Discovery of Chemicals to Either Clear or Indicate Amyloid Aggregates by Targeting Memory‐Impairing Anti‐Parallel Aβ Dimers

Amyloid‐β (Aβ) oligomers are implicated in Alzheimer disease (AD). However, their unstable nature and heterogeneous state disrupts elucidation of their explicit role in AD progression, impeding the development of tools targeting soluble Aβ oligomers. Herein parallel and anti‐parallel variants of Aβ(1–40) dimers were designed and synthesized, and their pathogenic properties in AD models characterized. Anti‐parallel dimers induced cognitive impairments with increased amyloidogenesis and cytotoxicity, and this dimer was then used in a screening platform. Through screening, two FDA‐approved drugs, Oxytetracycline and Sunitinib, were identified to dissociate Aβ oligomers and plaques to monomers in 5XFAD transgenic mice. In addition, fluorescent Astrophloxine was shown to detect aggregated Aβ in brain tissue and cerebrospinal fluid samples of AD mice. This screening platform provides a stable and homogeneous environment for observing Aβ interactions with dimer‐specific molecules.     

Imaging the In Vivo Degradation of Tissue Engineering Implants by Use of Supramolecular Radiopaque Biomaterials

For in situ tissue engineering (TE) applications it is important that implant degradation proceeds in concord with neo‐tissue formation to avoid graft failure. It will therefore be valuable to have an imaging contrast agent (CA) available that can report on the degrading implant. For this purpose, a biodegradable radiopaque biomaterial is presented, modularly composed of a bisurea chain‐extended polycaprolactone (PCL2000‐U4U) elastomer and a novel iodinated bisurea‐modified CA additive (I‐U4U). Supramolecular hydrogen bonding interactions between the components ensure their intimate mixing. Porous implant TE‐grafts are prepared by simply electrospinning a solution containing PCL2000‐U4U and I‐U4U. Rats receive an aortic interposition graft, either composed of only PCL2000‐U4U (control) or of PCL2000‐U4U and I‐U4U (test). The grafts are explanted for analysis at three time points over a 1‐month period. Computed tomography imaging of the test group implants prior to explantation shows a decrease in iodide volume and density over time. Explant analysis also indicates scaffold degradation. (Immuno)histochemistry shows comparable cellular contents and a similar neo‐tissue formation process for test and control group, demonstrating that the CA does not have apparent adverse effects. A supramolecular approach to create solid radiopaque biomaterials can therefore be used to noninvasively monitor the biodegradation of synthetic implants.     

Third-order Nonlinear Optical Properties of Octa-substituted Metal-free Phthalocyanine Thin Films

Third-order nonlinear optical susceptibility, χ⁽³⁾ of symmetrically octa-substituted metal-free phthalocyanine thin films measured by the third-harmonic generation technique are reported. The metal-free phthalocyanine has been found to show a χ⁽³⁾ (−3ω; ω,ω, ω) value as large as 7.73×10⁻¹² esu at 1.80 μm. The figure of merit, χ⁽³⁾/α, was estimated to be 4.17×10¹⁷ esu cm at 1.05 μm and 6.97×10¹⁶ esu cm at 1.65 μm. Both linear and third-order optical properties of liquid-crystalline metal-free phthalocyanines are discussed     

Sturmian Ground States in Classical Lattice–Gas Models

Journal of Statistical Physics - We construct for the first time examples of non-frustrated, two-body, infinite-range, one-dimensional classical lattice–gas models without periodic...     

In Vivo Endoscopic Tissue Identification by Rapid Evaporative Ionization Mass Spectrometry (REIMS)

Gastrointestinal cancers are a leading cause of mortality, accounting for 23 % of cancer‐related deaths worldwide. In order to improve outcomes from these cancers, novel tissue characterization methods are needed to facilitate accurate diagnosis. Rapid evaporative ionization mass spectrometry (REIMS) is a technique developed for the in vivo classification of human tissue through mass spectrometric analysis of aerosols released during electrosurgical dissection. This ionization technique was further developed by utilizing surface induced dissociation and was integrated with an endoscopic polypectomy snare to allow in vivo analysis of the gastrointestinal tract. We tested the classification performance of this novel endoscopic REIMS method in vivo. It was shown to be capable of differentiating between healthy layers of the intestinal wall, cancer, and adenomatous polyps based on the REIMS fingerprint of each tissue type in vivo.     

On nondegenerate coupling forms

The aim of the present paper is to investigate new classes of symplectically fat fibre bundles. We prove a general existence theorem for fat vectors with respect to the canonical invariant connections. Based on this result we give new proofs of some constructions of symplectic structures. This includes twistor bundles and locally homogeneous complex manifolds. The proofs are conceptually simpler and allow for obtaining more general results.     

Sorption of hydrophobic molecules by organic/inorganic mesostructures

During the synthesis of micelle-templated silica an intermediate inorganic/organic mesostructure is obtained with an hexagonal arrangement of channels filled by surfactant molecules. The ability of such a mesostructure to solubilize organic molecules from an aqueous solution was investigated. To that end, silica/cationic surfactant mesostructures were prepared under various conditions and their stability toward surfactant release in water was first compared in order to select materials as stable as possible. Swelled mesostructures were also used. The sorption from solution of hydrophobic molecules was then studied. The affinity of the molecules for the mesostructures is directly related to their hydrophobic character as it is derived from their octanol/water partition coefficient. A cooperative effect between hydrophobic molecules and the cationic surfactant that stabilizes the surfactant inside the mesostructure was observed. Interaction energies between the solutes and the mesostructures were determined by microcalorimetry. They varied in accordance with the hydrophobic character of the molecule and, at low sorption amounts, they were of the same order of magnitude as the solubilization enthalpies in bulk micelles. When the sorption increases, the surfactant layer in the mesostructure is not allowed to swell as the free micelle does, and steric limitations in the headgroup area render sorption less favorable.