Versatile Near-Infrared Super-Resolution Imaging of Amyloid Fibrils with the Fluorogenic Probe CRANAD-2

CRANAD-2 is a fluorogenic curcumin derivative used for near-infrared detection and imaging in vivo of amyloid aggregates, which are involved in neurodegenerative diseases. We explore the performance of CRANAD-2 in two super-resolution imaging techniques, namely stimulated emission depletion (STED) and single-molecule localization microscopy (SMLM), with markedly different fluorophore requirements. By conveniently adapting the concentration of CRANAD-2, which transiently binds to amyloid fibrils, we show that it performs well in both techniques, achieving a resolution in the range of 45–55 nm. Correlation of SMLM with atomic force microscopy (AFM) validates the resolution of fine features in the reconstructed super-resolved image. The good performance and versatility of CRANAD-2 provides a powerful tool for near-infrared nanoscopic imaging of amyloids in vitro and in vivo.     

Experimental and Theoretical Studies on the Rearrangement of 2‐Oxoazepane α,α‐Amino Acids into 2′‐Oxopiperidine β2,3,3‐Amino Acids: An Example of Intramolecular Catalysis

Enantiopure β‐amino acids represent interesting scaffolds for peptidomimetics, foldamers and bioactive compounds. However, the synthesis of highly substituted analogues is still a major challenge. Herein, we describe the spontaneous rearrangement of 4‐carboxy‐2‐oxoazepane α,α‐amino acids to lead to 2′‐oxopiperidine‐containing β^2,3,3‐amino acids, upon basic or acid hydrolysis of the 2‐oxoazepane α,α‐amino acid ester. Under acidic conditions, a totally stereoselective synthetic route has been developed. The reordering process involved the spontaneous breakdown of an amide bond, which typically requires strong conditions, and the formation of a new bond leading to the six‐membered heterocycle. A quantum mechanical study was carried out to obtain insight into the remarkable ease of this rearrangement, which occurs at room temperature, either in solution or upon storage of the 4‐carboxylic acid substituted 2‐oxoazepane derivatives. This theoretical study suggests that the rearrangement process occurs through a concerted mechanism, in which the energy of the transition states can be lowered by the participation of a catalytic water molecule. Interestingly, it also suggested a role for the carboxylic acid at position 4 of the 2‐oxoazepane ring, which facilitates this rearrangement, participating directly in the intramolecular catalysis.     

Evaluating cost impacts on reverse logistics using an Economic Order Quantity (EOQ) model with environmental and social considerations

Central European Journal of Operations Research - Societal awareness and legislation changes concerning sustainability have affected how organizations generate value for stakeholders, as well as...     

Design and development of a two‐dimensional system based on hydrophilic and reversed‐phase liquid chromatography with on‐line sample treatment for the simultaneous separation of excreted xenobiotics and endogenous metabolites in urine

In the present work we describe a two‐dimensional liquid chromatographic system (2D‐LC) with detection by mass spectrometry (MS) for the simultaneous separation of endogenous metabolites of clinical interest and excreted xenobiotics deriving from exposure to toxic compounds. The 2D‐LC system involves two orthogonal chromatographic modes, hydrophilic interaction liquid chromatography (HILIC) to separate polar endogenous metabolites and reversed‐phase (RP) chromatography to separate excreted xenobiotics of low and intermediate polarity. Additionally, the present proposal has the novelty of incorporating an on‐line sample treatment based on the use of restricted access materials (RAMs), which permits the direct injection of urine samples into the system. The work is focused on the instrumental coupling, studying all possible options and attempting to circumvent the problems of solvent incompatibility between the RAM device and the two chromatographic columns, HILIC and RP. The instrumental configuration developed, RAM‐HILIC‐RPLC‐MS/MS, allows the simultaneous assessment of urinary metabolites of clinical interest and excreted compounds derived from exposure to toxic agents with minimal sample manipulation. Thus, it may be of interest in areas such as occupational and environmental toxicology in order to explore the possible relationship between the two types of compounds. Copyright © 2015 John Wiley & Sons, Ltd.     

An alternative approach for non-linear optimal control problems based on the method of moments

We propose an alternative method for computing effectively the solution of non-linear, fixed-terminal-time, optimal control problems when they are given in Lagrange, Bolza or Mayer forms. This method works well when the nonlinearities in the control variable can be expressed as polynomials. The essential of this proposal is the transformation of a non-linear, non-convex optimal control problem into an equivalent optimal control problem with linear and convex structure. The method is based on global optimization of polynomials by the method of moments. With this method we can determine either the existence or lacking of minimizers. In addition, we can calculate generalized solutions when the original problem lacks of minimizers. We also present the numerical schemes to solve several examples arising in science and technology.     

Roughness reduction in submicron waveguides by low-molecular weight development

Roughness reduction of a submicron waveguide profile in chemically amplified negative resist is here performed by proper selection of an alkali-based developer, taking into account that its smaller molecules lead to smoother resist surface by altering the developing mechanism of aggregate extraction performed with standard quaternary ammonium hydroxide. Roughness is then analyzed by means of classical Atomic Force Microscope inspection; furthermore, a non-invasive line edge roughness analysis approach based on top-down scanning electron microscope acquisition gives comparable results, in terms of standard deviation and molecular aggregate periodicity.     

Three solutions for a mixed boundary value problem involving the one-dimensional p-Laplacian

This paper deals with two mixed nonlinear boundary value problems depending on a parameter λ. For each of them we prove the existence of at least three generalized solutions when λ lies in an exactly determined open interval. Usefulness of this information on the interval is then emphasized by means of some consequences. Our main tool is a very recent three critical points theorem stated in [Topol. Methods Nonlinear Anal. 22 (2003) 93-104].     

The generalized second law in phantom dominated universes in the presence of black holes

This Letter considers the generalized second law of gravitational thermodynamics in two scenarios featuring a phantom dominated expansion plus a black hole. The law is violated in both scenarios.