Reproducibility of Biomolecular Corona Experiments: A Primer for Reliable Results

The biomolecular corona is a key component controlling the identity of nanomaterials in physiological environments. Studies aimed at identifying factors shaping the biomolecular corona have proliferated in the last decade but have been performed by research groups with different backgrounds. Efforts made within the scientific community to guarantee the reproducibility of experimental data have identified protocol standardization as an indispensable step for advancing knowledge in this arena. To contribute to fulfill this gap, here the relevance of interoperator variability in biomolecular corona studies and the benefits arising from automated systems usage are explored. Moreover, the role of molecular crowding during nanoparticle-biofluid incubation and the effect of washing the pellet during corona isolation are thoroughly investigated. It is believed that the findings will help researchers enhance the accuracy of experimental design and reporting.     

Enzyme-amplified electrochemical hybridization assay based on PNA, LNA and DNA probe-modified micro-magnetic beads

In the present study, we investigated the properties of PNA and LNA capture probes in the development of an electrochemical hybridization assay. Streptavidin-coated paramagnetic micro-beads were used as a solid phase to immobilize biotinylated DNA, PNA and LNA capture probes, respectively. The target sequence was then recognized via hybridization with the capture probe. After labeling the biotinylated hybrid with a streptavidin–enzyme conjugate, the electrochemical detection of the enzymatic product was performed onto the surface of a disposable electrode. The assay was applied to the analytical detection of biotinylated DNA as well as RNA sequences. Detection limits, calculated considering the slope of the linear portion of the calibration curve in the range 0–2 nM were found to be 152, 118 and 91 pM, coupled with a reproducibility of the analysis equal to 5, 9 and 6%, calculated as RSD%, for DNA, PNA and LNA probes respectively, using the DNA target. In the case of the RNA target, the detection limits were found to be 51, 60 and 78 pM for DNA, PNA and LNA probes respectively.     

Rapid approach to 3,5-disubstituted 1,4-benzodiazepines via the photo-fries rearrangement of anilides

Different anilides derived from carboxylic acids and substituted anilines have been submitted to the photochemically induced Fries rearrangement giving the corresponding o-amino phenones under conditions that are compatible with the presence of acid-labile groups (such as N-Boc or TBDMSO) on R1 and R3. These compounds, not easily obtained in other ways, are useful building blocks for the preparation of benzocondensated heterocycles. After coupling with N-Boc amino acids and TFA-mediated deprotection, the products cyclized to the corresponding 3,5-disubstituted 1,4-benzodiazepin-2-ones, privileged structures predominantly active in the central nervous system. The same results were obtained by coupling with N-Cbz-protected alpha-amino acids followed by microwave assisted hydrogenolysis. When the Fries rearrangement was carried out on the anilide derived from N-Boc-Ala-OH and the further coupling done with N-Cbz-(OMe)Asp-OH, the formed benzodiazepines could be inserted in a peptide chain for the preparation of conformationally constrained peptidomimetics.     

Methylaminated potassium fulleride, (CH3NH2)K3C60: towards hyperexpanded fulleride lattices

Co-intercalation of methylamine molecules into the cubic K3C60 lattice affords the fulleride (CH3NH2)K3C60, which was characterized by Raman and MAS 13C and 1H NMR spectroscopy. The high-resolution synchrotron X-ray powder diffraction technique was employed to determine its crystal structure at ambient temperature. We find that CH3NH2 bonds to K+ ions residing in the pseudo-octahedral interstices, thereby providing an efficient and facile route to hyperexpanded close-packed strongly anisotropic fulleride lattices, while retaining the electronic contact between the C603- anions. Preliminary evidence for the occurrence of a transition to an antiferromagnetic state at low temperature is also presented, consistent with the proximity of the present system to the metal-insulator boundary of the electronic phase diagram of C603- fullerides.     

Cooperative Jahn-Teller distortion, phase transitions, and weak ferromagnetism in the KCrF3 perovskite

At ambient conditions, the ternary fluoride with formula KCrF3 adopts a perovskite-type structure and incorporates the Jahn-Teller active Cr2+ (d4) whose electronic configuration and magnetic response are analogous to those of Mn3+ (d4) and Cu2+ (d9). These ingredients make it an attractive system to study owing to the striking similarities with LaMnO3 and the expected strong interplay between spin, orbital, and structural ordering phenomena. Indeed, probing the properties of KCrF3 as a function of temperature (5 < T < 300 K) has revealed a structurally and magnetically far richer phase diagram than hitherto supposed. We found that KCrF3 exhibits large cooperative Jahn-Teller distortions which are driven by orbital ordering, a series of temperature induced complex structural transitions, and weak ferromagnetism which is reminiscent of what is observed in LaMnO3.     

Implicit Shape Reconstruction of Unorganized Points Using PDE-Based Deformable 3D Manifolds

<正>In this work we consider the problem of shape reconstruction from an unorganized data set which has many important applications in medical imaging,scientific computing,reverse engineering and geometric modelling.The reconstructed surface is obtained by continuously deforming an initial surface following the Partial Differential Equation(PDE)-based diffusion model derived by a minimal volume-like variational formulation.The evolution is driven both by the distance from the data set and by the curvature analytically computed by it.The distance function is computed by implicit local interpolants defined in terms of radial basis functions.Space discretization of the PDE model is obtained by finite co-volume schemes and semi-implicit approach is used in time/scale.The use of a level set method for the numerical computation of the surface reconstruction allows us to handle complex geometry and even changing topology, without the need of user-interaction.Numerical examples demonstrate the ability of the proposed method to produce high quality reconstructions.Moreover,we show the effectiveness of the new approach to solve hole filling problems and Boolean operations between different data sets.     

Dual CD system-modified MEEKC method for the determination of clemastine and its impurities

A dual system of CDs was used for the first time in MEEKC with the aim of determining clemastine and its three main related impurities in both drug substances and tablets. The addition of methyl-β-cyclodextrin and heptakis(2,6-di-O-methyl)-β-cyclodextrin to the microemulsion pseudo-stationary phase was essential to increase the resolving power of the system to obtain a baseline separation among the compounds. The best microemulsion composition was identified by mixture design and the effects of the factors concentrations of CDs and voltage were investigated by a response surface study applying a Central Composite Design. In both cases, Derringer's desirability function made it possible to find the global optimum, which corresponded to the following combination: microemulsion, 89.8% 10 mM borate buffer pH 9.2, 1.5% n-heptane and 8.7% of SDS/n-butanol in 1:2 ratio; 18 mM methyl-β-cyclodextrin, 38 mM heptakis(2,6-di-O-methyl)-β-cyclodextrin, 17 kV. By applying these conditions, the separation was completed in about 5.5 min. The method was validated following International Conference on Harmonisation guidelines and was applied to a real sample of clemastine tablets.     

A three-dimensional symmetry result for a phase transition equation in the genuinely nonlocal regime

We consider bounded solutions of the nonlocal Allen–Cahn equation

$$\begin{aligned} (-\Delta )^s u=u-u^3\qquad { \text{ in } }\mathbb {R}^3, \end{aligned}$$

under the monotonicity condition \(\partial _{x_3}u>0\) and in the genuinely nonlocal regime in which \(s\in \left( 0,\frac{1}{2}\right) \). Under the limit assumptions

$$\begin{aligned} \lim _{x_n\rightarrow -\infty } u(x',x_n)=-1\quad { \text{ and } }\quad \lim _{x_n\rightarrow +\infty } u(x',x_n)=1, \end{aligned}$$

it has been recently shown in Dipierro et al. (Improvement of flatness for nonlocal phase transitions, 2016) that u is necessarily 1D, i.e. it depends only on one Euclidean variable. The goal of this paper is to obtain a similar result without assuming such limit conditions. This type of results can be seen as nonlocal counterparts of the celebrated conjecture formulated by De Giorgi (Proceedings of the international meeting on recent methods in nonlinear analysis (Rome, 1978), Pitagora, Bologna, pp 131–188, 1979).