A 2-D systems approach to river pollution modelling

The paper presents some applications of 2-D systems theory to the problem of modeling the river pollution processes and the associated selfpurification phenomena. The dynamical evolution of the biological oxygen demand (BOD) and the dissolved oxygen (DO) in a one-dimensional river model is discussed under various physical assumptions.     

Derivatives of benzimidazol-2-ylquinoline and benzimidazol-2-ylisoquinoline as selective A1 adenosine receptor antagonists with stimulant activity on human colon motility

A number of quinolines and isoquinolines connected in various ways to a substituted benzimidazol-2-yl system were synthesized and evaluated as novel antagonists of adenosine receptors (ARs) by competition experiments using human A(1), A(2A), and A(3) ARs. The new compounds were designed based on derivatives of 2-(benzimidazol-2-yl)quinoxaline, previously reported as potent and selective antagonists of A(1) and A(3) ARs. Among these, 3-[4-(ethylthio)-1H-benzimidazol-2-yl]isoquinoline 4b exhibited the best combination of potency toward the A(1) AR (K(i) =1.4 nM) and selectivity against the A(2A) (K(i) >10 μM), A(2B) (K(i)>10 μM), and A(3) ARs (K(i)>1 μM). Functional experiments in circular smooth muscle preparations of isolated human colon showed that 4b behaves as a potent and selective antagonist of the A(1) AR in the neuromuscular compartment of this intestinal region. Biological and pharmacological data suggest that 4b is a suitable starting point for the development of novel agents endowed with stimulant properties on colonic activity.     

Revisiting with updated hardware an old spectroscopic technique: circularly polarized luminescence

Among the various chiroptical spectroscopic techniques available today, circularly polarized luminescence (CPL) plays a minor role and is still used by a limited number of specialists. The cost of the few commercial instruments available and the complexity of homemade apparatuses have strongly limited the widespread application of this technique. New technological approaches, such as the use of light-emitting diode (LED) sources, may significantly simplify the required instrumentation and encourage new potential users. Calibration procedure and the quantitative determination of CPL and total luminescence intensity as well as the corresponding g ratio are described.     

Vibrational Non-Equilibrium at Catalytic Surfaces

Inclusion in a surface reaction scheme of fast V-V up-pumping processes, bound to the anharmonicity of the vibrational levels of mobile surface species, can lead to quasi-steady states characterized by non-equilibrium Treanor vibrational distribution functions, with > 0 levels over-populated with respect to Boltzmann equilibrium. Non-equilibrium distributions are shown to depend on the intensity of the chemisorption processes active under the working conditions of the catalyst. The shape of these distributions determines the surface reaction rate, and reactions with widely different true activation energies can proceed at comparable speeds at finite surface temperatures. This provides an interpretation of the isokinetic relationship in heterogeneous catalysis based on a non-Boltzmann picture of the catalytic surface.     

6-Substituted pyrrolo[3,4-c]pyrazoles: an improved class of CDK2 inhibitors

We have recently reported a new class of CDK2/cyclin A inhibitors based on a bicyclic tetrahydropyrrolo[3,4-c]pyrazole scaffold. The introduction of small alkyl or cycloalkyl groups in position 6 of this scaffold allowed variation at the other two diversity points. Conventional and polymer-assisted solution phase chemistry provided a way of generating compounds with improved biochemical and cellular activity. Optimization of the physical properties and pharmacokinetic profile led to a compound which exhibited good efficacy in vivo on A2780 human ovarian carcinoma.     

Diffusion of PAH in potato and carrot slices and application for a potato model

A method for quantifying the effect of medium composition on the diffusive mass transfer of hydrophobic organic chemicals through thin layers was applied to plant tissue. The method employs two silicone disks, one serving as source and one as sink for a series of PAHs diffusing through thin layers of water, potato tissue, and carrot tissue. Naphthalene, phenanthrene, anthracene, and fluoranthene served as model substances. Their transfer from source to sink disk was measured by HPLC to determine a velocity rate constant proportional to the diffusive conductivity. The diffusive flux through the plant tissue was modeled using Fick's first law of diffusion. Both the experimental results and the model suggest that mass transfer through plant tissue occurs predominantly through pore water and that, therefore, the mass transfer ratio between plant tissue and water is independent of the hydrophobicity of the chemical. The findings of this study provide a convenient method to estimate the diffusion of nonvolatile organic chemicals through various plant materials. The application to a radial diffusion model suggests that "growth dilution" rendersthe concentration of highly hydrophobic chemicals in potatoes below their equilibrium partitioning level. This is in agreement with field results for the bioconcentration of PAHs in potatoes.     

Identification of Structural Features of 2‐Alkylidene‐1,3‐Dicarbonyl Derivatives that Induce Inhibition and/or Activation of Histone Acetyltransferases KAT3B/p300 and KAT2B/PCAF

Dysregulation of the activity of lysine acetyltransferases (KATs) is related to a variety of diseases and/or pathological cellular states; however, their role remains unclear. Therefore, the development of selective modulators of these enzymes is of paramount importance, because these molecules could be invaluable tools for assessing the importance of KATs in several pathologies. We recently found that diethyl pentadecylidenemalonate (SPV106) possesses a previously unobserved inhibitor/activator activity profile against protein acetyltransferases. Herein, we report that manipulation of the carbonyl functions of a series of analogues of SPV106 yielded different activity profiles against KAT2B and KAT3B (pure KAT2B activator, pan‐inhibitor, or mixed KAT2B activator/KAT3B inhibitor). Among the novel compounds, a few derivatives may be useful chemical tools for studying the mechanism of lysine acetylation and its implications in physiological and/or pathological processes.     

Opposite Modulation of Cell Migration by Distinct Subregions of Urokinase Connecting Peptide

Functional analysis of isolated protein domains may uncover cryptic activities otherwise missed. The serine protease urokinase (uPA) has a clear‐cut motogen activity that is catalytically independent and resides in its amino‐terminal growth factor domain (GFD, residues 1‐49) and connecting peptide region (CP, residues 132–158). To functionally dissect the CP region, we analysed the biological activity of two synthetic peptides corresponding to the N‐terminal [uPA‐(135–143), residues 135–143] and C‐terminal [uPA‐(144–158), residues 144–158] CP subregions. Most of the chemotactic activity of connecting peptide‐derived peptide (CPp, [uPA‐(135–158)]) for embryonic kidney HEK293/uPAR‐25 cells is retained by uPA‐(144–158) at nanomolar concentrations. In contrast, uPA‐(135–143) inhibits basal, CPp ‐, vitronectin‐ and fibronectin‐induced cell migration. Radioreceptor binding assays on intact HEK293 cells revealed that uPA‐(135–143) and uPA‐(144–158) are both able to compete with [¹²⁵I]‐CPp, albeit with different binding affinities. The consequences of phospho‐mimicking, S138E substitution, were studied using [138E]uPA‐(135–158) and [138E]uPA‐(135–143) peptides. Unlike CPp, [138E]uPA‐(135–158) and [138E]uPA‐(135–143) exhibit remarkable inhibitory properties. Finally, analysis of the conformational preferences of the peptides allowed to identify secondary structure elements exclusively characterising the stimulatory CPp and uPA‐(144–158) versus the inhibitory uPA‐(135–143), [138E]uPA‐(135–158) and [138E]uPA‐(135–143) peptides. In conclusion, these data shed light on the cryptic activities of uPA connecting peptide, revealing the occurrence of two adjacent regions, both competing for binding to cell surface but conveying opposite signalling on cell migration.