Structural insights into peptide self-assembly using photo-induced crosslinking experiments and discontinuous molecular dynamics

Determining the structure of the (oligomeric) intermediates that form during the self-assembly of amyloidogenic peptides is challenging because of their heterogeneous and dynamic nature. Thus, there is need for methodology to analyze the underlying molecular structure of these transient species. In this work, a combination of fluorescence quenching, photo-induced crosslinking (PIC) and molecular dynamics simulation was used to study the assembly of a synthetic amyloid-forming peptide, Aβ_16-22. A PIC amino acid containing a trifluormethyldiazirine (TFMD) group—Fmoc(TFMD)Phe—was incorporated into the sequence (Aβ*_16–22). Electrospray ionization ion-mobility spectrometry mass-spectrometry (ESI-IMS-MS) analysis of the PIC products confirmed that Aβ*_16–22 forms assemblies with the monomers arranged as anti-parallel, in-register β-strands at all time points during the aggregation assay. The assembly process was also monitored separately using fluorescence quenching to profile the fibril assembly reaction. The molecular picture resulting from discontinuous molecule dynamics simulations showed that Aβ_16-22 assembles through a single-step nucleation into a β-sheet fibril in agreement with these experimental observations. This study provides detailed structural insights into the Aβ_16-22 self-assembly processes, paving the way to explore the self-assembly mechanism of larger, more complex peptides, including those whose aggregation is responsible for human disease.     

Investigating measurements of fine particle (PM2.5) emissions from the cooking of meals and mitigating exposure using a cooker hood

There is growing awareness that indoor exposure to particulate matter with diameter ≤ 2.5 μm (PM_2.5) is associated with an increased risk of adverse health effects. Cooking is a key indoor source of PM_2.5 and an activity conducted daily in most homes. Population scale models can predict occupant exposures to PM_2.5, but these predictions are sensitive to the emission rates used. Reported emission rates are highly variable and are typically for the cooking of single ingredients and not full meals. Accordingly, there is a need to assess PM_2.5 emissions from the cooking of complete meals. Mean PM_2.5 emission rates and source strengths were measured for four complete meals. Temporal PM_2.5 concentrations and particle size distributions were recorded using an optical particle counter (OPC), and gravimetric sampling was used to determine calibration factors. Mean emission rates and source strengths varied between 0.54—3.7 mg/min and 15—68 mg, respectively, with 95% confidence. Using a cooker hood (apparent capture efficiency > 90%) and frying in non‐stick pans were found to significantly reduce emissions. OPC calibration factors varied between 1.5 and 5.0 showing that a single value cannot be used for all meals and that gravimetric sampling is necessary when measuring PM_2.5 concentrations in kitchens.     

Surface structure and quenching effects in BiFeO3-BaTiO3 ceramics

The structure and properties of Mn-doped 0.67BiFeO₃-0.33BaTiO₃ ceramics are systematically investigated with respect to the effects of annealing prior to rapid cooling by quenching in air. Air-quenching induces a change in crystal structure from pseudo-cubic to rhombohedral, with higher quenching temperatures leading to an increased rhombohedral distortion. These structural changes are correlated with the appearance of more well-defined ferroelectric domain configurations. It is shown that the surface preparation procedures for XRD measurements can induce significant changes in the peak profiles, indicating differences in crystal structure between the surface and bulk regions. Frequency dispersion in the temperature-dependent relative permittivity for the as-sintered sample is significantly reduced after quenching, accompanied by enhancement of the Curie point and improved temperature-stability of piezoelectric properties. It is proposed that the formation of defect clusters by A-site cation diffusion during cooling is circumvented by quenching, leading to the observed modification of structural distortion and ferroelectric properties.     

Development of low-loss lead-germanate glass for mid-infrared fiber optics: II. preform extrusion and fiber fabrication

For lead-germanate glass fibers, reducing the content of hydroxyl (OH) groups and the formation of metallic Pb species is essential to pave the way for their applications as low-loss mid-IR fiber optics since OH and metallic Pb species cause intense absorption and scattering loss, respectively, in the mid-IR spectral range. The first part of this study reported the optimization of the glass melting procedure to obtain low amount of OH while preventing formation of metallic Pb species in lead-germanate glass. Here, the second part of this study reports the investigation of the process conditions to fabricate low-loss lead-germanate glass fiber through further understanding of the co-effects of glass melting and heat treatment atmospheres on the formation of nano- and micron-scale metallic Pb species in both the as-produced and heat treated lead-germanate glasses. Finally, using this advance in knowledge, we successfully fabricated low-loss lead-germanate glass fibers with no presence of reduced metallic Pb particles by optimizing dehydration agent, glass melting, preform extrusion and fiber drawing conditions. The optimized fabrication conditions reduced the unstructured fiber loss by almost one order to <0.3 dB/m at 1.55 μm.     

Production of Particle‐Stabilized Nonspherical Emulsion Drops in Simple Shear Flow

Nonspherical drops are of interest in the formation of microcapsules in life sciences like food, pharmacy, and cosmetics, agro and fine chemicals as well as material sciences. Out of many systems, particle‐stabilized emulsion drops, so‐called Pickering emulsions, exhibit an interesting formulation. Systems with Pickering particles applied in an excess amount were investigated. During deformation, the particles fully covered the enlarged drop interfaces and prevented its relaxation to a spherical drop shape. Nonspherical drops could be produced in simple shear flow using an adequate process routine. The production in a simple device is a promising high‐throughput alternative to microfluidic devices.     

Cigarette characteristics,smoker characteristics,and the relationship to cigarette fires

Data were collected from eight cities on a wide range of cigarette and smoker characteristics for a sample of smokers. Of these, 564 smokers had had fires and were identified through fire department response to those fires, while the other 1,611 smokers had not had fires and were identified through a telephone sample survey of the communities. The characteristics analyzed included those that had shown evidence of a relationship to the risk of a cigarette-initiated fire, either in laboratory studies or in previous statistical analyses of fire experience.The smoker characteristics analyzed were household income, education, age, gender, and race. The cigarette characteristics analyzed were filter, tobacco column length, filter length, circumference, density, amount of tobacco, menthol, citrate, porosity, and pack type. In addition, a variable was used to control for the smoker's city.After controlling for all smoker characteristics and city, logistic regression modeling showed four cigarette characteristics to be significant: filter, filter length, porosity, and type of pack. Filter, filter length, and porosity all affect air intake, which, therefore, appears to be an important physical element in the combustion process associated with risk. Analysis limited to filtered cigarettes only showed the same characteristics to be significant, plus tobacco column length. Extension of the analysis to two-way interaction terms did not change any of the conclusions on which cigarette characteristics are important, but it did indicate that the role of pack type was different for men and women.Sensitivity analyses, shown in the appendix, supported the main conclusions that cigarette characteristics are significant after controlling for smoker characteristics and that the four specific cigarette characteristics—filter, filter length, porosity, and pack—are the ones that are significant. These analyses checked the impact of cluster sampling, sensitivity to missing data on smoker characteristics, and sensitivity to nonfire smoker cases with responses by people other than the smokers themselves.All this means that there are already cigarettes commercially available that exhibit a reduced propensity for ignition when one controls for smoker characteristics.This report was originally written as the final report in June 1993 as part of CPSC-P-91-1147 Contract Cigarette Fire Incident Study that the National Fire Protection Association conducted for the U.S. Consumer Product Safety Commission.Harwood, formerly with the Consumer Product Safety Commission, is retired.