Identification of Fibrinogen as a Plasma Protein Binding Partner for Lecanemab Biosimilar IgG: Implications for Alzheimer's Disease Therapy.

OBJECTIVE: Recombinant monoclonal therapeutic antibodies like lecanemab, which target amyloid beta in Alzheimer's disease, offer a promising approach for modifying the disease progression. Due to its relatively short half-life, Lecanemab, administered as a bi-monthly infusion (typically 10mg/kg) has a relatively brief half-life. Interaction with abundant plasma proteins binder in the bloodstream can affect pharmacokinetics of drugs, including their half-life. In this study we investigated potential plasma protein binding interaction to lecanemab using lecanemab biosimilar. METHODS: Lecanemab biosimilar used in this study was based on publicly available sequences. ELISA and Western blotting were used to assess lecanemab biosimilar immunoreactivity in the fractions human plasma sample obtained through size exclusion chromatography. The binding of lecanemab biosimilar to candidate binders was confirmed by Western blotting, ELISA, and surface plasmon resonance analysis. RESULTS: Using a combination of equilibrium dialysis, ELISA, and Western blotting in human plasma, we first describe the presence of likely plasma protein binding partner to lecanemab biosimilar, and then identify fibrinogen as one of them. Utilizing surface plasmon resonance, we confirmed that lecanemab biosimilar does bind to fibrinogen, although with lower affinity than to monomeric amyloid beta. CONCLUSION: In the context of lecanemab therapy, these results imply that fibrinogen levels could impact the levels of free antibodies in the bloodstream and that fibrinogen might serve as a reservoir for lecanemab. More broadly, these results indicate that plasma protein binding may be an important consideration when clinically utilizing therapeutic antibodies in neurodegenerative disease.

Characterization of Spatial Distribution of Trap Across the Substrate in Metal-Insulator-Semiconductor Structure with Band Bending Effect.

We report the technique of trap distribution extraction according to the vertical position of the substrate in the p-MOSFET. This study was conducted on a single device. This technique is an experimental method. Ctrap was extracted based on the deep depletion C-V characteristics. In VFB, the trap level is neutral. When bias is applied, the energy band bends, resulting in modulation of the quasi-Fermi level. The area created by the bending of the energy band is equal to the area created by the Fermi level modulation. The trap level existing in this area becomes charged. Considering this, the spatial distribution of Trap was extracted. The trap extracted by the proposed method has a maximum value at the interface, rapidly decreases, and is distributed up to 8 nm in the vertical direction. The study of trap spatial distribution is expected to be applicable to the separation of trap interface state and bulk trap extraction later.

Characterization of Subgap Density-of-States by Sub-Bandgap Optical Charge Pumping in In0.53Ga0.47As Metal-Oxide-Semiconductor Field-Effect Transistors.

We report an experimental characterization of the interface states (Dit(E)) by using the subthreshold drain current with optical charge pumping effect in In0.53Ga0.47As metal-oxide-semiconductor fieldeffect transistors (MOSFETs). The interface states are derived from the difference between the dark and photo states of the current-voltage characteristics. We used a sub-bandgap photon (i.e., with the photon energy lower than the bandgap energy, Eph < Eg) to optically excite trapped carriers over the bandgap in In0.53Ga0.47As MOSFETs. We combined a gate bias-dependent capacitance model to determine the channel length-independent oxide capacitance. Then, we estimated the channel length-independent interface states in In0.53Ga0.47As MOSFETs having different channel lengths (Lch = 5, 10, and 25 [µm]) for a fixed overlap length (Lov = 5 [µm]).

Flexible carbon nanotube Schottky diode and its integrated circuit applications.

Carbon nanotubes (CNTs), a low-dimensional material currently popular in industry and academia, are promising candidates for addressing the limits of existing semiconductors. In particular, CNTs are attractive candidates for flexible electronic materials due to their excellent flexibility and potential applications. In this work, we demonstrate a flexible CNT Schottky diode based on highly purified, preseparated, solution-processed 99% semiconducting CNTs and an integrated circuit application using the CNT Schottky diodes. Notably, the fabricated flexible CNT diode can greatly modulate the properties of the contact formed between the semiconducting CNT and the anode electrode via the control gate bias, exhibiting a high rectification ratio of up to 2.5 × 105. In addition, we confirm that the electrical performance of the CNT Schottky diodes does not significantly change after a few thousand bending/releasing cycles of the flexible substrate. Finally, integrated circuit (IC) applications of logic circuits (OR and AND gates) and an analog circuit (a half-wave rectifier) were presented through the use of flexible CNT Schottky diode combinations. The correct output responses are successfully achieved from the circuit applications; hence, we expect that our findings will provide a promising basis for electronic circuit applications based on CNTs.