Structure and Dynamics of Oligonucleotides in the Gas Phase

By combining ion‐mobility mass spectrometry experiments with sub‐millisecond classical and ab initio molecular dynamics we fully characterized, for the first time, the dynamic ensemble of a model nucleic acid in the gas phase under electrospray ionization conditions. The studied oligonucleotide unfolds upon vaporization, loses memory of the solution structure, and explores true gas‐phase conformational space. Contrary to our original expectations, the oligonucleotide shows very rich dynamics in three different timescales (multi‐picosecond, nanosecond, and sub‐millisecond). The shorter timescale dynamics has a quantum mechanical nature and leads to changes in the covalent structure, whereas the other two are of classical origin. Overall, this study suggests that a re‐evaluation on our view of the physics of nucleic acids upon vaporization is needed.     

Charge mapping in 3(10)-helical peptide chains by oxidation of the terminal ferrocenyl group

Two series of 3(10)-helical peptides of different lengths and rigidity, based on the strongly foldameric α-aminoisobutyric acid and containing a terminal ferrocenyl unit, have been synthesized. Oxidation-state sensitive spectroscopic tags of helical peptides, the N-H groups, allowed mapping of the charge delocalization triggered by oxidation of the terminal ferrocenyl moiety and were monitored by IR spectroelectrochemistry.     

Densely Functionalized 2-Methylideneazetidines: Evaluation as Antibacterials

Twenty-two novel, variously substituted nitroazetidines were designed as both sulfonamide and urethane vinylogs possibly endowed with antimicrobial activity. The compounds under study were obtained following a general procedure recently developed, starting from 4-nitropentadienoates deriving from a common β-nitrothiophenic precursor. While being devoid of any activity against fungi and Gram-negative bacteria, most of the title compounds performed as potent antibacterial agents on Gram-positive bacteria (E. faecalis and three strains of S. aureus), with the most potent congener being the 1-(4-chlorobenzyl)-3-nitro-4-(p-tolyl)azetidine 22, which displayed potency close to that of norfloxacin, the reference antibiotic (minimum inhibitory concentration values 4 and 1–2 μg/mL, respectively). Since 22 combines a relatively efficient activity against Gram-positive bacteria and a cytotoxicity on eucharyotic cells only at 4-times higher concentrations (inhibiting concentration on 50% of the cultured eukaryotic cells: 36 ± 10 μM, MIC: 8.6 μM), it may be considered as a promising hit compound for the development of a new series of antibacterials selectively active on Gram-positive pathogens. The relatively concise synthetic route described herein, based on widely available starting materials, could feed further structure–activity relationship studies, thus allowing for the fine investigation and optimization of the toxico-pharmacological profile.     

Groups with many normal or self-normalizing subgroups

In this paper groups in which the set Σ of the normal or self-normalizing subgroups is large will be studied. In particular it will be characterized locally graded groups satisfying the minimal condition on subgroups which do not belong to Σ and locally finite groups for which the set Σ is dense in the lattice of all subgroups.     

Computing spin networks

We expand a set of notions recently introduced providing the general setting for a universal representation of the quantum structure on which quantum information stands. The dynamical evolution process associated with generic quantum information manipulation is based on the (re)coupling theory of SU (2) angular momenta. Such scheme automatically incorporates all the essential features that make quantum information encoding much more efficient than classical: it is fully discrete; it deals with inherently entangled states, naturally endowed with a tensor product structure; it allows for generic encoding patterns. The model proposed can be thought of as the non-Boolean generalization of the quantum circuit model, with unitary gates expressed in terms of 3nj coefficients connecting inequivalent binary coupling schemes of n + 1 angular momentum variables, as well as Wigner rotations in the eigenspace of the total angular momentum. A crucial role is played by elementary j-gates (6j symbols) which satisfy algebraic identities that make the structure of the model similar to “state sum models” employed in discretizing topological quantum field theories and quantum gravity. The spin network simulator can thus be viewed also as a Combinatorial QFT model for computation. The semiclassical limit (large j) is discussed.     

Determination of amphetamines in human urine by liquid chromatography with fluorimetric detection using a solid-phase extraction procedure

A precise and feasible HPLC method has been developed for the analysis of amphetamine (AMPH), methamphetamine (MAMPH) and methylenedioxymethamphetamine (MDMA, ecstasy) in human urine. A chromatographic run on a C8 Genesis (150 mm x 4.6 mm, 5 microm) column maintained at 30 degrees C lasts about 17 min, using a mobile phase composed of ACN (12%) and a pH 2.5 phosphate buffer (88%) containing 0.3% triethylamine. Mirtazapine was used as the internal standard. Good linearity was found in the 100-2000 ng/mL concentration range for AMPH and MAMPH and in the 12-2000 ng/mL concentration range for MDMA. The pretreatment of urine samples was carried out by means of a careful SPE procedure on C2 cartridges. The extraction yields were very satisfactory for all analytes, with average values greater than 97%. The leading conditions allowed the determination of AMPH, MAMPH and MDMA with satisfactory precision and accuracy. The method has been successfully applied to the determination of the analytes in urine of AMPH users.     

Bose–Einstein condensation in satisfiability problems

This paper is concerned with the complex behavior arising in satisfiability problems. We present a new statistical physics-based characterization of the satisfiability problem. Specifically, we design an algorithm that is able to produce graphs starting from a k-SAT instance, in order to analyze them and show whether a Bose–Einstein condensation occurs. We observe that, analogously to complex networks, the networks of k-SAT instances follow Bose statistics and can undergo Bose–Einstein condensation. In particular, k-SAT instances move from a fit-get-rich network to a winner-takes-all network as the ratio of clauses to variables decreases, and the phase transition of k-SAT approximates the critical temperature for the Bose–Einstein condensation. Finally, we employ the fitness-based classification to enhance SAT solvers (e.g., ChainSAT) and obtain the consistently highest performing SAT solver for CNF formulas, and therefore a new class of efficient hardware and software verification tools.     

On the Numerical Solution to a Nonlinear Wave Equation Associated with the First Painlev′e Equation: an Operator-Splitting Approach

The main goal of this article is to discuss the numerical solution to a nonlinear wave equation associated with the first of the celebrated Painlevé transcendent ordinary differential equations. In order to solve numerically the above equation, whose solutions blow up in finite time, the authors advocate a numerical methodology based on the Strang’s symmetrized operator-splitting scheme. With this approach, one can decouple nonlinearity and differential operators, leading to the alternate solution at every time step of the equation as follows: (i) The first Painlevé ordinary differential equation, (ii) a linear wave equation with a constant coefficient. Assuming that the space dimension is two, the authors consider a fully discrete variant of the above scheme, where the space-time discretization of the linear wave equation sub-steps is achieved via a Galerkin/finite element space approximation combined with a second order accurate centered time discretization scheme. To handle the nonlinear sub-steps, a second order accurate centered explicit time discretization scheme with adaptively variable time step is used, in order to follow accurately the fast dynamic of the solution before it blows up. The results of numerical experiments are presented for different coefficients and boundary conditions. They show that the above methodology is robust and describes fairly accurately the evolution of a rather “violent” phenomenon.     

Unravelling the Phytochemical Composition and the Pharmacological Properties of an Optimized Extract from the Fruit from Prunus mahaleb L.: From Traditional Liqueur Market to the Pharmacy Shelf

Prunus mahaleb L. fruit has long been used in the production of traditional liqueurs. The fruit also displayed scavenging and reducing activity, in vitro. The present study focused on unravelling peripheral and central protective effects, antimicrobial but also anti-COVID-19 properties exerted by the water extract of P. mahaleb. Anti-inflammatory effects were studied in isolated mouse colons exposed to lipopolysaccharide. Neuroprotection, measured as a blunting effect on hydrogen-peroxide-induced dopamine turnover, was investigated in hypothalamic HypoE22 cells. Antimicrobial effects were tested against different Gram+ and Gram- bacterial strains. Whereas anti-COVID-19 activity was studied in lung adenocarcinoma H1299 cells, where the gene expression of ACE2 and TMPRSS2 was measured after extract treatment. The bacteriostatic effects induced on Gram+ and Gram- strains, together with the inhibition of COX-2, TNFα, HIF1α, and VEGFA in the colon, suggest the potential of P. mahaleb water extract in contrasting the clinical symptoms related to ulcerative colitis. The inhibition of the hydrogen peroxide-induced DOPAC/DA ratio indicates promising neuroprotective effects. Finally, the downregulation of the gene expression of ACE2 and TMPRSS2 in H1299 cells, suggests the potential to inhibit SARS-CoV-2 virus entry in the human host. Overall, the results support the valorization of the local cultivation of P. mahaleb.