A Hot‐Segment‐Based Approach for the Design of Cross‐Amyloid Interaction Surface Mimics as Inhibitors of Amyloid Self‐Assembly

The design of inhibitors of protein–protein interactions mediating amyloid self‐assembly is a major challenge mainly due to the dynamic nature of the involved structures and interfaces. Interactions of amyloidogenic polypeptides with other proteins are important modulators of self‐assembly. Here we present a hot‐segment‐linking approach to design a series of mimics of the IAPP cross‐amyloid interaction surface with Aβ (ISMs) as nanomolar inhibitors of amyloidogenesis and cytotoxicity of Aβ, IAPP, or both polypeptides. The nature of the linker determines ISM structure and inhibitory function including both potency and target selectivity. Importantly, ISMs effectively suppress both self‐ and cross‐seeded IAPP self‐assembly. Our results provide a novel class of highly potent peptide leads for targeting protein aggregation in Alzheimer’s disease, type 2 diabetes, or both diseases and a chemical approach to inhibit amyloid self‐assembly and pathogenic interactions of other proteins as well.     

On the completeness of root vectors generated by systems of coupled hyperbolic equations

The paper is the second in a set of two papers, which are devoted to a unified approach to the problem of completeness of the generalized eigenvectors (the root vectors) for a specific class of linear non‐selfadjoint unbounded matrix differential operators. The list of the problems for which such operators are the dynamics generators includes the following: (a) initial boundary‐value problem (IBVP) for a non‐homogeneous string with both distributed and boundary damping; (b) IBVP for small vibrations of an ideal filament with a one‐parameter family of dissipative boundary conditions at one end and with a heavy load at the other end; this filament problem is treated for two cases of the boundary parameter: non‐singular and singular; (c) IBVP for a three‐dimensional damped wave equation with spherically symmetric coefficients and both distributed and boundary damping; (d) IBVP for a system of two coupled hyperbolic equations constituting a Timoshenko beam model with variable coefficients and boundary damping; (e) IBVP for a coupled Euler‐Bernoulli and Timoshenko beam model with boundary energy dissipation (the model known in engineering literature as bending‐torsion vibration model); (f) IBVP for two coupled Timoshenko beams model, which is currently accepted as an appropriate model describing vibrational behavior of a longer double‐walled carbon nanotube. Problems have been discussed in the first paper of the aforementioned set. Problems are discussed in the present paper.     

Synthesis of Novel Lipophilic Polyamines via Ugi Reaction and Evaluation of Their Anticancer Activity

Natural polyamines (PAs) are involved in the processes of proliferation and differentiation of cancer cells. Lipophilic synthetic polyamines (LPAs) induce the cell death of various cancer cell lines. In the current paper, we have demonstrated a new method for synthesis of LPAs via the multicomponent Ugi reaction and subsequent reduction of amide groups by PhSiH₃. The anticancer activity of the obtained compounds was evaluated in the A-549, MCF7, and HCT116 cancer cell lines. For the first time, it was shown that the anticancer activity of LPAs with piperazine fragments is comparable with that of aliphatic LPAs. The presence of a diglyceride fragment in the structure of LPAs appears to be a key factor for the manifestation of high anticancer activity. The findings of the study strongly support further research in the field of LPAs and their derivatives.     

Nonlinear Optical Properties of Benzylic Amide [2] Catenanes: A Novel Versatile Photonic Material

Abstract

Benzylic amide catenanes are a class of synthetically-accessible interlocked molecular rings which can rotate one through the other depending on the nature of the local environment. The rings contain four phenyl units each and interlocking also affords their packing in novel, highly interacting ways that may lead to unexpected properties thus opening up the possibility of developing new materials. Third harmonic generation in benzylic amide catenane solutions was measured at a wavelength of γ = 1064 nm, with the fundamental and the harmonic wavelengths in the region of transparency of the material. The thoroughly non resonant value of the hyperpolarisability γ(-3ω; ω, ω, ω) was found to be (6.5 ± 0.7) × 10^?35 esu with a negligible imaginary part, in agreement with the value of (6.8 ± 0.9) × 10^?35 esu calculated from a bond-additivity model of hyperpolarisability. The static second order hyperpolarisability predicted by a Molecular Orbital model was about a factor four less than the experimental value. Second hyperpolarizability values of several solvents were also measured at the fundamental wavelength of γ = 1064 nm.     

Structural and dynamical analysis of monodisperse and polydisperse colloidal systems

We present a semigrand ensemble Monte Carlo and Brownian dynamics simulation study of structural and dynamical properties of polydisperse soft spheres interacting via purely repulsive power-law potentials with a varying degree of "softness." Comparisons focus on crystal and amorphous phases at their coexistence points. It is shown through detailed structural analysis that as potential interactions soften, the "quality of crystallinity" of both monodisperse and polydisperse systems deteriorates. In general, polydisperse crystalline phases are characterized by a more ordered structure than the corresponding monodisperse ones (i.e., for the same potential softness). This counter-intuitive feature originates partly from the fact that particles of different sizes may be accommodated more flexibly in a crystal structure and from the reality that coexistence (osmotic) pressure is substantially higher for polydisperse systems. These trends diminish for softer potentials. Potential softness eventually produces substitutionally disordered crystals. However, substitutional order is apparent for the hard-spherelike interactions. Diffusionwise, crystals appear quite robust with a slight difference in the vibrational amplitudes of small and large particles. This difference, again, diminishes with potential softness. Overcrowding in amorphous polydisperse suspensions causes "delayed" diffusion at intermediate times.     

A networking method to compare theories: metacognition in problem solving reformulated within the Anthropological Theory of the Didactic

An important role of theory in research is to provide new ways of conceptualizing practical questions, essentially by transforming them into scientific problems that can be more easily delimited, typified and approached. In mathematics education, theoretical developments around ‘metacognition’ initially appeared in the research domain of Problem Solving closely related to the practical question of how to learn (and teach) to solve non-routine problems. This paper presents a networking method to approach a notion as ‘metacognition’ within a different theoretical perspective, as the one provided by the Anthropological Theory of the Didactic. Instead of trying to directly ‘translate’ this notion from one perspective to another, the strategy used consists in going back to the practical question that is at the origin of ‘metacognition’ and show how the new perspective relates this initial question to a very different kind of phenomena. The analysis is supported by an empirical study focused on a teaching proposal in grade 10 concerning the problem of comparing mobile phone tariffs.     

The effect of organoclay and graphene on the crystallization of PP in ABS/PP blends

In the present research, the isothermal and non-isothermal crystallization of polypropylene (PP) phase in PP-rich poly(acrylonitrile–butadiene–styrene)/polypropylene (ABS/PP) blends was studied. The effect of nanofillers’ incorporation and specialty of organically modified montmorillonite (OMMT) and graphene, into the prepared blends on the isothermal and non-isothermal crystallization of PP phase, were investigated. Moreover, kinetic study of their isothermal crystallization process was carried out, by applying the Avrami equation. The addition of ABS to the PP matrix increased the crystallization rate of PP at 130 °C. The incorporation of OMMT in pure PP accelerated slightly the crystallization process, whereas in ABS/PP blends, it seemed to retard crystallization, due to interactions between ABS phase and organoclay. The incorporation of graphene in pure PP accelerated impressively its isothermal crystallization, while the addition of ABS in graphene/PP nanocomposite slowed down the crystallization rate of PP. The effect of ABS and nanofillers, separately or in combination, on the crystallization of PP phase was reflected on the kinetic parameters of the Avrami equation. Regarding the non-isothermal crystallization, ABS/PP blends presented higher crystallization temperature (T _c) compared to pure PP. The organoclay reinforcement did not have any obvious effect on this temperature, whereas graphene caused significant increase, acting as nucleating agent. The presence of ABS to PP increased the concentration of the β-crystalline phase, reaching its maximum value at 30 mass% ABS content. The organoclay decreased the β-PP in ABS/PP blends, whereas graphene eliminated it.     

The Besicovitch–Federer projection theorem is false in every infinite-dimensional Banach space

The theme of the article is the study of the unipotent part of Arthur’s trace formula for general linear groups. The case of regular (or “regular by blocks”) unipotent orbits has been treated in another paper (cf. [10]). Here we are interested in the contribution of Richardson orbits that are induced by Levi subgroups with two-by-two distinct blocks. In this case, the contribution is remarkably given by a global unipotent weighted orbital integral. As a corollary, we get integral formulas for some of Arthur’s global coefficients. We also present a new construction of Arthur’s local unipotent weighted orbital integral and an explicit computation of some of them.