High-penetration levels of distributed photovoltaic (PV) generation on an electrical distribution circuit present several challenges and opportunities for distribution utilities. Rapidly varying irradiance conditions may cause voltage sags and swells that cannot be compensated by slowly responding utility equipment resulting in a degradation of power quality. Although not permitted under current standards for interconnection of distributed generation, fast-reacting, VAR-capable PV inverters may provide the necessary reactive power injection or consumption to maintain voltage regulation under difficult transient conditions. As side benefit, the control of reactive power injection at each PV inverter provides an opportunity and a new tool for distribution utilities to optimize the performance of distribution circuits, e.g., by minimizing thermal losses. We discuss and compare via simulation various design options for control systems to manage the reactive power generated by these inverters. An important design decision that weighs on the speed and quality of communication required is whether the control should be centralized or distributed (i.e., local). In general, we find that local control schemes are able to maintain voltage within acceptable bounds. We consider the benefits of choosing different local variables on which to control and how the control system can be continuously tuned between robust voltage control, suitable for daytime operation when circuit conditions can change rapidly, and loss minimization better suited for nighttime operation.
Abstract The development of methods to synthesize protein oligomers with precisely controlled number and configuration of components will enable artificial protein complexes and nanostructures with diverse biological and medical applications. Using DNA hybridization to link protein-DNA conjugates provides for a programmability that can be difficult to achieve with other methods, such as engineering multiple orthogonal protein-protein interfaces. However, it is still difficult to construct well-defined protein assemblies, and the challenge is magnified if only a single type of building block is used. To overcome this hurdle, we use a DNA origami as an “assembler” to guide the linking of protein-DNA conjugates using a series of oligonucleotide hybridization and displacement operations. We constructed several isomeric protein nanostructures on a DNA origami platform by using a C3-symmetric building block comprised of a protein trimer modified with DNA handles. By changing the number of protein-DNA building blocks attached to the origami, and the sequence of the linking and displacement strands added, we were able to produce dimers, two types of trimer structures, and three types of tetramer assemblies. Our approach expands the scope for the precise design and assembly of protein-based nanostructures, and will enable the formulation of functional protein complexes with stoichiometric and geometric control.
In dynamic nucleic acids nanotechnology, strand displacement is a widely used mechanism where one strand from a hybridized duplex is exchanged with an invading strand which binds to a toehold, a single-stranded region on the duplex. With proper design and kinetic control, strand displacement is used to perform logic operations on molecular level to trigger the conformational change in nanostructures, initiate cascaded reactions, or even for in vivo diagnostics and treatments. While systematic experimental studies have been carried out to probe the kinetics of strand displacement in DNA, there has not been a comparable systematic work done for RNA or RNA-DNA hybrid systems. Here, we experimentally study how toehold length, toehold location (5′ or 3′ end of the strand) and mismatches influence the strand displacement kinetics. Through comparing the reaction rates, combined with previous theoretical studies, we observed reaction acceleration with increasing toehold length and placement of toehold at 5′end of the substrate. We find that mismatches closer to the interface of toehold and duplex slow down the reaction more than remote mismatches. Comparison of RNA displacement and DNA displacement with hybrid displacement (RNA invading DNA or DNA invading RNA) is in part explainable by the thermodynamic stabilities of the respective toehold regions, but also suggest that the rearrangement from B-form to A-form helix in case of RNA invading DNA might play a role in the kinetics. The measured kinetics of toehold-mediated strand displacement will be important in understanding and construction of more complex dynamic nucleic acid systems.
Desmocollin-1 (DSC1) is a desmosomal transmembrane glycoprotein that maintains cell-to-cell adhesion. DSC1 was previously associated with lymph node metastasis of luminal A breast tumors and was found to increase migration and invasion of MCF7 cells in vitro. Therefore, we focused on DSC1 role in cellular and molecular mechanisms in luminal A breast cancer and its possible therapeutic modulation.Western blotting was used to select potential inhibitor decreasing DSC1 protein level in MCF7 cell line. Using atomic force microscopy we evaluated effect of DSC1 overexpression and modulation on cell morphology. The LC-MS/MS analysis of total proteome on Orbitrap Lumos and RNA-Seq analysis of total transcriptome on Illumina NextSeq 500 were performed to study the molecular mechanisms associated with DSC1. Pull-down analysis with LC-MS/MS detection was carried out to uncover DSC1 protein interactome in MCF7 cells.Analysis of DSC1 protein levels in response to selected inhibitors displays significant DSC1 downregulation (p-value ≤ 0.01) in MCF7 cells treated with NF-κB inhibitor parthenolide. Analysis of mechanic cell properties in response to DSC1 overexpression and parthenolide treatment using atomic force microscopy reveals that DSC1 overexpression reduces height of MCF7 cells and conversely, parthenolide decreases cell stiffness of MCF7 cells overexpressing DSC1. The LC-MS/MS total proteome analysis in data-independent acquisition mode shows a strong connection between DSC1 overexpression and increased levels of proteins LACRT and IGFBP5, increased expression of IGFBP5 is confirmed by RNA-Seq. Pathway analysis of proteomics data uncovers enrichment of proliferative MCM_BIOCARTA pathway including CDK2 and MCM2-7 after DSC1 overexpression. Parthenolide decreases expression of LACRT, IGFBP5 and MCM_BIOCARTA pathway specifically in DSC1 overexpressing cells. Pull-down assay identifies DSC1 interactions with cadherin family proteins including DSG2, CDH1, CDH3 and tyrosine kinase receptors HER2 and HER3; parthenolide modulates DSC1-HER3 interaction.Our systems biology data indicate that DSC1 is connected to mechanisms of cell cycle regulation in luminal A breast cancer cells, and can be effectively modulated by parthenolide.
Nucleic acid interactions under crowded environments are of great importance for biological processes and nanotechnology. However, the kinetics and thermodynamics of nucleic acid interactions in a crowded environment remain poorly understood. We use a coarse-grained model of DNA to study the kinetics and thermodynamics of DNA duplex and hairpin formation in crowded environments. We find that crowders can increase the melting temperature of both an 8-mer DNA duplex and a hairpin with a stem of 6-nt depending on the excluded volume fraction of crowders in solution and the crowder size. The crowding induced stability originates from the entropic effect caused by the crowding particles in the system. Additionally, we study the hybridization kinetics of DNA duplex formation and the formation of hairpin stems, finding that the reaction rate k on is increased by the crowding effect, while k off is changed only moderately. The increase in k on mostly comes from increasing the probability of reaching a transition state with one base pair formed. A DNA strand displacement reaction in a crowded environment is also studied with the model and we find that rate of toehold association is increased, with possible applications to speeding up strand displacement cascades in nucleic acid nanotechnology.
The package includes information to model thermodynamics, kinetic and mechanical properties of DNA with the oxDNA package. The examples mentioned are discussed in our publication: https://arxiv.org/abs/2104.11567
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