This series is home to publications and data sets from the Bourns College of Engineering at the University of California, Riverside.
Functional neuroimaging studies have consistently implicated the left rostrolateral prefrontal cortex (RLPFC) as playing a crucial role in the cognitive operations supporting episodic memory and analogical reasoning. However, the degree to which the left RLPFC causally contributes to these processes remains underspecified. We aimed to assess whether targeted anodal stimulation-thought to boost cortical excitability-of the left RLPFC with transcranial direct current stimulation (tDCS) would lead to augmentation of episodic memory retrieval and analogical reasoning task performance in comparison to cathodal stimulation or sham stimulation. Seventy-two healthy adult participants were evenly divided into three experimental groups. All participants performed a memory encoding task on Day 1, and then on Day 2, they performed continuously alternating tasks of episodic memory retrieval, analogical reasoning, and visuospatial perception across two consecutive 30-min experimental sessions. All groups received sham stimulation for the first experimental session, but the groups differed in the stimulation delivered to the left RLPFC during the second session (either sham, 1.5 mA anodal tDCS, or 1.5 mA cathodal tDCS). The experimental group that received anodal tDCS to the left RLPFC during the second session demonstrated significantly improved episodic memory source retrieval performance, relative to both their first session performance and relative to performance changes observed in the other two experimental groups. Performance on the analogical reasoning and visuospatial perception tasks did not exhibit reliable changes as a result of tDCS. As such, our results demonstrate that anodal tDCS to the left RLPFC leads to a selective and robust improvement in episodic source memory retrieval.
CRISPR-Cas9 is a bacterial immune system with exciting applications for genome editing. In spite of extensive experimental characterization, the active site chemistry of the RuvC domain-which performs DNA cleavages-has remained elusive. Its knowledge is key for structure-based engineering aimed at improving DNA cleavages. Here, we deliver an in-depth characterization by using quantum-classical (QM/MM) molecular dynamics (MD) simulations and a Gaussian accelerated MD method, coupled with bioinformatics analysis. We disclose a two-metal aided architecture in the RuvC active site, which is poised to operate DNA cleavages, in analogy with other DNA/RNA processing enzymes. The conformational dynamics of the RuvC domain further reveals that an "arginine finger" stably contacts the scissile phosphate, with the function of stabilizing the active complex. Remarkably, the formation of a catalytically competent state of the RuvC domain is only observed upon the conformational activation of the other nuclease domain of CRISPR-Cas9-i.e., the HNH domain-such allowing concerted cleavages of double stranded DNA. This structure is in agreement with the available experimental data and remarkably differs from previous models based on classical mechanics, demonstrating also that only quantum mechanical simulations can accurately describe the metal-aided active site in CRISPR-Cas9. This fully catalytic structure-in which both the HNH and RuvC domains are prone to perform DNA cleavages-constitutes a stepping-stone for understanding DNA cleavage and specificity. It calls for novel experimental verifications and offers the structural foundations for engineering efforts aimed at improving the genome editing capability of CRISPR-Cas9.
Allosteric regulation plays an important role in many biological processes, such as signal transduction, transcriptional regulation, and metabolism. Allostery is rooted in the fundamental physical properties of macromolecular systems, but its underlying mechanisms are still poorly understood. A collection of contributions to a recent interdisciplinary CECAM (Center Européen de Calcul Atomique et Moléculaire) workshop is used here to provide an overview of the progress and remaining limitations in the understanding of the mechanistic foundations of allostery gained from computational and experimental analyses of real protein systems and model systems. The main conceptual frameworks instrumental in driving the field are discussed. We illustrate the role of these frameworks in illuminating molecular mechanisms and explaining cellular processes, and describe some of their promising practical applications in engineering molecular sensors and informing drug design efforts.
Direct pulmonary delivery is a promising step in developing effective gene therapies for respiratory disease. Gene therapies can be used to treat the root cause of diseases, rather than just the symptoms. However, developing effective therapies that do not cause toxicity and that successfully reach the target site at therapeutic levels is challenging. We have developed a polymer-DNA complex utilizing polyethylene imine (PEI) and DNA, which was then encapsulated into poly(lactic acid)-co-monomethoxy poly(ethylene glycol) (PLA-mPEG) microparticles via double emulsion, solvent evaporation. Then, the resultant particle size, porosity, and encapsulation efficiency were measured as a function of altering preparation parameters. Microsphere formation was confirmed from scanning electron micrographs and the aerodynamic particle diameter was measured using an aerodynamic particle sizer. Several formulations produced particles with aerodynamic diameters in the 0-5 μm range despite having larger particle diameters which is indicative of porous particles. Furthermore, these aerodynamic diameters correspond to high deposition within the airways when inhaled and the measured DNA content indicated high encapsulation efficiency. Thus, this formulation provides promise for developing inhalable gene therapies.
This study investigates a secure wireless communication
scheme which combines two of the most effective strategies
to combat (passive) eavesdropping, namely mixing information
with artificial noise at the transmitter and jamming from a
full-duplex receiver. All nodes are assumed to possess multiple
antennas, which is known as a MIMOME network. The channel
state information (CSI) of Eve is known to Eve but not to
Alice and Bob. While such setup has been investigated in related
works, new and important insights are revealed in this work. We
investigate the design of optimal jamming parameters to achieve
higher secrecy, and in particular we focus on two important cases
corresponding to Bob using either a simple jamming or a smart
jamming. Furthermore, simulations are presented to highlight
the effectiveness of the proposed strategies.
Collinear antiferromagnets (AFs) support two degenerate magnon excitations carrying opposite spin polarizations, by which magnons can function as electrons in various spin-related phenomena. In an insulating ferromagnet(F)/AF/F trilayer, we explore the magnon-mediated interlayer coupling by calculating the magnon thermal energy in the AF as a function of the orientations of the Fs. The effect manifests as an interlayer exchange interaction and a perpendicular magnetic anisotropy; they both depend on temperature and the AF thickness. In particular, the exchange interaction turns out to be antiferromagnetic at low temperatures and ferromagnetic at high temperatures, whose magnitude can be 10-100 μeV for nanoscale separations, allowing experimental verification.