Bridging the Bridging Imidazolate in the Bimetallic Center of the Cu/Zn SOD1 and ALS

Metallation status of human Cu/Zn superoxide dismutase 1 (SOD1) plays a pivotal role in the pathogenesis of amyotrophic lateral sclerosis (ALS). All of the amino acids found in the bimetallic center have been associated with ALS except for two positions. H63 which forms the bridging imidazolate ion in the bimetallic center and K136 which is not directly involved in coordination but located in the bimetallic center were not reported to be mutated in any of the identified ALS cases. In this study, we investigated the structure and flexibility of five SOD1 variants by using classical molecular dynamics simulations. These variants include three substitutions on the non-ALS-linked positions; H63A, H63R, K136A and ALS-linked positions; G37R, H46R/H48D. We have generated four systems for each variant differing in metallation and presence of the intramolecular disulfide bond. Overall, a total of 24 different dimers including the wild-type were generated and simulated at two temperatures, 298 and 400 K. We have monitored backbone mobility, fluctuations and compactness of the dimer structures to assess whether the hypothetical mutations would behave similar to the ALS-linked variants. Results showed that particularly two mutants, H63R and K136A, drastically affected the dimer dynamics by increasing the fluctuations of the metal binding loops compared with the control mutations. Further, these variants resulted in demetallation of the dimers, highlighting probable ALS toxicity that could be elicited by the SOD1 variants of H63R and K136A. Overall, this study bridges two putative SOD1 positions in the metallic center and ALS, underlining the potential use of atomistic simulations for studying disease variants.

Investigation of 1/f and Lorentzian Noise in TMAH-treated Normally-Off GaN MISFETs

A tetramethyl ammonium hydroxide (TMAH)-treated normally-off Gallum nitride (GaN) metal-insulator-semiconductor field-effect transistor (MISFET) was fabricated and characterized using low-frequency noise (LFN) measurements in order to find the conduction mechanism and analyze the trapping behavior into the gate insulator as well as the GaN buffer layer. At the on-state, the noise spectra in the fabricated GaN device were 1/fγ properties with γ ≈ 1, which is explained by correlated mobility fluctuations (CMF). On the other hand, the device exhibited Lorentzian or generation-recombination (g-r) noises at the off-state due to deep-level trapping/de-trapping into the GaN buffer layer. The trap time constants (τi) calculated from the g-r noises became longer when the drain voltage increased up to 5 V, which was attributed to deep-level traps rather than shallow traps. The severe drain lag was also investigated from pulsed I-V measurement, which is supported by the noise behavior observed at the off-state.

Charge carrier mobility fluctuations due to the capture–emission process

It is shown that the free charge carrier capture–emission process causes both the charge carrier density and mobility fluctuations. In this report we present the calculation results in order to find how the capture–emission process affects the free charge carrier mobility and mobility fluctuations. The carrier mobility dependence on phonon, impurity and carrier–carrier scatterings, and the mobility dependence on the electric field and the energy gap variation due to the doping level were taken into account. It is also shown that fluctuations of the charge carrier density and mobility due to the capture–emission process are completely correlated, and that their relaxation times are the same as for the charge capture–emission process. The general expression for estimation of active capture centre density in the volume of a homogeneous sample from the low-frequency noise measurements is presented.

Electron Mobility Non-Damping Fluctuations in Semiconductors

Equilibrium state disturbance and restoration processes of an electron gas interacting with phonon system in an equilibrium semiconductor have been investigated. Damping peculiarities of small deviations (fluctuations) of electron system from equilibrium state due to electron-acoustic phonon random scattering have been analyzed. A second-order linear partial differential equation for symmetric component of fluctuation of electron distribution function was obtained via linearization of the Boltzmann equation. This equation describes the chaotic movement of electrons along the energy axis, which can be interpreted as diffusion in momentum space. Another equation which describes the time dependence of electron lattice mobility fluctuations was obtained. It was shown that in the Boltzmann equation linearization approximation, lattice mobility fluctuations do not decay over time. The time dependence of the mobility fluctuations is described by stochastic harmonic function with random amplitude and random initial phase.