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.     

Revealing Nanomechanical Domains and Their Transient Behavior in Mixed-Halide Perovskite Films

Halide perovskites are a versatile class of semiconductors employed for high performance emerging optoelectronic devices, including flexoelectric systems, yet the influence of their ionic nature on their mechanical behavior is still to be understood. Here, a combination of atomic-force, optical, and compositional X-ray microscopy techniques is employed to shed light on the mechanical properties of halide perovskite films at the nanoscale. Mechanical domains within and between morphological grains, enclosed by mechanical boundaries of higher Young's Modulus (YM) than the bulk parent material, are revealed. These mechanical boundaries are associated with the presence of bromide-rich clusters as visualized by nano-X-ray fluorescence mapping. Stiffer regions are specifically selectively modified upon light soaking the sample, resulting in an overall homogenization of the mechanical properties toward the bulk YM. This behavior is attributed to light-induced ion migration processes that homogenize the local chemical distribution, which is accompanied by photobrightening of the photoluminescence within the same region. This work highlights critical links between mechanical, chemical, and optoelectronic characteristics in this family of perovskites, and demonstrates the potential of combinational imaging studies to understand and design halide perovskite films for emerging applications such as photoflexoelectricity.     

Carbon Cathode Wear in Aluminium Electrolysis Cells

JOM - Autopsies of six spent potlinings with different carbon cathode block grades, amperage regimes and cell designs were conducted at three separate smelters to reveal possible mechanisms causing...     

Activity-Directed Synthesis: A Flexible Approach for Lead Generation

Activity-directed synthesis (ADS) is a structure-blind, functional-driven molecular discovery approach. In this Concept, four case studies highlight the general applicability of ADS and showcase its flexibility to support different medicinal chemistry strategies. ADS deliberately harnesses reactions with multiple possible outcomes, and allows many chemotypes to be evaluated in parallel. Resources are focused on bioactive molecules, which emerge in tandem with associated synthetic routes. Some of the future challenges for ADS are highlighted, including the realisation of an autonomous molecular discovery platform. The prospects for ADS to become a mainstream lead generation approach are discussed.     

Systematic literature review on city logistics: overview,classification and analysis

City logistics is one of the significant branches of supply chain management, dealing with the logistics and transportation activities in urban areas. This research area has recently appropriated an exponential growth of publications. This paper presents a bibliometric analysis along with a systematic literature review to organise the results of surveying more than 370 papers and research works published since 2010. We identify the top contributing research topics. The most common keywords used in the city logistics literature are referred to in order to propose six research categories identifying the main innovative research perspectives.     

Understanding structure ignition vulnerabilities using mock‐up sections of attached wood fencing assemblies

Firebrand production from structure combustion becomes a key factor in the magnitude of how quickly a large outdoor fire may spread. Post‐fire disaster investigations suggest that attached building components, such as wood fencing assemblies are known to be prone to ignition in these fires, and may provide pathways to structure ignition. Here, a comparison of ignition results from full‐scale fencing assembly experiments conducted using a full‐scale wind tunnel facility, to mock‐ups of full‐scale fencing assemblies using the recently developed experimental capability at the National Research Institute of Fire and Disaster (NRIFD) are discussed. In both experimental facilities, the fencing assemblies were exposed to firebrand showers using custom built continuous feed firebrand generators with size and mass distributions similar to those generated from structure combustion. Similar ignition behaviors were observed between the full‐scale fencing assemblies and the mock‐up of full‐scale fencing assemblies. Additional experiments are required for other fencing assembly types to further verify these important findings.     

Corrosion Inhibition of Mild Steel in Aqueous HCl using Bitter Leaf and Fenugreek Seed Oils

Protection of Metals and Physical Chemistry of Surfaces - Bitter leaf and Fenugreek seed oils were extracted from their parent seed plants for use as corrosion inhibitors for mild steel in HCl....     

Lighting the Path: Light Delivery Strategies to Activate Photoresponsive Biomaterials In Vivo

Photoresponsive biomaterials are experiencing a transition from in vitro models to in vivo demonstrations that point toward clinical translation. Dynamic hydrogels for cell encapsulation, light-responsive carriers for controlled drug delivery, and nanomaterials containing photosensitizers for photodynamic therapy are relevant examples. Nonetheless, the step to the clinic largely depends on their combination with technologies to bring light into the body. This review highlights the challenge of photoactivation in vivo, and presents strategies for light management that can be adopted for this purpose. The authors’ focus is on technologies that are materials-driven, particularly upconversion nanoparticles that assist in “direct path” light delivery through tissue, and optical waveguides that “clear the path” between external light source and in vivo target. The authors’ intention is to assist the photoresponsive biomaterials community transition toward medical technologies by presenting light delivery concepts that can be integrated with the photoresponsive targets. The authors also aim to stimulate further innovation in materials-based light delivery platforms by highlighting needs and opportunities for in vivo photoactivation of biomaterials.