A phenomenological model of whole brain dynamics using a network of neural oscillators with power-coupling.

We present a general, trainable oscillatory neural network as a large-scale model of brain dynamics. The model has a cascade of two stages - an oscillatory stage and a complex-valued feedforward stage - for modelling the relationship between structural connectivity and functional connectivity from neuroimaging data under resting brain conditions. Earlier works of large-scale brain dynamics that used Hopf oscillators used linear coupling of oscillators. A distinctive feature of the proposed model employs a novel form of coupling known as power coupling. Oscillatory networks based on power coupling can accurately model arbitrary multi-dimensional signals. Training the lateral connections in the oscillator layer is done by a modified form of Hebbian learning, whereas a variation of the complex backpropagation algorithm does training in the second stage. The proposed model can not only model the empirical functional connectivity with remarkable accuracy (correlation coefficient between simulated and empirical functional connectivity- 0.99) but also identify default mode network regions. In addition, we also inspected how structural loss in the brain can cause significant aberration in simulated functional connectivity and functional connectivity dynamics; and how it can be restored with optimized model parameters by an in silico perturbational study.

An Inbuilt Electronic Pawl Gates Orbital Information Processing and Controls the Rotation of a Double Ratchet Rotary Motor.

A direct external input energy source (e.g., light, chemical reaction, redox potential, etc.) is compulsory to supply energy to rotary motors for accomplishing rotation around the axis. The stator leads the direction of rotation, and a sustainable rotation requires two mutual input energy supplies (e.g., light and heat, light and pH or metal ion, etc.); however, there are some exceptions (e.g., covalent single bond rotors and/or motors). On the contrary, our experiment suggested that double ratchet rotary motors (DRMs) can harvest power from available thermal noise, kT, for sustainable rotation around the axis. Under a scanning tunneling microscope, we have imaged live thermal noise movement as a dynamic orbital density and resolved the density diagram up to the second derivative. A second input energy can synchronize multiple rotors to afford a measurable output. Therefore, we hypothesized that rotation control in a DRM must be evolved from an orbital-level information transport channel between the two coupled rotors but was not limited to the second input energy. A DRM comprises a Brownian rotor and a power stroke rotor coupled to a -C≡C- stator, where the transport of information through coupled orbitals between the two rotors is termed the vibrational information flow chain (VIFC). We test this hypothesis by studying the DRM's density functional theory calculation and variable-temperature 1H nuclear magnetic resonance. Additionally, we introduced inbuilt pawl-like functional moieties into a DRM to create different electronic environments by changing proton intercalation interactions, which gated information processing through the VIFC. The results show the VIFC can critically impact the motor's noise harvesting, resulting in variable rotational motions in DRMs.

The century-old picture of a nerve spike is wrong: filaments fire, before membrane.

In 1907, Lapicque proposed that an electric field passes through the neuronal membrane and transmits a signal. Subsequently, a "snake curve" or spike was used to depict the means by which a linear flat current undergoes a sudden Gaussian or Laplacian peak. This concept has been the accepted scenario for more than 115 years even appearing in textbooks on the subject. It was not noted that the membrane spike should have a cylindrical shape. A nerve spike having a dot shape on membrane surface cannot propagate through a cylindrical surface since it would dissipate instantaneously. A nerve spike should have the appearance of a ring, encompassing the diameter of a cylindrical axon or dendron. However, this subtle change has remarkable implications. Maintaining a circular form of an electric field is not easy, especially at the surface of an organic object. Here, we suggest that neuroscience could redefine itself if we accept that a nerve spike is not a localized 3D Gaussian or Laplacian wave packet, rather it is a 3D ring encompassing the diameter of a neural branch.

Electrophysiology using coaxial atom probe array: live imaging reveals hidden circuits of a hippocampal neural network.

Since the 1960s, it is held that when a neuron fires, a nerve spike passes only through the selective branches, the calculated choice is a key to learning by rewiring. It is argued by chemically estimating the membrane's ion channel density that different axonal branches get active to pass the spike-branches blink at firing at different time domains. Here, using a new time-lapse dielectric imaging, we visualize the classic branch selection process; thenceforth, hidden circuits operating at different time domains become visible. The fractal grid of coaxial probes captures wireless snapshots of material's vibration at various depths below the membrane by setting a suitable frequency. Thus far, branch selection observed emitted energy or particle but never the emitters, what they do. As each dielectric material transmits and reflects signals of different frequencies, we image live how filaments search for many branch-made circuits, choose a unique pathway 103 times faster than a single nerve spike. It reveals that neural branches and circuit visible in a microscope are not absolute, there coexist many circuits each operating in different dime domains, operating at a time.NEW & NOTEWORTHY Using dielectric resonance scanner, we show electromagnetic field connections between physically separated neurons. Electromagnetic field creates field lines that pass through gap junctions, connect Axon initial segment with the dendrites through Soma, and connect axonal or dendritic branches even if there is no synaptic junction. Consequently, many distinct loops connecting various branches form coexisting circuits. Our discovery suggests that physically appearing neural circuit is a fractional view of many simultaneously operating circuits in different time domains in a neural network.

Correction: Speedy one-pot electrochemical synthesis of giant octahedrons from in situ generated pyrrolidinyl PAMAM dendrimer.

Correction for 'Speedy one-pot electrochemical synthesis of giant octahedrons from in situ generated pyrrolidinyl PAMAM dendrimer' by Anup Singhania et al., Soft Matter, 2020, 16, 9140-9146, DOI: 10.1039/D0SM00819B.

Filaments and four ordered structures inside a neuron fire a thousand times faster than the membrane: theory and experiment.

The current action potential paradigm considers that all components beneath the neuron membrane are inconsequential. Filamentary communication is less known to the ionic signal transmission; recently, we have proposed that the two are intimately linked through time domains. We modified the atom probe-connected dielectric resonance scanner to operate in two-time domains, milliseconds and microseconds simultaneously for the first time. We resonate the ions for imaging rather than neutralizing them as patch clamps do; resonant transmission images the ion flow 103 times faster than the existing methods. We revisited action potential-related events by scanning in and around the axon initial segment (AIS). Four ordered structures in the cytoskeletal filaments exchange energy ~250 µs before a neuron fires, editing spike-time-gap-key to the brain's cognition. We could stop firing above a threshold or initiate a fire by wirelessly pumping electromagnetic signals. We theoretically built AIS, whose simulated electromagnetic energy exchange matched the experiment. Thus far, the scanner could detect & link uncorrelated biological events unfolding over 106 orders in the time scale simultaneously. Our experimental findings support a new dielectric resonator model of neuron functioning in various time domains, thus suggesting the dynamic anatomy of electrical activity as information-rich.

Speedy one-pot electrochemical synthesis of giant octahedrons from in situ generated pyrrolidinyl PAMAM dendrimer.

A novel electrochemical synthesis via a radical generation pathway is described here for the generation of a quaternary megamer structure from secondary dendrimers. The reaction is rapid and completes in <5 min. We have used lower/higher generation poly(amido)amine (PAMAM) dendrimers with carboxylic acid groups at the terminals. A precise electrocatalytic reaction at >3.5 V activates the carboxylic groups to undergo anodic oxidation (-e-) and produce radical carboxylate anions on the dendrimer surface. The reaction further goes through a decarboxylative elimination. Successive self-assembly creates billions of polydispersed and extremely stable ∼500 nm octahedron nanostructures, which we failed to destroy even by using a 20 kV electron beam. This is a new route for the speedy synthesis of important futuristic materials of well-defined shape. It has applications in building designer organic crystals for solar cells, organic electronics, rapid protein gelation, rapid protein crystallization, etc.

Radio Waveguide-Double Ratchet Rotors Work in Unison on a Surface to Convert Heat into Power.

Synchronizing thousands of 100% efficient rotors in a macrodevice for harvesting noise is unapprehended. Thermodynamically, realizing a thermal gradient at the atomic scale is critical. Harvesting free thermal energy or noise by resonance has a hidden clause; either externally activating a directed self-powered motion or constructing a nanoscale power supply. To accomplish this, we combined two rotor concepts, Brownian rotor, BR, and power stroke, PS, rotors available in living systems in two planes of a single molecule. Quantum tunneling images reveal how a radio-wave guided synchronization of PS-BR combination tweaks rotational dynamics of a rotor to bypass the necessity of temperature gradient (ΔT). Live imaging of thermal noise movement as electron density between a pair of molecular planes helped in optimizing the rotor design. The rotor's monolayer harvests heat from the liquid's Brownian noise and electromagnetic noise, together delivering a finite, usable power. The chip supplies the power if we wet the surface or shine electric noise.

Computational analysis of NIRS and BOLD signal from neurovascular coupling with three neuron-system feedforward inhibition network.

Several neurological disorders occur due to hypoxic condition in brain arising from impairment of cerebral functionality, which can be controlled by neural stimulation driven vasoactive response mediated through biological response in astrocyte, a phenomenon known as neurovascular coupling. Brain can adjust with the problem of hypoxic condition by causing vasodilation with the help of this mechanism. To deduce the mechanism behind vasodilation of blood vessel caused by neuronal stimulus, current study articulates a mathematical model involving neuronal system feedforward inhibition network model (FFI) with two other functional components of neurovascular coupling, i.e. astrocyte and smooth muscle cell lining blood vessel. This study includes the neural inhibition network system where glutamatergic pyramidal neuron and GABAergic interneuron act antagonistically with each other. The proposed model successfully includes the implication of the inhibition system to design mathematical model for neurovascular coupling. Result of the proposed model shows that the increase in neuronal stimulus from 20 to 60 µA/cm2 has the ability to increase the vasodilatory activity of blood tissue vasculature. Oxygenation level and hemodynamic response due to input synaptic stimulation has been calculated by regional cerebral oxygenation level (rS02) and blood oxygen level dependent (BOLD) imaging signal which supports vasodilation of blood vessel with increase in synaptic input stimulus.

In-vivo & in-vitro toxicity test of molecularly engineered PCMS: A potential drug for wireless remote controlled treatment.

PC, PCM, PCS, and PCMS are our designed & synthesized ∼8 nm PAMAM dendrimer (P) -based organic supramolecular systems, for example, PCMS has 32 molecular motors (M), 4 pH sensors (S) and 2 multi-level molecular electronic switches (C). We have reported earlier following a preliminary in-vitro test that the synthesized PCMS can selectively target cancer cell nucleotides if triggered wirelessly by an electromagnetic pulse. Here to further verify its drug potential, we have studied the preliminary efficacy, toxicity, and pharmacokinetics of P derivatives (PC, PCM, PCMS) in-vivo and in-vitro. We used ethanol-induced gastric inflammation model and cultured human gastric epithelial cells AGS to examine to the toxicity of PAMAM dendrimers cell permeability and toxicity, in (a) the cultured human gastric epithelium cells (AGS), and in (b) the gastric ulcer mice model. Here we report that the toxicity of PAMAM dendrimer (>G3.5) P can be reduced by adding C, M and S. Gastric ulcer is the primary stage of the manifestation of acute inflammation, even gastric epithelial cancer. Ethanol causes ulceration (ulcer index 30), thus upregulates both pro and active MMP-9. A 50 µl PCMS dose prior to ethanol administration reduces ulceration by ∼80% and downregulates MMP-9 and prevents oxidative damages of gastric tissue by ECM remodeling. Alcohol's inflammation of mouse stomach causes up-regulation of both pro and active MMP-9, resulting in oxidative damages of gastric tissue by ECM remodeling. PCMS in particular dose window reverses & alters ECM remodeling, thus, neutralizing alcohol-induced inflammation & generation of ROS.

A simultaneous one pot synthesis of two fractal structures via swapping two fractal reaction kinetic states.

We introduce a new class of fractal reaction kinetics wherein two or more distinct fractal structures are synthesized as parts of a singular cascade reaction in a single chemical beaker. Two examples: sphere ↔ spiral & triangle ↔ square fractals, grow 10(6) orders from a single dendrimer (8 nm) to the visible scale.

Inventing a co-axial atomic resolution patch clamp to study a single resonating protein complex and ultra-low power communication deep inside a living neuron cell.

To read the signals of single molecules in vitro on a surface, or inside a living cell or organ, we introduce a coaxial atom tip (coat) and a coaxial atomic patch clamp (COAPAP). The metal-insulator-metal cavity of these probes extends to the atomic scale (0.1[Formula: see text]nm), it eliminates the cellular or environmental noise with a S/N ratio 105. Five ac signals are simultaneously applied during a measurement by COAT and COAPAP to shield a true signal under environmental noise in five unique ways. The electromagnetic drive in the triaxial atomic tips is specifically designed to sense anharmonic vibrational and transmission signals for any system between 0.1[Formula: see text]nm and 50[Formula: see text]nm where the smallest nanopatch clamp cannot reach. COAT and COAPAP reliably pick up the atomic scale vibrations under the extreme noise of a living cell. Each protein's distinct electromagnetic, mechanical, electrical and ionic vibrational signature studied in vitro in a protected environment is found to match with the ones studied inside a live neuron. Thus, we could confirm that by using our probe blindly we could hold on to a single molecule or its complex in the invisible domain of a living cell. Our decade long investigations on perfecting the tools to measure bio-resonance of all forms and simultaneously in all frequency domains are summarized. It shows that the ratio of emission to absorption resonance frequencies of a biomaterial is around [Formula: see text], only a few in the entire em spectrum are active that regulates all other resonances, like mechanical, ionic, etc.

Inventing atomic resolution scanning dielectric microscopy to see a single protein complex operation live at resonance in a neuron without touching or adulterating the cell.

A substantial ion flow in a normally wet protein masks any other forms of signal transmission. We use hysteresis and linear conduction (both are artifacts) as a marker to precisely wet a protein, which restricts the ionic conduction (hysteresis disappears), and at the same time, it is not denatured (quantized conductance and Raman spectra are intact). Pure electric visualization of proteins at work by eliminating the screening of ions, electrons, would change the way we study biology. Here we discuss the technical challenges resolved for imaging a protein or live cell using nonlinear dielectric response (spatial distribution of conductance, capacitance and phase, GCP trio). We electromagnetically triggered electrical, mechanical, thermal and ionic resonant vibrations in a protein. During resonant oscillations, we imaged the protein using resonant scanning tunneling microscopy of biomaterials (Brestum) and during ionic firing we imaged live what happens inside an axon core of a neuron by using our atomic scale scanning dielectric microscopy (Asadim). Both Asadim and Brestum are housed in a homebuilt scanning tunneling microscope (bio-STM) and a special micro-grid developed by us (patent JP-5187804) for fractal supercomputing. We found the trick to turn a membrane transparent and see inside without making any physical contact. We image live that a protein molecule adopts a unique configuration for each resonance frequency, - thus far unknown to biology. "Membrane alone fires" is found to be wrong after a century, micro-neuro-filaments communicate prior to firing to decide its necessity and then regulate it suitably. We introduce a series of technologies e.g., fractal grid, point contact, micro THz antenna, to discover that from atomic structure to a living cell, the biomaterials vibrate collectively.

An organic jelly made fractal logic gate with an infinite truth table.

Widely varying logic gates invented over a century are all finite. As data deluge problem looms large on the information processing and communication industry, the thrust to explore radical concepts is increasing rapidly. Here, we design and synthesis a molecule, wherein, the input energy transmits in a cycle inside the molecular system, just like an oscillator, then, we use the molecule to make a jelly that acts as chain of oscillators with a fractal like resonance band. Hence, with the increasing detection resolution, in the vacant space between two energy levels of a given resonance band, a new band appears, due to fractal nature, generation of newer energy levels never stops. This is natural property of a linear chain oscillator. As we correlate each energy level of the resonance band of organic jelly, as a function of pH and density of the jelly, we realize a logic gate, whose truth table is finite, but if we zoom any small part, a new truth table appears. In principle, zooming of truth table would continue forever. Thus, we invent a new class of infinite logic gate for the first time.

Resonant oscillation language of a futuristic nano-machine-module: eliminating cancer cells & Alzheimer aß plaques.

Nano-machine-module is designed and synthesized as a futuristic drug (PCMS) for cancer and Alzheimers by doping 2 Nile Red molecules in the cavity of a 5(th) generation PAM AM dendrimer P, and attaching 32 molecular rotors M, 4 pH sensors S on its surface. Molecular rotors and sensors enable the dendritic box surface to target specific sites, minimizing termination of healthy cells, e.g. cancer cells, nuclei acids (DNA) & spirals of Abeta Amyloid are disintegrated. Combined Excitation Emission Spectroscopy (CEES) shows directed energy transfer along M↔C↔S, this energy transmission path is itself an oscillation, and we image live resonant oscillation of the PCMS and the target molecular system. PCMS engages into resonant oscillations with spiral molecular structures. PCMS is designed to sense microsatellite instability & spirals with resonance frequencies in the kHz range. PCM is toxic, but the toxicity disappears as S is added to derive PCMS. PCMS does not even affect the dynamic instability of microtubule, a basic operator of living cells.

Live visualizations of single isolated tubulin protein self-assembly via tunneling current: effect of electromagnetic pumping during spontaneous growth of microtubule.

As we bring tubulin protein molecules one by one into the vicinity, they self-assemble and entire event we capture live via quantum tunneling. We observe how these molecules form a linear chain and then chains self-assemble into 2D sheet, an essential for microtubule, --fundamental nano-tube in a cellular life form. Even without using GTP, or any chemical reaction, but applying particular ac signal using specially designed antenna around atomic sharp tip we could carry out the self-assembly, however, if there is no electromagnetic pumping, no self-assembly is observed. In order to verify this atomic scale observation, we have built an artificial cell-like environment with nano-scale engineering and repeated spontaneous growth of tubulin protein to its complex with and without electromagnetic signal. We used 64 combinations of plant, animal and fungi tubulins and several doping molecules used as drug, and repeatedly observed that the long reported common frequency region where protein folds mechanically and its structures vibrate electromagnetically. Under pumping, the growth process exhibits a unique organized behavior unprecedented otherwise. Thus, "common frequency point" is proposed as a tool to regulate protein complex related diseases in the future.

Atomic water channel controlling remarkable properties of a single brain microtubule: correlating single protein to its supramolecular assembly.

Microtubule nanotubes are found in every living eukaryotic cells; these are formed by reversible polymerization of the tubulin protein, and their hollow fibers are filled with uniquely arranged water molecules. Here we measure single tubulin molecule and single brain-neuron extracted microtubule nanowire with and without water channel inside to unravel their unique electronic and optical properties for the first time. We demonstrate that the energy levels of a single tubulin protein and single microtubule made of 40,000 tubulin dimers are identical unlike conventional materials. Moreover, the transmitted ac power and the transient fluorescence decay (single photon count) are independent of the microtubule length. Even more remarkable is the fact that the microtubule nanowire is more conducting than a single protein molecule that constitutes the nanowire. Microtubule's vibrational peaks condense to a single mode that controls the emergence of size independent electronic/optical properties, and automated noise alleviation, which disappear when the atomic water core is released from the inner cylinder. We have carried out several tricky state-of-the-art experiments and identified the electromagnetic resonance peaks of single microtubule reliably. The resonant vibrations established that the condensation of energy levels and periodic oscillation of unique energy fringes on the microtubule surface, emerge as the atomic water core resonantly integrates all proteins around it such that the nanotube irrespective of its size functions like a single protein molecule. Thus, a monomolecular water channel residing inside the protein-cylinder displays an unprecedented control in governing the tantalizing electronic and optical properties of microtubule.

A new approach to extract multiple distinct conformers and co-existing distinct electronic properties of a single molecule by point-contact method.

Conventionally, it is assumed that a single molecule has only one absolute electronic property. Molecular electronics, molecular machines, intelligent drugs are some of the fields that require atomic scale control of molecular properties. In spite of remarkable achievements in the last two decades, absolute control of molecular properties has not been achieved. Here, experimental evidences argue against assigning a fixed property to a molecule. A molecule might structurally accommodate itself to the new environment and its electronic properties might change accordingly. By isolating electronic properties of all the conformers of a Rose Bengal molecule one by one, a map of its complete electronic properties is drawn here. The existing concept of one absolute electronic property of a molecule is true only for those molecules, which have only one stable conformer. For others, depending on the conformer, multiple distinct electronic properties may co-exist, leading to a variable output in an electronic characterization. Thus, we present a generalized method for characterizing/resolving collective electronic properties that emerge statistically. The method could be used for designing molecular switches for collective and evolutionary information processing.

Origin of negative differential resistance in a strongly coupled single molecule-metal junction device.

A new mechanism is proposed to explain the origin of negative differential resistance (NDR) in a strongly coupled single molecule-metal junction. A first-principles quantum transport calculation in a Fe-terpyridine linker molecule sandwiched between a pair of gold electrodes is presented. Upon increasing the applied bias, it is found that a new phase in the broken symmetry wave function of the molecule emerges from the mixing of occupied and unoccupied molecular orbitals. As a consequence, a nonlinear change in the coupling between the molecule and the lead is evolved resulting in NDR. This model can be used to explain NDR in other classes of metal-molecule junction devices.