MFPA: Mixed-Signal Field Programmable Array for Energy-Aware Compressive Signal Processing

Compressive Sensing (CS) is a signal processing technique which reduces the number of samples taken per frame to decrease energy, storage, and data transmission overheads, as well as reducing time taken for data acquisition in time-critical applications. The tradeoff in such an approach is increased complexity of signal reconstruction. While several algorithms have been developed for CS signal reconstruction, hardware implementation of these algorithms is still an area of active research. Prior work has sought to utilize parallelism available in reconstruction algorithms to minimize hardware overheads; however, such approaches are limited by the underlying limitations in CMOS technology. Herein, the MFPA (Mixed-signal Field Programmable Array) approach is presented as a hybrid spin-CMOS reconfigurable fabric specifically designed for implementation of CS data sampling and signal reconstruction. The resulting fabric consists of 1) slice-organized analog blocks providing amplifiers, transistors, capacitors, and Magnetic Tunnel Junctions (MTJs) which are configurable to achieving square/square root operations required for calculating vector norms, 2) digital functional blocks which feature 6-input clockless lookup tables for computation of matrix inverse, and 3) an MRAM-based nonvolatile crossbar array for carrying out low-energy matrix-vector multiplication operations. The various functional blocks are connected via a global interconnect and spin-based analog-to-digital converters. Simulation results demonstrate significant energy and area benefits compared to equivalent CMOS digital implementations for each of the functional blocks used: this includes an 80% reduction in energy and 97% reduction in transistor count for the nonvolatile crossbar array, 80% standby power reduction and 25% reduced area footprint for the clockless lookup tables, and roughly 97% reduction in transistor count for a multiplier built using components from the analog blocks. Moreover, the proposed fabric yields 77% energy reduction compared to CMOS when used to implement CS reconstruction, in addition to latency improvements

Structural analysis of proteins by isotope-edited FTIR spectroscopy

Structure determination of multidomain proteins or protein membrane complexes is one of the most challenging tasks in modern structural biology. High-resolution techniques, like NMR or X-ray crystallography, are limited to molecules of moderate size or those that can be crystallized easily. Both methods encounter serious technical obstacles in structural analysis of protein membrane systems. This work describes an emerging biophysical technique that combines segmental isotope labeling or proteins with Fourier transform infrared (FTIR) spectroscopy, which provides site-specific structural information on proteins and allows structural characterization of protein membrane complexes. Labeling of a segment of the protein with (13)C results in infrared spectral resolution of the labeled and unlabeled parts and thus allows identification of structural changes in specific domains/segments of the protein that accompany functional transitions. Segmental isotope labeling also allows determination of the precise configuration of protein membrane complexes by polarized attenuated total reflection FTIR (ATR-FTIR) spectroscopy. These new developments offer solutions to functionally important site-specific structural changes in proteins and protein membrane complexes that are hard to approach using conventional methods

Relationship between membrane phosphatidylinositol-4,5-bisphosphate and receptor-mediated inhibition of native neuronal M channels

The relationship between receptor-induced membrane phosphatidylinositol-4'5'-bisphosphate (PIP2) hydrolysis and M-current inhibition was assessed in single-dissociated rat sympathetic neurons by simultaneous or parallel recording of membrane current and membrane-to-cytosol translocation of the fluorescent PIP2/inositol 1,4,5-trisphosphate (IP3)-binding peptide green fluorescent protein-tagged pleckstrin homology domain of phospholipase C (GFP-PLC delta-PH). The muscarinic receptor agonist oxotremorine-M produced parallel time- and concentration-dependent M-current inhibition and GFP-PLC delta-PH translocation; bradykinin also produced parallel time- dependent inhibition and translocation. Phosphatidylinositol-4-phosphate-5-kinase (PI5-K) overexpression reduced both M-current inhibition and GFP-PLC delta-PH translocation by both oxotremorine-M and bradykinin. These effects were partly reversed by wortmannin, which inhibits phosphatidylinositol-4-kinase (PI4-K). PI5-K overexpression also reduced the inhibitory action of oxotremorine-M on PIP2-gated G-protein-gated inward rectifier (Kir3.1/3.2) channels; bradykinin did not inhibit these channels. Overexpression of neuronal calcium sensor-1 protein (NCS-1), which increases PI4-K activity, did not affect responses to oxotremorine-M but reduced both fluorescence translocation and M-current inhibition by bradykinin. Using an intracellular IP3 membrane fluorescence-displacement assay, initial mean concentrations of membrane [PIP2] were estimated at 261 mu M (95% confidence limit; 192-381 mu M), rising to 693 mu M (417-1153 mu M) in neurons overexpressing PI5-K. Changes in membrane [PIP2] during application of oxotremorine-M were calculated from fluorescence data. The results, taken in conjunction with previous data for KCNQ2/3 (Kv7.2/Kv7.3) channel gating by PIP2 (Zhang et al., 2003), accorded with the hypothesis that the inhibitory action of oxotremorine-M on M current resulted from depletion of PIP2. The effects of bradykinin require additional components of action, which might involve IP3-induced Ca2+ release and consequent M-channel inhibition (as proposed previously) and stimulation of PIP2 synthesis by Ca2+-dependent activation of NCS-1

Leveraging Signal Transfer Characteristics and Parasitics of Spintronic Circuits for Area and Energy-Optimized Hybrid Digital and Analog Arithmetic

While Internet of Things (IoT) sensors offer numerous benefits in diverse applications, they are limited by stringent constraints in energy, processing area and memory. These constraints are especially challenging within applications such as Compressive Sensing (CS) and Machine Learning (ML) via Deep Neural Networks (DNNs), which require dot product computations on large data sets. A solution to these challenges has been offered by the development of crossbar array architectures, enabled by recent advances in spintronic devices such as Magnetic Tunnel Junctions (MTJs). Crossbar arrays offer a compact, low-energy and in-memory approach to dot product computation in the analog domain by leveraging intrinsic signal-transfer characteristics of the embedded MTJ devices. The first phase of this dissertation research seeks to build on these benefits by optimizing resource allocation within spintronic crossbar arrays. A hardware approach to non-uniform CS is developed, which dynamically configures sampling rates by deriving necessary control signals using circuit parasitics. Next, an alternate approach to non-uniform CS based on adaptive quantization is developed, which reduces circuit area in addition to energy consumption. Adaptive quantization is then applied to DNNs by developing an architecture allowing for layer-wise quantization based on relative robustness levels. The second phase of this research focuses on extension of the analog computation paradigm by development of an operational amplifier-based arithmetic unit for generalized scalar operations. This approach allows for 95% area reduction in scalar multiplications, compared to the state-of-the-art digital alternative. Moreover, analog computation of enhanced activation functions allows for significant improvement in DNN accuracy, which can be harnessed through triple modular redundancy to yield 81.2% reduction in power at the cost of only 4% accuracy loss, compared to a larger network. Together these results substantiate promising approaches to several challenges facing the design of future IoT sensors within the targeted applications of CS and ML

Co- and Post-translocation Roles for HSP90 in Cholera Intoxication

Cholera toxin (CT) moves from the cell surface to the endoplasmic reticulum (ER) where the catalytic CTA1 subunit separates from the rest of the toxin. CTA1 then unfolds and passes through an ER translocon pore to reach its cytosolic target. Due to its intrinsic instability, cytosolic CTA1 must be refolded to achieve an active conformation. The cytosolic chaperone Hsp90 is involved with the ER to cytosol export of CTA1, but the mechanistic role of Hsp90 in CTA1 translocation remains unknown. Moreover, potential post-translocation roles for Hsp90 in modulating the activity of cytosolic CTA1 have not been explored. Here, we show by isotope-edited Fourier transform infrared spectroscopy that Hsp90 induces a gain-of-structure in disordered CTA1 at physiological temperature. Only the ATP-bound form of Hsp90 interacts with disordered CTA1, and refolding of CTA1 by Hsp90 is dependent upon ATP hydrolysis. In vitro reconstitution of the CTA1 translocation event likewise required ATP hydrolysis by Hsp90. Surface plasmon resonance experiments found that Hsp90 does not release CTA1, even after ATP hydrolysis and the return of CTA1 to a folded conformation. The interaction with Hsp90 allows disordered CTA1 to attain an active state, which is further enhanced by ADP-ribosylation factor 6, a host cofactor for CTA1. Our data indicate CTA1 translocation involves a process that couples the Hsp90-mediated refolding of CTA1 with CTA1 extraction from the ER. The molecular basis for toxin translocation elucidated in this study may also apply to several ADP-ribosylating toxins that move from the endosomes to the cytosol in an Hsp90-dependent process

Modulation of Toxin Stability by 4-Phenylbutyric Acid and Negatively Charged Phospholipids

AB toxins such as ricin and cholera toxin (CT) consist of an enzymatic A domain and a receptor-binding B domain. After endocytosis of the surface-bound toxin, both ricin and CT are transported by vesicle carriers to the endoplasmic reticulum (ER). The A subunit then dissociates from its holotoxin, unfolds, and crosses the ER membrane to reach its cytosolic target. Since protein unfolding at physiological temperature and neutral pH allows the dissociated A chain to attain a translocation-competent state for export to the cytosol, the underlying regulatory mechanisms of toxin unfolding are of paramount biological interest. Here we report a biophysical analysis of the effects of anionic phospholipid membranes and two chemical chaperones, 4-phenylbutyric acid (PBA) and glycerol, on the thermal stabilities and the toxic potencies of ricin toxin A chain (RTA) and CT A1 chain (CTA1). Phospholipid vesicles that mimic the ER membrane dramatically decreased the thermal stability of RTA but not CTA1. PBA and glycerol both inhibited the thermal disordering of RTA, but only glycerol could reverse the destabilizing effect of anionic phospholipids. In contrast, PBA was able to increase the thermal stability of CTA1 in the presence of anionic phospholipids. PBA inhibits cellular intoxication by CT but not ricin, which is explained by its ability to stabilize CTA1 and its inability to reverse the destabilizing effect of membranes on RTA. Our data highlight the toxin-specific intracellular events underlying ER-to-cytosol translocation of the toxin A chain and identify a potential means to supplement the long-term stabilization of toxin vaccines

Collective charge excitations along cell membranes

A significant part of the thin layers of counter-ions adjacent to the exterior and interior surfaces of a cell membrane form quasi-two-dimensional (2D) layers of mobile charge. Collective charge density oscillations, known as plasmon modes, in these 2D charged systems of counter-ions are predicted in the present paper. This is based on a calculation of the self-consistent response of this system to a fast electric field fluctuation. The possibility that the membrane channels might be using these excitations to carry out fast communication is suggested and experiments are proposed to reveal the existence of such excitations.Comment: 4 two-column pages, 3 figure