Efficient organic monoliths prepared by γ-radiation induced polymerization in the evaluation of histone deacetylase inhibitors by capillary(nano)-high performance liquid chromatography and ion trap mass spectrometry

New monolithic HPLC columns were prepared by γ-radiation-triggered polymerization of hexyl methacrylate and ethylene glycol dimethacrylate monomers in the presence of porogenic solvents. Polymerization was carried out directly within capillary (250-200 μm I.D.) and nano (100-75 μm I.D.) fused-silica tubes yielding highly efficient columns for cap(nano)-LC applications. The columns were applied in the complete separation of core (H2A, H2B, H3, and H4) and linker (H1) histones under gradient elution with UV and/or electrospray ionization (ESI) ion trap mass spectrometry (MS) detections. Large selectivity towards H1, H2A-1, H2A-2, H2B, H3-1, H3-2 and H4 histones and complete separation were obtained within 8 min time windows, using fast gradients and very high linear flow velocities, up to 11 mm/s for high throughput applications. The method developed was the basis of a simple and efficient protocol for the evaluation of post-translational modifications (PTMs) of histones from NCI-H460 human non-small-cell lung cancer (NSCLC) and HCT-116 human colorectal carcinoma cells. The study was extended to monitoring the level of histone acetylation after inhibition of Histone DeACetylase (HDAC) enzymes with suberoylanilide hydroxamic acid (SAHA), the first HDAC inhibitor approved by the FDA for cancer therapy. Attractive features of our cap(nano)-LC/MS approach are the short analysis time, the minute amount of sample required to complete the whole procedure and the stability of the polymethacrylate-based columns. A lab-made software package ClustMass was ad hoc developed and used to elaborate deconvoluted mass spectral data (aligning, averaging, clustering) and calculate the potency of HDAC inhibitors, expressed through a Relative half maximal Inhibitory Concentration parameter, namely R_IC(50) and an averaged acetylation degree.     

Experimental evidence of bifurcating nonlinear normal modes in piecewise linear systems

A system with piecewise linear restoring forces, typical of damaged beams with a breathing crack, exhibits bifurcations characterized by the onset of superabundant modes in internal resonance with a significantly different shape than that of modes on a fundamental branch. A 2-DOF frame with piecewise linear stiffness is analyzed by means of an experimental investigation; the frame is forced by an harmonic base excitation and the operative modal shapes as well as the response amplitude are directly measured; the results are compared with numerical outcomes for different damping values. This study shows that the shapes and the frequencies of certain nonlinear normal modes (NNMs) of the related autonomous system strongly affect the forced response, in both the numerical and the experimental environments. Therefore, it is possible to match the NNM with the forced response of the system, leading to the prospect of identifying the severity and position of the damage from experimental tests.     

Practical synthesis of novel purine analogues as Hsp90 inhibitors

The development of a straightforward synthesis of 4-amino-6-benzyl-6H-pyrrolo[3,4-d]pyrimidine and 7-amino-2-benzyl-2H-pyrazolo[4,3-d]pyrimidine derivatives allowed for the preparation of a small family of potential Hsp90 inhibitors. Some of the newly synthesized compounds showed Hsp90 inhibitory activity in preliminary biological assays.     

Sul primo principio della termodinamica per I materiali semplici

It is known that the correct formulation of rational thermodynamics for mixtures requires an inequality more general than the Clausius-Duhem principle. On the other hand, in a recent paper on the thermodynamics of “interstitial working”[2] it was pointed out the need to correct the classical balance law of internal energy. There is no good reason for modifying both, however. It is worth to derive, hence, the most general expression of the Second Law by keeping the First in its classical form, as shown in a previous paper [4], or, what is the object of this article, to look for the most general formulation of the First Law assuming the Clausius-Duhem inequality as the Second. As a consequence of results obtained here, the statement of the First Principle needs not to be changed in the class of “simple material”. Thus, it is worth noting that a generalized expression of the First Law applies only non-simple materials, like as Korteweg fluids.

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Lavoro eseguito nell'ambito delle attività del G.N.F.M. del C.N.R. e dei progetti di ricerca ministeriali 40% e 60%.     

Scalar quantum electrodynamics on lattice correlation inequalities and infinite volume limit

We consider Wilson's lattice approximation to scalar Quantum Electrodynamics. We establish correlation inequalities of Griffiths-Kelly-Sherman type and a rigorous transfer matrix formalism, from which existence and non triviality of the infinite volume limit follow.     

Use of high-efficiency packed columns for gas-solid chromatography : V. Micropacked columns

Micropacked columns are constructed using graphitized carbon black as a support for gas-liquid-solid chromatography. Their effectiveness is evaluated in terms of Van Deemter plots, flow-rates, inlet pressure and column capacity. It is shown that such columns, by choosing an appropriate liquid phase, can be used for a wide range of temperatures and types of compound. Analytical applications connected with the analysis of complex organic mixtures in water are discussed. The problems of the analysis of air pollutants are also considered.     

Scalar Quantum Electrodynamics on the lattice as classical statistical mechanics

Wilson's lattice approximation allows us to apply classical statistical mechanics ideas to the study of Scalar Quantum Electrodynamics. Our main tools are Griffiths-Kelly-Sherman inequalities, the transfer matrix formalism and exponential bounds. Our main result is the existence of the infinite volume limit for every value of the coupling parameters.