Polymer formulated self-amplifying RNA vaccine is partially protective against influenza virus infection in ferrets.

COVID-19 has demonstrated the power of RNA vaccines as part of a pandemic response toolkit. Another virus with pandemic potential is influenza. Further development of RNA vaccines in advance of a future influenza pandemic will save time and lives. As RNA vaccines require formulation to enter cells and induce antigen expression, the aim of this study was to investigate the impact of a recently developed bioreducible cationic polymer, pABOL for the delivery of a self-amplifying RNA (saRNA) vaccine for seasonal influenza virus in mice and ferrets. Mice and ferrets were immunized with pABOL formulated saRNA vaccines expressing either haemagglutinin (HA) from H1N1 or H3N2 influenza virus in a prime boost regime. Antibody responses, both binding and functional were measured in serum after immunization. Animals were then challenged with a matched influenza virus either directly by intranasal inoculation or in a contact transmission model. While highly immunogenic in mice, pABOL-formulated saRNA led to variable responses in ferrets. Animals that responded to the vaccine with higher levels of influenza virus-specific neutralizing antibodies were more protected against influenza virus infection. pABOL-formulated saRNA is immunogenic in ferrets, but further optimization of RNA vaccine formulation and constructs is required to increase the quality and quantity of the antibody response to the vaccine.

Overgeneral and specific autobiographical memory predict the course of depression: an updated meta-analysis.

Impairments in retrieving event-level, specific autobiographical memories, termed overgeneral memory (OGM), are recognised as a feature of clinical depression. A previous meta-analytic review assessing how OGM predicts the course of subsequent depressive symptoms showed small effects for correlations and regression analyses when baseline depressive symptoms were controlled for. We aimed to update this study and examine whether their findings replicate given the decade of research that has been published since. A systematic literature review using the same eligibility criteria as the previous meta-analysis led to a doubling of eligible studies (32 v. 15). The results provided more precise estimates of effect sizes, and largely support the finding that OGM predicts the course of depressive symptoms. The effects were generally small, but significantly larger among clinical samples, compared to studies with non-clinical samples. There was some evidence that higher age was associated with stronger effects, and longer follow-up was associated with weaker effects. The findings on other moderating variables that were analysed were mixed. Continued research into this modifiable cognitive process may help to provide an avenue to better understand and treat highly prevalent and impactful depressive disorders.

Changing the future: An initial test of Future Specificity Training (FeST).

A range of psychiatric disorders are characterised by impairments in episodic future thinking (EFT), and particularly simulating specific, spatiotemporally-located future events. No study has examined whether training can lead to sustained improvement in specific EFT. In this study, participants (N = 60; M age = 31, SD = 13.2) were randomized to a two-session, group-based future thinking program (Future Specificity Training; FeST) or wait-list. At follow-up the training group, relative to wait-list, showed large, statistically-significant improvements in the ability to mentally simulate specific EFT (d = .82), increases in detail (d = 1.32), use of mental imagery (d = 1.32), anticipated (d = 1.78) and anticipatory pleasure (d = 1.07), perceived control (d = 1.20), and likelihood of occurrence (d = 1.09). Some effects were also observed on positive, generalised future self-states. In the context of inherent limitations of subjective reporting in trials, this study provides evidence that EFT specificity can be enhanced, and the effects of FeST indicate a possible avenue to disrupt psychopathological processes.

Nanotube field electron emission: principles, development, and applications.

There is a growing trend to apply field emission (FE) electron sources in vacuum electronic devices due to their fast response, high efficiency and low energy consumption compared to thermionic emission ones. Carbon nanotubes (CNTs) have been regarded as a promising class of electron field emitters since the 1990s and have promoted the development of FE technology greatly because of their high electrical and thermal conductivity, chemical stability, high aspect ratio and small size. Recent studies have shown that FE from CNTs has the potential to replace conventional thermionic emission in many areas and that it exhibits advanced features in practical applications. Consequently, FE from nanotubes and applications thereof have attracted much attention. This paper provides a comprehensive review of both recent advances in CNT field emitters and issues related to applications of CNT based FE. FE theories and principles are introduced, and the early development of field emitters is related. CNT emitter types and their FE performance are discussed. The current situation for applications based on nanotube FE is reviewed. Although challenges remain, the tremendous progress made in CNT FE over the past ten years indicates the field's development potential.

A 2D MEMS mirror with sidewall electrodes applied for confocal MACROscope imaging.

This paper presents microelectromechanical system micromirrors with sidewall electrodes applied for use as a Confocal MACROscope for biomedical imaging. The MACROscope is a fluorescence and brightfield confocal laser scanning microscope with a very large field of view. In this paper, a microelectromechanical system mirror with sidewall electrodes replaces the galvo-scanner and XYZ-stage to improve the confocal MACROscope design and obtain an image. Two micromirror-based optical configurations are developed and tested to optimize the optical design through scanning angle, field of view and numerical aperture improvement. Meanwhile, the scanning frequency and control waveform of the micromirror are tested. Analysing the scan frequency and waveform becomes a key factor to optimize the micromirror-based confocal MACROscope. When the micromirror is integrated into the MACROscope and works at 40 Hz, the micromirror with open-loop control possesses good repeatability, so that the synchronization among the scanner, XYZ-stage and image acquisition can be realized. A laser scanning microscope system based on the micromirror with 2 µm width torsion bars was built and a 2D image was obtained as well. This work forms the experimental basis for building a practical confocal MACROscope.

Design and evaluation of quantum dot sensors for making superficial x-ray energy radiation measurements.

The extraordinary physical properties of quantum dot (QD) materials such as high radiation sensitivity and good radiation resistivity indicate their potential for use in the fabrication of radiation sensors. This paper reports the design and fabrication of two kinds of radiation sensors based on ZnO and CdTe QDs. Both sensors are characterized using a Gulmay Medical D3000 DXR unit for superficial x-ray irradiation with source photon energies that range from 36.9 to 64.9 keV. The QD radiation sensors exhibit excellent linearity with respect to different photon energy doses, radiation source to device surface distances, and field sizes. The effects of the electrode separation and the area density of the QD layer are also investigated. All sensors characterized show an outstanding repeatability under photon irradiation, with a signal variation less than 1%.

Electromechanical interactions in a carbon nanotube based thin film field emitting diode.

Carbon nanotubes (CNTs) have emerged as promising candidates for biomedical x-ray devices and other applications of field emission. CNTs grown/deposited in a thin film are used as cathodes for field emission. In spite of the good performance of such cathodes, the procedure to estimate the device current is not straightforward and the required insight towards design optimization is not well developed. In this paper, we report an analysis aided by a computational model and experiments by which the process of evolution and self-assembly (reorientation) of CNTs is characterized and the device current is estimated. The modeling approach involves two steps: (i) a phenomenological description of the degradation and fragmentation of CNTs and (ii) a mechanics based modeling of electromechanical interaction among CNTs during field emission. A computational scheme is developed by which the states of CNTs are updated in a time incremental manner. Finally, the device current is obtained by using the Fowler-Nordheim equation for field emission and by integrating the current density over computational cells. A detailed analysis of the results reveals the deflected shapes of the CNTs in an ensemble and the extent to which the initial state of geometry and orientation angles affect the device current. Experimental results confirm these effects.

Enhancing dielectrophoresis effect through novel electrode geometry.

This paper presents an original device to enhance dielectrophoresis (DEP) effects through novel geometry of the electrodes. Implemented with a simple single-layer metal process, our microchip device consists of individually triangular-shaped electrodes in a parallel array. When activated with DEP waveforms, the novel-shaped electrodes generate horizontal bands of increasing electric fields. With these bands of electric fields, dielectric microbeads in a suitable medium can be manipulated to form a straight horizontal line at a predictable location over the electrodes. Further experiments show that the location of the microbeads is sensitive to the frequency of the applied DEP waveforms. By changing the frequencies, the line of microbeads can be shifted vertically along the electrodes. In addition, horizontal movements of the microbeads can be achieved with traveling wave DEP. With an accurate control of both vertical and horizontal positions and a potential multi-lane separation strategy, our device delivers substantial improvements over the existing electrode array devices.

Multiphase electrodes for microbead control applications: integration of DEP and electrokinetics for bio-particle positioning.

Advances in microfabrication have introduced new possibilities for automated, high-throughput biomedical investigations and analysis. Physical effects such as dielectrophoresis (DEP) and AC electrokinetics can be used to manipulate particles in solution to coordinate a sequence of bioanalytical processing steps. DEP is accomplished with non-uniform electric fields that can polarize particles (microbeads, cells, viruses, DNA, proteins, etc.) in suspension causing translational or rotational movement. AC electrokinetics is another phenomena involved with movement of particles in suspension with electric fields and is comprised of both electro-thermal and electro-osmotic effects. This paper investigates single layer electrodes that are effective for particle localization and clustering based on DEP and AC electrokinetic effects. We demonstrate a novel multi-electrode setup capable of clustering particles into an array of discrete bands using activated and electrically floating electrodes. These bands shift to adjacent regions on the electrode surface by altering the electrode activation scheme. The predictability of particle placement to specific locations provides new opportunities for integration and coordination with raster scanning lasers or a charge coupled device (CCD) for advanced biomedical diagnostic devices, and more sophisticated optical interrogation techniques.

Identification of a unique glomerular factor X activator in murine lupus nephritis.

The role of glomerular procoagulant activity (PCA) was studied in mice (MRL/lpr, NZBxWF,, and BXSB) that are known to develop lupus nephritis. In young mice (6 to 8 wk) without renal disease, there was no increase in spontaneous glomerular PCA. In contrast, older (5 to 8 mo) autoimmune mice had significant augmentation in glomerular PCA, coinciding with the histologic appearance of severe glomerulonephritis and renal fibrin deposition. The PCA was characterized as a serine protease that directly activated factor X. This factor X activator is not tissue factor because (1) expression of PCA was not dependent on factor VII; (2) a monoclonal antibody against the factor X activator inhibited glomerular PCA, but not tissue factor; (3) the molecular weight (66 kD) of the activator was different from that of tissue factor; and (4) concanavalin A inhibited tissue factor but not glomerular PCA. Immunohistochemical studies localized the factor X activator to the glomerular mesangium and capillary wall of 4- to 6-mo-old diseased MRL/lpr mice. Immunogold-labeled antibody bound to the dense deposits, macrophages, and endothelial cells of diseased glomeruli. These studies define the role of a unique glomerular factor X activator in murine lupus nephritis.