detectors to be placed within a few scattering lengths of the measured neurons, and new classes of molecularly engineered sensors might obviate cumbersome hardware architectures. We also study the physics of powering and communicating with microscale devices embedded in brain tissue and find that, while radio-frequency electromagnetic data transmission suffers from a severe power–bandwidth tradeoff, communication via infrared light or ultrasound may allow high data rates due to the possibility of spatial multiplexing. The use of embedded local recording and wireless data transmission would only be viable, however, given major improvements to the power efficiency of microelectronic devices

The novel Fh8 and H fusion partners for soluble protein expression in Escherichia coli : a comparison with the traditional gene fusion technology

The Escherichia coli host system is an advantageous choice for simple and inexpensive recombinant protein production but it still presents bottlenecks at expressing soluble proteins from other organisms. Several efforts have been taken to overcome E. coli limitations, including the use of fusion partners that improve protein expression and solubility. New fusion technologies are emerging to complement the traditional solutions. This work evaluates two novel fusion partners, the Fh8 tag (8 kDa) and the H tag (1 kDa), as solubility enhancing tags in E. coli and their comparison to commonly used fusion partners. A broad range comparison was conducted in a small-scale screening and subsequently scaled-up. Six difficult-to-express target proteins (RVS167, SPO14, YPK1, YPK2, Frutalin and CP12) were fused to eight fusion tags (His, Trx, GST, MBP, NusA, SUMO, H and Fh8). The resulting protein expression and solubility levels were evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis before and after protein purification and after tag removal. The Fh8 partner improved protein expression and solubility as the well-known Trx, NusA or MBP fusion partners. The H partner did not function as a solubility tag. Cleaved proteins from Fh8 fusions were soluble and obtained in similar or higher amounts than proteins from the cleavage of other partners as Trx, NusA or MBP. The Fh8 fusion tag therefore acts as an effective solubility enhancer, and its low molecular weight potentially gives it an advantage over larger solubility tags by offering a more reliable assessment of the target protein solubility when expressed as a fusion protein.The financial support of the EMBL Heidelberg, Germany and Fundacao para a Ciencia e Tecnologia (FCT), Portugal, is acknowledged: the fellowship SFRH/BD/46482/2008 to Sofia J. Costa and the project PTDC/CVT/103081/2008. The authors wish to acknowledge Anne-Claude Gavin for providing four of the constructs for this study (RVS167, SPO14, YPK1, and YPK2) and Emmanuel Poilpre for the experimental help (both from the EMBL Heidelberg, Germany)

Highly multiplexed subcellular RNA sequencing in situ

Understanding the spatial organization of gene expression with single-nucleotide resolution requires localizing the sequences of expressed RNA transcripts within a cell in situ. Here, we describe fluorescent in situ RNA sequencing (FISSEQ), in which stably cross-linked complementary DNA (cDNA) amplicons are sequenced within a biological sample. Using 30-base reads from 8102 genes in situ, we examined RNA expression and localization in human primary fibroblasts with a simulated wound-healing assay. FISSEQ is compatible with tissue sections and whole-mount embryos and reduces the limitations of optical resolution and noisy signals on single-molecule detection. Our platform enables massively parallel detection of genetic elements, including gene transcripts and molecular barcodes, and can be used to investigate cellular phenotype, gene regulation, and environment in situ

Characterisation of the Trichinella spiralis deubiquitinating enzyme, TsUCH37, an evolutionarily conserved proteasome interaction partner.

Trichinella spiralis is a parasitic nematode that infects mammals indiscriminately. Although the biggest impact of trichinellosis is observed in developing countries, the parasite is found on all continents except Antarctica. In humans, Trichinella infection contributes globally to helminth related morbidity and disability adjusted life years. In animals, infection is implicated as a serious agricultural problem and drug treatment is largely ineffective. During chronic infection, larvae invade skeletal muscle cells, forming a nurse cell complex in which they become encysted. The nurse cell is a product of the severe disruption of the host cell homeostasis. Proteins of the Ub/proteasome pathway are highly conserved throughout evolution, and considering their importance in the regulation of cell homeostasis, provide interesting and novel therapeutic targets for various diseases. In order to target this system in parasites, pathogen proteins that play a role in this pathway must be identified. We report the identification of the first T. spiralis deubiquitinating enzyme, and show evidence that the function of this protein as a proteasome interaction partner has been evolutionarily conserved. We show that members of this enzyme family are important for T. spiralis survival and that the use of inhibitor compounds may help elucidate their role in infection