Scalable and reversible axonal neuromodulation of the sympathetic chain for cardiac control

Maladaptation of the sympathetic nervous system contributes to the progression of cardiovascular disease and risk for sudden cardiac death, the leading cause of mortality worldwide. Axonal modulation therapy (AMT) directed at the paravertebral chain blocks sympathetic efferent outflow to the heart, and may be a promising strategy to mitigate excess disease-associated sympathoexcitation. The present work evaluates AMT, directed at the sympathetic chain, in blocking sympathoexcitation using a porcine model. In anesthetized porcine (n=14), we applied AMT to the right T1-T2 paravertebral chain and performed electrical stimulation of the distal portion of the right sympathetic chain (RSS). RSS-evoked changes in heart rate, contractility, ventricular activation recovery interval (ARI), and norepinephrine release were examined with and without kilohertz frequency alternating current block (KHFAC). To evaluate efficacy of AMT in the setting of sympathectomy, evaluations were performed in the intact state and repeated after left and bilateral sympathectomy. We found strong correlations between AMT intensity and block of sympathetic stimulation-evoked changes in cardiac electrical and mechanical indices (r=0.83-0.96, effect size d=1.9-5.7), as well as evidence of sustainability and memory. AMT significantly reduced RSS-evoked left ventricular interstitial norepinephrine release, as well as coronary sinus norepinephrine levels. Moreover, AMT remained efficacious following removal of the left sympathetic chain, with similar mitigation of evoked cardiac changes and reduction of catecholamine release. With growth of neuromodulation, an on-demand or reactionary system for reversible AMT may have therapeutic potential for cardiovascular disease-associated sympathoexcitation.

Modulation and Signal Detection for Diffusive-Drift Molecular Communication with a Mobile Receiver

Molecular communication (MC), which allows nanomachines to communicate with each other by using chemical molecules, is considered to be a promising method for communications in liquid environment. Available works on MC mainly focus on modulation and signal detection schemes for MC systems with fixed nanomachines, i.e., fixed molecular communication (FMC) systems. However, the more complex systems with mobile nanomachines (i.e., mobile molecular communication (MMC) systems) have been largely unexplored. This paper considers a MMC system with a fixed transmitter and a mobile receiver communicating over diffusive-drift channels of a limited boundary. We first propose a new modulation scheme to address the issue of misalignment in the signal detection of MMC systems by adopting three types of molecules in the signal modulation and modulating the transmitted signals into blocks with equal length to avoid the transferring of a signal error in the current block on the signal detection in other blocks. We then propose a new signal detection scheme of the MMC systems by calculating the distance between the transmitter and the receiver based on a distance prediction method and detecting signals at the receiver based on the decided adaptive concentration threshold in each time interval. To verify the efficiency of our proposed scheme, we then conducted extensive simulations by the Monte Carlo simulation, and comparisons are also made among our proposed schemes, a well-known fixed threshold signal detection scheme, the CATD scheme, the PAD scheme, and a low complexity signal detection scheme for MMC systems in terms of the BER (bit error rate). Results show that our proposed schemes can outperform these schemes regarding the BER.

A Survey on Mining Cryptocurrencies

Advanced monetary standards have acquired huge ubiquity nowadays. Bitcoin is the decentralized, disseminated, distributed virtual cash known cryptographic money. Bitcoin mining chips away at standard of the blockchain, which is believed to be one of this present century’s sharp advancement. The blockchain is the arrangement of blocks that are associated so that in the current block there is the hash of the past block. Any adjustment of information in any block in a blockchain brings about a blunder in the entire blockchain. A strategy called mining, where excavators settle a complex numerical riddle, produces Bitcoins. The excavators contend as quickly as time permits to mine the Bitcoin and guarantee the award. Mining should be possible by a solitary individual or by a pool, where a lot of excavators join to mine a solitary block in an organization.

Probability Models of Distributed Proof Generation for zk-SNARK-Based Blockchains

The paper is devoted to the investigation of the distributed proof generation process, which makes use of recursive zk-SNARKs. Such distributed proof generation, where recursive zk-SNARK-proofs are organized in perfect Mercle trees, was for the first time proposed in Latus consensus protocol for zk-SNARKs-based sidechains. We consider two models of a such proof generation process: the simplified one, where all proofs are independent (like one level of tree), and its natural generation, where proofs are organized in partially ordered set (poset), according to tree structure. Using discrete Markov chains for modeling of corresponding proof generation process, we obtained the recurrent formulas for the expectation and variance of the number of steps needed to generate a certain number of independent proofs by a given number of provers. We asymptotically represent the expectation as a function of the one variable n/m, where n is the number of provers m is the number of proofs (leaves of tree). Using results obtained, we give numerical recommendation about the number of transactions, which should be included in the current block, idepending on the network parameters, such as time slot duration, number of provers, time needed for proof generation, etc.

Privacy-preserving inpainting for outsourced image

In this article, a framework of privacy-preserving inpainting for outsourced image and an encrypted-image inpainting scheme are proposed. Different with conventional image inpainting in plaintext domain, there are two entities, that is, content owner and image restorer, in our framework. Content owner first encrypts his or her damaged image for privacy protection and outsources the encrypted, damaged image to image restorer, who may be a cloud server with powerful computation capability. Image restorer performs inpainting in encrypted domain and sends the inpainted and encrypted image back to content owner or authorized receiver, who can acquire final inpainted result in plaintext domain through decryption. In our encrypted-image inpainting scheme, with the assist of Johnson–Lindenstrauss transform that can preserve Euclidean distance between two vectors before and after encryption, the best-matching block with the smallest distance to current block can be found and utilized for patch filling in Paillier-encrypted image. To eliminate mosaic effect after decryption, weighted mean filtering in encrypted domain is conducted with Paillier homomorphic properties. Experimental results show that our privacy-preserving inpainting framework can be effectively applied in secure cloud computing, and the proposed encrypted-image inpainting scheme achieves comparable visual quality of inpainted results with some typical inpainting schemes in plaintext domain.

Non-monotonic kilohertz frequency neural block thresholds arise from amplitude- and frequency-dependent charge imbalance

Reversible block of nerve conduction using kilohertz frequency electrical signals has substantial potential for treatment of disease. However, the ability to block nerve fibers selectively is limited by poor understanding of the relationship between waveform parameters and the nerve fibers that are blocked. Previous in vivo studies reported non-monotonic relationships between block signal frequency and block threshold, suggesting the potential for fiber-selective block. However, the mechanisms of non-monotonic block thresholds were unclear, and these findings were not replicated in a subsequent in vivo study. We used high-fidelity computational models and in vivo experiments in anesthetized rats to show that non-monotonic threshold-frequency relationships do occur, that they result from amplitude- and frequency-dependent charge imbalances that cause a shift between kilohertz frequency and direct current block regimes, and that these relationships can differ across fiber diameters such that smaller fibers can be blocked at lower thresholds than larger fibers. These results reconcile previous contradictory studies, clarify the mechanisms of interaction between kilohertz frequency and direct current block, and demonstrate the potential for selective block of small fiber diameters.

Transfer effects in auditory temporal preparation occur using an unfilled but not filled foreperiod

How quickly participants respond to a “go” after a “warning” signal is partly determined by the time between the two signals (the foreperiod) and the distribution of foreperiods. According to Multiple Trace Theory of Temporal Preparation (MTP), participants use memory traces of previous foreperiods to prepare for the upcoming go signal. If the processes underlying temporal preparation reflect general encoding and memory principles, transfer effects (the carryover effect of a previous block’s distribution of foreperiods to the current block) should be observed regardless of the sensory modality in which signals are presented. Despite convincing evidence for transfer effects in the visual domain, only weak evidence for transfer effects has been documented in the auditory domain. Three experiments were conducted to examine whether such differences in results are due to the modality of the stimulus or other procedural factors. In each experiment, two groups of participants were exposed to different foreperiod distributions in the acquisition phase and to the same foreperiod distribution in the transfer phase. Experiment 1 used a choice-reaction time (RT) task, and the warning signal remained on until the go signal, but there was no evidence for transfer effects. Experiments 2 and 3 used a simple- and choice-RT task, respectively, and there was silence between the warning and go signals. Both experiments revealed evidence for transfer effects, which suggests that transfer effects are most evident when there is no auditory stimulation between the warning and go signals.

Oxidant-Resistant LRRC8A/C Anion Channels Support Superoxide Production by Nox1

ABSTRACTTumor necrosis factor-α (TNFα) activates NADPH Oxidase 1 (Nox1) in vascular smooth muscle cells (VSMCs), producing superoxide (O2•-) required for subsequent signaling. LRRC8 family proteins A-E comprise volume-regulated anion channels (VRACs). The required subunit LRRC8A physically associates with Nox1, and VRAC activity is required for Nox activity and the inflammatory response to TNFα. LRRC8 channel currents are modulated by oxidants, suggesting that oxidant sensitivity and proximity to Nox1 may play a physiologically relevant role. In VSMCs, LRRC8C knockdown (siRNA) recapitulated the effects of siLRRC8A, inhibiting TNFα-induced extracellular and endosomal O2•- production, receptor endocytosis, NF-κB activation, and proliferation. In contrast, siLRRC8D potentiated NF-κB activation. Nox1 co-immunoprecipitated with 8C and 8D, and co-localized with 8D at the plasma membrane and in vesicles. We compared VRAC currents mediated by homomeric and heteromeric 8C and 8D channels expressed in HEK293 cells. The oxidant chloramine T (ChlorT, 1 mM) weakly inhibited LRRC8C, but potently inhibited 8D currents. ChlorT exposure also greatly reduced subsequent current block by DCPIB, implicating external sites of oxidation. Substitution of the extracellular loop domains (EL1, EL2) of 8D onto 8C conferred significantly stronger ChlorT-dependent inhibition. 8A/C channel activity is thus more effectively maintained in the oxidized microenvironment expected to result from Nox1 activation at the plasma membrane. Increased ratios of 8D:8C expression may potentially depress inflammatory responses to TNFα. LRRC8A/C channel downregulation represents a novel strategy to reduce TNFα-induced inflammation.Key PointsLRRC8A-containing anion channels associate with Nox1 and regulate superoxide production and TNFα signaling. Here we show that .LRRC8C and 8D also co-immunoprecipitate with Nox1 in vascular smooth muscle cells.LRRC8C knockdown inhibited TNFα-induced O2•- production, receptor endocytosis, NF-κB activation, and proliferation while LRRC8D knockdown enhanced NF-κB activation. Significant changes in LRRC8 isoform expression in human atherosclerosis and psoriasis suggest compensation for increased inflammation.The oxidant chloramine-T (ChlorT, 1 mM) weakly (∼25%) inhibited 8C currents but potently (∼80%) inhibited 8D currents. Substitution of the two extracellular loop (EL) domains of 8D onto 8C conferred significantly stronger ChlorT-dependent inhibition.ChlorT also impaired current block by DCPIB, which occurs through interaction with EL1, further implicating external sites of oxidation.8A/C channels most effectively maintain activity in an oxidized microenvironment, as is expected to result from Nox1 activity at the plasma membrane.

Simplification on Cross-Component Linear Model in Versatile Video Coding

To improve coding efficiency by exploiting the local inter-component redundancy between the luma and chroma components, the cross-component linear model (CCLM) is included in the versatile video coding (VVC) standard. In the CCLM mode, linear model parameters are derived from the neighboring luma and chroma samples of the current block. Furthermore, chroma samples are predicted by the reconstructed samples in the collocated luma block with the derived parameters. However, as the CCLM design in the VVC test model (VTM)-6.0 has many conditional branches in its processes to use only available neighboring samples, the CCLM implementation in parallel processing is limited. To address this implementation issue, this paper proposes including the neighboring sample generation as the first process of the CCLM, so as to simplify the succeeding CCLM processes. As unavailable neighboring samples are replaced with the adjacent available samples by the proposed CCLM, the neighboring sample availability checks can be removed. This results in simplified downsampling filter shapes for the luma sample. Therefore, the proposed CCLM can be efficiently implemented by employing parallel processing in both hardware and software implementations, owing to the removal of the neighboring sample availability checks and the simplification of the luma downsampling filters. The experimental results demonstrate that the proposed CCLM reduces the decoding runtime complexity of the CCLM mode, with negligible impact on the Bjøntegaard delta (BD)-rate.