The experimental demonstration of a p-type 2D WSe transistor with a ferroelectric perovskite BaTiO gate oxide is presented. The 30 nm thick BaTiO gate stack shows a robust ferroelectric hysteresis with a remanent polarization of 20 μC/cm and further enables a capacitance equivalent thickness of 0.5 nm in the hybrid WSe/BaTiO stack due to its high dielectric constant of 323.
View Article and Find Full Text PDFTherapies that target the serotonin 2A receptor (5-HTR) are promising. However, probes are needed to better understand the role of 5-HTR. Here, we design and synthesize a photoswitch and photoswitchable 5-HTR ligand based on highly potent agonist TCB-2 and arylazopyrazole, which also boasts photoswitchable G protein β-arrestin pathway bias.
View Article and Find Full Text PDFThe magnetoelectric behavior of epitaxial Fe-Ga microstructures on top of a (001)-oriented PMN-PT piezoelectric substrate is imaged with magnetic X-ray microscopy. Additionally, the micron-scale strain distribution in PMN-PT is characterized by X-ray microdiffraction and examined with respect to the results of the Fe-Ga magnetoelectric switching. The magnetic reorientation of Fe-Ga is found to be strongly correlated with size, shape, and crystallographic orientation of the microstructures.
View Article and Find Full Text PDFHere, we present a protocol to deliver nanoliter volumes of Toll-like receptor (TLR) agonist onto a culture of nuclear factor κB (NF-κB) reporter macrophages using fluidic force microscopy and a micron-scale probe. We describe steps for quantifying the dose of agonist by modeling their diffusion with experimental inputs. We then detail procedures for quantifying and categorizing macrophage responses to individual and varied doses and combining agonist concentration and macrophage response to analyze the NF-κB response to localized TLR stimulation.
View Article and Find Full Text PDFThe innate immune system initiates early response to infection by sensing molecular patterns of infection through pattern-recognition receptors (PRRs). Previous work on PRR stimulation of macrophages revealed significant heterogeneity in single cell responses, suggesting the importance of individual macrophage stimulation. Current methods either isolate individual macrophages or stimulate a whole culture and measure individual readouts.
View Article and Find Full Text PDFThe academic and industrial communities have proposed two-dimensional (2D) transition metal dichalcogenide (TMD) semiconductors as a future option to supplant silicon transistors at sub-10nm physical gate lengths. In this Comment, we share the recent progress in the fabrication of complementary metal-oxide-semiconductor (CMOS) devices based on stacked 2D TMD nanoribbons and specifically highlight issues that still need to be resolved by the 2D community in five crucial research areas: contacts, channel growth, gate oxide, variability, and doping. While 2D TMD transistors have great potential, more research is needed to understand the physical interactions of 2D materials at the atomic scale.
View Article and Find Full Text PDFOrthogonal recreation of the signaling profile of a chemical synapse is a current challenge in neuroscience. This is due in part to the kinetics of synaptic signaling, where neurotransmitters are rapidly released and quickly cleared by active reuptake machinery. One strategy to produce a rapid rise in an orthogonally controlled signal is via photocaged compounds.
View Article and Find Full Text PDFDendritic cell (DC) activation via pathogen-associated molecular patterns (PAMPs) is critical for antigen presentation and development of adaptive immune responses, but the stochastic distribution of DC responses to PAMP signaling, especially during the initial stages of immune activation, is poorly understood. In this study, we isolate a unique DC subpopulation via preferential phagocytosis of microparticles (MPs) and characterize this subpopulation of "first responders" (FRs). We present results that show these cells (1) can be isolated and studied via both increased accumulation of the micron-sized particles and combinations of cell surface markers, (2) show increased responses to PAMPs, (3) facilitate adaptive immune responses by providing the initial paracrine signaling, and (4) can be selectively targeted by vaccines to modulate both antibody and T cell responses in vivo.
View Article and Find Full Text PDFDopaminergic pathways control highly consequential aspects of physiology and behavior. One of the most therapeutically important and best-studied receptors in these pathways is dopamine receptor D (DRD2). Unfortunately, DRD2 is challenging to study with traditional molecular biological techniques, and most drugs designed to target DRD2 are ligands for many other receptors.
View Article and Find Full Text PDFWe construct ferroelectric (LuFeO_{3})_{m}/(LuFe_{2}O_{4}) superlattices with varying index m to study the effect of confinement on topological defects. We observe a thickness-dependent transition from neutral to charged domain walls and the emergence of fractional vortices. In thin LuFeO_{3} layers, the volume fraction of domain walls grows, lowering the symmetry from P6_{3}cm to P3c1 before reaching the nonpolar P6_{3}/mmc state, analogous to the group-subgroup sequence observed at the high-temperature ferroelectric to paraelectric transition.
View Article and Find Full Text PDFAdjuvants are added to vaccines to enhance the immune response and provide increased protection against disease. In the last decade, hundreds of synthetic immune adjuvants have been created, but many induce undesirable levels of proinflammatory cytokines including TNF-α and IL-6. Here we present small molecule NF-κB inhibitors that can be used in combination with an immune adjuvant to both decrease markers associated with poor tolerability and improve the protective response of vaccination.
View Article and Find Full Text PDFBioluminescence imaging with luciferase-luciferin pairs is commonly used for monitoring biological processes in cells and whole organisms. Traditional bioluminescent probes are limited in scope, though, as they cannot be easily distinguished in biological environments, precluding efforts to visualize multicellular processes. Additionally, many luciferase-luciferin pairs emit light that is poorly tissue penetrant, hindering efforts to visualize targets in deep tissues.
View Article and Find Full Text PDFResults of switching behavior of the improper ferroelectric LuFeO are presented. Using a model set of films prepared under controlled chemical and growth-rate conditions, it is shown that defects can reduce the quasi-static switching voltage by up to 40% in qualitative agreement with first-principles calculations. Switching studies show that the coercive field has a stronger frequency dispersion for the improper ferroelectrics compared to a proper ferroelectric such as PbTiO .
View Article and Find Full Text PDFWe report a study that seeks to find a correlation between the overall sensitization potential quantified by the expression of IL-8 by stimulated monocytes and the chemical structure of a model contact allergen, 2,4-dinitrochlorobenzene (DNCB). We show that structure and reactivity of the chemical compounds play an important role in activation of the monocytes and subsequent inflammation in tissue. However, we observed a non-linear correlation between the rate of reaction and biological activity indicating a required balance of stability and reactivity.
View Article and Find Full Text PDFPathogens comprise a diverse set of immunostimulatory molecules that activate the innate immune system during infection. The immune system recognizes distinct combinations of pathogenic molecules leading to multiple immune activation events that cooperate to produce enhanced immune responses, known as 'immune synergies'. Effective immune synergies are essential for the clearance of pathogens, thus inspiring novel adjuvant design to improve vaccines.
View Article and Find Full Text PDFImproving the efficiency of gas separation technology is a challenge facing modern industry, since existing methods for gas separation, including hollow-fiber membrane contactors, vacuum swing adsorption, and cryogenic distillation, represents a significant portion of the world's energy consumption. Here, we report an enhancement in the release rate of carbon dioxide and oxygen of a thermal swing gas desorption unit using a counter-current amplification method inspired by fish. Differing from a conventional counter-current extraction system, counter-current amplification makes use of parallel capture fluid channels separated by a semipermeable membrane in addition to the semipermeable membrane separating the capture fluid channel and the gas release channel.
View Article and Find Full Text PDFDesigning new liquids for CO absorption is a challenge in CO removal. Here, achieving low regeneration energies while keeping high selectivity and large capacity are current challenges. Recent cooperative metal-organic frameworks have shown the potential to address many of these challenges.
View Article and Find Full Text PDFPhotothermal processes are utilized across a variety of fields, from separations to medicine, and are an area of active research. Herein, the action of a solar simulator upon carbon black nanoparticles is shown to result in photothermally initiated chain-growth polymerization of methyl acrylate, butyl acrylate, and methyl methacrylate initiated by benzoyl peroxide. With use of methyl acrylate as the model system, products from this reaction are shown to be apparently indistinguishable on the molecular level, but result in unique microstructures relative to the thermal controls.
View Article and Find Full Text PDFIn the study of host-pathogen interactions, vaccines and drug delivery, particulate delivery system are widely used to mimic pathogen size, pattern recognition receptor agonist presentation, and target cells or organs. However, some of the polymeric systems used in particulate delivery have inherent inflammatory properties that are variable and nonspecific. These properties enhance their adjuvant activity, but confound the analysis of signaling mechanisms.
View Article and Find Full Text PDFWe report a set of brominated luciferins for bioluminescence imaging. These regioisomeric scaffolds were accessed by using a common synthetic route. All analogues produced light with firefly luciferase, although varying levels of emission were observed.
View Article and Find Full Text PDFHerein, the synthesis and characterization of an alkyne-modified luciferin is reported. This bioluminescent probe was accessed using C-H activation methodology and was found to be stable in solution and capable of light production with firefly luciferase. The luciferin analogue was also cell permeant and emitted more redshifted light than d-luciferin, the native luciferase substrate.
View Article and Find Full Text PDFBioluminescence imaging with luciferase enzymes requires access to light-emitting, small-molecule luciferins. Here, we describe a rapid method to synthesize d-luciferin, the substrate for firefly luciferase (Fluc), along with a novel set of electronically modified analogues. Our procedure utilizes a relatively rare, but synthetically useful dithiazolium reagent to generate heteroaromatic scaffolds in a divergent fashion.
View Article and Find Full Text PDFThe phosphorylation state and corresponding activity of the retinoblastoma tumor suppressor protein (Rb) are modulated by a balance of kinase and phosphatase activities. Here we characterize the association of Rb with the catalytic subunit of protein phosphatase 1 (PP1c). A crystal structure identifies an enzyme docking site in the Rb C-terminal domain that is required for efficient PP1c activity toward Rb.
View Article and Find Full Text PDFA light-activated NO donor, [Mn(PaPy(3))(NO)]ClO(4) (1a), has been incorporated into HEMA-based polymer hydrogel and the nitrosyl-polymer conjugate materials 1a(x) · HG and 1a(x) · HG(MB) have been characterized. The NO releasing properties and antibacterial capabilities of these materials in conjunction with growth attenuators such as hydrogen peroxide and methylene blue (MB) are reported. Since the nitrosyl releases NO only upon exposure to light, materials like 1a(x) · HG(MB) could be used as wound dressings that deliver NO under controlled conditions.
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