An amplified mosquito dihydrofolate reductase gene: amplicon size and chromosomal distribution

Correct interpretation of conspicuous blood flow velocity waveforms cannot rely solely on the evaluation of uteroplacental vascular Doppler flow patterns by means of angle-independent indices such as the resistance or pulsatility index. In addition to the degree of pulsatility, the waveform shape between the systolic and diastolic peak values is of considerable consequence. A subdivision of the total flow waveform into orthogonal polynomial components allows both pulsatility evaluation and notching to be registered, providing a higher sensitivity in identification of pathological vascular resistance. Accurate recording and assessment of the flow waveform is therefore an important qualitative criterion for the classification of Doppler flow patterns in pregnancies with reduced uteroplacental perfusion.     

Mechanically adaptive thermoplastic polyurethane/cellulose nanocrystal composites: Process-driven structure–property relationships

To enable filament extrusion additive manufacturing of mechanically adaptive nanocomposites, the effect of melt extrusion on the tensile modulus and mechanical adaptiveness of cellulose nanocrystal (CNC)/thermoplastic polyurethane (TPU) composites was investigated. TPU (Texin RxT70A) was processed with 10 wt % CNC in multiple formats, including solvent-cast films and melt extrusion-produced filaments. CNC orientation is characterized by polarized Raman spectroscopy and small-angle X-ray scattering (SAXS) and found to be uniaxially oriented in extruded filaments, and randomly oriented in solvent-cast films. Dynamic mechanical analysis results show the addition of 10 wt % CNC increases the pure TPU storage modulus from 10 to 60–70 MPa in the dry state for solvent-cast and extruded nanocomposites. Following water saturation, all CNC-containing samples reach a similar wet storage modulus of approximately 26 MPa, regardless of CNC orientation and thermal history. Fickian diffusion scaling factors (6.8 to 11.6) scale closely to the time-dependent empirical scaling factors (4.9 to 7.2), confirming the rate of mechanical adaptivity is driven by water diffusion through sample thickness. Our results suggest that mechanical adaptivity is retained following processing, enabling use as a feedstock for extrusion-based additive manufacturing of CNC/TPU composites for mechanically adaptive parts. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 46992.     

Controlled Individual Skyrmion Nucleation at Artificial Defects Formed by Ion Irradiation

Magnetic skyrmions are particle‐like deformations in a magnetic texture. They have great potential as information carriers in spintronic devices because of their interesting topological properties and favorable motion under spin currents. A new method of nucleating skyrmions at nanoscale defect sites, created in a controlled manner with focused ion beam irradiation, in polycrystalline magnetic multilayer samples with an interfacial Dzyaloshinskii–Moriya interaction, is reported. This new method has three notable advantages: 1) localization of nucleation; 2) stability over a larger range of external field strengths, including stability at zero field; and 3) existence of skyrmions in material systems where, prior to defect fabrication, skyrmions were not previously obtained by field cycling. Additionally, it is observed that the size of defect nucleated skyrmions is uninfluenced by the defect itself—provided that the artificial defects are controlled to be smaller than the inherent skyrmion size. All of these characteristics are expected to be useful toward the goal of realizing a skyrmion‐based spintronic device. This phenomenon is studied with a range of transmission electron microscopy techniques to probe quantitatively the magnetic behavior at the defects with applied field and correlate this with the structural impact of the defects.     

Photon Upconversion Hydrogels for 3D Optogenetics

The ability to optically induce biological responses in 3D has been dwarfed by the physical limitations of visible light penetration to trigger photochemical processes. However, many biological systems are relatively transparent to low-energy light, which does not provide sufficient energy to induce photochemistry in 3D. To overcome this challenge, hydrogels that are capable of converting red or near-IR (NIR) light into blue light within the cell-laden 3D scaffolds are developed. The upconverted light can then excite optically active proteins in cells to trigger a photochemical response. The hydrogels operate by triplet–triplet annihilation upconversion. As proof-of-principle, it is found that the hydrogels trigger an optogenetic response by red/NIR irradiation of HeLa cells that have been engineered to express the blue-light sensitive protein Cry2olig. While it is remarkable to photoinduce the clustering of Cry2olig with blanket NIR irradiation in 3D, it is also demonstrated how the hydrogels trigger clustering within a single cell with great specificity and spatiotemporal control. In principle, these hydrogels may allow for photochemical control of cell function within 3D scaffolds, which can lead to a wealth of fundamental studies and biochemical applications.     

Transthyretin Mimetics as Anti‐β‐Amyloid Agents: A Comparison of Peptide and Protein Approaches

β‐Amyloid (Aβ) aggregation is causally linked to neuronal pathology in Alzheimer's disease; therefore, several small molecules, antibodies, and peptides have been tested as anti‐Aβ agents. We developed two compounds based on the Aβ‐binding domain of transthyretin (TTR): a cyclic peptide cG8 and an engineered protein mTTR, and compared them for therapeutically relevant properties. Both mTTR and cG8 inhibit fibrillogenesis of Aβ, with mTTR inhibiting at a lower concentration than cG8. Both inhibit aggregation of amylin but not of α‐synuclein. They both bind more Aβ aggregates than monomer, and neither disaggregates preformed fibrils. cG8 retained more of its activity in the presence of biological materials and was more resistant to proteolysis than mTTR. We examined the effect of mTTR or cG8 on Aβ binding to human neurons. When mTTR was co‐incubated with Aβ under oligomer‐forming conditions, Aβ morphology was drastically changed and Aβ‐cell deposition significantly decreased. In contrast, cG8 did not affect morphology but decreased the amount of Aβ deposited. These results provide guidance for further evolution of TTR‐mimetic anti‐amyloid agents.     

Phase IIa safety and immunogenicity of a therapeutic vaccine, TA-GW, in persons with genital warts

A fusion protein vaccine consisting of human papillomavirus 6 L2E7 with Alhydrogel was developed for the treatment of genital warts. Twenty-seven subjects with genital warts received 3 immunizations over 4 weeks in an open-label study. The vaccine was well-tolerated, and all subjects made serum IgG antibodies, predominantly IgG1, against L2E7. Nineteen of 25 tested persons made antigen-specific T cell proliferative responses to L2E7, and peripheral blood mononuclear cells when cultured with L2E7 in vitro produced both interferon-gamma and interleukin (IL)-5, although IL-5 predominated after the final vaccination. Five subjects completely cleared warts within 8 weeks. Subjects whose warts were not cleared by 8 weeks were offered conventional therapy. Recurrence of warts was not seen in any of the 13 persons whose warts cleared by vaccine alone or with conventional therapy. While these preliminary results of the use of this therapeutic immunogen are encouraging, proof of efficacy will require randomized double-blind trials.     

Survival of toxigenic Escherichia coli on chamomile,peppermint, green,black, ginger,and cinnamon teas during storage and brewing

In this study, the persistence of toxigenic Escherichia coli (E. coli) on dried chamomile, peppermint, ginger, cinnamon, black and green teas stored under 4, 10, and 25°C was determined. The E. coli survival rate in ginger and cinnamon teas decreased below 0 on Day 5. In the other tested teas, E. coli survivability showed a downward trend over time, but never dropped to 0. Chamomile tea retained the greatest population of viable E. coli. Meanwhile, die-off of E. coli was higher at 25°C compared to lower temperatures. Additionally, fate of E. coli during brewing at 60, 70 and 80°C was evaluated. The E. coli population was reduced to below 2 Log colony forming units (CFU)/g after 1 min at 80°C, At the same time, the E. coli survival at 60°C was higher than that at 70°C in all tested teas. The data indicated that if E. coli survives after storage of prepared teas, it may also survive and grow after the brewing process, especially if performed using temperatures <80°C. Finally, we analyzed the correlations between temperature, time, tea varieties and E. coli survival, and successfully constructed a random forest regression model. The results of this study can be used to predict changes in E. coli during storage and fate during the brewing process. Results will form the basis of undertaking a risk assessment.