In silico study of PEI-PEG-squalene-dsDNA polyplex formation: the delicate role of the PEG length in the binding of PEI to DNA

Using a two step simulation protocol the atomistic interactions between PEG and b-PEI and the effect of these interactions on DNA binding were determined

Decreased mitochondrial DNA content drives OXPHOS dysregulation in chromophobe renal cell carcinoma

Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma (RO) are closely related, rare kidney tumors. Mutations in complex I (CI)-encoding genes play an important role in dysfunction of the oxidative phosphorylation (OXPHOS) system in RO but are less frequently observed in chRCC. As such, the relevance of OXPHOS status and role of CI mutations in chRCC remain unknown. To address this issue, we performed proteome and metabolome profiling as well as mitochondrial whole-exome sequencing to detect mitochondrial alterations in chRCC tissue specimens. Multi-omic analysis revealed downregulation of electron transport chain (ETC) components in chRCC that differed from the expression profile in RO. A decrease in mitochondrial (mt)DNA content, rather than CI mutations, was the main cause for reduced OXPHOS in chRCC. There was a negative correlation between protein and transcript levels of nuclear DNA- but not mtDNA-encoded ETC complex subunits in chRCC. In addition, the reactive oxygen species scavenger glutathione (GSH) was upregulated in chRCC due to decreased expression of proteins involved in GSH degradation. These results demonstrate that distinct mechanisms of OXPHOS exist in chRCC and RO and that expression levels of ETC complex subunits can serve as a diagnostic marker for this rare malignancy

RTN in GexSe1-x OTS Selector Devices

Random telegraph noise (RTN) signals in GexSe1-x ovonic threshold switching (OTS) selector have been analyzed in this work, both before and after the first-fire (FF) operation and at on- and off-states. It is observed that RTN appears after the FF, and its absolute amplitude at the off-state is small and negligible in comparison with the RTN signals in RRAM devices. At the on-state, large RTN signals are observed, which can either partially or fully block the conduction path, supporting that a conductive filament is formed or activated by FF and then modulated during switching. Statistical analysis reveals that the relative RTN amplitude at on-state in GexSe1-x OTS selector is smaller than or equivalent to those in RRAM devices

Doped GeSe materials for selector applications

We report on the thermal and electrical performance of nitrogen (N) and carbon (C) doped GeSe thin films for selector applications. Doping of GeSe successfully improved its thermal stability to 450 degrees C. N doping led to a decrease in the off-state leakage and an increase in threshold voltage (V-th), while C doping led to an increase in leakage and reduced V-th. Hence, we show an effective method to tune the electrical parameters of GeSe selectors by using N and C as dopants

Stochastic computing based on volatile GeSe ovonic threshold switching selectors

Stochastic computing (SC) is a special type of digital compute strategy where values are represented by the probability of 1 and 0 in stochastic bit streams, which leads to superior hardware simplicity and error-tolerance. In this paper, we propose and demonstrate SC with GeSe based Ovonic Threshold Switching (OTS) selector devices by exploiting their probabilistic switching behavior. The stochastic bit streams generated by OTS are demonstrated with good computation accuracy in both multiplication operation and image processing circuit. Moreover, the bit distribution has been statistically studied and linked to the collective defect de/localization behavior in the chalcogenide material. Weibull distribution of the delay time supports the origin of such probabilistic switching, facilitates further optimization of the operation condition, and lays the foundation for device modelling and circuit design. Considering its other advantages such as simple structure, fast speed, and volatile nature, OTS is a promising material for implementing SC in a wide range of novel applications, such as image processors, neural networks, control systems and reliability analysis

Ovonic threshold-switching GexSey chalcogenide materials : stoichiometry, trap nature, and material relaxation from first principles

Density functional theory simulations are used to identify the structural factors that define the material properties of ovonic threshold switches (OTS). They show that the nature of mobility-gap trap states in amorphous Ge-rich Ge50Se50 is related to Ge-Ge bonds, whereas in Se-rich Ge30Se70 the Ge valence-alternating-pairs and Se lone-pairs dominate. To obtain a faithful description of the electronic structure and delocalization of states, it is required to combine hybrid exchange-correlation functionals with large unit-cell models. The extent of localization of electronic states depends on the applied external electric field. Hence, OTS materials undergo structural changes during electrical cycling of the device, with a decrease in the population of less exothermic Ge-Ge bonds in favor of more exothermic Ge-Se. This reduces the amount of charge traps, which translates into coordination changes, an increase in mobility-gap, and subsequently changes in the selector-device electrical parameters. The threshold voltage drift process can be explained by natural evolution of the nonpreferred Ge-Ge bonds (or "chains"/clusters thereof) in Ge-rich GexSe1-x. The effect of extrinsic doping is shown for Si and N, which introduce strong covalent bonds into the system, increase both mobility-gap and crystallization temperature, and decrease the leakage current

GeSe-based Ovonic Threshold Switching Volatile True Random Number Generator

In this paper, we propose and demonstrate a novel technique for true random number generator (TRNG) application using GeSe-based Ovonic threshold switching (OTS) selector devices. The inherent variability in OTS threshold voltage results in a bimodal distribution of on/off states which can be easily converted into digital bits. The experimental evaluation shows that the proposed TRNG enables the generation of high-quality random bits that passed 12 tests in the National Institute of Standards and Technology statistical test suite without complex external circuits for post-processing. The randomness is further evidenced by the prediction rate of ∼50% using machine learning algorithm. Compared with the TRNGs based on non-volatile memories, the volatile nature of OTS avoids the reset operation, thus further simplifying the operation and improving the generation frequency

Structural changes during the switching transition of chalcogenide selector devices

Ovonic threshold switches are a favored choice for chalcogenide-based amorphous (a-) GeSex selector devices used in cross-point arrays of nonvolatile memories. Previous models of their nonlinear high-field conduction proposed a largely electronic-only switching mechanism, within a fixed density of electronic states. Here, we use a density functional molecular-dynamics supercell calculation to show that the high-current excited state configuration of a-GeSex has structural changes such as additional Ge-Ge bonds and overcoordinated Ge sites, giving lower effective mass, more delocalized conduction states, and a lower ON resistance.We acknowledge the funding from the EC H2020 project Phase change switch

Papillary Renal Cell Carcinomas Rewire Glutathione Metabolism and Are Deficient in Both Anabolic Glucose Synthesis and Oxidative Phosphorylation

Papillary renal cell carcinoma (pRCC) is a malignant kidney cancer with a prevalence of 7–20% of all renal tumors. Proteome and metabolome profiles of 19 pRCC and patient-matched healthy kidney controls were used to elucidate the regulation of metabolic pathways and the underlying molecular mechanisms. Glutathione (GSH), a main reactive oxygen species (ROS) scavenger, was highly increased and can be regarded as a new hallmark in this malignancy. Isotope tracing of pRCC derived cell lines revealed an increased de novo synthesis rate of GSH, based on glutamine consumption. Furthermore, profound downregulation of gluconeogenesis and oxidative phosphorylation was observed at the protein level. In contrast, analysis of the The Cancer Genome Atlas (TCGA) papillary RCC cohort revealed no significant change in transcripts encoding oxidative phosphorylation compared to normal kidney tissue, highlighting the importance of proteomic profiling. The molecular characteristics of pRCC are increased GSH synthesis to cope with ROS stress, deficient anabolic glucose synthesis, and compromised oxidative phosphorylation, which could potentially be exploited in innovative anti-cancer strategies

Dependence of switching probability on operation conditions in GexSe1-x ovonic threshold switching selectors

Ovonic threshold switching (OTS) selector is a promising candidate to suppress the sneak current paths in resistive switching memory (RRAM) arrays. Variations in the threshold voltage (Vth), and the hold voltage (Vhd) have been reported, but a quantitative analysis of the switching probability dependence on the OTS operation conditions is still missing. A novel characterization method is developed in this work, and the time-to-switch-on/off (ton/toff) at a constant VOTS is found following the Weibull distribution, based on which the dependence of switching probability on pulse bias and time can be extracted and extrapolated, and the switching probability can be ensured with appropriately chosen operation conditions. The difference between square and triangle switching pulses is also explained. This provides a practical guidance for predicting the switching probability under different operation conditions and for designing reliable one-selector-one-RRAM (1S1R) arrays