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We are developing robot controllers based on biomimetic design principles. The goal is to realise the adaptive capabilities of the animal models in natural environments. We report feasibility studies of a hybrid architecture that instantiates a command and coordinating level with computed discrete-time map-based (DTM) neuronal networks and the central pattern generators with analogue VLSI (Very Large Scale Integration) electronic neuron (aVLSI) networks. DTM networks are realised using neurons based on a 1-D or 2-D Map with two additional parameters that define silent, spiking and bursting regimes. Electronic neurons (ENs) based on Hindmarsh–Rose (HR) dynamics can be instantiated in analogue VLSI and exhibit similar behaviour to those based on discrete components. We have constructed locomotor central pattern generators (CPGs) with aVLSI networks that can be modulated to select different behaviours on the basis of selective command input. The two technologies can be fused by interfacing the signals from the DTM circuits directly to the aVLSI CPGs. Using DTMs, we have been able to simulate complex sensory fusion for rheotaxic behaviour based on both hydrodynamic and optical flow senses. We will illustrate aspects of controllers for ambulatory biomimetic robots. These studies indicate that it is feasible to fabricate an electronic nervous system controller integrating both aVLSI CPGs and layered DTM exteroceptive reflexes.

This paper presents a fully integrated on-chip switched-capacitor (SC) DC–DC converter that supports a programmable regulated power supply ranging from 2.6 to 3.2 V out of a 5 V input supply. The proposed 4-to-3 step-down topology utilizes two conventional 2-to-1 step-down topologies; each of them (2-to-1_up and 2-to-1_dw) has a different flying capacitance to maximize the load current driving capability while minimizing the bottom-plate capacitance loss. The control circuits use a low power supply provided by a small internal low-drop output (LDO) connected to the internal load voltage (VL_dw) from the 2-to-1_dw, and low swing level-shifted gate-driving signals are generated using the internal load voltage (VL_dw). Therefore, the proposed implementation reduces control circuit and switching power consumptions. The programmable power supply voltage is regulated by means of a pulse frequency modulation (PFM) technique with the compensated two-stage operational transconductance amplifier (OTA) and the current-starved voltage controlled oscillator (VCO) to maintain high efficiency over a wide range of load currents. The proposed on-chip SC DC–DC converter is designed and simulated using high-voltage 0.35 μm bipolar, complementary metal-oxide-semiconductor (CMOS) and DMOS (BCDMOS) technology. It achieves a peak efficiency of 74% when delivering an 8 mA load current at a 3.2 V supply voltage level, and it provides a maximum output power of 48 mW (IL = 15 mA at VL_up = 3.2 V) at 70.5% efficiency. The proposed on-chip SC voltage regulator shows better efficiency than the ideal linear regulator over a wide range of output power, from 2.6 mW to 48 mW. The 18-phase interleaving technique enables the worst-case output voltage ripple to be less than 5.77% of the load voltage.

This work presents the design, hardware implementation, and performance analysis of novel asynchronous AES (advanced encryption standard) Key Expander and Round Function, which offer increased side-channel attack (SCA) resistance. These designs are based on a delay-insensitive (DI) logic paradigm known as null convention logic (NCL), which supports useful properties for resisting SCAs including dual-rail encoding, clock-free operation, and monotonic transitions. Potential benefits include reduced and more uniform switching activities and reduced signal-to-noise (SNR) ratio. A novel method to further augment NCL AES hardware with random voltage scaling technique is also presented for additional security. Thereby, the proposed components leak significantly less side-channel information than conventional clocked approaches. To quantitatively verify such improvements, functional verification and WASSO (weighted average simultaneous switching output) analysis have been carried out on both conventional synchronous approach and the proposed NCL based approach using Mentor Graphics ModelSim and Xilinx simulation tools. Hardware implementation has been carried out on both designs exploiting a specified side-channel attack standard evaluation FPGA board, called SASEBO-GII, and the corresponding power waveforms for both designs have been collected. Along with the results of software simulations, we have analyzed the collected waveforms to validate the claims related to benefits of the proposed cryptohardware design approach.

Human regulatory T cells (Treg) suppress other immune cells. Their dysfunction contributes to the pathophysiology of autoimmune diseases, including type 1 diabetes (T1D). Infusion of Tregs is being clinically evaluated as a novel way to prevent or treat T1D. Genetic modification of Tregs, most notably through the introduction of a chimeric antigen receptor (CAR) targeting Tregs to pancreatic islets, may improve their efficacy. We evaluated CAR targeting of human Tregs to monocytes, a human b cell line and human islet β cells in vitro. Targeting of HLAA2- CAR (A2-CAR) bulk Tregs to HLA-A2+ cells resulted in dichotomous cytotoxic killing of human monocytes and islet β cells. In exploring subsets and mechanisms that may explain this pattern, we found that CD39 expression segregated CAR Treg cytotoxicity. CAR Tregs from individuals with more CD39low/- Tregs and from individuals with genetic polymorphism associated with lower CD39 expression (rs10748643) had more cytotoxicity. Isolated CD39-CAR Tregs had elevated granzyme β expression and cytotoxicity compared to the CD39+ CAR Treg subset. Genetic overexpression of CD39 in CD39low CAR Tregs reduced their cytotoxicity. Importantly, β cells upregulated protein surface expression of PD-L1 and PD-L2 in response to A2-CAR Tregs. Blockade of PDL1/PD-L2 increased β cell death in A2-CAR Treg co-cultures suggesting that the PD-1/PD-L1 pathway is important in protecting islet β cells in the setting of CAR immunotherapy. In summary, introduction of CAR can enhance biological differences in subsets of Tregs. CD39+ Tregs represent a safer choice for CAR Treg therapies targeting tissues for tolerance induction. [ABSTRACT FROM AUTHOR]

Lymphocyte activation gene-3 (LAG-3) is an inhibitory receptor expressed on activated T cells and an emerging immunotherapy target. Domain 1 (D1) of LAG-3, which has been purported to directly interact with major histocompatibility complex class II (MHCII) and fibrinogen-like protein 1 (FGL1), has been the major focus for the development of therapeutic antibodies that inhibit LAG-3 receptor-ligand interactions and restore T cell function. Here, we present a high-resolution structure of glycosylated mouse LAG-3 ectodomain, identifying that cis-homodimerization, mediated through a network of hydrophobic residues within domain 2 (D2), is critically required for LAG-3 function. Additionally, we found a previously unidentified key protein-glycan interaction in the dimer interface that affects the spatial orientation of the neighboring D1 domain. Mutation of LAG-3 D2 residues reduced dimer formation, dramatically abolished LAG-3 binding to both MHCII and FGL1 ligands, and consequentially inhibited the role of LAG-3 in suppressing T cell responses. Intriguingly, we showed that antibodies directed against D1, D2, and D3 domains are all capable of blocking LAG-3 dimer formation and MHCII and FGL-1 ligand binding, suggesting a potential allosteric model of LAG-3 function tightly regulated by dimerization. Furthermore, our work reveals unique epitopes, in addition to D1, that can be targeted for immunotherapy of cancer and other human diseases. [ABSTRACT FROM AUTHOR]