Chemical Antibody Mimics Inhibit Cadherin-Mediated Cell–Cell Adhesion: A Promising Strategy for Cancer Therapy

One of the most promising strategies to treat cancer is the use of therapeutic antibodies that disrupt cell–cell adhesion mediated by dysregulated cadherins. The principal site where cell–cell adhesion occurs encompasses Trp2 found at the N-terminal region of the protein. Herein, we employed the naturally exposed highly conserved peptide Asp1-Trp2-Val3-Ile4-Pro5-Pro6-Ile7, as epitope to prepare molecularly imprinted polymer nanoparticles (MIP-NPs) to recognize cadherins. Since MIP-NPs target the site responsible for adhesion, they were more potent than commercially available therapeutic antibodies for inhibiting cell–cell adhesion in cell aggregation assays, and for completely disrupting three-dimensional tumor spheroids as well as inhibiting invasion of HeLa cells. These biocompatible supramolecular anti-adhesives may potentially be used as immunotherapeutic or sensitizing agents to enhance antitumor effects of chemotherapy.     

Personalized Metabolic Profile by Synergic Use of NMR and HRMS

A new strategy that takes advantage of the synergism between NMR and UHPLC–HRMS yields accurate concentrations of a high number of compounds in biofluids to delineate a personalized metabolic profile (SYNHMET). Metabolite identification and quantification by this method result in a higher accuracy compared to the use of the two techniques separately, even in urine, one of the most challenging biofluids to characterize due to its complexity and variability. We quantified a total of 165 metabolites in the urine of healthy subjects, patients with chronic cystitis, and patients with bladder cancer, with a minimum number of missing values. This result was achieved without the use of analytical standards and calibration curves. A patient’s personalized profile can be mapped out from the final dataset’s concentrations by comparing them with known normal ranges. This detailed picture has potential applications in clinical practice to monitor a patient’s health status and disease progression.     

Electroreduction of oxygen on octadecylmercaptan self-assembled monolayers

The reduction of oxygen has been studied on octadecylmercaptan self-assembled monolayers adsorbed on gold substrates in borate buffer solutions with a rotating disc electrode. A great inhibition of the oxygen reduction and other electrochemical reactions by these monolayers has been found. However, after polarisation at -0.80 V(SHE) the protecting properties of the film against electron transfer reactions are lost, and a behaviour similar to bare gold is observed. Ex situ XPS indicates that the thiol monolayer has not been desorbed to a large extent during oxygen reduction. Disorders of the monolayer structure and desorption of thiol molecules are proposed as the main reasons for the accessibility of electrochemical reactions to the surface.     

Adsorption of self-assembled monolayers of mercaptan on gold

XPS and AES are suitable techniques for studying organic monolayers on metals if radiation doses are kept low. The adsorption of self-assembled (SA) mercaptan monolayers on gold is a process in two stages. The adsorption to near completeness is very rapid. However, the process of orientation of the carbon chains, which is responsible for the blocking of electrochemical reactions takes much longer, as could be shown by ARXPS (angle resolved X-ray photo electron spectroscopy). Adsorption under potential control allows electrochemical experiments during the adsorption process as e.g. the measurement of the capacity of the electric double layer. Furthermore the control of the potential guarantees sure that the metal/liquid interface is well defined during the adsorption process.     

Chemical Antibody Mimics Inhibit Cadherin‐Mediated Cell–Cell Adhesion: A Promising Strategy for Cancer Therapy

One of the most promising strategies to treat cancer is the use of therapeutic antibodies that disrupt cell–cell adhesion mediated by dysregulated cadherins. The principal site where cell–cell adhesion occurs encompasses Trp2 found at the N‐terminal region of the protein. Herein, we employed the naturally exposed highly conserved peptide Asp1‐Trp2‐Val3‐Ile4‐Pro5‐Pro6‐Ile7, as epitope to prepare molecularly imprinted polymer nanoparticles (MIP‐NPs) to recognize cadherins. Since MIP‐NPs target the site responsible for adhesion, they were more potent than commercially available therapeutic antibodies for inhibiting cell–cell adhesion in cell aggregation assays, and for completely disrupting three‐dimensional tumor spheroids as well as inhibiting invasion of HeLa cells. These biocompatible supramolecular anti‐adhesives may potentially be used as immunotherapeutic or sensitizing agents to enhance antitumor effects of chemotherapy.     

Increase in productivity by networking mass spectrometer data systems

Three personal computers (PCs) are linked in an ethernet network using D-Link LenSmart protocol. Resource sharing and data transfer at very high speed between two different gas chromatography/mass spectrometry (GC/MS) data systems are obtained.     

Analytical investigations about the presence of prednisolone in cow urine

Since 2008, the analyses carried out in the Lombardia region as part of National Residue Control Plans have evidenced unexpected frequent detection of the corticosteroid prednisolone (PRED) in cow urine samples taken to the slaughterhouse. Considering the scarce plausibility of these high frequent findings, analytical investigations were started to ascertain the real presence of this corticosteroid. The applied confirmatory method involved liquid-chromatography low-resolution tandem mass spectrometry (triple quadrupole) as instrumental technique, and it was validated in compliance with the requirements of the Commission Decision 2002/657/EC. However, recently some criticism regarding Commission Decision 2002/657/EC identification criteria has been pointed out, experimentally demonstrating false positive results (wrong identification) although these criteria have been strictly observed. Therefore, considering the serious implications (i.e. the possibility that PRED could be considered endogenous in particular animal conditions), studies were carried out to investigate the reliability of PRED identification through the change of the chromatographic conditions (mobile phases, gradient and analytical column) of the confirmatory procedure routinely applied. Further confirmation came from the application of high-resolution mass spectrometry technique (MS(2) and MS(3) experiments) to analyze incurred cow urines samples. All the obtained results confirmed definitively the real presence of this corticosteroid excluding false-positive findings in routine analysis. In addition, other experiments demonstrated that high-resolution mass spectrometers (Time of Flight and Orbitrap technologies) could be successfully applied to routine determination of steroid residues in biological fluids at very low concentrations (< 1?μg?L(-1) ). Copyright ? 2012 John Wiley & Sons, Ltd.     

Minimal Morse flows on compact manifolds

In this paper we prove, using the Poincaré-Hopf inequalities, that a minimal number of non-degenerate singularities can be computed in terms only of abstract homological boundary information. Furthermore, this minimal number can be realized on some manifold with non-empty boundary satisfying the abstract homological boundary information. In fact, we present all possible indices and types (connecting or disconnecting) of singularities realizing this minimal number. The Euler characteristics of all manifolds realizing this minimal number are obtained and the associated Lyapunov graphs of Morse type are described and shown to have the lowest topological complexity.     

Electroreduction of oxygen on octadecylmercaptan self-assembled monolayers

The reduction of oxygen has been studied on octadecylmercaptan self-assembled monolayers adsorbed on gold substrates in borate buffer solutions with a rotating disc electrode. A great inhibition of the oxygen reduction and other electrochemical reactions by these monolayers has been found. However, after polarisation at –0.80 V_SHE the protecting properties of the film against electron transfer reactions are lost, and a behaviour similar to bare gold is observed. Ex situ XPS indicates that the thiol monolayer has not been desorbed to a large extent during oxygen reduction. Disorders of the monolayer structure and desorption of thiol molecules are proposed as the main reasons for the accessibility of electrochemical reactions to the surface.     

Adsorption of self-assembled monolayers of mercaptan on gold

XPS and AES are suitable techniques for studying organic monolayers on metals if radiation doses are kept low. The adsorption of self-assembled (SA) mercaptan monolayers on gold is a process in two stages. The adsorption to near completeness is very rapid. However, the process of orientation of the carbon chains, which is responsible for the blocking of electrochemical reactions takes much longer, as could be shown by ARXPS (angle resolved X-ray photo electron spectroscopy). Adsorption under potential control allows electrochemical experiments during the adsorption process as e.g. the measurement of the capacity of the electric double layer. Furthermore the control of the potential guarantees sure that the metal/liquid interface is well defined during the adsorption process.