Insertion of Calcium-Permeable AMPA Receptors during Epileptiform Activity In Vitro Modulates Excitability of Principal Neurons in the Rat Entorhinal Cortex

Epileptic activity leads to rapid insertion of calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (CP-AMPARs) into the synapses of cortical and hippocampal glutamatergic neurons, which generally do not express them. The physiological significance of this process is not yet fully understood; however, it is usually assumed to be a pathological process that augments epileptic activity. Using whole-cell patch-clamp recordings in rat entorhinal cortex slices, we demonstrate that the timing of epileptiform discharges, induced by 4-aminopyridine and gabazine, is determined by the shunting effect of Ca2+-dependent slow conductance, mediated predominantly by K+-channels. The blockade of CP-AMPARs by IEM-1460 eliminates this extra conductance and consequently increases the rate of discharge generation. The blockade of NMDARs reduced the additional conductance to a lesser extent than the blockade of CP-AMPARs, indicating that CP-AMPARs are a more significant source of intracellular Ca2+. The study’s main findings were implemented in a mathematical model, which reproduces the shunting effect of activity-dependent conductance on the generation of discharges. The obtained results suggest that the expression of CP-AMPARs in principal neurons reduces the discharge generation rate and may be considered as a protective mechanism.

Comprehensive Sensing Current Analysis and Its Guideline for the Worst-Case Scenario of RRAM Read Operation

In this paper, the dependence of sensing currents on various device parameters is comprehensively studied by simulating the complete crossbar array rather than its equivalent analytical model. The worst-case scenario for read operation is strictly analyzed and defined in terms of selected location and data pattern, respectively, based on the effect of parasitic sneak paths and interconnection resistance. It is shown that the worst-case data pattern depends on the trade-off between the shunting effect of the parasitic sneak paths and the current injection effect of the parasitic sneak leakage, thus requiring specific analysis in practical simulations. In dealing with that, we propose a concept of the threshold array size incorporating the trade-off to define the parameter-dependent worst-case data pattern. This figure-of-merit provides guidelines for the worst-case scenario analysis of the crossbar array read operations.

Adaptive Resistance Spot Welding Process that Reduces the Shunting Effect for Automotive High-Strength Steels

Although short-pitch resistance spot welding (RSW) significantly increases vehicle body strength, its application has been limited because of the associated shunting effect. In this study, a reference-based adaptive RSW process intended to minimize the shunting effect was proposed, and a related RSW system that controls welding current and power was developed to implement the adaptive method. The proposed RSW method compensates for the heat input loss caused by the shunting effect based on the estimated weld pitch and reference data obtained under suitable welding conditions. An exponential model was developed using a unique indicator (i.e., the ratio of the adaptive welding heat input to the reference welding heat input until the reference welding power curve peak) to estimate the weld pitch. A logistic growth model was next developed based on the relationship of the nugget diameter, heat input, and weld pitch to estimate the heat input compensation. A unique strategy using power control with a modified reference power curve was applied to supply the calculated heat input compensation. The experimental results intended to validate the proposed adaptive RSW process indicated that the proposed process effectively reduced the shunting effect and produced an improved nugget shape relative to the conventional RSW process.

Markers of Local Inflammation and Bone Resorption in the Acute Diabetic Charcot Foot

Objective. Due to the localized nature of Charcot foot, systemically altered levels of inflammation markers can be difficult to measure. The aim of this study was to investigate whether it is possible to detect an arteriovenous (A-V) flux in any locally produced inflammatory biomarkers from an acute Charcot foot by comparing local and systemic measurements. Methods. We included patients with acute diabetic Charcot foot. Blood was sampled from the vena saphena magna on the distal part of the crus bilaterally as well as from the arteria radialis. To minimize the A-V shunting effect, the feet were externally cooled with ice water prior to resampling. Results. Both before and after cooling, the A-V flux of interleukin-6 (IL-6) between the Charcot feet and the arterial level was significantly higher than the flux between the healthy feet and the arterial level (Δvaluebefore: 7.25 versus 0.41 pg/mL, resp., p=0.008; Δvalueafter: 10.04 versus 1.68 pg/mL, resp., p=0.032). There were no differences in the fluxes for other markers of inflammation. Conclusion. We have found an increased A-V flux of IL-6 in the acute diabetic Charcot foot compared to the healthy foot in the same patients.