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Image analysis technique has been proved to be very effective in the quantification of particles size and morphology distributions in different work areas. In the present work this technique was combined with the discriminant factorial analysis (DFA) in order to allow the automatic identification of single bubbles (isolated bubbles without influence of surrounded bubbles) in multiphase systems. With the previous methodology it has been possible to distinguish online and automatically among three different classes of bubbles (single bubbles and medium complexity and large complexity bubbles groups), allowing for the first time the computation of the local bubble population complexity in the system. The automatic and correct characterization of the single bubbles allowed the correct determination of bubble size and, consequently, the specific interfacial area a at different experimental conditions. Agreement between automated and manual classification, measured in terms of a performance index, is 98% for single bubbles identification. Further, the present work describes the application of such methodology to the study of temperature, type of gas sparger, and liquid phase properties (viscosity and surface tension) influence on the individual components of volumetric liquid side mass transfer coefficient, k L a. The results show that the different experimental parameters and liquid properties act by a particular way on k L and a.

Supramolecular hydrogels rely on small molecules that self-assemble in water as a result of the cooperative effect of several relatively weak intermolecular interactions. Peptide-based low molecular weight hydrogelators have attracted enormous interest owing to the simplicity of small molecules combined with the versatility and biocompatibility of peptides. In this work, naproxen, a well known non-steroidal anti-inflammatory drug, was N-conjugated with various dehydrodipeptides to give aromatic peptide amphiphiles that resist proteolysis. Molecular dynamic simulations were used to obtain insight into the underlying molecular mechanism of self-assembly and to rationalize the design of this type of hydrogelators. The results obtained were in excellent agreement with the experimental observations. Only dehydrodipeptides having at least one aromatic amino acid gave hydrogels. The characterization of the hydrogels was carried out using transmission electron microscopy (TEM), circular dichroism (CD), fluorescence spectroscopy and also rheological assays. Results and discussion SynthesisFive new dehydrodipeptides N-protected with naproxen (Npx) were prepared from the corresponding methyl esters of N-tertbutoxycarbonyl-β-hydroxydipeptides. The strategy deployed involved a dehydration reaction followed by cleavage of the tert-butoxycarbonyl group (Boc), reaction with (S)-(+)naproxen chloride and alkaline hydrolysis of the methyl esters (Scheme 1). The dehydroamino acids used were dehydrophenylalanine (∆Phe) and dehydroaminobutyric acid (∆Abu). This synthetic methodology was chosen to avoid racemization issues concerning the naproxen moiety. The N,Cdiprotected dipeptides having a β-hydroxyamino acid (Scheme 1, 1a-e) were dehydrated in good to high yields by treatment with tert-butyldicarbonate (Boc 2 O) and 4dimethylaminopyridine (DMAP) followed by N,N,N',N'tetramethylguanidine (TMG) 17 (Scheme 1, 2a-e). The Boc group was removed with trifluoroacetic acid (TFA) (Scheme 1, 3a-e) and the N-deprotected dehydrodipeptides were conjugated with (S)-(+)-naproxen (Scheme 1, 4a-e). Finally, the methyl esters were removed by treatment with a solution of NaOH (1 M) affording compounds 5a-e in good yields (Scheme 1).

Mammalian protein kinase C (PKC) isoforms have been subject of particular attention because of their ability to modulate apoptotic proteins. However, the roles played by each PKC isoform in apoptosis are still unclear. Here, expression of individual mammalian PKC isoforms in Saccharomyces cerevisiae is used as a new approach to study the role of each isoform in apoptosis. The four isoforms tested, excepting PKC-δ, stimulate S. cerevisiae acetic-acid-induced apoptosis essentially through a mitochondrial ROS-dependent pathway. However, their co-expression with Bcl-xL reveals a PKC-isoform-dependent modulation of Bcl-xL anti-apoptotic activity. A yeast pathway homologue to the mammalian SAPK/JNK is responsible for acetic-acid-induced Bcl-xL phosphorylation that is differently modulated by PKC isoforms. The data obtained suggest conservation of an ancient mechanism of apoptosis regulation in yeast and mammals and offer new insights into mammalian apoptosis modulation by PKC isoforms.

We have developed a modification of our previously reported high-yielding method for the synthesis of N,N-diacyldehydroamino acid derivatives to prepare N-monoprotected dehydroamino acids and dehydrodipeptides. Thus, several dehydroalanine, dehydroaminobutyric acid and dehydrophenylalanine derivatives have been prepared by treating the corresponding L-serine, L-threonine and D,L-3-phenylserine (threo-type) derivatives with 1 equiv. of di-tert-butyl dicarbonate and 4-(dimethylamino)pyridine. The reaction proceeded with the initial formation of an O-tert-butyl carbonate which, by treament with N,N,NЈ,NЈ-tetramethylguanidine, underwent β elimination to give the corresponding dehydroamino acid derivative. This two-step method can be carried out as a one-pot procedure and is stereoselective, giving only the Z isomer. The N-monoprotected dehydroamino acids were treated with N-bromosuccinimide and thereafter

We have proposed recently that the DO3A-N-α-(amino)propionate chelator and its amide conjugates are leads to targeted, high relaxivity, safe contrast agents for magnetic resonance imaging. In this work we illustrate further the expeditious nature and robustness of the synthetic methodologies developed by preparing the DO3A-N-(α-pyrenebutanamido)propionate chelator. Its Gd(3+) chelate retains the optimized water exchange, high stability and inertness of the parent complex. The pyrene moiety imparts concentration-dependent self-assembly properties and aggregation-sensitive fluorescence emission to the Gd(3+) complex. The Gd(3+) complex displays pyrene-centred fluorescence whilst the Yb(3+) and Nd(3+) complexes exhibit sensitized lanthanide-centred near-infrared luminescence. The aggregated form of the complex displays high relaxivity (32 mM(-1) s(-1), 20 MHz, 25 °C) thanks to simultaneous optimization of the rotational correlation time and of the water exchange rate. The relaxivity is however still limited by chelate flexibility. This report demonstrates that the DO3A-N-(α-amino)propionate chelator is a valuable platform for constructing high relaxivity CA using simple design principles and robust chemistries accessible to most chemistry labs.

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