Quantitative energy dispersive X-ray microanalysis of electron beam-sensitive alloyed nanoparticles.

An energy dispersive X-ray spectrometry (EDXS) method is developed to evaluate the composition of alloyed nanoparticles (NPs) where one of the alloying elements is removed under the electron beam during microanalysis with a transmission electron microscope (TEM). The method is demonstrated for alloyed Au-Ag NPs of a diameter ranging from 6 to 20 nm produced by laser evaporation of a water-suspended Ag-Au powder mixture of varying composition. Series of EDXS spectra are recorded for 30 NPs from samples with five different Ag:Au ratios revealing Ag depletion from NPs during electron irradiation. By studying the evolution of NPs composition as a function of dose, the initial Ag content for each NP is extrapolated. The rate of Ag depletion is discussed in terms of sputtering and knock-on damage. On average, approximately one Ag atom is lost from the NP for each Ag L X-ray detected. To assess the limitations of microanalysis in these sensitive nanoscale structures, the concept of detectability limit is adapted to our method. This benchmark is then evaluated for Ag in Au-Ag NPs of various sizes and acquisition times. This study should be regarded as a guide for the design of analytical TEM measurements of beam-sensitive NPs.     

Dual acquisition magic-angle spinning solid-state NMR-spectroscopy: simultaneous acquisition of multidimensional spectra of biomacromolecules

Fast data collection: a general method for dual data acquisition of multidimensional magic-angle spinning solid-state NMR experiments is presented. The method uses a simultaneous Hartmann-Hahn cross-polarization from (1)H to (13)C and (15)N nuclei and exploits the long-living (15)N polarization for parallel acquisition of two multidimensional experiments.     

Polyelectrolyte Capsules as Carriers for Growth Factor Inhibitor Delivery to Hepatocellular Carcinoma

The efficient internalization of TGF‐beta inhibitor‐loaded polyelectrolyte capsules and particles is studied in two HCC cell lines. Two polyelectrolyte pairs (biocompatible but not degradable and biodegradable crosslinked with gluteraldehyde) are employed for coating. The capsules are characterized by SEM. LY is successfully loaded inside the core and embedded between polymer layers. MS is used to quantify the loading efficiency by comparing post‐loading and core‐loading methods, since both coated templates and hollow shells are used as carriers. CLSM confirms dissolution of the pre‐formed multilayer upon enzymatic degradation as the method of release, and migration assays demonstrate a higher inhibition efficiency of TGF‐beta in tailored biodegradable capsules compared to free LY administration.

     

Oxazolidin-2-one-containing pseudopeptides that fold into beta-bend ribbon spirals

Three sets of oligomers containing the 4-carboxy-5-methyloxazolidin-2-one (Oxd) moiety have been synthesized with the aim of checking whether these molecules are able to fold in ordered structures: A set [Boc-(L-Ala-L-Oxd)(n)-OR], B set [Boc-(L-Ala-D-Oxd)(n)-OR], and C set [Boc-(Aib-L-Oxd)(n)-OR] preferential conformations have been analyzed with IR absorption, NMR, and CD. We have noticed that in these oligomers three stabilizing effects are active: (i) the rigid Oxd -CO-N(CH<)-CO- moiety, which always tend to assume a trans conformation; (ii) the formation of Oxd C=O...H-(alpha)C intramolecolar H-bonds; (iii) the alternate formation of 1 <-- 4 intramolecular C=O...H-N H-bonds. Through the analysis of the experimental data, we could demonstrate that only the oligomers of the B set are able to meet all three requirements listed above. By a deeper insight into the CD spectra, we gathered that the secondary structure adopted by the B set oligomers is a beta-bend ribbon spiral, which is a subtype of the 3(10)-helix.     

Computational Reduction for Parametrized PDEs: Strategies and Applications

In this paper we present a compact review on the mostly used techniques for computational reduction in numerical approximation of partial differential equations. We highlight the common features of these techniques and provide a detailed presentation of the reduced basis method, focusing on greedy algorithms for the construction of the reduced spaces. An alternative family of reduction techniques based on surrogate response surface models is briefly recalled too. Then, a simple example dealing with inviscid flows is presented, showing the reliability of the reduced basis method and a comparison between this technique and some surrogate models.     

Transmission‐mode diamond white‐beam position monitor at NSLS

Two transmission‐mode diamond X‐ray beam position monitors installed at National Synchrotron Light Source (NSLS) beamline X25 are described. Each diamond beam position monitor is constructed around two horizontally tiled electronic‐grade (p.p.b. nitrogen impurity) single‐crystal (001) CVD synthetic diamonds. The position, angle and flux of the white X‐ray beam can be monitored in real time with a position resolution of 500 nm in the horizontal direction and 100 nm in the vertical direction for a 3 mm × 1 mm beam. The first diamond beam position monitor has been in operation in the white beam for more than one year without any observable degradation in performance. The installation of a second, more compact, diamond beam position monitor followed about six months later, adding the ability to measure the angular trajectory of the photon beam.     

Responsible nanotechnology development

Chelated gadolinium ions, e.g., Gd-DTPA, are today used clinically as contrast agents for magnetic resonance imaging (MRI). An attractive alternative contrast agent is composed of gadolinium oxide nanoparticles as they have shown to provide enhanced contrast and, in principle, more straightforward molecular capping possibilities. In this study, we report a new, simple, and polyol-free way of synthesizing 4?C5-nm-sized Gd₂O₃ nanoparticles at room temperature, with high stability and water solubility. The nanoparticles induce high-proton relaxivity compared to Gd-DTPA showing r ₁ and r ₂ values almost as high as those for free Gd³⁺ ions in water. The Gd₂O₃ nanoparticles are capped with acetate and carbonate groups, as shown with infrared spectroscopy, near-edge X-ray absorption spectroscopy, X-ray photoelectron spectroscopy and combined thermogravimetric and mass spectroscopy analysis. Interpretation of infrared spectroscopy data is corroborated by extensive quantum chemical calculations. This nanomaterial is easily prepared and has promising properties to function as a core in a future contrast agent for MRI.     

Repositioning of Quinazolinedione-Based Compounds on Soluble Epoxide Hydrolase (sEH) through 3D Structure-Based Pharmacophore Model-Driven Investigation

The development of new bioactive compounds represents one of the main purposes of the drug discovery process. Various tools can be employed to identify new drug candidates against pharmacologically relevant biological targets, and the search for new approaches and methodologies often represents a critical issue. In this context, in silico drug repositioning procedures are required even more in order to re-evaluate compounds that already showed poor biological results against a specific biological target. 3D structure-based pharmacophoric models, usually built for specific targets to accelerate the identification of new promising compounds, can be employed for drug repositioning campaigns as well. In this work, an in-house library of 190 synthesized compounds was re-evaluated using a 3D structure-based pharmacophoric model developed on soluble epoxide hydrolase (sEH). Among the analyzed compounds, a small set of quinazolinedione-based molecules, originally selected from a virtual combinatorial library and showing poor results when preliminarily investigated against heat shock protein 90 (Hsp90), was successfully repositioned against sEH, accounting the related built 3D structure-based pharmacophoric model. The promising results here obtained highlight the reliability of this computational workflow for accelerating the drug discovery/repositioning processes.     

Allylsulfones through Palladium-Catalyzed Allylic C−H Sulfonylation of Terminal Alkenes

Two previously unknown protocols for Pd-catalyzed allylic C−H sulfonylation of terminal alkenes have been developed. While the former consists of a direct Pd(II)-catalyzed oxidative C−H allylic sulfonylation in the presence of sulfinate anions, the latter involves a sequential one-pot Pd(II)-catalyzed C−H allylic acetoxylation followed by a Pd(0)-catalyzed sulfonylation. The scope of both protocols was studied on 25 examples.