Channel Conductance Research Articles

Monolithic In2Se3–In2O3 heterojunction for multibit non-volatile memory and logic operations using optoelectronic inputs

Stable ferroelectricity at room-temperature down to the monolayer limit, harnessed with strong sensitivity towards visible-to-near-infrared illumination in α-In2Se3, facilitates its potential as versatile building block for developing ultrathin multifunctional photonic integrated networks. Herein, we demonstrated a planar ferroelectric-semiconductor heterojunction (FeS-HJ) field-effect transistor (FET) fabricated out of α-In2Se3 and In2O3, where the ferroelectric-polarization state in α-In2Se3 is utilized to control the device characteristics. The robust in-plane (IP) polarization flipping triggered by out-of-plane (OOP) electrostatic field along with clear anticlockwise hysteresis loop were readily revealed by scanning Kelvin-probe force microscopy (KPFM) and electrical probing. The orthogonally tangled ferroelectric switching was used to manipulate the HJ channel conductance and thereby to realize non-volatile memory (NVM) states. Moreover, gate-tuneable diode-like characteristics and superior photoresponse in HJ compared to its individual constitutes were observed. Utilizing the concurrent ferro-photonic coupling, high bandwidth optical inputs further tailored the outputs into four distinguished current states induced by different polarization directions. Our results pave the way for developing advanced (opto) electronic devices with diverse signal modulation capability to realize next generation low-power neurocomputing, brain-inspired visionary systems, and on-chip optical communications.

Fabrication and characterization of InSb nanosheet/hBN/graphite heterostructure devices

Semiconductor InSb nanosheet/hexagonal boron nitride (hBN)/graphite trilayers are fabricated, and single- and double-gate devices made from the trilayers are realized and characterized. The InSb nanosheets employed in the trilayer devices are epitaxially grown, free-standing, zincblende crystals and are in micrometer lateral sizes. The hBN and graphite flakes are obtained by exfoliation. Each trilayer is made by successively stacking an InSb nanosheet on an hBN flake and on a graphite flake using a home-made alignment stacking/transfer setup. The fabricated single- and double-gate devices are characterized by electrical and/or magnetotransport measurements. In all these devices, the graphite and hBN flakes are employed as the bottom gates and the gate dielectrics. The measurements of a fabricated single bottom-gate field-effect device show that the InSb nanosheet in the device has an electron field-effect mobility of ∼7300 cm2 V−1 s−1 and a low gate hysteresis of ∼0.05 V at 1.9 K. The measurements of a double-gate Hall-bar device show that both the top and the bottom gate exhibit strong capacitive couplings to the InSb nanosheet channel and can thus tune the nanosheet channel conduction effectively. The electron Hall mobility in the InSb nanosheet of the Hall-bar device is extracted to be larger than 1.1 × 104 cm2 V−1 s−1 at a sheet electron density of ∼6.1 × 1011 cm −2 and 1.9 K and, thus, the device exhibits well-defined Shubnikov–de Haas oscillations.

Solution processed thin-film transistors with bilayer channel consisting of ZnO nanoparticles and SnO2

Owing to their many intriguing properties, transparent metal oxide semiconductors have become the most attractive alternatives for silicon-based semiconductors widely used today and been widely investigated by researchers. However, most of high performance metal oxide thin film transistor (TFT) relied on vacuum processing equipment and expensive rare element indium in the manufacturing process, the need for developing low cost indium-free metal oxide TFT has become urgent. In this work, a bilayer TFT composed of ZnO nanoparticles (NPs)/SnO2 was prepared by solution method. In this device structure, SnO2 film can provide high conductivity and carrier mobility, while the ZnO NPs in the upper layer can modulate and control channel conductance and further protect SnO2 film from air environment. The obtained device exhibits the excellent performances including μFE of 22.9 cm2V−1s−1 and Ion/Ioff about 1 × 107, subthreshold swing (SS) value about 0.36 V dec−1, and excellent environmental stability have been effectively achieved. Furthermore, the performance enhancement mechanism for the bilayer transistor with the help of simulation and related experiments was further explored. The bilayer ZnO NPs/SnO2 TFT has great cost advantage compared with indium based metal oxide TFTs and exhibits excellent potential in low cost thin-film electronic devices.

The role of axonal voltage-gated potassium channels in tDCS

BackgroundTranscranial direct current stimulation (tDCS) is a non-invasive sub-threshold stimulation, widely accepted for its amelioration of distinct neuropsychiatric disorders. The weak electric field of tDCS modulates the activity of cortical neurons, which in turn modifies brain functioning. However, the underlying mechanisms for that are not fully understood.Objective/Hypothesis: Previous studies demonstrated that the axons are the most sensitive subcellular compartment for tDCS-induced polarization. Moreover, it was posited that DCS-induced axonal polarization is amplified by modifying the conductance of ionic channels. We posit that voltage-gated potassium-channels that are highly expressed in axons play a crucial role in DCS-induced modulation of cortical neurons functioning. MethodsWe examined the involvement of voltage-gated potassium-channels in the active modulation of spontaneous vesicle release by DCS. For that, we measured spontaneous excitatory postsynaptic currents (sEPSCs) from layer-V motor cortex during DCS application, while co-applying distinct voltage-gated potassium-channels blockers. Moreover, we examined the role of Kv1 potassium channels in DCS-induced modulation of action potential waveform at axon terminals by recording action potentials at terminal axon blebs during DCS application while locally inhibiting the Kv1 potassium-channels. ResultsWe demonstrated that inhibiting voltage-gated potassium-channels occluded the DCS-induced modulation of subthreshold presynaptic vesicle release. Moreover, we showed that inhibiting Kv1 voltage-gated potassium-channels also occluded the DCS-induced modulation of action potential waveform at axon terminals. ConclusionWe suggest that DCS-induced depolarization inactivates the Kv1 potassium channels thus reducing potassium conductance, which amplifies axonal depolarization, subsequently enhancing the presynaptic component of synaptic transmission. Whereas DCS-induced hyperpolarization induces opposite effects.

VX770 Modulated Bicarbonate Conductance in CFTR‐expressing FRT Cell

The cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel expressed in epithelia and other tissues, is compromised by genetic mutations that cause cystic fibrosis (CF). Although CFTR is reportedly permeant to both Cl¯ and HCO3¯, high throughput screening studies identified drug scaffolds that enhanced Cl¯ conductance of mutated CFTR by ‘correcting’ processing deficiets and/or ‘potentiating’ aggregate conductance of channels in epithelial cell membranes while being agnostic to HCO3‐. Ongoing work seeks to determine whether mutated forms of CFTR exhibit typical HCO3¯ conductance and to access clinically‐used drugs for their effects on HCO3¯ conductance by wild‐type and mutated CFTR. Fisher rat thyroid (FRT) cells, which form electrically tight epithelial monolayers, express no functionally detectable CFTR and which traffick exogenously expressed CFTR to both the apical and basolateral membranes, were employed to assess transepithelial anion conductance in modified Ussing‐style flux chambers. Initial experiments employing FRT cells expressing human wtCFTR validated that forskolin‐stimulated conductance, which was inhibited by selective CFTR blockers, was proportional to extracellular Cl¯ concentration over the range of ~70‐140 mEq/l. Further, a clear increment in forskolin‐stimulated conductance was observed when HCO3¯ (25 mEq/l) was incorporated into the media. VX770 potentiated forskolin‐stimulated conductance, but had no effect in the absence of forskolin. Foskolin‐stimulated and VX770‐potentiated conductance was compared in base medium (100 mEq/l Cl‐) supplemented with 25 mEq/l HCO3‐ or Cl‐ and bicarbonate (B) conductance was quantified relative to Cl‐ (C) conductance (i.e., gB/gC). Following forskolin exposure the gB/gC ratio for wtCFTR was 0.62±0.20, a value that decreased to 0.11±0.10 following exposure to VX770, suggesting that VX770 may negatively impact gB. Forskolin‐ and VX770‐stimulated conductance across cells expressing F508del CFTR was nearly undetectable unless cells were pretreated with CFTR correctors. Following corrector exposure, forskolin stimulated and VX770 potentiated gC, but gB was virtually undetectable, suggesting that this variant may lack gB. Alternatively, forskolin stimulated little conductance across cells expressing G551D CFTR, but a substantial potentiation with VX770 was observed. Notably, the gB/gC ratio approached 1.0 for both foskolin stimulation and VX770 potentiation. Taken together, these results suggest that CFTR HCO3‐ conductance differs by disease‐associated variant and that gB of some variants are sensitive to VX770. Ongoing experiments are designed to determine the optimal forskolin concentration to maximize VX770 potentiation. Initial outcomes suggest that there is interaction between the CFTR variant and forskolin concentration dependence such that VX770‐potentiated conductance is maximized at different forskolin concentrations. Taken together, results from this investigation suggest that additional or alternative interventions may be required to optimize bicarbonate secretion and pH regulation in CF patients expressing alternative CFTR variants.

Biophysical Models of Minipig Right Atrial Ganglionic Plexus Principal Neurons Identified from Transcriptomics Data

The Right Atrial Ganglionic Plexus (RAGP) is a component of the intrinsic cardiac nervous system. Its neurons are critical to the cardiac pacemaker response to vagal stimulation, regulating sino‐atrial node activity. We developed single‐compartment computational models of RAGP principal neurons by incorporating ion channels identified from transcriptomics data from HT‐qPCR (High Throughput quantitative Polymerase Chain Reaction) and RNA‐sequencing of 405 principal neurons in female Yucatan minipig RAGP. Out of the ~200 genes in the transcriptomics map, we identified 13 genes that encode ion channel proteins, namely: Naf (Scn1a, Nav 1.1), KDR (Kcnc1, Kv 3.1; Kcnab1, Kv 1.1), P‐, N‐, L‐, T‐type Ca2+ (Cacna1a, Cav 2.1; Cacna1b, Cav 2.2; Cacna1c, Cav 1.2; Cacna1g, Cav 3.1; Cacna1i, Cav 3.3), KA (Kcnd2) and HCN1, HCN2, HCN3, HCN4. The corresponding Hodgkin‐Huxley‐based kinetic models of these ion channel isoforms were mined from databases: Ion Channel Genealogy, Channelpedia, and ModelDB. Since each ion channel gene had several kinetic models associated with it, we ran multiple simulations on the NetPyNE software to identify a single model per gene that would best represent the channel's dynamic behaviour in the assembled electrophysiological model. A binary transcriptomic map of the 13 genes showed 101 distinct ion channel combinations. Our 505 electrophysiological models (5 sets of the 101 cells) elicited two primary firing profiles. 65% elicited a single‐spike phasic response, ~32% elicited a tonic firing in response to a current clamp stimulus, and ~3% produced tonic firing that continued after the stimulus. The firing frequencies increased by ~13 Hz for every 0.1 nA increase in the current clamp stimulus and decreased by ~11 Hz for every 0.01 S/cm2 increase in KA channel conductance. Our electrophysiological models are available to the SPARC community in NetPyNE and NIH’s O2S2PARC platform. The models exhibit phasic and tonic excitability profiles with phasic being more prevalent. We next aim to incorporate neuromodulatory inputs and simulate a network of these neuronal models.

Loss, Gain and Altered Function of GlyR α2 Subunit Mutations in Neurodevelopmental Disorders.

Glycine receptors (GlyRs) containing the α2 subunit govern cell fate, neuronal migration and synaptogenesis in the developing cortex and spinal cord. Rare missense variants and microdeletions in the X-linked GlyR α2 subunit gene (GLRA2) have been associated with human autism spectrum disorder (ASD), where they typically cause a loss-of-function via protein truncation, reduced cell-surface trafficking and/or reduced glycine sensitivity (e.g., GLRA2Δex8-9 and extracellular domain variants p.N109S and p.R126Q). However, the GlyR α2 missense variant p.R323L in the intracellular M3-M4 domain results in a gain-of-function characterized by slower synaptic decay times, longer duration active periods and increases in channel conductance. This study reports the functional characterization of four missense variants in GLRA2 associated with ASD or developmental disorders (p.V-22L, p.N38K, p.K213E, p.T269M) using a combination of bioinformatics, molecular dynamics simulations, cellular models of GlyR trafficking and electrophysiology in artificial synapses. The GlyR α2V–22L variant resulted in altered predicted signal peptide cleavage and a reduction in cell-surface expression, suggestive of a partial loss-of-function. Similarly, GlyR α2N38K homomers showed reduced cell-surface expression, a reduced affinity for glycine and a reduced magnitude of IPSCs in artificial synapses. By contrast, GlyR α2K213E homomers showed a slight reduction in cell-surface expression, but IPSCs were larger, with faster rise/decay times, suggesting a gain-of-function. Lastly, GlyR α2T269M homomers exhibited a high glycine sensitivity accompanied by a substantial leak current, suggestive of an altered function that could dramatically enhance glycinergic signaling. These results may explain the heterogeneity of clinical phenotypes associated with GLRA2 mutations and reveal that missense variants can result in a loss, gain or alteration of GlyR α2 function. In turn, these GlyR α2 missense variants are likely to either negatively or positively deregulate cortical progenitor homeostasis and neuronal migration in the developing brain, leading to changes in cognition, learning, and memory.

Effect of DNA Aptamer Concentration on the Conductivity of a Water-Gated Al:ZnO Thin-Film Transistor-Based Biosensor.

Field-effect transistor-based biosensors (bio-FETs) are promising candidates for the rapid high-sensitivity and high-selectivity sensing of various analytes in healthcare, clinical diagnostics, and the food industry. However, bio-FETs still have several unresolved problems that hinder their technological transfer, such as electrical stability. Therefore, it is important to develop reliable, efficient devices and establish facile electrochemical characterization methods. In this work, we have fabricated a flexible biosensor based on an Al:ZnO thin-film transistor (TFT) gated through an aqueous electrolyte on a polyimide substrate. In addition, we demonstrated techniques for establishing the operating range of such devices. The Al:ZnO-based devices with a channel length/width ratio of 12.35 and a channel thickness of 50 nm were produced at room temperature via magnetron sputtering. These Al:ZnO-based devices exhibited high field-effect mobility (μ = 6.85 cm2/Vs) and threshold voltage (Vth = 654 mV), thus showing promise for application on temperature-sensitive substrates. X-ray photoelectron spectroscopy was used to verify the chemical composition of the deposited films, while the morphological aspects of the films were assessed using scanning electron and atomic force microscopies. The gate–channel electric capacitance of 40 nF/cm2 was determined using electrochemical impedance spectroscopy, while the electrochemical window of the gate–channel system was determined as 1.8 V (from −0.6 V to +1.2 V) using cyclic voltammetry. A deionized water solution of 10 mer (CCC AAG GTC C) DNA aptamer (molar weight −2972.9 g/mol) in a concentration ranging from 1–1000 pM/μL was used as an analyte. An increase in aptamer concentration caused a proportional decrease in the TFT channel conductivity. The techniques demonstrated in this work can be applied to optimize the operating parameters of various semiconductor materials in order to create a universal detection platform for biosensing applications, such as multi-element FET sensor arrays based on various composition nanostructured films, which use advanced neural network signal processing.

Vertically stacked, low-voltage organic ternary logic circuits including nonvolatile floating-gate memory transistors

Multi-valued logic (MVL) circuits based on heterojunction transistor (HTR) have emerged as an effective strategy for high-density information processing without increasing the circuit complexity. Herein, an organic ternary logic inverter (T-inverter) is demonstrated, where a nonvolatile floating-gate flash memory is employed to control the channel conductance systematically, thus realizing the stabilized T-inverter operation. The 3-dimensional (3D) T-inverter is fabricated in a vertically stacked form based on all-dry processes, which enables the high-density integration with high device uniformity. In the flash memory, ultrathin polymer dielectrics are utilized to reduce the programming/erasing voltage as well as operating voltage. With the optimum programming state, the 3D T-inverter fulfills all the important requirements such as full-swing operation, optimum intermediate logic value (~VDD/2), high DC gain exceeding 20 V/V as well as low-voltage operation (< 5 V). The organic flash memory exhibits long retention characteristics (current change less than 10% after 104 s), leading to the long-term stability of the 3D T-inverter. We believe the 3D T-inverter employing flash memory developed in this study can provide a useful insight to achieve high-performance MVL circuits.

Controlling the threshold voltage of a semiconductor field-effect transistor by gating its graphene gate

The threshold voltage of a field-effect transistor (FET) determines its switching and limits the scaling of the supply voltage in the logic gates. Here we demonstrate a GaAs FET with a monolayer graphene gate in which the threshold voltage was externally controlled by an additional control gate. The graphene gate forms a Schottky junction with the transistor channel, modulating the channel conductivity. The control gate sets the work function of the graphene gate, controlling the Schottky barrier height and therefore the threshold voltage, and reduces the subthreshold swing down to ~60 mV dec−1. The change of the threshold voltage was large enough to turn the initially depletion mode FETs into the enhancement mode FETs. This allowed to realize logic gates with a positive switching threshold in which the threshold voltage of each transistor was independently set. The presented FETs can also be operated as dual-gate FETs, which was demonstrated by realizing frequency mixers.

Opening of glutamate receptor channel to subconductance levels

Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated ion channels that open their pores in response to binding of the agonist glutamate1–3. An ionic current through a single iGluR channel shows up to four discrete conductance levels (O1–O4)4–6. Higher conductance levels have been associated with an increased number of agonist molecules bound to four individual ligand-binding domains (LBDs)6–10. Here we determine structures of a synaptic complex of AMPA-subtype iGluR and the auxiliary subunit γ2 in non-desensitizing conditions with various occupancy of the LBDs by glutamate. We show that glutamate binds to LBDs of subunits B and D only after it is already bound to at least the same number of LBDs that belong to subunits A and C. Our structures combined with single-channel recordings, molecular dynamics simulations and machine-learning analysis suggest that channel opening requires agonist binding to at least two LBDs. Conversely, agonist binding to all four LBDs does not guarantee maximal channel conductance and favours subconductance states O1 and O2, with O3 and O4 being rare and not captured structurally. The lack of subunit independence and low efficiency coupling of glutamate binding to channel opening underlie the gating of synaptic complexes to submaximal conductance levels, which provide a potential for upregulation of synaptic activity.

Early Effects of Metabolic Syndrome on ATP-Sensitive Potassium Channels from Rat Pancreatic Beta Cells.

Metabolic syndrome (MS) is a cluster of metabolic signs that increases the risk of developing type 2 two diabetes mellitus and cardiovascular diseases. MS leads to pancreatic beta cell exhaustion and decreased insulin secretion through unknown mechanisms in a time-dependent manner. ATP-sensitive potassium channels (KATP channels), common targets of anti-diabetic drugs, participate in the glucose-stimulated insulin secretion, coupling the metabolic status and electrical activity of pancreatic beta cells. We investigated the early effects of MS on the conductance, ATP and glybenclamide sensitivity of the KATP channels. We used Wistar rats fed with a high-sucrose diet (HSD) for 8 weeks as a MS model. In excised membrane patches, control and HSD channels showed similar unitary conductance and ATP sensitivity pancreatic beta cells in their KATP channels. In contrast, MS produced variability in the sensitivity to glybenclamide of KATP channels. We observed two subpopulations of pancreatic beta cells, one with similar (Gly1) and one with increased (Gly2) glybenclamide sensitivity compared to the control group. This study shows that the early effects of MS produced by consuming high-sugar beverages can affect the pharmacological properties of KATP channels to one of the drugs used for diabetes treatment.

Scn1b expression in the adult mouse heart modulates Na+ influx in myocytes and reveals a mechanistic link between Na+ entry and diastolic function.

Voltage-gated sodium channels (VGSCs) are macromolecular assemblies composed of a number of proteins regulating channel conductance and properties. VGSCs generate Na+ current (INa) in myocytes and play fundamental roles in excitability and impulse conduction in the heart. Moreover, VGSCs condition mechanical properties of the myocardium, a process that appears to involve the late component of INa. Variants in the gene SCN1B, encoding the VGSC β1- and β1B-subunits, result in inherited neurological disorders and cardiac arrhythmias. But the precise contributions of β1/β1B-subunits and VGSC integrity to the overall function of the adult heart remain to be clarified. For this purpose, adult mice with cardiac-restricted, inducible deletion of Scn1b (conditional knockout, cKO) were studied. Myocytes from cKO mice had increased densities of fast (+20%)- and slow (+140%)-inactivating components of INa, with respect to control cells. By echocardiography and invasive hemodynamics, systolic function was preserved in cKO mice, but diastolic properties and ventricular compliance were compromised, with respect to control animals. Importantly, inhibition of late INa with GS967 normalized left ventricular filling pattern and isovolumic relaxation time in cKO mice. At the cellular level, cKO myocytes presented delayed kinetics of Ca2+ transients and cell mechanics, defects that were corrected by inhibition of INa. Collectively, these results document that VGSC β1/β1B-subunits modulate electrical and mechanical function of the heart by regulating, at least in part, Na+ influx in cardiomyocytes.NEW & NOTEWORTHY We have investigated the consequences of deletion of Scn1b, the gene encoding voltage-gated sodium channel β1-subunits, on myocyte and cardiac function. Our findings support the notion that Scn1b expression controls properties of Na+ influx and Ca2+ cycling in cardiomyocytes affecting the modality of cell contraction and relaxation. These effects at the cellular level condition electrical recovery and diastolic function in vivo, substantiating the multifunctional role of β1-subunits in the physiology of the heart.

Multi-channel contactless conductivity detection device for online detection of free-flow electrophoresis separation

现有自由流电泳(FFE)装置因不具备在线检测功能,其实用性仍然存在明显不足。针对这一问题,该工作发展了一种多通道电容耦合式非接触电导检测(MC-C4D)装置并开发了自动测量软件。MC-C4D装置采用了并行分时的非接触电导检测技术,即由多个同样的非接触电导检测模块并行排列,而单个电导检测模块又由多个非接触电导检测池组成,采用模拟开关切换这些检测池,能够分时检测流经相应检测池溶液的电导率。多个电导检测模块的检测池总数等于FFE的组分数,它们分别串行接入到FFE各流路中,这样MC-C4D装置就可在线并行分时在线测量各组分溶液的电导率。为验证所设计MC-C4D装置的检测性能,采用配制的氯化钾标准溶液作为检测对象对MC-C4D装置进行了标定和测试。实验数据表明,MC-C4D装置电导率检测范围为0.015~2.5 mS/cm,检出限(LOD)为0.002 mS/cm,日内相对标准偏差(RSD, n=3)为2.31%,测量相对误差(RE)为3.03%和通道间测量相对偏差为1.60%,这些参数表明该装置检测范围较大,LOD低,重复性好,准确性高,通道间测量相对偏差小。另外,将MC-C 4D装置应用于往复式自由流等电聚焦电泳(RFFIEF)在蛋白质聚焦过程中对各组分溶液电导率进行实时在线检测,结果表明,所开发的MC-C4D装置不仅可实现对FFE各组分溶液电导率的实时在线检测,而且还可在RFFIEF实验中辅助掌握分离的实验进度,提高FFE装置的实用性。

Transient Receptor Potential channels (TRP) in GtoPdb v.2022.1

Transient Receptor Potential channels (TRP) in GtoPdb v.2022.1

Hybridization chain reaction for regulating surface capacitance of organic photoelectrochemical transistor toward sensitive miRNA detection

Photon-enabled bioelectronics has long been pursued in modern electronics due to their non-contact, remote-control, and even self-powered function interfacing the biological world with semiconductor devices. The debuting organic photoelectrochemical transistor (OPECT) relies on the photovoltage generated by the semiconductors to modulate the channel conductance, which enables light-fueled operation at zero gate bias. Inspired by the insulating nature of macrobiomolecules and surface capacitance mechanism, herein we demonstrate the biological regulation of the surface capacitance towards new OPECT biodetection, which was exemplified by a CdS quantum dots/TiO2 nanotubes photoanode accommodating hybridization chain reaction (HCR) amplification with the target of biomarker miRNA-17. Formation of the non-conducting DNA layer from the miRNA-17-oriented HCR could decrease the surface capacitance and increase the corresponding fractional potential drop, shifting the transfer curve horizontally to higher gate voltage and thus producing different drain currents. The OPECT biosensor exhibited a linear relationship with the miRNA-17 concentration on the logarithmic axis in the range from 1 pm. to 10 μm with a detection limit of 1 pm. This work not only represented a generic methodology of miRNA detection, but also provided a universal mechanism for the operation of advanced OPECT bioanalytics.

Pattern formation in a thermosensitive neural network

Pattern formation and synchronization stability in the network are dependent on cooperation between nodes and the local kinetics as well. Temperature has a significant effect on the membrane potential by regulating the channel conductance and excitability of neurons. Thermistor is a smart sensor and its resistance value changes with temperature. A nonlinear circuit composed of thermistors is effective to detect the changes in surroundings temperature. In this paper, a temperature-induced pattern formation in a two-dimensional regular lattice network composed of thermosensitive neurons is studied. Numerical simulations are performed to research the effect of parameters (coupling amplitude) and temperature spatial gradient distribution of neural network on pattern formation and synchronization stability. The bifurcation analysis of the membrane potential reveals the conversion in electrical activity and pattern selection. The results show that neural membrane potential can present distinct firing patterns with the change of temperature. The electrical synapse coupling between neurons promotes effective signals propagation in the network. It is found that the collective dynamic behavior of the network is changed by taming the coupling intensity. The Hamilton energy is estimated to predict the mode selection in neural activities. The energy can be ordered in the network under the temperature gradient distribution. Our results confirm that electrical synapse coupling and temperature spatial gradient distribution can be controlled to affect the neural activities in nervous system.

Variation in CFTR-dependent 'β-sweating' among healthy adults.

The genetic disease cystic fibrosis (CF) results when mutations in the gene for the anion channel CFTR reduce CFTR’s activity below a critical level. CFTR activity = N·PO·γ (number of channels x open probability x channel conductance). Small molecules are now available that partially restore CFTR function with dramatic improvements in health of CF subjects. Continued evaluation of these and other compounds in development will be aided by accurate assessments of CFTR function. However, measuring CFTR activity in vivo is challenging and estimates vary widely. The most accurate known measure of CFTR activity in vivo is the ‘β/M’ ratio of sweat rates, which is produced by stimulation with a β-adrenergic agonist cocktail referenced to the same individual’s methacholine-stimulated sweat rate. The most meaningful metric of CFTR activity is to express it as a percent of normal function, so it is critical to establish β/M carefully in a population of healthy control subjects. Here, we analyze β/M from a sample of 50 healthy adults in which sweat rates to cholinergic and β-adrenergic agonists were measured repeatedly (3 times) in multiple, (~50) identified sweat glands from each individual (giving ~20,000 measurements). The results show an approximately 7-fold range, 26–187% of the WT average set to 100%. These provide a benchmark against which other measures of CFTR activity can be compared. Factors contributing to β/M variation in healthy controls are discussed.

Manipulating Strain in Transistors: From Mechanically Sensitive to Insensitive

AbstractThe rapid development of flexible and stretchable materials has portrayed a bright future of flexible electronics in pursuing the concept of “Internet of Things.” Transistors, as one of the fundamental units in electronic devices, are being widely studied in exploring the possibility of increasing their flexibility and/or stretchability to fulfill the requirement in flexible electronics, from basic logic circuits to intelligent devices. However, the mechanical stimuli induced by bending and stretching activities can lead to unexpected performance degradations. Here, an in‐depth analysis of approaches to modulating the sensitivity of flexible and stretchable transistors, from a mechanically sensitive type to an insensitive type is demonstrated. Starting with the structural design, the mechanism of sensitivity modulation is explicitly analyzed, such as effects based on the modulation of dielectric capacitance, conductance of active channels, or contact resistance at interfaces in sensitive transistors and strain patterning technology applied to an insensitive type. The sensitivity modulation for transistors is further analyzed regarding material utilization based on different dimensional forms. Finally, the potential applications where flexible and stretchable transistors can be employed as an outlook are discussed.

Light Stimulation of Neurons on Organic Photocapacitors Induces Action Potentials with Millisecond Precision.

Nongenetic optical control of neurons is a powerful technique to study and manipulate the function of the nervous system. This research has benchmarked the performance of organic electrolytic photocapacitor (OEPC) optoelectronic stimulators at the level of single mammalian cells: human embryonic kidney (HEK) cells with heterologously expressed voltage-gated K+ channels and hippocampal primary neurons. OEPCs act as extracellular stimulation electrodes driven by deep red light. The electrophysiological recordings show that millisecond light stimulation of OEPC shifts conductance-voltage plots of voltage-gated K+ channels by ≈30mV. Models are described both for understanding the experimental findings at the level of K+ channel kinetics in HEK cells, as well as elucidating interpretation of membrane electrophysiology obtained during stimulation with an electrically floating extracellular photoelectrode. A time-dependent increase in voltage-gated channel conductivity in response to OEPC stimulation is demonstrated. These findings are then carried on to cultured primary hippocampal neurons. It is found that millisecond time-scale optical stimuli trigger repetitive action potentials in these neurons. The findings demonstrate that OEPC devices enable the manipulation of neuronal signaling activities with millisecond precision. OEPCs can therefore be integrated into novel in vitro electrophysiology protocols, and the findings can inspire in vivo applications.