Tunable Thermoresponsive Pyrrolidone‐Based Polymers from Pyroglutamic Acid,a Bio‐Derived Resource

A series of pyrrolidone‐based polymers is prepared from pyroglutamic acid, a bio‐derived resource. Polymers bearing simple alkoxy substituents (e.g., methoxy, ethoxy, and butoxy) are soluble in common organic solvents and possess glass transition temperatures that are dependent on the length of the alkoxy residue. Replacing these substituents with an ether moiety (CH₃OCH₂CH₂O—) affords a highly sensitive and reversible thermoresponsive polymer with a lower critical solution temperature (LCST) of 42 °C in water. Copolymers composed of repeat units bearing both the ether and simple alkoxy residues are found to exhibit LCSTs that are highly dependent on the nature of the hydrophobic alkoxy residue suggesting that the LCSTs of these polymers can be successfully tuned by simply tailoring the copolymer structure.     

Energetic proton emission in heavy ion collisions at intermediate energy: Pre-equilibrium and cooperative effects

Energetic proton emission has been investigated as a function of the centrality in the reaction ⁵⁸Ni + ⁵⁸Ni at 30 AMeV. Protons with energy extending up to a relevant fraction of the total available energy in the reaction were measured and studied. The dependence on the reaction centrality has been extensively investigated and data have been compared with the results of microscopic transport calculations. The more striking observation concerns the extremely energetic proton (E^NN _P ≥ 130 MeV) multiplicity which is found to increase almost quadratically with the number of participant nucleons thus indicating the onset of a mechanism beyond one and two-body dynamics.     

ortho‐C−H Arylation of Benzoic Acids with Aryl Bromides and Chlorides Catalyzed by Ruthenium

A system consisting of catalytic amounts of [(p‐cym)RuCl₂]₂/PEt₃?HBF₄, K₂CO₃ as the base, and NMP as the solvent efficiently mediates the ortho‐C?H arylation of benzoic acids with aryl bromides at 100 °C. Replacing the phosphine ligand with the amino acid dl ‐pipecolinic acid enables the analogous transformation with aryl chlorides. The key advantage of this broadly applicable transformation is the use of an inexpensive ruthenium catalyst in combination with simple carboxylates as directing groups, which can either be tracelessly removed or used as anchor points for decarboxylative ipso substitutions.     

On plastic dynamic flexure of plates

Summary This paper discusses the rigid-plastic flexure of plates subjected to dynamic loading. A piecewise linear yield surface and small displacements are assumed. The plate is discretized by assuming the constant moment mixed triangular element of Herrmann. Under the above assumptions the dynamic loading of plates is turned into a problem in linear inequalities which is a priori discretized in time. An approximate technique is developed, which takes into account the influence of the strain-hardening and the strain rate sensitivity of material. Some numerical examples of plates subjected to a given velocity distribution confirm the efficiency of this approach.

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Sommario Si analizza il problema della flessione rigidoplastica di una lastra soggetta a carichi dinamici. La lastra viene discretizzata assumendo l'elemento triangolare misto a stato di sollecitazione costante di Herrmann. Tale assunzione insieme alle ipotesi di piccoli spostamenti e di superficie di plasticizzazione lineare a tratti, consente di ricondurre il caricamento dinamico della lastra ad un problema retto da diseguaglianze lineari, che risulta discretizzato a priori nel tempo. Attraverso una tecnica approssimata si valuta l'influenza che hanno sulla risposta dinamica della struttura, l'incrudimento e la sensibilità alle velocità di deformazione del materiale. L'efficienza del procedimento è verificata attraverso alcuni esempi numerici di lastre di diversa geometria sottoposte ad una prefissata distribuzione di velocità.

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Research supported by the National Research Council (C.N.R.P.A.d.I.S.) of Italy.     

New 4-Aminoproline-Based Small Molecule Cyclopeptidomimetics as Potential Modulators of α4β1 Integrin

Integrin α₄β₁ belongs to the leukocyte integrin family and represents a therapeutic target of relevant interest given its primary role in mediating inflammation, autoimmune pathologies and cancer-related diseases. The focus of the present work is the design, synthesis and characterization of new peptidomimetic compounds that are potentially able to recognize α₄β₁ integrin and interfere with its function. To this aim, a collection of seven new cyclic peptidomimetics possessing both a 4-aminoproline (Amp) core scaffold grafted onto key α₄β₁-recognizing sequences and the (2-methylphenyl)ureido-phenylacetyl (MPUPA) appendage, was designed, with the support of molecular modeling studies. The new compounds were synthesized through SPPS procedures followed by in-solution cyclization maneuvers. The biological evaluation of the new cyclic ligands in cell adhesion assays on Jurkat cells revealed promising submicromolar agonist activity in one compound, namely, the c[Amp(MPUPA)Val-Asp-Leu] cyclopeptide. Further investigations will be necessary to complete the characterization of this class of compounds.     

Symmetry-Induced Emergence of a Pseudo-Qutrit in the Dipolar Coupling of Two Qubits

We investigate a system of two identical and distinguishable spins 1/2, with a direct magnetic dipole–dipole interaction, in an external magnetic field. Constraining the hyperfine tensor to exhibit axial symmetry generates the notable symmetry properties of the corresponding Hamiltonian model. In fact, we show that the reduction of the anisotropy induces the invariance of the Hamiltonian in the 3×3 subspace of the Hilbert space of the two spins in which S^2 invariably assumes its highest eigenvalue of 2. By means of appropriate mapping, it is then possible to choose initial density matrices of the two-spin system that evolve in such a way as to exactly simulate the time evolution of a pseudo-qutrit, in the sense that the the actual two-spin system nests the subdynamics of a qutrit regardless of the strength of the magnetic field. The occurrence of this dynamic similitude is investigated using two types of representation for the initial density matrix of the two spins. We show that the qutrit state emerges when the initial polarizations and probability vectors of the two spins are equal to each other. Further restrictions on the components of the probability vectors are reported and discussed.     

Negative Modulation of the Angiogenic Cascade Induced by Allosteric Kinesin Eg5 Inhibitors in a Gastric Adenocarcinoma In Vitro Model

Eg5 is a kinesin essential in bipolar spindle formation, overexpressed in tumours, thus representing a new target in cancer therapy. We aimed at evaluating the anti-cancer activity of Eg5 thiadiazoline inhibitors 2 and 41 on gastric adenocarcinoma cells (AGS), focusing on the modulation of angiogenic signalling. Docking studies confirmed a similar interaction with Eg5 to that of the parent compound K858. Thiadiazolines were also tested in combination with Hesperidin (HSD). Cell cycle analysis reveals a reduction of G1 and S phase percentages when 41 is administered as well as HSD in combination with K858. Western blot reveals Eg5 inhibitors capability to reduce PI3K, p-AKT/Akt and p-Erk/Erk expressions; p-Akt/Akt ratio is even more decreased in HSD+2 sample than the p-Erk/Erk ratio in HSD+41 or K858. VEGF expression is reduced when HSD+2 and HSD+41 are administered with respect to compounds alone, after 72 h. ANGPT2 gene expression increases in cells treated with 41 and HSD+2 compared to K858. The wound-healing assay highlights a reduction in the cut in HSD+2 sample compared to 2 and HSD. Thus, Eg5 inhibitors appear to modulate angiogenic signalling by controlling VEGF activity even better if combined with HSD. Overall, Eg5 inhibitors can represent a promising starting point to develop innovative anti-cancer strategies.