Liquid–liquid phase separation of intrinsically disordered proteins into mesoscopic, dynamic, liquid-like supramolecular condensates is thought to govern critical cellular functions. These condensates can mature from a functional liquid-like state to a pathological gel-like or solid-like state. Here, we present a unique case to demonstrate that an unusual cascade of intermolecular charge-transfer coupled with a multitude of transient noncovalent interactions and conformational fluctuations can promote liquid phase condensation of a pH-responsive, intrinsically disordered, oligopeptide repeat domain of a melanosomal protein. At neutral cytosolic pH, the repeat domain forms highly dynamic, mesoscopic, permeable, liquid-like droplets possessing rapid internal diffusion and torsional fluctuations. These liquid condensates mature via pervasive intermolecular charge-transfer and persistent backbone interactions driving the liquid-to-solid phase transition into heterogeneous solid-like aggregates that are structurally and morphologically distinct from typical amyloids formed at mildly acidic melanosomal pH. Our findings reveal the regulatory role of the repeat domain as a specific pH-sensor that critically controls the phase transition and self-assembly processes akin to prion-like low-complexity domains modulating intracellular phase separation.

Augmented growth of MWCNT-primed wheat, enhancement in grain number, biomass, stomatal density, xylem-phloem size, epidermal cells, and water uptake is observed while finding no DNA damage. This opens up an entirely new aspect to using cost-effective nanomaterials (the MWCNTs were produced in-house) for enhancing the performance of crop plants. © 2017 Society of Chemical Industry.

System safety analysis techniques are well established and are used extensively during the design of safety-critical systems. Despite this, most of the techniques are highly subjective and dependent on the skill of the practitioner. Since these analyses are usually based on an informal system model, it is unlikely that they will be complete, consistent, and error free. In fact, the lack of precise models of the system architecture and its failure modes often forces the safety analysts to devote much of their effort to finding undocumented details of the system behavior and embedding this information in the safety artifacts such as the fault trees.In this paper we propose an approach, ModelBased Safety Analysis, in which the system and safety engineers use the same system models created during a model-based development process. By extending the system model with a fault model as well as relevant portions of the physical system to be controlled, automated support can be provided for much of the safety analysis. We believe that by using a common model for both system and safety engineering and automating parts of the safety analysis, we can both reduce the cost and improve the quality of the safety analysis. Here we present our vision of model-based safety analysis and discuss the advantages and challenges in making this approach practical.

Safety analysis techniques have traditionally been performed manually by the safety engineers. Since these analyses are based on an informal model of the system, it is unlikely that these analyses will be complete, consistent, and error-free. Using precise formal models of the system as the basis of the analysis may help reduce errors and provide a more thorough analysis. Further, these models allow automated analysis, which may reduce the manual effort required. The process of creating system models suitable for safety analysis closely parallels the model-based development process that is increasingly used for critical system and software development. By leveraging the existing tools and techniques, we can create formal safety models using tools that are familiar to engineers and we can use the static analysis infrastructure available for these tools. This paper reports our initial experience in using model-based safety analysis on an example system taken from the ARP Safety Assessment guidelines document.

Biomolecular condensates formed via liquid-liquid phase separation (LLPS) are involved in a myriad of critical cellular functions and debilitating neurodegenerative diseases. Elucidating the role of intrinsic disorder and conformational heterogeneity of intrinsically disordered proteins/regions (IDPs/IDRs) in these phase-separated membrane-less organelles is crucial to understanding the mechanism of formation and regulation of biomolecular condensates. Here we introduce a unique single-droplet surface-enhanced Raman scattering (SERS) methodology that utilizes surface-engineered, plasmonic, metal nanoparticles to unveil the inner workings of mesoscopic liquid droplets of Fused in Sarcoma (FUS) in the absence and presence of RNA. These highly sensitive measurements offer unprecedented sensitivity to capture the crucial interactions, conformational heterogeneity, and structural distributions within the condensed phase in a droplet-by-droplet manner. Such an ultra-sensitive single-droplet vibrational methodology can serve as a potent tool to decipher the key molecular drivers of biological phase transitions of a wide range of biomolecular condensates involved in physiology and disease.

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This paper describes the use of automated analysis tools, such as model-checkers [5] and theorem provers [13], to search for potential sources of mode confusion in a representative specification of the mode logic of a Flight Guidance System [11].