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

ANALYSIS OF THE PRESSURE DISTRIBUTION PATTERN AND THE CONTROLLING BALANCE DURING KICK MOVEMENT OF TAI-CHI CHUAN

The purpose of this study was to compare the pressure distribution patterns of the stable kick and unstable kick from the kick movement of a Tai-Chi Chuan athlete. A national elite female Tai-Chi Chuan athlete was the subject for this study. The Tekscan HR Mat Pressure Measurement System was used to collect the vertical ground reaction force and the pressure history of the standing foot in right kicking movement and left kicking movement. All the data of the standing foot were divided into metatarsals, tarsals and phalanges to calculate the partial force and partial pressure. The pressure-time diagram of the phalanges, metatarsals and tarsals indicated that the pressure histories trended to be stable in each time as the lefl kick completed, and the phalanges produced 'snatchy' and larger pressures acting on the ground

Assessing impacts of typhoons and the Chi-Chi earthquake on Chenyulan watershed landscape pattern in Central Taiwan using landscape metrics

The Chi-Chi earthquake (M-L = 7.3) occurred in the central part of Taiwan on September 21, 1999. After the earthquake, typhoons Xangsane and Toraji produced heavy rainfall that fell across the eastern and central parts of Taiwan on November 2000 and July 2001. This study uses remote sensing data, landscape metrics, multivariate statistical analysis, and spatial autocorrelation to assess how earthquake and typhoons affect landscape patterns. It addresses variations of the Chenyulan watershed in Nantou County, near the earthquake's epicenter and crossed by Typhoon Toraji. The subsequent disturbances have gradually changed landscape of the Chenyulan watershed. Disturbances of various types, sizes, and intensities, following various tracks, have various effects on the landscape patterns and variations of the Chenyulan watershed. The landscape metrics that are obtained by multivariate statistical analyses showed that the disturbances produced variously fragmented patches, interspersed with other patches and isolated from patches of the same type across the entire Chenyulan watershed. The disturbances also affected the isolation, size, and shape-complexity of patches at the landscape and class levels. The disturbances at the class level more strongly affected spatial variations in the landscape as well as patterns of grasslands and bare land, than variations in the watershed farmland and forest. Moreover, the earthquake with high magnitude was a starter to create these landscape variations in space in the Chenyulan watershed. The cumulative impacts of the disturbances on the watershed landscape pattern had existed, especially landslides and grassland in the study area, but were not always evident in space and time in landscape and other class levels

Design and fabrication of densely integrated silicon quantum dots using a VLSI compatible hydrogen silsesquioxane electron beam lithography process

Hydrogen silsesquioxane (HSQ) is a high resolution negative-tone electron beam resist allowing for direct transfer of nanostructures into silicon-on-insulator. Using this resist for electron beam lithography, we fabricate high density lithographically defined Silicon double quantum dot (QD) transistors. We show that our approach is compatible with very large scale integration, allowing for parallel fabrication of up to 144 scalable devices. HSQ process optimisation allowed for realisation of reproducible QD dimensions of 50 nm and tunnel junction down to 25 nm. We observed that 80% of the fabricated devices had dimensional variations of less than 5 nm. These are the smallest high density double QD transistors achieved to date. Single electron simulations combined with preliminary electrical characterisations justify the reliability of our device and process

Macrospin approximation and quantum effects in models for magnetization reversal

The thermal activation of magnetization reversal in magnetic nanoparticles is controlled by the anisotropy-energy barrier. Using perturbation theory, exact diagonalization and stability analysis of the ferromagnetic spin-s Heisenberg model with coupling or single-site anisotropy, we study the effects of quantum fluctuations on the height of the energy barrier. Opposed to the classical case, there is no critical anisotropy strength discriminating between reversal via coherent rotation and via nucleation/domain-wall propagation. Quantum fluctuations are seen to lower the barrier depending on the anisotropy strength, dimensionality and system size and shape. In the weak-anisotropy limit, a macrospin model is shown to emerge as the effective low-energy theory where the microscopic spins are tightly aligned due to the ferromagnetic exchange. The calculation provides explicit expressions for the anisotropy parameter of the effective macrospin. We find a reduction of the anisotropy-energy barrier as compared to the classical high spin-s limit.Comment: 10 pages, 11 figure

Effect of Finite Granularity of Detectors on Anisotropy Coefficients

The coefficients that describe the anisotropy in the azimuthal distribution of particles are lower when the particles are recorded in a detector with finite granularity and measures only hits. This arises due to loss of information because of multiple hits in any channel. The magnitude of this loss of signal depends both on the occupancy and on the value of the coefficient. These correction factors are obtained for analysis methods differing in detail, and are found to be different.Comment: 11 pages including 2 figure

Observations of quasi-periodic solar X-ray emission as a result of MHD oscillations in a system of multiple flare loops

We investigate the solar flare of 20 October 2002. The flare was accompanied by quasi-periodic pulsations (QPP) of both thermal and nonthermal hard X-ray emissions (HXR) observed by RHESSI in the 3-50 keV energy range. Analysis of the HXR time profiles in different energy channels made with the Lomb periodogram indicates two statistically significant time periods of about 16 and 36 seconds. The 36-second QPP were observed only in the nonthermal HXR emission in the impulsive phase of the flare. The 16-second QPP were more pronounced in the thermal HXR emission and were observed both in the impulsive and in the decay phases of the flare. Imaging analysis of the flare region, the determined time periods of the QPP and the estimated physical parameters of magnetic loops in the flare region allow us to interpret the observations as follows. 1) In the impulsive phase energy was released and electrons were accelerated by successive acts with the average time period of about 36 seconds in different parts of two spatially separated, but interacting loop systems of the flare region. 2) The 36-second periodicity of energy release could be caused by the action of fast MHD oscillations in the loops connecting these flaring sites. 3) During the first explosive acts of energy release the MHD oscillations (most probably the sausage mode) with time period of 16 seconds were excited in one system of the flare loops. 4) These oscillations were maintained by the subsequent explosive acts of energy release in the impulsive phase and were completely damped in the decay phase of the flare.Comment: 14 pages, 4 figure

Violation of the Mott-Ioffe-Regel Limit: High-temperature Resistivity of Itinerant Magnets Srn+1RunO3n+1 (n=2,3,infinity) and CaRuO3

Srn+1RunO3n+1 represents a class of layered materials whose physical properties are a strong function of the number of Ru-O layers per unit cell, n. This series includes the p-wave superconductor Sr2RuO4 (n=1), enhanced paramagnetic Sr3Ru2O7 (n=2), nearly ferromagnetic Sr4Ru3O10 (n=3) and itinerant ferromagnetic SrRuO3 (n=infinity). In spite of a wide spectrum of physical phenomena, this series of materials along with paramagnetic CaRuO3 shares two major characteristics, namely, robust Fermi liquid behavior at low temperatures and anomalous transport behavior featured by linear temperature dependence of resistivity at high temperature where electron wavepackets are no longer clearly defined. There is no crossover separating such two fundamentally different states. In this paper, we report results of our study that systematically addresses anisotropy and temperature dependence of basal-plane and c-axis resistivity as a function of n for the entire Srn+1RunO3n+1 series and CaRuO3 and for a wide temperature range of 1.7 K<T<900 K. It is found that the anomalous transport behavior correlates with magnetic susceptibility and becomes stronger with decreasing dimensionality. Implications of these results are discussed