Links between directional derivatives through multidirectional mean value inequalities

We prove in the general setting of lower semicontinuous functions on Banach spaces the relation between the Rockafellar directional derivative and the mixed lower limit of the lower Dini derivatives. As a byproduct we derive the famous inclusions of tangent cones of closed sets in Banach spaces. The results are established using as principal tool multidirectional mean value inequalities [Aussel et al., SIAM J Optim 9(3), 690–706 (1999)].     

Evidence of a monoclinic-like amorphous phase in composites of LDPE with spherical, fibrous and laminar nanofillers as studied by infrared spectroscopy

Well-dispersed nanocomposites of LDPE with spherical silica and laminar and fibrous silicates have been prepared by melt compounding with nanofiller compositions ranging from 50 to 5 wt%. Spatial dispersion and size domains of the aggregates in the composites series have been evaluated by electron microscopies (SEM and TEM). The methylene rocking (700-740 cm⁻¹) and bending (1400-1480 cm⁻¹) modes of LDPE in these composites were studied by FTIR spectroscopy. When the nanofiller is present in a 40 or 50 wt%, the amorphous phase of polyethylene adopts a monoclinic arrangement. This arrangement is due to the confinement induced by the nanofillers on the polymer matrix. When the fibrous silicate or the spherical silica are used as nanofillers, a dilution of the concentrated composite or annealing bring about a relaxing of the amorphous structure of the polymer, and the monoclinic-like conformations disappear. When the nanofiller is a laminar silicate, dilution or annealing only partly eliminate the monoclinic-like structure, which remains in all cases an important fraction of the polymeric matrix.     

Theoretical study of CO and H2O interaction on (110) and (101) Zirconia surfaces

Theoretical calculations of CO and H₂O adsorption on (110) and (101) tetragonal Zirconia surfaces were carried out using ONIOM2 methodology. The calculations showed that the adsorption processes are exothermic reactions with energy values of −28.4 kcal/mol for H₂O on the (110) surface, −51.0 kcal/mol for H₂O on the (101) surface, −21.7 kcal/mol for CO on (110) surface and −23.4 kcal/mol for CO on (101) surface. Analysis of the results suggest that different kinds of basic sites can be found on the (110) and (101) surfaces. In both (110) and (101) surfaces, CO adsorption is on bridged (bonded to two Zr atoms on the (110) surface, bonded to one Zr and O atoms on the (101) surface). The calculations showed that ONIOM can be a powerful tool to study structural and thermodynamics properties of solid surfaces.     

Development and NMR validation of minimal pharmacophore hypotheses for the generation of fragment libraries enriched in heparanase inhibitors

A combined strategy based on the development of pharmacophore hypotheses and NMR approaches is reported for the identification of novel inhibitors of heparanase, a key enzyme involved in tumor metastasis through the remodeling of the subepithelial and subendothelial basement membranes, resulting in the dissemination of metastatic cancer cells. Several pharmacophore hypotheses were initially developed from the most active heparanase inhibitors known to date and, after their application to a pool of 27 known heparanase inhibitors and a database of 1,120 compounds approved by the FDA, a four-point pharmacophore model was selected as the most predictive. This model was subsequently applied to a database of 686 chemical fragments, and a subset of 100 fragments accomplishing completely or partially the four-point model was selected to perform nuclear magnetic resonance experiments to validate the hypothesis. The experimental studies confirmed the reliability of our pharmacophore model, its applicability to in silico databases in order to reduce the number of compounds to be experimentally screened, and the possibility of generating fragment libraries enriched in heparanase inhibitors. Rafael Gozalbes and Silvia Mosulén contributed equally to this work.     

Oxyma: An Efficient Additive for Peptide Synthesis to Replace the Benzotriazole‐Based HOBt and HOAt with a Lower Risk of Explosion[1]

Oxyma [ethyl 2‐cyano‐2‐(hydroxyimino)acetate] has been tested as an additive for use in the carbodiimide approach for formation of peptide bonds. Its performance in relation to those of HOBt and HOAt, which have recently been reported to exhibit explosive properties, is reported. Oxyma displayed a remarkable capacity to inhibit racemization, together with impressive coupling efficiency in both automated and manual synthesis, superior to those of HOBt and at least comparable to those of HOAt, and surpassing the latter coupling agent in the more demanding peptide models. Stability assays showed that there was no risk of capping the resin under standard coupling conditions. Finally, calorimetry assays (DSC and ARC) showed decomposition profiles for benzotriazole‐based additives that were consistent with their reported explosivities and suggested a lower risk of explosion in the case of Oxyma.     

Single‐Step Electrospinning of Bimodal Fiber Meshes for Ease of Cellular Infiltration

Bimodal fiber meshes with fiber diameters differing by one order of magnitude, are electrospun in a simple one‐step process, using a standard single syringe electrospin setup. The nano‐ and microfiber meshes combine the benefits of nanofibers (cell adhesion, proliferation) with those of microfibers (open structure, large pore size) and are therefore interesting as scaffolds for cellular infiltration.

     

Multiple Andreev reflections in diffusive SNS structures

We report new measurements on subgap energy structures originating from multiple Andreev reflections in mesoscopic SNS junctions. The junctions were fabricated in a planar geometry with high-transparency superconducting contacts of Al deposited on highly diffusive and surface δ -dopedn ^{+ +} -GaAs. For samples with a normal GaAs region of active length 0.3μ m, the Josephson effect with a maximal supercurrent I_c = 3μ A at T = 237 mK was observed. The subgap structure was observed as a series of local minima in the differential resistance at dc bias voltages V = ± 2Δ / (ne) with n = 1, 2, 4, i.e. only the even subgap positions. While at V = ± 2Δ / e(n = 1) only one dip is observed, then = 2 and the n = 4 subgap structures each consists of two separate dips in the differential resistance. The mutual spacing of these two dips is independent of temperature, and the mutual spacing of the n = 4 dips is half the spacing of the n = 2 dips. The voltage bias positions of the subgap differential resistance minima coincide with the maxima in the oscillation amplitude when a magnetic field is applied in an interferometer configuration, where one of the superconducting electrodes has been replaced by a flux-sensitive open loop.     

The feasibility of using dielectrophoresis for isolation of glioblastoma subpopulations with increased stemness

Cancer stem cells (CSCs) are aggressive subpopulations with increased stem‐like properties. CSCs are usually resistant to most standard therapies and are responsible for tumor repropagation. Similar to normal stem cells, isolation of CSCs is challenging due to the lack of reliable markers. Antigen‐based sorting of CSCs usually requires staining with multiple markers, making the experiments complicated, expensive, and sometimes unreliable. Here, we study the feasibility of using dielectrophoresis (DEP) for isolation of glioblastoma cells with increased stemness. We culture a glioblastoma cell line in the form of neurospheres as an in vitro model for glioblastoma stem cells. We demonstrate that spheroid forming cells have higher expression of stem cell marker, nestin. Next, we show that dielectric properties of neurospheres change as a result of changing culture conditions. Our results indicate that spheroid forming cells need higher voltages to experience the same DEP force magnitude compared to normal monolayer cultures of glioblastoma cell line. This study confirms the possibility of using DEP to isolate glioblastoma stem cells.     

Organocatalytic asymmetric vinylogous 1,4-addition of α,α-Dicyanoolefins to chalcones under a bio-based reaction media: Discovery of new Michael adducts with antiplasmodial activity

The organocatalysed asymmetric vinylogous Michael addition of α,α-dicyanoolefins to α,β-unsaturated aldehydes and ketones have been reported in the last decade, however, chalcones have been poorly explored. Moreover, a considerable part of the publications in this theme still employs undesirable solvents, such as toluene and THF, with concerns related to health and environmental safety. We report herein the use of a bifunctional catalyst derived from a Cinchona alkaloid to perform the enantio- and diastereoselective Michael addition of α,α-dicyanoolefins to chalcones using 2-MeTHF as solvent. The Michael adducts were obtained in moderate to good yields and were evaluated for their antiplasmodial and cytotoxic activity.     

Proof‐of‐Concept Studies Directed toward the Formation of Metallic Ag Nanostructures from Ag3PO4 Induced by Electron Beam and Femtosecond Laser

In this work, for the first time, the instantaneous nucleation and growth processes of Ag nanoparticles on Ag₃PO₄ mediated by femtosecond laser pulses are reported and analyzed. The investigated samples are pure Ag₃PO₄ sample, electron‐irradiated Ag₃PO₄ sample, and laser‐irradiated sample. Complete characterization of the samples is performed using X‐ray diffraction (XRD), Rietveld refinements, field emission scanning electron microscopy, and energy dispersive spectroscopy (EDS). XRD confirms that the irradiated surface layer remains crystalline, and according to EDS analysis, the surface particles are composed primarily of Ag nanoparticles. This method not only offers a one‐step route to synthesize Ag nanoparticles using laser‐assisted irradiation with particle size control, but also reports a complex process involving the formation and subsequent growth of Ag nanoparticles through an unexpected additive‐free in situ fabrication process.