Microfluidic Preparation of Polymer-Nucleic Acid Nanocomplexes Improves Nonviral Gene Transfer

As the designs of polymer systems used to deliver nucleic acids continue to evolve, it is becoming increasingly apparent that the basic bulk manufacturing techniques of the past will be insufficient to produce polymer-nucleic acid nanocomplexes that possess the uniformity, stability, and potency required for their successful clinical translation and widespread commercialization. Traditional bulk-prepared products are often physicochemically heterogeneous and may vary significantly from one batch to the next. Here we show that preparation of bioreducible nanocomplexes with an emulsion-based droplet microfluidic system produces significantly improved nanoparticles that are up to fifty percent smaller, more uniform, and are less prone to aggregation. The intracellular integrity of nanocomplexes prepared with this microfluidic method is significantly prolonged, as detected using a high-throughput flow cytometric quantum dot Förster resonance energy transfer nanosensor system. These physical attributes conspire to consistently enhance the delivery of both plasmid DNA and messenger RNA payloads in stem cells, primary cells, and human cell lines. Innovation in processing is necessary to move the field toward the broader clinical implementation of safe and effective nonviral nucleic acid therapeutics, and preparation with droplet microfluidics represents a step forward in addressing the critical barrier of robust and reproducible nanocomplex productio

Geometry-based Direct Simulation for Multi-Material Soft Robots

Robots fabricated by soft materials can provide higher flexibility and thus better safety while interacting with natural objects with low stiffness such as food and human beings. However, as many more degrees of freedom are introduced, the motion simulation of a soft robot becomes cumbersome, especially when large deformations are presented. Moreover, when the actuation is defined by geometry variation, it is not easy to obtain the exact loads and material properties to be used in the conventional methods of deformation simulation. In this paper, we present a direct approach to take the geometric actuation as input and compute the deformed shape of soft robots by numerical optimization using a geometry-based algorithm. By a simple calibration, the properties of multiple materials can be modeled geometrically in the framework. Numerical and experimental tests have been conducted to demonstrate the performance of our approach on both cable-driven and pneumatic actuators in soft robotics

How identifying circumgalactic gas by line-of-sight velocity instead of the location in 3D space affects O VI measurements

Galaxie

Charge Storage Effect in a Trilayer Structure Comprising Germanium Nanocrystals

A metal-insulator-semiconductor (MIS) device with a trilayer insulator structure consisting of sputtered SiO₂ (~50nm)/evaporated pure germanium (Ge) layer (2.4nm)/rapid thermal oxide (~5nm) was fabricated on a p-type Si substrate. The MIS device was rapid thermal annealed at 1000°C. Capacitance-voltage (C-V) measurements showed that, after rapid thermal annealing at 1000°C for 300s in Ar, the trilayer device exhibited charge storage property. The charge storage effect was not observed in a device with a bilayer structure without the Ge middle layer. With increasing rapid thermal annealing time from 0 to 400s, the width of the C-V hysteresis of the trilayer device increased significantly from 1.5V to ~11V, indicating that the charge storage capability was enhanced with increasing annealing time. High-resolution transmission electron microscopy results confirmed that with increasing annealing time, the 2.4nm amorphous middle Ge layer crystallized gradually. More Ge nanocrystals were formed and the crystallinity of the Ge layer improved as the annealing time was increased. When the measurement temperature was increased from –50°C to 150°C, the width of the hysteresis of the MIS device reduced from ~10V to ~6V. This means that the charge storage capability of the trilayer structure decreases with increasing measurement temperature. This is due to the fact that the leakage current in the trilayer structure increases with increasing measurement temperature.Singapore-MIT Alliance (SMA

Synthesis of Germanium Nanocrystals and its Possible Application in Memory Devices

A novel method of synthesizing and controlling the size of germanium nanocrystals was developed. A tri-layer structure comprising of a thin (~5nm) SiO₂ layer grown using rapid thermal oxidation (RTO), followed by a layer of Ge+SiO₂ of varying thickness (6 - 20 nm) deposited using the radio frequency (r.f.) co-sputtering technique and a SiO₂ cap layer (50nm) deposited using r.f. sputtering, was investigated. It was verified using TEM that germanium nanocrystals of sizes ranging from 6 – 20 nm were successfully fabricated after thermal annealing of the tri-layer structure under suitable conditions. The nanocrystals were found to be well confined by the RTO SiO₂ and the cap SiO₂ under specific annealing conditions. The electrical properties of the tri-layer structure have been characterized using MOS capacitor test devices. A significant hysteresis can be observed from the C-V measurements and this suggests the charge storage capability of the nanocrystals. The proposed technique has the potential for fabricating memory devices with controllable nanocrystals sizes.Singapore-MIT Alliance (SMA

The usefulness of serum adenosine deaminase 2 (ADA2) activity in adults for the diagnosis of pulmonary tuberculosis

AbstractRapid diagnosis of Mycobacterium tuberculosis remains an obstacle for therapy of tuberculosis (TB). Adenosine deaminase isoform 2 (ADA2) is produced by activated macrophages and has been used for diagnosis of TB from extra-pulmonary sites. However, few studies adequately address whether serum ADA2 activity is useful for diagnosis of active pulmonary tuberculosis (PTB). We prospectively measured serum ADA2 activity in 110 patients with pulmonary disease (65 cases with active PTB and 45 cases with other respiratory diseases) and 78 healthy volunteers (eight with tuberculin skin test positive). The serum ADA2 for the diagnosis of PTB had the sensitivity of 36·9%, the specificity of 84·5%, the positive predictive value of 10·9% and the negative predictive value of 96·2%. We concluded that serum ADA2 activity is neither useful to diagnosis of active PTB nor to differentiate from other respiratory diseases

Adaptive slicing based on efficient profile analysis

Adaptive slicing is an important computational task required in the layer-based manufacturing process. Its purpose is to find an optimal trade-off between the fabrication time (number of layers) and the surface quality (geometric deviation error). Most of the traditional adaptive slicing algorithms are computationally expensive or only based on local evaluation of errors. To tackle these problems, we introduce a method to efficiently generate slicing plans by a new metric profile that can characterize the distribution of deviation errors along the building direction. By generalizing the conventional error metrics, the proposed metric profile is a density function of deviation errors, which measures the global deviation errors rather than the in-plane local geometry errors used in most prior methods. Slicing can be efficiently evaluated based on metric profiles in contrast to the expensive computation on models in boundary-representation. An efficient algorithm based on dynamic programming is proposed to find the best slicing plan. Our adaptive slicing method can also be applied to models with weighted features and can serve as the inner loop to search the best building direction. The performance of our approach is demonstrated by experimental tests on different examples

G protein signaling-biased agonism at the k-opioid receptor is maintained in striatal neurons

Biased agonists of G protein-coupled receptors may present a means to refine receptor signaling in a way that separates side effects from therapeutic properties. Several studies have shown that agonists that activate the k-opioid receptor (KOR) in a manner that favors G protein coupling over b-Arrestin2 recruitment in cell culture may represent a means to treat pain and itch while avoiding sedation and dysphoria. Although it is attractive to speculate that the bias between G protein signaling and b-Arrestin2 recruitment is the reason for these divergent behaviors, little evidence has emerged to show that these signaling pathways diverge in the neuronal environment. We further explored the influence of cellular context on biased agonism at KOR ligand-directed signaling toward G protein pathways over b-Arrestin-dependent pathways and found that this bias persists in striatal neurons. These findings advance our understanding of how a G protein-biased agonist signal differs between cell lines and primary neurons, demonstrate that measuring [35S]GTPgS binding and the regulation of adenylyl cyclase activity are not necessarily orthogonal assays in cell lines, and emphasize the contributions of the environment to assessing biased agonism

The effects of the bacterial interaction with visible-light responsive titania photocatalyst on the bactericidal performance

Bactericidal activity of traditional titanium dioxide (TiO2) photocatalyst is effective only upon irradiation by ultraviolet light, which restricts the potential applications of TiO2 for use in our living environments. Recently carbon-containing TiO2 was found to be photoactive at visible-light illumination that affords the potential to overcome this problem; although, the bactericidal activity of these photocatalysts is relatively lower than conventional disinfectants. Evidenced from scanning electron microscopy and confocal Raman spectral mapping analysis, we found the interaction with bacteria was significantly enhanced in these anatase/rutile mixed-phase carbon-containing TiO2. Bacteria-killing experiments indicate that a significantly higher proportion of all tested pathogens including Staphylococcus aureus, Shigella flexneri and Acinetobacter baumannii, were eliminated by the new nanoparticle with higher bacterial interaction property. These findings suggest the created materials with high bacterial interaction ability might be a useful strategy to improve the antimicrobial activity of visible-light-activated TiO2