The pool of quality control proteins (QC) that maintains protein-folding homeostasis (proteostasis) is dynamic but can become depleted in human disease. A challenge has been in quantitatively defining the depth of the QC pool. With a new biosensor, flow cytometry-based methods and mathematical modeling we measure the QC capacity to act as holdases and suppress biosensor aggregation. The biosensor system comprises a series of barnase kernels with differing folding stability that engage primarily with HSP70 and HSP90 family proteins. Conditions of proteostasis stimulation and stress alter QC holdase activity and aggregation rates. The method reveals the HSP70 chaperone cycle to be rate limited by HSP70 holdase activity under normal conditions, but this is overcome by increasing levels of the BAG1 nucleotide exchange factor to HSPA1A or activation of the heat shock gene cluster by HSF1 overexpression. This scheme opens new paths for biosensors of disease and proteostasis systems.

DC and pulse voltage-induced metal-insulator transition (MIT) in epitaxial VO2 two terminal devices were measured at various stage temperatures. The power needed to switch the device to the ON-state decrease linearly with increasing stage temperature, which can be explained by the Joule heating effect. During transient voltage induced MIT measurement, the incubation time varied across 6 orders of magnitude. Both DC I-V characteristic and incubation times calculated from the electrothermal simulations show good agreement with measured values, indicating Joule heating effect is the cause of MIT with no evidence of electronic effects. The width of the metallic filament in the ON-state of the device was extracted and simulated within the thermal model.

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Oxide‐based resistive switching devices are a leading contender for the next generation memories. Before use, each device has to go through a conditioning process called electroformation which has been suggested to be initiated by the accumulation of oxygen vacancies. Here, experimental evidence is presented which shows that both Ta2O5‐x‐ and TiO2‐x‐based crossbar devices, exhibit characteristic electronic instability leading to a reversible constriction of the current flow to a narrow filament prior to permanent change. Thus, it is asserted, electroformation is initiated through purely electronic and reversible events, to be followed later by structural changes in the material, like oxygen vacancy redistribution. Furthermore, the electronic instability responsible for electroformation also gives rise to negative differential resistance (NDR) and that this characteristics appears to involve two distinct mechanisms: a thermal one in which Joule heating causes resistance to decrease as current increases and a second electronic mechanism that appears not to require Joule heating for NDR. Using a combination of thermometry and thermal modeling, a self‐consistent temperature and filament radius as a function of power are found for the 5 μm cross‐bar devices. In the thermal NDR regime, the filament appears to be ∼500 nm in diameter and has a peak temperature of ∼300 °C, while in the adiabatic regime, the estimated filament diameter is much smaller (<50 nm) and the maximum temperature inside it exceeds 800 °C.

Huntington's disease is a neurodegenerative disorder associated with the expansion of the polyglutamine tract in the exon-1 domain of the huntingtin protein (htte1). Above a threshold of 37 glutamine residues, htte1 starts to aggregate in a nucleation-dependent manner. A 17-residue N-terminal fragment of htte1 (N17) has been suggested to play a crucial role in modulating the aggregation propensity and toxicity of htte1. Here, we identify N17 as a potential target for novel therapeutic intervention using the molecular tweezer CLR01. A combination of biochemical experiments and computer simulations shows that binding of CLR01 induces structural rearrangements within the htte1 monomer and inhibits htte1 aggregation, underpinning the key role of N17 in modulating htte1 toxicity.